Significant primary tumor volume loss occurs early during radiotherapy for locally advanced NSCLC. Greater relative tumor volume loss during treatment correlates with improved disease control and overall survival. Thus, kV-CBCT has potential to be used as a practical prognostic imaging marker.
BackgroundClinical and pathologic markers of prognosis and patterns of failure help guide clinicians in selecting patients for adjuvant therapy after surgical resection for pancreatic adenocarcinoma (PDAC). Recent studies have reported the prognostic utility of microRNA profiling in numerous malignancies. Here, we review and summarize the current literature regarding associations between microRNA expression and overall survival in PDAC patients.Materials and MethodsWe conducted a systematic search in the PubMed database to identify all primary research studies reporting prognostic associations between tumor and/or serum microRNA expression and overall survival in PDAC patients. Eligible articles were reviewed by the authors and relevant findings are summarized below.ResultsWe found 53 publications that fit our search criteria. In total, 23 up-regulated and 49 down-regulated miRNAs have been associated with worse overall survival. MiR-21 is the most commonly reported miRNA, appearing in 19 publications, all of which report aberrant over-expression and association with shorter survival in PDAC. Other miRNAs that appear in multiple publications include miR-10b, −21, −34a, −155, −196a, −198, −200c, −203, −210, −218, −222, and −328. We summarize the preclinical and clinical data implicating these miRNAs in various molecular signaling pathways and cellular functions.ConclusionsThere is growing evidence that miRNA expression profiles have the potential to provide tumor-specific prognostic information to assist clinicians in more appropriately selecting patients for adjuvant therapy. These molecules are often aberrantly expressed and exhibit oncogenic and/or tumor suppressor functions in PDAC. Additional efforts to develop prognostic and predictive molecular signatures, and further elucidate miRNA mechanisms of action, are warranted.
Treatment for locally-advanced rectal cancer (LARC) typically consists of neoadjuvant chemoradiation followed by total mesorectal excision. Recently, there has been growing interest in non-operative management for patients who are medically-inoperable or wish to avoid surgical morbidity and permanent colostomy. Approximately 50% of patients who receive pre-operative neoadjuvant chemoradiation develop some degree of pathologic response. Approximately 10-20% of patients are found to have a complete pathologic response, a finding which has frequently been shown to predict better clinical outcomes, including local-regional control, distant metastasis and survival. Many recent studies have evaluated the role of molecular biomarkers in predicting response to neoadjuvant therapy. MicroRNAs (miRNAs) are an emerging class of biomarkers that have the potential to predict which patients are most likely to benefit from pre-operative therapy and from a selective surgical approach. Here, we review the published literature on microRNAs as prognostic and predictive biomarkers in rectal cancer after pre-operative therapy. In the future, the development of prospectively validated miRNA signatures will allow clinical implementation of miRNAs as prognostic and predictive signatures in LARC.
The incidence of DVT in ED patients who had urgent after-hours DVS was no different than in those whose DVS was delayed until regular hours. High pretest probability can be achieved with clinical evaluation prior to DVS, and this guided the decision to prophylactically anticoagulate but did not impact the decision to perform urgent DVS. Most patients eventually found to have DVT did receive prophylactic anticoagulation, and delay of DVS did not result in complications. We believe that most patients in whom there is high clinical suspicion for DVT can safely get prophylactic anticoagulation and delayed DVS. Patients in whom there is low clinical suspicion should not get urgent DVS.
Background: To report our institutional experience with intraoperative radiotherapy for persistent or recurrent head and neck cancer. Methods: Sixty-one patients were treated with salvage surgery and intraoperative radiation therapy (IORT). Fifty-eight patients (95%) had previously received external beam radiotherapy (EBRT) as a component of their definitive therapy. Fortyfour patients (72%) had squamous cell carcinoma (SCC). Surgical margins were positive in 28 patients (46%). IORT was prescribed to a median dose of 12.5 Gy (range, 10-17.5). Twenty-three patients (38%) received a course of postoperative EBRT (median 45 Gy). Clinical outcomes were retrospectively reviewed and univariate analysis was performed using log-rank tests to correlate clinical outcomes with histology, surgical margin, and adjuvant therapy. Results: Median follow-up among surviving patients was 15.9 months. Median progression-free survival (PFS) and overall survival (OS) were 9.8 and 19.1 months, respectively. One-and 2-year rates of locoregional control (LRC) were 59% and 35%, respectively. One-and 2-year rates of PFS were 39% and 19%, respectively. One-and 2-year rates of OS were 62% and 42%, respectively. Overall survival was better for non-SCC histology (P = .03). For SCC patients, negative surgical margin showed a trend toward improved PFS (P = .09) and OS (P = .06). There was one grade-5 toxicity due to carotid rupture. Conclusions: IORT has shown effective LRC and OS with an acceptably low rate of severe toxicity at our institution. OS was significantly better for non-SCC histology. For SCC patients, there is a trend toward improved PFS and OS associated with negative surgical margins.
K E Y W O R D Shead and neck cancer, recurrence, salvage intraoperative radiotherapy
Resectable pancreatic adenocarcinoma (PC) is generally managed with surgery followed by chemotherapy, but the role of postoperative chemoradiation (pCRT) is controversial. We sought to identify a microRNA (miRNA) expression profile associated with higher risk for local-regional recurrence (LRR), which might help identify patients that may benefit from pCRT. Total RNA was isolated from viable tumor from 88 patients who underwent PC resection with or without chemotherapy, but did not receive radiation. Digital miRNA expression profiling was performed and risk scores were calculated based on the expression levels of the four most significantly correlated miRNAs, and dichotomized about the median to detect correlations between risk group, LRR and overall survival (OS). Two cohorts from The Cancer Genome Atlas (TCGA) and Seoul National University (SNU) were used for validation. Patients with high-risk scores had significantly worse LRR (p = 0.001) and worse OS (p = 0.034). Two-year OS rates for the high-and low-risk groups were 27.7% and 52.2%, respectively. On multivariable analysis, the risk score remained significantly associated with LRR (p = 0.018). When validated on TCGA data, a high-risk score was associated with worse OS on univariate (p = 0.03) and multivariable analysis (p = 0.017). When validated on the SNU cohort, a high-risk score was likewise associated with worse OS (p = 0.042). We have developed a 4-miRNA molecular signature that is associated with risk of LRR and OS after PC resection and validated on two separate cohorts. This signature has the potential to select patients most likely to benefit from pCRT, and should be tested further.
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