Metastatic Xp11 Research Articles

Systemic Therapy in Patients With Metastatic Xp11.2 Translocation Renal Cell Carcinoma.

Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC) is a unique subtype with poor prognosis, its response to systemic therapy is not fully understood, we evaluated the benefit of systemic therapy in these patients. Between May 2006 and December 2019, patients diagnosed with Xp11.2 tRCC from Peking university cancer hospital were collected. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Metastatic Xp11.2 tRCC was found in 45 patients. The median PFS and median OS was 7.4 months (4.5-8.8) and 17.9 months (12.4-24.4), respectively. First-line treatment mainly included sunitinib (n=14), sorafenib (n=15), axitinib (n=6), and pazopanib (n=5), and the median PFS of these regimens were 7.4 months, 5.4 months, 9.4 months, 8.9 months, respectively. Two patients who received Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) plus immune checkpoint inhibitor (ICI) as first line therapy had a PFS of more than 16.6 months and more than 25.6 months, respectively. Twenty-four patients received subsequent therapies, which included VEGFR-TKI/ICI, VEGFR-TKI and mTOR inhibitor. The ORR and median PFS was 33% and 7.1 months, 7.7% and 4.3 months, 0% and 2.1 months for these treatments, respectively. The estimated median OS was 17.3 months (95% CI, 11.2 to not reached) in patients with TKI/ICI treatment and 11.0 months (95% CI, 6.1 to not reached) without TKI/ICI treatment in subsequent therapies (P=.04). Patients with serous cavity effusion or IMDC poor risk groups had significantly shorter median PFS and median OS. Metastatic Xp11.2 tRCC is an aggressive disease. VEGFR-TKI agents appeared to demonstrate some efficacy, VEGFR-TKI /ICI combination might be a useful tool for the treatment of metastatic Xp11.2 tRCC.

Systemic therapy in patients with metastatic Xp11.2 translocation renal cell carcinoma.

341 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 tRCC was found in 45 patients. The median PFS and median OS was 7.4 months (4.5 - 8.8) and 17.9 months (12.4 - 24.4), respectively. First-line treatment mainly included sunitinib (n = 14), sorafenib (n = 15), axitinib (n = 6), and pazopanib (n = 5), and the median PFS of these regimens were 7.4 months, 5.4 months, 9.4 months, 8.9 months, respectively. Two patients who received Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) plus immune checkpoint inhibitor (ICI) as first line therapy had a PFS of more than 16.6 months and more than 25.6 months, respectively. Twenty-four patients received subsequent therapies, which included VEGFR-TKI/ICI, axitinib and mTOR inhibitor, the median PFS for these regimens was 8.5, 7.2 and 2.0 months, respectively. Patients with serous cavity effusion or IMDC poor risk groups had significantly shorter median PFS and median OS. Conclusions: Metastatic Xp11.2 tRCC is an aggressive disease. VEGFR-TKI agents appeared to demonstrate some efficacy, VEGFR-TKI/ICI combination might be a useful tool for the treatment of metastatic Xp11.2 tRCC.

Clinicopathologic features of Xp11.2 translocation renal cell carcinoma and its response to target therapy.

e16559 Background: Xp11.2 translocation renal cell carcinoma (RCC) is a unique RCC subtype with high malignant potential and poor prognosis, its natural course and response to systemic therapy are not fully understood. We analyzed the clinic features of this distinct entity and the benefit of systemic therapy in these patients. Methods: Between May 2006 and December 2019, 1113 consecutive patients diagnosed with RCC from Peking university cancer hospital (Beijing, China) were reviewed, data of the clinical characteristics and outcome of patients with metastatic Xp11.2 RCC were retrospectively collected. Tumor response to systemic therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Results: Metastatic Xp11.2 translocation RCC was found in 41 cases. The median PFS and Median OS was 6.3 months (4.4 - 8.8) and 17.3 months (12.4 - 21.8) for the whole cohort, respectively. First-line treatment mainly included sunitinib (n = 12), sorafenib (n = 13), axitinib (n = 6), and pazopanib (n = 4), and the median PFS of these regimens was 5.4 months, 5.1 months, 9.4 months, 8.3 months, respectively. Twenty-three patients received subsequent therapies, the median PFS and the median OS was 4.3 months and 12 months for the second-line therapy(n = 21), 4.3 months and 14.1 months for the third-line therapy(n = 11), 2.4 months and 9.6 months for the fourth-line therapy(n = 6). Conclusions: Metastatic Xp11.2 translocation RCC is an aggressive disease. Vascular endothelial growth factor receptor - tyrosine kinase inhibitor (VEGFR-TKI) agents appeared to demonstrate some efficacy, the combination of VEGFR-TKI and immune checkpoint inhibitor (ICI) might be a useful tool for the treatment of metastatic Xp11.2 translocation RCC.

A case of metastatic Xp11.2 translocation renal cell carcinoma successfully managed by cytoreductive nephrectomy followed by axitinib therapy.

