A narrative review of the evolving landscape of the management of metastatic gastric cancer: the role of targeted therapies.

Background and Objective: Gastric cancer is the fifth most common cancer worldwide and the fourth leading cause of cancer-related death. Unfortunately, patients often present with advanced disease at diagnosis, which is directly related to its high mortality. Numerous trials, as early as the 1980's, have shown that cytotoxic chemotherapy improves survival. This review will focus on targeted therapies and immunotherapies which have emerged as treatment options for metastatic gastric cancer, often used in conjunction with cytotoxic chemotherapy. Here we will review the relevant clinical trials of targeted therapies and immunotherapies in the treatment of metastatic gastric cancer. Methods: We performed an extensive review of articles in the PubMed database pertaining to targeted therapies and immunotherapies in the treatment of metastatic gastric cancer. Additionally, updated guidelines from the National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) were reviewed. Key Content and Findings: Cytotoxic chemotherapy remains the backbone of treatment of metastatic gastric cancer, but the development of targeted therapies and immunotherapy have revolutionized its treatment with improved survival and outcomes. Therapies have been developed which target human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor receptor-2 (VEGFR-2), and tyrosine kinase pathways. Novel targeted therapies are currently being investigated with promising results thus far. Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has proven to be a significant advancement in the treatment of gastric cancer. Conclusions: Targeted therapies and immunotherapies have improved survival and outcomes in metastatic gastric cancer, however more research is needed to make even greater strides.

Real-world evaluation of effectiveness and tolerance of chemotherapy for early-stage breast cancer in older women.

PURPOSE: Older patients with early-stage breast cancer (ESBC) tend to receive less aggressive treatment, have higher mortality rates, and are underrepresented in clinical trials. Outcomes, tolerance and toxicity of chemotherapy are underreported. Thus, we assessed the outcomes of chemotherapy in the real-world in a community oncology setting. METHODS: We retrospectively chart reviewed consecutive older patients (≥ 70 years) with ESBC diagnosed between January 1, 2010, and December 31, 2016, who received chemotherapy at our institution. Study outcomes were survival estimates. Logistic regression determined associations with measures of intolerance. RESULTS: Of 1296 patients, 229 received chemotherapy. Overall, 24% had early chemotherapy cessation; 18% had dose reductions; and 27% had dose delays. Severe, life threatening and lethal toxicities occurred in 38%, 1.3%, and 2.2%, respectively; constitutional toxicity (37%) was the most common. The 1- and 3-year overall survivals were 94% and 79%; 1- and 3-year breast-specific survivals were 96% and 89%, while 1- and 3-year disease-free survivals were 95% and 82%, respectively. Anthracyclines were the most poorly tolerated regimen having associations with hospital visits (OR 10.97, 95% CI 2.10-57.23) and severe toxicities (OR 5.28, 95% CI 1.27-21.89). Anti-HER2 therapies (OR 3.03, 95% CI 1.18-7.78) and poorer performance status (PS) (OR 7.48, 95% CI 1.75-31.98) were associated with severe toxicities. Older age (> 80 years) was associated with early cessation of therapy (OR 3.64, 95% CI 1.34-9.83). CONCLUSIONS: Chemotherapy can be effectively delivered to older patients with ESBC and is reasonably well tolerated. The high rate of anthracycline intolerability, poorer PS, and advanced age should be considered when tailoring treatment regimens.

Risk factors, clinical outcomes, and natural history of uveal melanoma: a single-institution analysis.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. We describe the characteristics of UM patients at a tertiary referral center in the Mid-Southern United States, and explore associations and predictors of outcomes. This is a retrospective cohort study of patients with UM seen at West Cancer Center, from 07/2006 to 08/2017. Clinical characteristics and their relationship to outcomes (time-to-death and metastasis) were explored using Cox regression analysis. We identified 208 patients, 51% males, 97% Caucasians, 80% were symptomatic, with a median follow-up of 2.34 years, IQR (1.01-3.03), of which 19.2% died during follow-up. Metastases were diagnosed in 19% (4 older patients had metastases at diagnosis), 53% of those by surveillance. Without considering metastases as a time-varying covariate, age (HR = 1.06/year, CI 1.0-1.1; p < 0.001), headaches (HR = 5.7, CI 1.6-20.5; p = 0.03), and tumor stage (T) were significant covariates for time-to-death. Tumor stages T3 versus T1 (HR = 6.4; CI 1.5-27.7; p = 0.01) and T4 versus T1 (HR = 5.98; CI 1.3-27.8; p = 0.02) were associated with worse outcomes. When considering metastases as a time-varying covariate (HR = 35.8, CI 17-75.2; p < 0.001), only age remains in the model (HR = 1.04/year; p < 0.001). However, tumor stage (p < 0.001), headaches (p = 0.008), and age (p < 0.001) are associated with time-to-metastasis. One in five patients developed metastasis which was the most influential factor on mortality. Predictors of mortality were metastasis, age, tumor stage, and headache as a reported symptom. Surveillance successfully diagnosed metastatic disease in most patients. Most patients had symptoms preceding their UM diagnosis highlighting an opportunity for earlier recognition of UM.

Age-Related Chromosomal Aberrations in Patients with Diffuse Large B-Cell Lymphoma: An In Silico Approach.

Background: In diffuse large B-cell lymphoma (DLBCL), chromosomal aberrations are known to increase with advancing age. Our study aims to determine if there are other genetic aberrations associated with DLBCL based on age. Methods: Using the Mitelman Database of Genetic Aberrations, we were able to find 749 cases of DLBCL with genomic aberrations with a median age of 62 years. Patients with DLBCL chromosomal aberration analysis results were divided into four groups based on age (0 - 30, 31 - 50, 51 - 70, > 71 years) and examined by chi-square analysis and Mantel-Cox for survival analysis. Results: Ten aberrations were found to be significant with a particular age range: t(2;3), trisomy 19p13, trisomy 18q21, trisomy 3, trisomy 7, trisomy 14, trisomy 16, trisomy 18, monosomy 3 and monosomy 11, and survival ranged from 7 to 25 months. Conclusion: This suggests that patients with DLBCL are likely to accumulate specific translocations depending on their age at the onset of DLBCL.

Spontaneous intramural small bowel hematoma in a patient with acute myeloid leukaemia receiving chemotherapy and nilotinib.

Spontaneous intramural small bowel hematoma (SISBH) is a rare, acute abdominal condition, with increasing incidence in recent years. Excessive anticoagulation with vitamin K antagonists is the most common aetiology. We report the case of a large acute jejunal intramural hematoma in a patient with newly diagnosed acute myeloid leukaemia receiving chemotherapy and nilotinib. The patient presented with abdominal pain, haematochezia, acute anaemia and thrombocytopenia. CT of the abdomen and pelvis revealed SISBH. The patient was managed conservatively with supportive management and cessation of nilotinib therapy. The patient's symptoms improved, with subsequent CT imaging confirming resolution. This case highlights an uncommon cause of gastrointestinal bleed usually diagnosed only after radiological imaging. A correct diagnosis is important as SISBH usually responds to conservative measures, and may obviate the patient from unnecessary invasive investigations.