Familial Papillary Thyroid Carcinoma: A Retrospective Analysis

Background. Whether or not the familial form of papillary thyroid carcinoma is more aggressive than the sporadic form of the disease remains controversial. Methods. To explore this question and whether or not increased aggressiveness is more apparent in families with multiple affected members, we performed a chi square by trend analysis on our patients clinical and pathologic data comparing: first degree families with three or more affected members versus first degree families with two affected members versus sporadic cases of papillary thyroid carcinoma. Results. No statistically significant trends were seen for any presenting surgical pathology parameter, age at presentation, length of follow-up or gender distribution. The familial groups exhibited significant trends for higher rates of reoperation (P = 0.05) and/or requiring additional radioactive iodine therapy (P = 0.03), distant metastases (P = 0.003) and deaths (P = 0.01). These aggressive features were most apparent in certain families with three or more affected members. Conclusions. Using the chi square by trend analysis, a significant trend was seen for the familial form of papillary thyroid cancer to possess more aggressive features than the sporadic disease. Prompt recognition of the familial nature of the disease may provide earlier diagnosis and treatment in similarly affected family members

A Rare Association of Mixed Autoimmune Hemolytic Anemia with Gastric Carcinoma

This case report outlines a 70-year-old female patient who presented with a concurrent mixed autoimmune hemolytic anemia (AIHA) and a gastric adenocarcinoma. Her treatment course of these two diseases is summarized, which included supportive care, neoadjuvant chemotherapy for her gastric adenocarcinoma, steroids, rituximab, and surgical resection of the tumor. This approach ultimately led to the stabilization of her AIHA and primary cure for her solid malignancy. We briefly review both AIHA and gastric adenocarcinoma as clinical entities, propose working causes of hemolytic anemia including gastric adenocarcinoma, and outline a successful treatment pathway for these two concurrent conditions

Radiation and immune checkpoint inhibitors in the treatment of oligometastatic non-small-cell lung cancer: a practical review of rationale, recent data, and research questions

The combined use of stereotactic ablative radiotherapy (SABR) and immune checkpoint inhibitors (ICIs) is an emerging treatment paradigm for oligometastatic non-small-cell lung cancer (NSCLC). Recent phase I and II trial data suggest that SABR to multiple metastases in addition to ICI use is safe and effective with promising progression-free survival and overall survival signals. There is great interest in capitalizing on combined immunomodulation from these two modalities for the treatment of oligometastatic NSCLC. Ongoing trials seek to validate the safety, efficacy, and preferred sequencing of SABR and ICI. This narrative review of the role of SABR when combined with ICI in oligometastatic NSCLC discusses the rationale for this bimodality treatment, summarizes recent clinical trial evidence, and proposes key principles of management based on the available evidence

Targeting histone deacetylase enhances the therapeutic effect of Erastin-induced ferroptosis in EGFR-activating mutant lung adenocarcinoma.

Background Intrinsic or acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is common, thus strategies for the management of EGFR-TKIs resistance are urgently required. Ferroptosis is a recently discovered form of cell death that has been implicated in tumorigenesis and resistance treatment. Accumulating evidence suggests that ferroptosis can be therapeutically exploited for the treatment of solid tumors; however, whether ferroptosis can be targeted to treat EGFR mutant lung cancer and/or overcome the resistance to EGFR-TKIs is still unknown. Methods The effect of ferroptosis inducers on a panel of EGFR mutant lung cancer cell lines, including those with EGFR-TKI intrinsic and acquired (generated by long-term exposure to the third-generation EGFR-TKI osimertinib), was determined using cytotoxicity assays. Further, drug candidates to enhance the effect of ferroptosis inducers were screened through implementing WGCNA (weighted gene co-expression network analysis) and CMAP (connectivity map) analysis. Flow cytometry-based apoptosis and lipid hydroperoxides measurement were used to evaluate the cell fates after treatment. Results Compared with EGFR-TKI-sensitive cells, those with intrinsic or acquired resistance to EGFR-TKI display high sensitivity to ferroptosis inducers. In addition, Vorinostat, a clinically used inhibitor targeting histone deacetylase, can robustly enhance the efficacy of ferroptosis inducers, leading to a dramatic increase of hydroperoxides in EGFR mutant lung cancer cells with intrinsic or acquired resistance to EGFR-TKI. Mechanistically, Vorinostat promotes ferroptosis via xCT downregulation. Conclusions Ferroptosis-inducing therapy shows promise in EGFR-activating mutant lung cancer cells that display intrinsic or acquired resistance to EGFR-TKI. Histone deacetylase inhibitor (HDACi) Vorinostat can further promote ferroptosis by inhibiting xCT expression

Discovery of Novel Integrin Ligands from Combinatorial Libraries Using a Multiplex “Beads on a Bead” Approach

The development of screening approaches to identify novel affinity ligands has paved the way for a new generation of molecular targeted nanomedicines. Conventional methods typically bias the display of the target protein to ligands during the screening process. We have developed an unbiased multiplex “beads on a bead” strategy to isolate, characterize, and validate high affinity ligands from OBOC libraries. Novel non-RGD peptides that target α_vβ₃ integrin were discovered that do not affect cancer or endothelial cell biology. The peptides identified here represent novel integrin-targeted agents that can be used to develop targeted nanomedicines without the risk of increased tumor invasion and metastasis

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: a multicentered retrospective analysis

Abstract Background Colorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists. Methods Patients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined. Results Five hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08–0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33–0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33–0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38–1.02, p = 0.06). Conclusions In resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival

Real-World Analysis of Durvalumab after Chemoradiation in Stage III Non-Small-Cell Lung Cancer

The 2017 PACIFIC trial heralded the incorporation of routine adjuvant durvalumab following curative-intent chemoradiation for stage III non-small-cell lung cancer (NSCLC). However, carefully selected clinical trial populations can differ significantly from real-world populations, which can have implications on treatment toxicities and outcomes, making it difficult to accurately counsel patients. Consequently, we performed a real-world, retrospective analysis of outcomes and toxicities in 118 patients with stage III NSCLC treated with durvalumab after platinum-based chemoradiotherapy. The data were collected from patients who underwent treatment at a single, tertiary-level Canadian cancer centre from May 2018 to October 2020. The variables collected included patient demographics, treatment specifics, progression-free survival, overall survival, and immune-related adverse events (IRAE) from durvalumab. Descriptive statistics were used for toxicity analysis, and progression-free survival and overall survival estimates were calculated using the Kaplan–Meier method. The statistical analyses indicated a 64.4% (n = 76) toxicity rate, with a 21% (n = 25) toxicity rate of grade 3+ IRAEs. The most common documented IRAEs were pneumonitis (n = 44; 40%), followed by rash (n = 20; 18%) and thyroid dysfunction (n = 17; 15%). FEV1 and DLCO were not found to be associated predictors of pneumonitis toxicity. The median PFS and OS were estimated to be >1.7 years and >2.7 years, respectively