Targeted medications for metastatic adult Xp11.2 translocation renal cell carcinoma (RCC) remain to be identified. We herein report a case of metastatic Xp11.2 translocation RCC controlled with cytoreductive nephrectomy (CN) and axitinib therapy. A 57-year-old woman complained of fatigue and low back pain. Imaging studies revealed a right renal tumor, with multiple lung and mediastinal lymph node metastases. Although the patient received 10 mg axitinib therapy for 5 months at the hospital she was initially admitted to, the size of the primary and metastatic lesions was not reduced. Thus, she was referred to the Tokyo Women's Medical University Hospital (Tokyo, Japan) for further treatment, where she underwent CN. On macroscopic examination, almost the entire kidney was replaced by a yellowish brown tumor >80 mm in diameter. Immunohistochemical examination confirmed the diagnosis of Xp11.2 translocation RCC. One month after surgery, axitinib therapy was resumed and the size of the metastatic lesions gradually decreased. These findings suggest that axitinib therapy is effective for adult Xp11.2 translocation RCC.

Commentary on “Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma.” Choueiri TK, Lim ZD, Hirsch, MS, Tamboli P, Jonasch E, McDermott DF, Dal Cin P, Corn P, Vaishampayan U, Heng DY, Tannir NM, Dana-Farber Cancer Institute, Boston, MA: Cancer 2010;116:5219–25

Commentary on “Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma.” Choueiri TK, Lim ZD, Hirsch, MS, Tamboli P, Jonasch E, McDermott DF, Dal Cin P, Corn P, Vaishampayan U, Heng DY, Tannir NM, Dana-Farber Cancer Institute, Boston, MA: Cancer 2010;116:5219–25

A case study of metastatic Xp11.2 translocation renal cell carcinoma effectively treated with sunitinib

We report a case of Xp11.2 translocation renal cell carcinoma (RCC) whose lung metastases were effectively treated with sunitinib. A 43-year-old woman presenting with upper abdominal pain was diagnosed with a left renal tumor. Laparoscopic left radical nephrectomy was performed. Histopathological examination of the surgical specimen revealed a clear-cell carcinoma of the left kidney. Two years later, multiple lung metastases were detected and the patient was treated daily with 50mg sunitinib. A computed tomography scan performed after 2 cycles of sunitinib treatment revealed partial regression of these metastases. The partial regression has been maintained for >3years. In retrospective evaluation of the primary RCC, tumor cells showed strong nuclear staining for transcription factor E3 (TFE3) protein and TFE3 split-fluorescence in-situ hybridization revealed translocation involving the TFE3 gene. These findings strongly support diagnosis of Xp11.2 translocation RCC.

Vascular endothelial growth factor-targeted therapy for the treatment of adult metastatic Xp11.2 translocation renal cell carcinoma.

Adult "translocation" renal cell carcinoma (RCC), bearing transcription factor E3 (TFE3) gene fusions at Xp11.2, is a recently recognized, unique entity for which prognosis and therapy remain poorly understood. In the current study, the authors investigated the effect of vascular endothelial growth factor (VEGF)-targeted therapy in this distinct subtype of RCC. A retrospective review was conducted to describe the clinical characteristics and outcome of adult patients with metastatic Xp11.2 RCC who had strong TFE3 nuclear immunostaining and received anti-VEGF therapy. Tumor response to anti-VEGF therapy was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. The Kaplan-Meier method was used to estimate progression-free survival (PFS) and overall survival (OS) distributions. Fifteen patients were identified, of whom 10, 3, and 2 received sunitinib, sorafenib, and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of the patients was 41 years, and the female:male ratio was 4:1. Initial histologic description included clear cell (n = 8 patients), papillary (n = 1 patient), or mixed clear cell/papillary RCC (n = 6 patients). Five patients had received prior systemic therapy. Five patients had undergone fluorescent in situ hybridization analysis and all demonstrated a translocation involving chromosome Xp11.2. When treated with VEGF-targeted therapy, 3 patients achieved a partial response, 7 patients had stable disease, and 5 patients developed progressive disease. The median PFS and OS of the entire cohort were 7.1 months and 14.3 months, respectively. Adult-onset, translocation-associated metastatic RCC is an aggressive disease that affects a younger population of patients with a female predominance. In the current study, VEGF-targeted agents appeared to demonstrate some efficacy.

Response to Sorafenib in a Patient with Metastatic Xp11 Translocation Renal Cell Carcinoma

Sorafenib, a multikinase inhibitor of tumour-cell proliferation and angiogenesis, has been shown to have a role in the treatment of metastatic renal cell carcinoma (RCC). Xp11 translocation carcinoma is a rare subtype of RCC. We report an 18-year-old male patient with metastatic Xp11 translocation RCC who was responsive to sorafenib treatment. Six weeks after commencement of treatment with sorafenib, a CT scan of the patient showed increased central necrosis of the kidney mass and para-aortic lymph nodes as well as regression of the lung and pleural masses. The patient had a progression-free survival of 12 months, and overall survival of 15 months. The most severe adverse effects were grade 3 dermatitis and grade 3 anaemia. This case has demonstrated for the first time that sorafenib is active against Xp11 translocation RCC.

