Senescence-Associated Secretory Phenotype Determines Survival and Therapeutic Response in Cervical Cancer.

Molecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an impact on disease specific survival (DSS) (Hazzard's ratio; HR = 1.51-2.1). Surprisingly, all ten proteins are implicated in senescence-associated secreted phenotype (SASP), a hallmark of cellular senescence. Machine learning using Ridge regression of these SASP proteins can robustly stratify patients with high SASP, which is associated with poor survival, and patients with low SASP associated with good survival (HR = 3.09-4.52). Furthermore, brachytherapy, an effective therapy for cervical cancer, greatly improves survival in SASP-high patients (HR = 3.3, p < 5 × 10-5) but has little impact on survival of SASP-low patients (HR = 1.5, p = 0.31). These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer.

Clinical calculator predictive of chemotherapy benefit in stage 1A uterine papillary serous cancers.

OBJECTIVE: Determine the utility of a clinical calculator to predict the benefit of chemotherapy in stage IA uterine papillary serous cancer (UPSC). PATIENTS AND METHODS: Data were collected from NCDB from years 2010-2014. Based on demographic and surgical characteristics, a clinical score was developed using the random survival forest machine learning algorithm. RESULTS: Of 1,751 patients with stage IA UPSC, 1,012 (58%) received chemotherapy and 739 (42%) did not. Older age (HR 1.06), comorbidities (HR 1.31), larger tumor size (HR 1.27), lymphovascular invasion (HR 1.86), positive peritoneal cytology (HR 2.62), no pelvic lymph node dissection (HR 1.51), and no chemotherapy (HR 2.16) were associated with poorer prognosis. Compared to no chemotherapy, patients who underwent chemotherapy had a 5-year overall survival of 80% vs. 67%. To better delineate those who may derive more benefit from chemotherapy, we designed a clinical calculator capable of dividing patients into low, moderate, and high-risk groups with associated 5-year OS of 86%, 73%, and 53%, respectively. Using the calculator to assess the relative benefit of chemotherapy in each risk group, chemotherapy improved the 5-year OS in the high (42% to 64%; p < 0.001) and moderate risk group (66% to 79%; p < 0.001) but did not benefit the low risk group (84% to 87%; p = 0.29). CONCLUSION: Our results suggest a clinical calculator is useful for counseling and personalizing chemotherapy for stage IA UPSC.

Combination of Hip Strengthening and Manipulative Therapy for the Treatment of Plantar Fasciitis: A Case Report.

OBJECTIVE: The purpose of this case report is to describe the management of using a combination of hip strengthening and manipulative therapy (MT) for a patient with plantar fasciitis. CLINICAL FEATURES: A 44-year-old patient reported heel pain for approximately 1 year before treatment. The patient reported plantar heel pain and tenderness at the calcaneal tuberosity. The pain was most noticeable in the morning but was reduced after a 30-minute walk. A diagnosis of plantar fasciitis was made at the initial assessment. INTERVENTION AND OUTCOMES: Initially, a clinical evaluation was performed to measure pain intensity (Numeric Pain Rating Scale), pressure-pain threshold (algometry), and perceived exertion (OMNI Resistance Exercise Scale). The patient then underwent 10 sessions of hip strengthening and MT over a period of 3 months. After the treatment, the intensity of pain and the pressure-pain threshold was reevaluated. The patient reported an improvement in pain intensity (baseline score = 6 vs final score = 1) and an increase in the pressure-pain threshold (initial score = 2.6 vs final score = 7.1). Perceived exertion was also improved after hip muscle strength training (initial score = 10 vs final score = 8). CONCLUSION: The combination of hip strengthening and MT improved foot pain in a patient with a clinical diagnosis of plantar fasciitis.