Kidney Medullary Carcinoma

Six cycles of the dose-dense methotrexate, vinblastine, adriamycin, and cisplatin-combined chemotherapy were completed after an ultrasound-guided percutaneous biopsy of the renal tumor. After chemotherapy, the size of the original tumor in the right kidney had decreased in size, as well as the other metastatic lesions.

To date, this patient continues to show a near complete response to this treatment regimen. To our knowledge, this is the first documented case of SMARCB1-deficient RMC without hemoglobinopathy to receive this treatment regimen and show such a response.

P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting

P1/2, N=86, Recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Jun 2026 | Trial primary completion date: Sep 2025 --> Jun 2026

RMC frequently presents with hematuria and is highly likely to spread to the retroperitoneal lymph nodes. Survival outcomes are improving with contemporary management. RCCU-MP is very rare and may be slightly less aggressive.

P2, N=314, Recruiting, National Cancer Institute (NCI) | N=224 --> 314

This tumor proliferation was INI1/SMARCB1-deficient, and expressed cytokeratins. Given the fact that the histopathological data showed an undifferentiated INI1-deficient carcinoma and that the patient has a kidney lesion and a sickle cell trait, the final diagnosis was lymph node metastasis of SMARCB1-deficient renal medullary carcinoma (OMS 2022).

Improved therapy targets for each kidney tumour can be achieved using immunohistochemistry (IHC) and molecular definition updates. This study aims to highlight new developments in the WHO 2022 categorization of renal tumours with regard to diagnostic, morphological, molecular, IHC, clinical, and prognostic updates.

These data provide new mechanistic insights into the complex interaction between Tax and NF-κB, therefore improving our understanding of HTLV-I oncogenic pathogenesis. They also expand our knowledge and establish a new animal model of macrophage neoplasms and adrenal tumors.

P2, N=267, Completed, Epizyme, Inc. | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Feb 2024

She was initiated on naproxen (NPX) at a dose of 250 mg two times per day. The patient responded to NPX, and after stabilisation, she underwent an adrenalectomy. There was a complete resolution of fever with normalisation of IL-6 levels postoperatively.

P2, N=267, Active, not recruiting, Epizyme, Inc. | Trial primary completion date: Jun 2024 --> Feb 2024

P1/2, N=100, Enrolling by invitation, Epizyme, Inc. | Trial completion date: Dec 2024 --> Nov 2025 | Trial primary completion date: Dec 2024 --> Nov 2025

Already, important management aspects are apparent for several of these entities, while emerging therapeutic angles are coming into view. A brief, clinically-oriented introduction of the entities in this new category, focusing on relevant diagnostic, molecular, and management aspects, is the subject of this review.

P2, N=224, Recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2024 --> Feb 2025 | Trial primary completion date: Feb 2024 --> Feb 2025

P2, N=30, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

P1/2, N=100, Enrolling by invitation, Epizyme, Inc. | Active, not recruiting --> Enrolling by invitation

It is important to exclude these specific tumor types in cases with similar morphologic spectrum before rendering a diagnosis of high-grade papillary RCC, collecting duct carcinoma, or RCC, NOS. Several gray areas exist within the spectrum of high-grade uncommon types of RCC, necessitating continued research to enhance diagnostic precision and therapeutic options.

P2, N=60, Not yet recruiting, National Cancer Institute (NCI)

The first clinical study of combination PARPi and ICB therapy in advanced kidney cancer did not show clinical benefit in multiple genomically defined metastatic RCC cohorts or RMC.

Sunitinib is the only single-agent tyrosine kinase inhibitor (TKI) to have demonstrated a clinicalbenefit (vs everolimus) in a study population with a broad range of histologic subtypes of metastatic nccRCC (Armstrong et al. The secondary endpoint is OS; safety will also be assessed. Enrollment is ongoing, and patients will be recruited across sites inEurope, North and South America, and the Asia-Pacific region.

P2, N=38, Active, not recruiting, Mayo Clinic | Trial completion date: Nov 2023 --> Nov 2024

P1, N=152, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

P2, N=267, Active, not recruiting, Epizyme, Inc. | Trial completion date: Dec 2024 --> Jun 2024

This prospective evaluation showed no evidence of clinical activity for pembrolizumab in patients with RMC, irrespective of PD-L1 or TIL levels.

Methods The SUNNIFORECAST study (NCT03075423) is a phase 2 randomised investigator-initiated trial of nivolumab with ipilimumab vs. standard of care in patients with previously untreated and advanced nccRCC. The diagnosis of molecular defined RCC is still problematic in daily diagnosis. The study was supported by a grant of BMS (BMS).

Sunitinib is the only TKI to have shown a clinical benefit (vs everolimus) in a broad range of histologic subtypes of metastatic nccRCC (Armstrong et al. The secondary endpoint is OS; safety will also be assessed. STELLAR-304 is currently recruiting patients in 29 countries in Europe, North and South America, and the Asia-Pacific region.

P2, N=10, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Jul 2024 --> Jul 2025

Conversely, high-intensity exercise associated with increased muscle mass may be a risk factor for renal medullary carcinoma, a rare RCC subtype that predominantly occurs in individuals with sickle hemoglobinopathies. Herein, we highlight methodologic challenges associated with studying the influence of obesity on RCC and review the clinical evidence and potential underlying mechanisms associating RCC with BMI and body composition.

P2, N=10, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024

Ferroptosis resistance links TAL cell survival with the high extracellular medullar iron concentrations associated with sickle cell trait, an environment propitious to the mutagenic events associated with RMC development. This unique environment may explain why RMC is the only SMARCB1-deficient tumour arising from epithelial cells, differentiating RMC from rhabdoid tumours arising from neural crest cells.

The unique management of each vhRCC subtype necessitates accurate pathologic diagnosis and dedicated research efforts. Herein, we discuss tailored recommendations for each vhRCC histology informed by ongoing research and clinical experience.

P1, N=42, Completed, Epizyme, Inc. | Active, not recruiting --> Completed

Although tazemetostat did not meet its primary efficacy endpoint in this population of refractory pediatric tumors (ORR: 5%, 90% CI 1%, 20%), 25% of patients with multiple histologic diagnoses experienced prolonged stable disease of > 6 months (range: 9-26 cycles), suggesting a potential effect of tazemetostat on disease stabilization.

Our results suggest that pevonedistat synergises with carboplatin to inhibit RMC cell and tumour growth through inhibition of DNA damage repair. These findings support the development of a clinical trial combining pevonedistat with platinum-based chemotherapy for RMC.

Further, reconstitution of SMARCB1 restored renal tumor sensitivity to hypoxic stress in vitro and in vivo. Together, our results demonstrate a physiological role for SMARCB1 degradation in response to hypoxic stress, connect the renal medullary hypoxia induced by SCT with an increased risk of SMARCB1-negative RMC, and shed light into the mechanisms mediating the resistance of SMARCB1-null renal tumors against angiogenesis inhibition therapies.

Our study showed no benefit for bevacizumab added to chemotherapy in metastatic RMC and CDC with higher than expected toxicity. Consequently, GC regimen remains a therapeutic option for RMC/CDC patients.

P2, N=202, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2022 --> Dec 2025 | Trial primary completion date: Dec 2022 --> Dec 2025

P1/2, N=100, Active, not recruiting, Epizyme, Inc. | Trial completion date: Apr 2024 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

Trending levels of serum biomarkers such as CA-125 in RMC may assist (1) predicting development or location of metastases, (2) correlate treatment response or efficacy (3) identify a new therapeutic target. Further work to evaluate the expression of markers on the RMC cell surface is ongoing.