Exceptional Response of Cryoablation Followed by Pembrolizumab in a Patient with Metastatic Cervical Carcinosarcoma with High Tumor Mutational Burden: A Case Report.

Cervical carcinosarcoma is an extremely rare type of neoplasm that lacks standard of care. Preclinical and clinical evidence has suggested that cryoablation in combination with immunotherapy may result in a synergistic effect, generating a more robust immune response to distant lesions. A few clinical trials have evaluated the efficacy of such combination treatment in a variety of solid tumors, but with conflicting results. This report describes the first clinical efficacy of cryoablation followed by pembrolizumab observed in a patient with tumor mutational burden (TMB)-high metastatic cervical carcinosarcoma that was negative for programmed cell death protein 1 expression, microsatellite instability stable, and had mutations in DNA polymerase epsilon (POLE). She had achieved complete response (CR) after 3 months of pembrolizumab treatment and had maintained CR as of the time of submission of this manuscript, with a progression-free survival of 11 months and counting. The case exhibited an exceptional response to cryoablation followed by pembrolizumab, potentially attributed to mutations in POLE, which lead to an extremely high TMB. This report paves the avenue for establishing treatment regimens for patients with TMB-high cervical carcinosarcoma. KEY POINTS: Owing to its rarity, cervical carcinosarcoma has not been well characterized, and currently, there is no standard of care for this disease. This report describes the first case of clinical efficacy of cryoablation followed by pembrolizumab observed in a patient with tumor mutational burden-high metastatic cervical carcinosarcoma. The case exhibited an exceptional response (maintained CR as of the time of submission of this article: 11 months) to cryoablation followed by pembrolizumab. This is the first POLE-mutated cervical carcinosarcoma case.

High-intensity focused ultrasound ablation for advanced pancreatic cancer.

AIMS: The aim of this study was to evaluate the efficacy, safety, and survival factors of high-intensity focused ultrasound (HIFU) ablation in the treatment of advanced pancreatic cancer. SUBJECTS AND METHODS: A retrospective analysis was conducted between September 2010 and March 2016. Advanced pancreatic cancer patients with HIFU treatment were enrolled in the analysis to evaluate the efficacy of local ablation, pain relief, and relative complications of HIFU therapy. The main factors that affected Overall survival rate (OSR) and median survival time (MST) were also analyzed. RESULTS: Eighty-six patients received HIFU treatment, with a total of 93 treatments performed, and 83 cases were evaluated. Complete response rate (RR) was 3.6% (3/83) and partial RR was 79.5% (66/83). After HIFU treatment, pain reduction was observed in 74 patients, and the total remission rate was 97.6% (74/76). The total MST was 9.9 months (2-58.7 months), the total OSR in 1 and 2 years was 41.5% and 9.6%, respectively. Minor complications occurred in 97.7% (42/43) patients, including transient fever, abdominal pain, skin burn, and amylase elevation. The univariate analysis showed that the clinical stage, treatment method, ablation efficacy, and combined treatment were significant prognostic factors. CONCLUSION: HIFU can significantly alleviate cancer-related pain and prolong the survival time of patients with pancreatic cancer.

Efficacy and safety of apatinib monotherapy in advanced bone and soft tissue sarcoma: An observational study.

Sarcomas are rare but malignant tumors with high risks of local recurrence and distant metastasis. Anti-angiogenic therapy is a potential strategy against un-controlled and not-organized tumor angiogenesis. We aimed to assess the safety and efficacy of apatinib, an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, in patients with advanced sarcoma. Thirty-one patients who received initial apatinib between September 2015 and August 2016 were retrospectively reviewed. Among them, 19 (61.3%) patients were heavily pretreated with two or more lines of cytotoxic chemotherapy. Apatinib was given at a start-dose of 425 mg qd. During therapy, 9 (29.0%) patients required dose interruption and 7 (22.6%) needed dose reduction, and the mean dosage of apatinib was 372.9 ± 68.4 mg/day. In the study cohort, one patient was treated as adjunctive therapy and 6 patients stopped treatment before radiographic response assessment. Thus, 24 patients were eligible for tumor response evaluation. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The progression free survival was 4.25 (95% confidence interval [CI], 2.22-5.11) months, whereas the overall survival was 9.43 (95% CI, 6.64-18.72) months. Compared with other histological subtypes, leiomyosarcoma did not show significant survival benefits. Most of the adverse events (AEs) were at grade 1 or 2. The main grade 3 AEs were hypertension (6.5%), hand foot skin reaction (6.5%), and diarrhea (3.2%). In conclusion, apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent sarcoma, giving rationale clinical evidence to conduct clinical trials.