Tailoring advanced breast cancer treatment after cyclin-dependent kinase 4/6 inhibitors progression - real-world data analysis.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) represent the gold standard of the hormone receptor positive human epidermal growth factor receptor 2 (HER-2) negative advanced breast cancer. However, optimal treatment after disease progression is a matter of debate. We aimed to assess predictive and prognostic factors associated with the treatment outcome following CDK4/6i progression. Methods: We retrospectively analyzed patients who progressed on CDK4/6i treatment between 2018 and 2024. Treatment based on molecular findings (PIK3CA mutation), genetic findings (BRCA1/2 germline mutation), or adapted to the change in the tumor phenotype in rebiopsy (anti-HER2 therapy in the transformation to HER-2-positive disease) was grouped into tailored treatment and compared to the endocrine-based therapy and chemotherapy alone. Results: Five hundred twelve patients were treated with CDK4/6i. Two hundred patients with disease progression were enrolled in the study. Duration of response to CDK4/6i was not predictive of the response to subsequent treatment, whereas the progression in the central nervous system was the worst prognostic factor. Thirty patients were ineligible for subsequent treatment. Survival after CDK4/6i progression was significantly longer in patients eligible for tailored treatment. The median PFS in patients with tailored treatment (n=19) was 13.5 months vs. 4.9 months in patients with non-tailored therapy (n=151; p=0.045). 12-month PFS was 54.1% with tailored treatment [95% CI 24.1-76.7%] compared to 18.5% with non-tailored therapy [95% CI 11.6-26.6%]. The median OS for patients treated with a tailored approach was not reached compared to 11.5 months with non-tailored treatment (p=0.016). The 24-month OS for patients treated with a tailored approach was 80.2% [95% CI 40.3-94.8%] compared to 21.1% [95% CI 12.2-31.7%] for patients with non-tailored treatment. Conclusions: Tailoring of subsequent treatment strategy seems to be essential for achieving long-term benefit. Further studies are required, as the prognosis after CDK4/6i progression remains dismal, especially in cases affecting the central nervous system.

Brain metastases of sarcoma: a rare phenomenon in rare tumours.

The usual site for distant metastases of sarcoma is lungs, while brain metastasis (BM) occurs much less frequently and usually late in the disease progression. Despite the advancement in cancer treatment, the outcome for patients with brain metastasis is poor, and their lifespan is short. The frequency of BM in sarcoma seems to be affected by the location and histology of the primary tumour. Sarcoma subtypes with a high propensity for brain metastasis are ASPS, leiomyosarcoma and osteosarcoma. There are no clear guidelines for the treatment of sarcoma brain metastasis. However, therapeutic options include surgery, radiotherapy and chemotherapy, and are often combined. Targeted therapies are a promising treatment option for sarcoma but require investigation in patients with BM. The following review presents the data on sarcoma brain metastasis incidence, treatment and prognosis.

Safety and Feasibility of Radiation Therapy Combined with CDK 4/6 Inhibitors in the Management of Advanced Breast Cancer.

The addition of CDK4/6 inhibitors to endocrine therapy in advanced hormone receptor-positive HER2-negative breast cancer has led to practice-changing improvements in overall survival. However, data concerning the safety of CDK4/6i combination with radiotherapy (RT) are conflicting. A retrospective evaluation of 288 advanced breast cancer patients (pts) treated with CDK4/6i was performed, and 100 pts also received RT. Forty-six pts received 63 RT courses concurrently and fifty-four sequentially before CDK4/6i initiation (76 RT courses). Neutropenia was common (79%) and more frequent during and after concurrent RT than sequential RT (86% vs. 76%); however, CDK4/6i dose reduction rates were similar. In patients treated with CDK4/6i alone, the dose reduction rate was 42% (79 pts) versus 38% with combined therapy, and 5% discontinued treatment due to toxicity in the combined group. The risk of CDK4/6i dose reduction was correlated with neutropenia grade, RT performed within the first two CDK4/6i cycles, and more than one concurrent RT; a tendency was observed in concurrent bone irradiation. However, on multivariate regression analysis, only ECOG 1 performance status and severe neutropenia at the beginning of the second cycle were found to be associated with a higher risk of CDK4/6i dose reduction. This largest single-center experience published to date confirmed the acceptable safety profile of the CDK4/6i and RT combination without a significantly increased toxicity compared with CDK4/6i alone. However, one might delay RT for the first two CDK4/6i cycles, when myelotoxic AE are most common.

Anti-androgen hormonal therapy for cancer and other diseases.

The development of targeted therapies has been a consistent goal for hormone-related diseases treatment. As a result of increased knowledge of the role of androgens in different diseases, anti-androgen treatment is becoming increasingly important in targeted therapy. Androgens play an important role in different disorders, therefore, androgen receptor signalling is a crucial factor in pathological conditions. The androgen receptor is a transcription factor activated by the testosterone metabolite 5α-dihydrotestosterone and regulates the expression of genes related to sexual differentiation, growth and survival of prostate cells, and to a certain extent, cancer progression. Herein, we review anti-androgen therapies in cancer and other selected diseases and provide examples where anti-androgen drugs can be used as both main and supportive treatments in the multimodal therapeutic scheme. Even in diseases with low serum levels of testosterone or DHT, anti-androgen therapy plays an important role in new treatments. Therefore, the use of anti-androgens is an appealing strategy in which to overcome resistance to primary treatment by assuring better therapy results. In this review, we take into account both older generation hormonal drugs and the new drug classes. Additionally, we review recent studies that suggest new anti-androgen agents have not entirely replaced some of the old standards.

Intrathecal morphine reduces blood loss during idiopathic scoliosis surgery: retrospective study of 256 pediatric cases.

BACKGROUND: This retrospective cohort study was designed to assess the impact of intrathecal morphine compared with no intrathecal morphine on blood loss and on hemodynamic stability during surgery for pediatric idiopathic scoliosis correction. METHODS: A retrospective review was done of 256 anesthetic charts who underwent scoliosis surgery between January 1993 and February 2012 by the same orthopedic surgeon. 128 patients were operated on before 2003 without intrathecal morphine (NITM group) and 128 were treated later on with intrathecal morphine (ITM group).Primary endpoints were a 20% decrease in blood loss in the ITM group and hemodynamic stability. RESULTS: Both groups were similar for age, girl/boy ratio, weight and duration of surgery. Blood loss was significantly greater in the NITM group: 1793.1 ± 964.3 ml vs 655.8 ± 323.0 ml (P < 0.0001). Overall mean decrease in blood loss was 63.4% between the NITM group and the ITM group. A significantly (P < 0.0001) greater number of patients from the NITM group (122) received blood transfusions as compared to the ITM group (30). The volume of blood transfused per patient was significantly greater in the NITM group (701.4 ± 492.5 ml) than in the ITM group (293.7 ± 170.9 ml) (P < 0.0001). Heart rate was stable intra-operatively in both groups. Variation in blood pressure >20% of baseline occurred more frequently in the NITM group (28.1%) than in the ITM group (14.8%) (P = 0.01). CONCLUSIONS: These data demonstrate that intrathecal morphine in pediatric surgical scoliosis correction significantly decreases intra-operative blood loss and transfusions and enhances blood pressure stability.

Large cell carcinoma of the lung and squamous cell carcinoma of the oropharynx presenting as uveitis.

Ocular manifestations of systemic malignancy may precede the diagnosis of cancer; some intraocular lymphomas can present initially as chronic uveitis. The two cases described were found to have underlying carcinomas of the lung and oropharynx. Both presented with chronic uveitis and decreased visual acuity that were not responding to antiinflammatory therapy.