Targeted agents in metastatic Xp11 translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network

BackgroundXp11 translocation renal cell carcinoma (RCC) is an RCC subtype affecting 15% of RCC patients <45 years. We analyzed the benefit of targeted therapy [vascular endothelial growth factor receptor (VEGFR)-targeted agents and/or mammalian target of rapamycin (mTOR) inhibitors] in these patients. Patients and methodsPatients with Xp11 translocation/TFE3 fusion gene metastatic RCC who had received targeted therapy were identified. Nuclear TFE3 positivity was confirmed by reviewing pathology slides. Responses according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. ResultsOverall, 53 patients were identified; 23 had metastatic disease, and of these 21 had received targeted therapy (median age 34 years). Seven patients achieved an objective response. In first line, median PFS was 8.2 months [95% confidence interval (CI) 2.6–14.7 months] for sunitinib (n = 11) versus 2 months (95% CI 0.8–3.3 months) for cytokines (n = 9) (log-rank P = 0.003). Results for further treatment (second, third, or fourth line) were as follows: all three patients receiving sunitinib had a partial response (median PFS 11 months). Seven of eight patients receiving sorafenib had stable disease (median PFS 6 months). One patient receiving mTOR inhibitors had a partial response and six patients had stable disease. Median OS was 27 months with a 19 months median follow-up. ConclusionIn Xp11 translocation RCC, targeted therapy achieved objective responses and prolonged PFS similar to those reported for clear-cell RCC.

Vascular endothelial growth factor (VEGF)-targeted therapy for the treatment of adult metastatic Xp11 translocation renal cell carcinoma.

4606 Background: Adult translocation renal cell carcinoma (RCC), bearing TFE3 gene fusions, is a recently recognized entity for which prognosis and therapy remain poorly understood. The effect of vascular-endothelial growth factor (VEGF)-targeted therapy in this histologic subtype is characterized. Methods: Clinical characteristics and treatment outcomes were evaluated in 15 patients with metastatic RCC with strong TFE-3 nuclear immunostaining who received anti-VEGF therapy at 4 US institutions. Response rate by RECIST and overall survival were documented. Results: Fifteen patients were included in this analysis for which 10, 3, and 2 received sunitinib, sorafenib and monoclonal anti-VEGF antibodies, respectively. The median follow-up was 19.1 months, the median age of patients was 40.8 years (range 18.3-64.8) and the male:female ratio was 3:12. All patients had an initial histologic diagnosis of clear cell (N=8), papillary (n=1) or mixed clear cell/papillary RCC (n=6). Five patients had prior systemic therapy (2 immunotherapy, 1 chemotherapy, 1 vaccine, 1 temsirolimus), 12 patients had prior nephrectomy, 13/15 had lymph node metastases and 6/15 had lung metastases. MSKCC risk groups were favorable, intermediate, poor and missing in 2, 9, 3, and 1 respectively. Four patients had FISH analysis and all demonstrated a translocation involving chromosome Xp11. When treated with VEGF-targeted therapy, 3 patients had a partial response, 7 patients had stable disease and 5 patients had progressive disease. The median tumor shrinkage was by 4.5% (range 48% shrinkage to 67% growth). The median progression-free survival and overall survival of the entire cohort was 7.13 and 14.3 months respectively. Conclusions: Adult-onset translocation-associated mRCC is an aggressive disease that affects a younger population with female predominance. VEGF targeted agents demonstrated efficacy in this small retrospective series. No significant financial relationships to disclose.

A Case of Adult Metastatic Xp11 Translocation Renal Cell Carcinoma Treated Successfully With Sunitinib

Renal cell carcinomas (RCC) associated with Xp11.2 translocations (transcription factor E3 gene fusions) are rare tumors predominantly reported in children. Although only a small number of adult Xp11.2 translocation RCC cases have been described, this is likely due to the possibility of this tumor being unrecognized because of its histologic similarity to either clear cell or papillary subtypes based on hematoxylin and eosin staining. Herein, we describe the first successful case of systemic treatment of metastatic Xp11 RCC with sunitinib, a currently accepted standard of care in metastatic RCC, and attempt to elucidate potential mechanisms behind sunitinib activity in this histologic subtype.

7104 Targeted agents in metastatic Xp11 Translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network

7104 Targeted agents in metastatic Xp11 Translocation/TFE3 gene fusion renal cell carcinoma (RCC): a report from the Juvenile RCC Network

Rapid Development of Metastatic Xp11 Translocation Renal Cell Carcinoma in a Girl Treated for Neuroblastoma

We report the case of a 5-year-old girl with metastatic renal cell carcinoma (RCC) diagnosed 19 months after treatment for neuroblastoma. Immunostaining of the secondary tumor was consistent with Xp11 translocation morphology. This is the second report of this translocation RCC presenting after neuroblastoma and the most rapid onset of RCC reported thus far. The literature regarding secondary RCC after neuroblastoma is reviewed and our case is placed within this historical context. As our understanding of the genetic changes in pediatric tumors advances, the reporting of these rare cases with specific emphasis on genetic testing provides a resource for clinicians and researchers.