• In our cohort of patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy and surgery.• The rate of pathological complete response (pCR) was 18.9%.• The 5-year rate of recurrence was 33.2%.• The 5-year overall survival rate was 77%.• Lymphovascular invasion in pathological specimen was associated with recurrence.• pCR was associated with less recurrence and better survival and should be considered as an oncological end point.• Aduvant chemotherapy was associated with better survival.• The patients who achieved pCR may not benefit from aduvant chemotherapy. Aim:To identify markers of recurrence and survival in patients with locally advanced rectal cancer who received neoadjuvant chemoradiotherapy and surgery. Materials & methods: A total of 280 patients were identified in Manitoba between 2007 and 2012. Demographics and clinical data were collected. Cox regression models were used to identify outcome predictors. Results: A total of 53 patients achieved pathological complete response (pCR) and 160 patients received adjuvant chemotherapy (ACT). The median follow-up duration was 2.06 years. Recurrence and survival rates at 5 years were 33.2 and 77.0%, respectively. pCR and lymphovascular invasion predicted recurrence. pCR and ACT predicted better survival. Conclusion: pCR is a significant predictor of recurrence and survival and may be considered as an oncological end point. The patients who achieve pCR may not derive additional survival benefit from ACT. Locally advanced rectal cancer (LARC) is defined as the presence of either T3-4 and/or node-positive disease in absence of distant metastases. Neoadjuvant chemoradiotherapy (NACRT) followed by radical surgery that includes total mesorectal excision is standard treatment for these patients [1,2]. The estimated 5-year overall survival (OS) and local recurrence (LR) rates were 76% and 6%, respectively, with the distant recurrence (DR) rate at 36% in CAO/ARO/AIO-94 study [2]. Similar results were reported by the European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group Trial 22921 [1] with a 5-year cumulative incidence of LR at 7.6% and DR at 34.4%.
Objectives: Perioperative chemotherapy (P-CT) or neoadjuvant chemoradiation (C-RT) followed by surgical resection is the standard of care for locally advanced esophageal cancer (LAEC). We present an institutional review and outcome of patients with LAEC treated with neoadjuvant C-RT or P-CT followed by surgery. Methods: Patients were identified through the Manitoba Cancer Registry. Overall survival (OS), recurrence-free survival (RFS), and time to recurrence (TTR) were compared using proportion hazard regression analysis. Metabolic and pathologic response rates were compared by the Fisher exact test. Results: Sixty-seven patients were treated with C-RT and 32 with P-CT. Fifty-two percent of the patients had pretreatment and posttreatment positron emission tomography scans before surgery. Ninety-five percent of the patients in C-RT and 91% in P-CT had a partial metabolic response or stable disease. Sixty-one percent of C-RT and 34% of P-CT patients had tumor regression grade (TRG) 0 to 1; 39% of C-RT and 66% of P-CT had TRG 2 to 3 (P=0.018). Median OS was 37 and 18 months for patients with TRG 0 to 1 and 2 to 3, respectively (P=0.013, hazard ratio [HR]=1.96). Three-year OS was 43% versus 37% (P=0.37, HR=1.30), RFS was 34% versus 26% (P=0.87, HR=0.96), and median TTR was 30 versus 13 months (P=0.07, HR=0.59) for C-RT and P-CT, respectively. Conclusions: C-RT was associated with a higher degree of pathologically tumor regression. Patients with major tumor regression had a better outcome than those with minimal to poor response. There was a trend toward improved TTR with C-RT but no difference in OS or RFS.
The standard of care for early-stage non-small cell lung cancer (NSCLC) is surgery. However, for medical inoperable patients stereotactic body radiation therapy (SBRT) is an alternative method. The aim of the study is to assess the overall survival (OS), progression-free survival (PFS) and local control (LC) of patients diagnosed with NSCLC in Manitoba, Canada, between 2013 and 2017 and managed with SBRT. Materials and methods This retrospective study included a total of 158 patients (60.13% of the population were females) that were diagnosed with stage I-II NSCLC and were treated with lung SBRT between 2013 and 2017 in Manitoba. Demographics and clinical data were retrospectively extracted from the electronic patient record. Kaplan-Meier and Cumulative incidence curves were used to describe the OS, PFS, and LC outcomes. Results From the 158 patients, 32 patients were treated with 60 Gy in eight fractions, while 121 patients were treated with 48 Gy in four fractions. Only 85 patients had biopsy-proven NSCLC. The median OS was 2.87 years (95% confidence interval [CI] 2.16-3.43). OS rates at one and two years were 85% and 66%, respectively. The median PFS was 2.03 years (95% CI 1.65-2.77). Furthermore, one-year and two-year PFS rates were 77% and 51%, respectively. Only 10 patients progressed locally at one year and 17 at two years, making the LC rate 93% at the one-year and 87% at the two-year mark. Conclusion These findings add to a growing evidence base supporting SBRT in the treatment of clinically suspected and biopsy-proven early-stage NSCLC patients.
adenocarcinoma (LUAD) tumor and non-malignant lung tissues from two cohorts (TCGA, n¼515; BCCA, n¼90) was analyzed. Weighted correlation network analysis (WGCNA) was applied to identify clusters (modules) of highly correlated genes across airway expression profiles. Combined module expression (eigengene scores) were used to: 1) identify modules negatively associated with FEV 1 and 2) calculate module preservation in lung tumors. Signaling network, pathway and gene ontology analyses were performed using IID, pathDIP, ClueGo and PARADIGM. Known and predicted protein-protein physical interactions (PPIs) were obtained from IID. Network analysis and visualization was performed in NAViGaTOR. Results: A module of 31 genes significantly co-expressed across small airways was negatively associated with FEV 1 and preserved in LUAD tumors. Genes in this module were enriched in functions associated with cell cycle progression, and known and/or predicted to physically interact in the protein complex critical to mediating G2/M progression. The forkhead transcription factor FOXM1 network was the most highly perturbed entity across 515 LUAD tumors. FOXM1 is an essential mitotic protein, known to regulate expression of genes involved in cell cycle progression, as well as stress response to ROS and DNA damage, angiogenesis and metastasis. COPD-related airway mRNA changes and genes highly altered at the DNA and mRNA level in LUAD tumors directly converge on the FOXM1 regulated mitotic complex proteins and/or FOXM1 transcription factor network. Conclusion: FOXM1 is overexpressed in multiple cancer types where it is correlated with poor prognosis and oncogenic transformation of epithelia through induction of genomic instability. The convergence of COPD and LUAD changes on this network may underlie increased LC risk in COPD patients, warranting further exploration as a target for COPD treatment and/or LC prevention or treatment.
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