Bone metastases as the initial presentation of hepatocellular carcinoma. Two case reports and a literature review.

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver and is the fifth most common cancer in the world; its incidence has been increasing in recent years. Extrahepatic spread is present at the time of diagnosis in only about 5 to 15% of patients. Skeletal metastasis of HCC occurs less frequently compared with other cancers and is considered a rare primary form of presentation. We report two cases of unsuspected HCC presenting with multiple bone lesions as the initial presentation. The first patient was a 76-year-old man with symptoms of fatigue and back pain. The PET-CT revealed the hypercaptant bone lesions and a liver lesion. The pathology report showed that the metastases were positive for the hepatic marker HEPAR-1, indicating that they had originated from the HCC. The second patient was a 56-year-old man. He presented to the emergency department for right shoulder pain and weakness of the entire right arm with no history of trauma. During hospitalization, the patient became quadriplegic. MRI revealed osseous blastic lesions in the cervical vertebrae and right shoulder. A CT-guided biopsy was performed in the cervical lesion and showed poorly differentiated carcinoma. Immunohistochemistry staining was positive for HEPAR-1. In conclusion, this cases show an unusual presentation of HCC with skeletal metastasis.

Impact of healthcare inequities on survival in Mexican patients with metastatic renal cell carcinoma.

Introduction: The survival of patients with metastatic renal cell carcinoma (mRCC) has improved dramatically due to novel systemic treatments. However, mRCC mortality continues to rise in Latin America. Methods: A retrospective, multicenter study of patients diagnosed with mRCC between 2010-2018 in Mexico City was conducted. The aim of the study was to evaluate the impact of healthcare insurance on access to treatment and survival in patients with mRCC. Results: Among 924 patients, 55.4%, 42.6%, and 1.9% had no insurance (NI), social security, (SS) and private insurance (PI), respectively. De novo metastatic disease was more common in NI patients (70.9%) compared to SS (47.2%) and PI (55.6%) patients (p<0.001). According to IMDC Prognostic Index, 20.2% were classified as favorable, 49% as intermediate, and 30.8% as poor-risk disease. Access to systemic treatment differed by healthcare insurance: 36.1%, 99.5%, and 100% for the NI, SS, and PI patients, respectively (p<0.001). NI patients received fewer lines of treatment, with 24.8% receiving only one line of treatment (p<0.001). Median overall survival (OS) was 13.9 months for NI, 98.9 months for SS, and 147.6 months for NI patients (p<0.001). In multivariate analysis, NI status, brain metastases, sarcomatoid features, bone metastases, no treatment were significantly associated with worse OS. Conclusion: OS in mRCC was affected by insurance availability in this resource-limited cohort of Mexican patients. These results underscore the need for effective strategies to achieve equitable healthcare access in an era of effective, yet costly systemic treatments.

Upfront Cytoreductive Nephrectomy for Metastatic Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors or Targeted Therapy: An Observational Study from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: The role of upfront cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) in the era of immune checkpoint inhibitors is unclear. OBJECTIVE: To evaluate the relationship between upfront CN and clinical outcomes in the setting of mRCC treated with immune checkpoint inhibitors or targeted therapy. DESIGN, SETTING, AND PARTICIPANTS: Using the International Metastatic RCC Database Consortium, we retrospectively identified patients diagnosed with de novo mRCC treated with immune checkpoint inhibitors or targeted therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Overall survival (OS) was compared between the two groups using the Kaplan-Meier method and multivariable Cox regressions adjusting for known prognostic factors. RESULTS AND LIMITATIONS: We identified a total of 4639 eligible patients with mRCC. Among the 4202 patients treated with targeted therapy and 437 patients treated with immune checkpoint inhibitors, 2326 (55%) and 234 (54%) patients received upfront CN prior to treatment start. In multivariable analyses, CN was associated with significantly better OS in both the immune checkpoint inhibitor-treated (hazard ratio [HR]: 0.61; 95% confidence interval [CI], 0.41-0.90, p = 0.013) and the targeted therapy treatment (HR: 0.72; 95% CI, 0.67-0.78, p < 0.001) group. There was no difference in OS benefit of CN between the immune checkpoint inhibitor and targeted therapy treatment groups (interaction p = 0.6). Limitations include selection of patients from large academic centers and the retrospective nature of the study. CONCLUSIONS: Upfront CN is associated with a significant OS benefit in selected patients treated by either immune checkpoint inhibitors or targeted therapy, and still has a role in selected patients in the era of immune checkpoint inhibitors. PATIENT SUMMARY: Before effective systemic therapies were available for metastatic kidney cancer, surgical removal of the primary (kidney) tumor was the mainstay of treatment. The role of removing the primary tumor has recently been called into question given that more effective systemic therapies have become available. In this study, we find that removal of the primary kidney tumor still has a benefit for selected patients treated with highly effective modern systemic therapies, including targeted therapies and immune checkpoint inhibitors.

