Precision cancer medicine: Concepts, current practice, and future developments.

Precision cancer medicine is a multidisciplinary team effort that requires involvement and commitment of many stakeholders including the society at large. Building on the success of significant advances in precision therapy for oncological patients over the last two decades, future developments will be significantly shaped by improvements in scalable molecular diagnostics in which increasingly complex multilayered datasets require transformation into clinically useful information guiding patient management at fast turnaround times. Adaptive profiling strategies involving tissue- and liquid-based testing that account for the immense plasticity of cancer during the patient's journey and also include early detection approaches are already finding their way into clinical routine and will become paramount. A second major driver is the development of smart clinical trials and trial concepts which, complemented by real-world evidence, rapidly broaden the spectrum of therapeutic options. Tight coordination with regulatory agencies and health technology assessment bodies is crucial in this context. Multicentric networks operating nationally and internationally are key in implementing precision oncology in clinical practice and support developing and improving the ecosystem and framework needed to turn invocation into benefits for patients. The review provides an overview of the diagnostic tools, innovative clinical studies, and collaborative efforts needed to realize precision cancer medicine.

Characteristics and treatment results of patients with gastroenteropancreatic neuroendocrine tumors in a tertiary care centre.

BACKGROUND: Gastroenteropancreatic Neuroendocrine tumors (GEP-NET) are rare neoplasms with limited reported data from the Middle East. Our study aims to report the clinicopathological feature, treatment patterns, and survival outcomes of patients with GEP-NET from our part of the world. METHODS: Medical records of patients diagnosed with GEP-NET between January 2011 and December 2016 at a single center in Saudi Arabia were reviewed retrospectively, and complete clinicopathological and treatment data were collected. Patients' survival was estimated by the Kaplan-Meier method. RESULTS: A total of 72 patients were identified with a median age of 51 years (range 27-82) and male-to-female ratio of (1.1). The most common tumor location was the pancreas (29.1%), followed by small bowel (25%), stomach (12.5%), rectum (8.3%), colon (8.3%), and appendix (6.9%). Forty-one patients (57%) had well-differentiated grade (G)1, 21 (29%) had G2, and 4 (6%) had G3. In five patients, the pathology was neuroendocrine carcinoma and in one it could not be classified. 54.2% of the patients were metastatic at diagnosis. Forty-two patients underwent surgical resection as primary management while 26 underwent systemic therapy, three patients were put on active surveillance, and one was treated endoscopically with polypectomy. The 5-year overall survival and progression-free survivals were 77.2% and 49%, respectively, for the whole group. Patients with G1 and 2 disease, lower Ki-67 index, and surgically treated as primary management had significantly better survival outcomes. CONCLUSION: Our study suggests that the most common tumor locations are similar to western reported data. However, there seems to be a higher incidence of metastatic disease at presentation than in the rest of the world.

Real-World Outcome and Prognostic Factors of Pazopanib in Advanced Soft Tissue Sarcoma.