Large retroperitoneal lymphadenopathy and increased risk of venous thromboembolism in patients receiving first-line chemotherapy for metastatic germ cell tumors: A study by the global germ cell cancer group (G3).

BACKGROUND: Metastatic germ cell tumor (mGCT) patients receiving chemotherapy have increased risk of life-threatening venous thromboembolism (VTE). Identifying VTE risk factors may guide thromboprophylaxis in this highly curable population. METHODS: Data were collected from mGCT patients receiving first-line platinum-based chemotherapy at 22 centers. Predefined variables included International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification, long-axis diameter of largest retroperitoneal lymph node (RPLN), Khorana score, and use of indwelling vascular access device (VAD). VTE occurring at baseline, during chemotherapy and within 90 days, was analyzed. RESULTS: Data from 1135 patients were collected. Median age was 31 years (range 10-74). IGCCCG risk was 64% good, 20% intermediate, and 16% poor. VTE occurred in 150 (13%) patients. RPLN >3.5 cm demonstrated highest discriminatory accuracy for VTE (AUC 0.632, P < .001) and was associated with significantly higher risk of VTE in univariable analysis (22% vs 8%, OR 3.0, P < .001) and multivariable analysis (OR 1.8, P = .02). Other significant risk factors included, Khorana score ≥3 (OR 2.6, P = .008) and VAD use (OR 2.7, P < .001). CONCLUSIONS: Large RPLN and VAD use are independent risk factors for VTE in mGCT patients receiving chemotherapy. VAD use should be minimized in this population and thromboprophylaxis might be considered for large RPLN.

Spontaneous regression as a 'burned-out' non-seminomatous testicular germ cell tumor: a case report and literature review.

Testicular germ cell tumors (TGCTs) are the most frequent type of cancer in young adults. An exceptional event is the spontaneous regression (SR) of the primary tumor. Herein, we describe a burned-out non-seminomatous TGCT case and relevant literature review. A 34-year-old male presenting with low back pain was found to have a retroperitoneal mass upon urotomography. During workup, a heterogeneous testicular mass was evident, and its biopsy showed findings that support the diagnosis of spontaneous tumoral regression. The patient underwent unilateral orchiectomy and a chemotherapy protocol was later initiated, with 85% regression of the retroperitoneal metastatic mass. No progression of the primary tumor has been found. The etiology of SR across different cancer types appears to be associated with the host's immune response and an angiogenic disturbance of the tumor microenvironment. The burned-out phenomenon is a rare event that needs further research into its molecular sequencing.

Outcomes of Metastatic Chromophobe Renal Cell Carcinoma (chrRCC) in the Targeted Therapy Era: Results from the International Metastatic Renal Cell Cancer Database Consortium (IMDC).

Background: Treatment outcomes are poorly characterized in patients with metastatic chromophobe renal cell cancer (chrRCC), a subtype of renal cell carcinoma. Objective: This retrospective series aims to determine metastatic chrRCC treatment outcomes in the targeted therapy era. Methods: A retrospective data analysis was performed using the IMDC dataset of 4970 patients to determine metastatic chrRCC treatment outcomes in the targeted therapy era. Results: 109/4970 (2.2%) patients had metastatic chrRCC out of all patients with mRCC treated with targeted therapy. These patients were compared with 4861/4970 (97.8%) clear cell mRCC (ccRCC) patients. Patients with metastatic chrRCC had a similar OS compared to patients with ccRCC (23.8 months (95% CI 16.7 - 28.1) vs 22.4 months (95% CI 21.4 - 23.4), respectively (p = 0.0908). Patients with IMDC favorable (18%), intermediate (59%) and poor risk (23%) had median overall survivals of 31.4, 27.3, and 4.8 months, respectively (p = 0.028). Conclusions: To the authors' knowledge, this is the largest series of metastatic chrRCC patients and these results set new benchmarks for survival in clinical trial design and patient counseling. The IMDC criteria risk categories seem to stratify patients into appropriate favourable, intermediate, and poor risk groups, although larger patient numbers are required. It appears that outcomes between metastatic chrRCC and ccRCC are similar when treated with conventional targeted therapies. Patients with metastatic chrRCC can be treated with tyrosine kinase inhibitors and enrolled in clinical trials to further measure outcomes in this rare patient population.