PURPOSE: Pazopanib has been approved for treating soft tissue sarcomas (STS) after chemotherapy. We aimed to evaluate the prognostic factors, clinical outcomes, and tolerability of pazopanib in patients with STS. PATIENTS AND METHODS: Forty-five patients treated between June 2015 and August 2019 were reviewed. Clinical outcome was measured by assessing the disease control rate (DCR) using Response Evaluation Criteria in Solid Tumors (version 1.1). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Adverse effects were assessed using the Common Terminology Criteria for Adverse Events (version 5.0). RESULTS: The median age of patients at diagnosis was 28 (interquartile range (IQR), 23-45) years. Pazopanib was used as the second-line treatment in 46.7% and the subsequent line in 53.3% of patients. The overall DCR was 55.6%, and at 8 and 12 weeks, it was 52.3% and 35.5%, respectively; the median duration of response was 7 (IQR: 2-18) months. Pazopanib-induced hypothyroidism was associated with DCR, with an odds ratio of 7 (95% confidence interval [95% CI: 1.7-27.5], p<0.01). The median PFS and OS were 4.1 (95% CI: 0.85-7.42) and 12.4 months (95% CI: 6.5-18.36), respectively. Hypothyroidism and response to pazopanib, better ECOG PS, histological subtypes desmoid tumor/aggressive fibromatosis (DT/AF), and alveolar soft part sarcoma (ASPS) were favorable prognostic factors for PFS. Hypothyroidism and response to pazopanib were significant favorable factors for OS. There was no statistical difference in the OS between patients using pazopanib as the second-line therapy and those using it as the subsequent-line therapy. CONCLUSION: Pazopanib is an effective treatment for STS. However, it showed variability in the clinical outcome in favor of ASPS and an outstanding response in the DT/AF subtype. Pazopanib-induced hypothyroidism is a good prognostic factor for disease control and is associated with prolonged PFS and OS.

Late Recurrence of Metastatic Meningioma in the Lung in a Patient with Endometrial Cancer: A Case Report.

BACKGROUND Meningiomas are the most frequently diagnosed of all primary brain tumors, including glioblastomas, and of all other central nervous system tumors. While non-malignant meningiomas account for 36.7% of all primary brain tumors, malignant meningioma is much less common, accounting for just 0.6%. The annual incidence of meningiomas in the United States is 5.3 per 100 000 people. The median age of diagnosis is 64, and incidence rises steadily with advancing age. Furthermore, extracranial metastatic meningioma remains extremely rare (0.1%), with the most common location for metastasis being the lung. CASE REPORT We report a case of a patient with biopsy-proven endometrial adenocarcinoma with suspicious lung nodule, Stage IVB. She was managed with chemotherapy followed by surgery and radiation. During her course of management, she was found to have progressive pulmonary nodules. Later, biopsy from the pulmonary nodules showed a metastatic meningioma. CONCLUSIONS Our case highlights the importance of early recognition of metastatic meningioma, especially when treating patients with a history of intracranial meningioma.

Association Between Neutrophil-Lymphocyte Ratio and Oncotype Dx Recurrence Score in Early-Stage Hormonal Receptor-Positive, HER2-Negative, Node-Negative Breast Cancer.

PURPOSE: The correlation between the preoperative neutrophil-to-lymphocyte ratio (NLR) and Oncotype DX® (ODX) recurrence score (RS) has not yet been established. We aimed to investigate the association between NLR and ODX RS in patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) early-stage breast cancer (BC). PATIENTS AND METHODS: This retrospective study included consecutive patients with HR+/HER2-, node-negative primary BC who underwent surgical tumor resection from 2011 to 2019. Receiver operating characteristic curve analysis was used to obtain an optimal NLR cutoff value. Logistic regression analyses were used to estimate associations between various parameters and ODX RS. Furthermore, the factors significantly associated with the ODX RS in multivariable analysis were incorporated in a separate model and estimated using logistic regression. RESULTS: A total of 160 patients were enrolled. The optimal preoperative NLR cutoff was 2.15. Multivariable analysis revealed that NLR and tumor grade (G1/G2 vs G3) were independent predictive factors of high RS cutoff (≥26). Moreover, including the two variables yielded a stronger association; patients with low NLR and low-grade tumors were unlikely to have high RS (≥26; odds ratio [OR] = 0.03, 95% confidence interval [CI]: 0.006-0.154; p < 0.001). Conversely, the presence of any of the following factors made patients unlikely to have low RS (<16; OR = 0.34, 95% CI: 0.16-0.73; p = 0.006): high NLR, high grade, or high Ki-67 levels (>20). CONCLUSION: NLR is a promising independent predictor of RS. Furthermore, in addition to tumor grade and Ki-67 level, they together are also a potential indicator of high and low RS. However, further studies are required to validate this hypothesis.