A three-lncRNA expression signature associated with the prognosis of gastric cancer patients

Abstract

Long noncoding RNAs (lncRNAs) have emerged as essential players in gene regulation. An ever-increasing number of lncRNAs has been found to be associated with the biogenesis and prognosis of gastric cancer (GC). We aimed to develop an lncRNA signature with prognostic value for survival outcomes of GC. Using an lncRNA mining approach, we analyzed the lncRNA expression profiles of 492 GC patients from the Gene Expression Omnibus (GEO), which consisted of the GSE62254 set (N = 300) and the GSE15459 set (N = 192). The associations between the lncRNAs' expression and survival outcome were evaluated. A set of three lncRNAs (LINC01140, TGFB2-OT1, and RP11-347C12.10) was identified to significantly correlate with overall survival. These lncRNAs were then combined to form a single prognostic signature. Based on this three-lncRNA expression signature, patients in the GSE62254 set were classified into high- and low-risk subgroups with significantly different overall survival (hazard ratio [HR] = 1.93, P < 0.001) and disease-free survival (HR = 1.91, P < 0.001). Good reproducibility for the prognostic value of this lncRNA signature was confirmed in the GSE15459 set. Further analysis showed that the prognostic value of this signature was independent of some clinical characteristics. Gene set enrichment analysis indicated that high-risk scores positively related to several molecular pathways of cancer metastasis. Our results suggest that this innovative lncRNA expression signature may be a useful biomarker for the prognosis of patients with GC based on bioinformatics analysis.

We found an innovative three-lncRNA expression signature that improves the prediction of survival for gastric cancer patients. These lncRNAs may be candidate biomarkers and therapeutic targets for gastric cancer.

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Post-Operative Stereotactic Radiosurgery for Resected Brain Metastases: A Comparison of Outcomes for Large Resection Cavities

Publication date: Available online 26 April 2017
Source:Practical Radiation Oncology
Author(s): Jim Zhong, Matthew J. Ferris, Jeffrey Switchenko, Robert H. Press, Zachary Buchwald, Jeffrey J. Olson, Bree R. Eaton, Walter J. Curran, Hui-Kuo G. Shu, Ian R. Crocker, Kirtesh R. Patel
PurposeAlthough historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed post-operative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and post-operative SRS are lacking. Here we compare outcomes in patients with large brain metastases > 4 cm to those with smaller metastases ≤ 4 cm treated with surgical resection followed by SRS to the resection cavity.Methods and materialsConsecutive patients with brain metastases treated at our institution with surgical resection and post-operative SRS were retrospectively reviewed. Patients were stratified into ≤ 4 cm and > 4 cm cohorts based on pre-operative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the two cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up.ResultsA total of 117 consecutive cases were identified. Of these patients, 90 (77%) had pre-operative tumors ≤ 4 cm, and 27 (23%) > 4 cm in greatest dimension. The only significant baseline difference between the two groups was a higher proportion of patients who underwent gross total resection in the ≤ 4 cm compared to the > 4 cm cohort, 76% vs. 48%, respectively (p<0.01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤ 4 cm and > 4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all p>0.05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size.ConclusionsBrain metastases > 4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review.



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Late Toxicity and Outcomes Following Radiation Therapy for Chest Wall Sarcomas in Pediatric Patients

Publication date: Available online 26 April 2017
Source:Practical Radiation Oncology
Author(s): John T. Lucas, Israel Fernandez-Pineda, Christopher L. Tinkle, Michael W. Bishop, Sue C. Kaste, Rajiv Heda, Andrew M. Davidoff, Matthew J. Krasin
PurposeTo investigate the contribution of radiotherapy to acute and late toxicity in pediatric chest wall sarcoma patients and evaluate dosimetric correlates of higher incidence toxicities such as scoliosis, and pneumonitis.Methods/MaterialsThe data from 23 consecutively treated pediatric patients with chest wall sarcomas of various histologies (desmoid, Ewing, rhabdomyosarcoma, non-rhabdomyosarcoma-soft tissue sarcomas (NRSTS) were reviewed to evaluate the relationship between end-organ radiation dose, clinical factors, and the risk of subsequent late effects (scoliosis, pneumonitis). Cobb angles were used to quantify the extent of scoliosis. Doses to the spine and lung were calculated from the radiation treatment plan.ResultsThe range of scoliosis identified on follow-up imaging ranged from −47.6 to 64 degrees (median 2.95°). No relationship was identified between either radiation dose to the ipsilateral or contralateral vertebral body or tumor size and the degree or direction of scoliosis. The extent of surgical resection and number and location of resected ribs affected the extent of scoliosis. The dominant predictor of extent of scoliosis at long-term follow-up was the extent of scoliosis following surgical resection. Radiation pneumonitis was uncommon and was not correlated with mean dose or volume of lung receiving 24Gy. However, one of three surviving patients who received whole pleural surface radiotherapy developed significant restrictive lung disease.ConclusionsAcute and late radiotherapy associated toxicities in pediatric chest wall sarcoma patients are modest. The degree of scoliosis following resection is a function of the extent of resection and of the number and location of ribs resected, and the degree of scoliosis at the last follow-up visit is a function of the extent of scoliosis following surgery. Differential radiotherapy dose across the vertebral body does not increase the degree of scoliosis. Severe restrictive pulmonary disease is a late complication of survivors after whole pleural surface radiotherapy.SummaryWe evaluated 23 pediatric patients with chest wall sarcoma on a prospective trial for acute and late toxicities related to multimodality care, with particular emphasis on restrictive pulmonary disease and scoliosis. Disease control was comparable to that in prior series, with distant failure being the most common progression event. Restrictive pulmonary disease was uncommon but seemed to be compounded by multimodality therapy. We observed a substantial effect of the extent of surgical resection and the number and location of ribs resected on the risk of postoperative scoliosis. The greatest predictor of continued scoliosis was the extent of scoliosis prior to radiotherapy.



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Radiation Oncology Residency Selection: A Post-Graduate Evaluation of Factor Importance and Survey of Variables Associated with Job Securement

Publication date: Available online 26 April 2017
Source:Practical Radiation Oncology
Author(s): Jeffrey V. Brower, Stanley L. Liauw, Abhinav V. Reddy, Daniel W. Golden
BackgroundMedical students often choose to pursue a career in Radiation Oncology with limited meaningful exposure to the field. We previously identified factors which were most influential to an applicant's rank list order. Here we sought to assess if residency graduates had differing views regarding those factors. We also polled recent graduates' attitudes of the current job market.Material and MethodsAn anonymous, internet-based survey was developed and distributed to graduates of radiation oncology residencies from 2003–06 and 2012–15 to assess the importance of factors with regard to residency selection, training, and job securement and attitudes toward the job market within the United States.ResultsResponses were received from 198 of 848 (23%) of those invited to participate. The respondents were divided into two cohorts for analysis, an "early" cohort (2001–09) and a "contemporary" cohort (2010–16) Respondents recalled "quality of clinical training," "perceived happiness of residents," and "sense of community among faculty and residents" as the three most important factors influencing the rank list; post-residency the most valued factors of the residency experience were "quality of clinical training," "geographic location," and "faculty mentorship." Factors that were assigned the greatest differential value in hindsight to influence the rank list included "faculty mentorship," "willingness of faculty to call employer," and "quality of alumni base." 64% of respondents reported the job market to be difficult or very difficult. This perception was more common among contemporary graduates (p<0.05). 60% of respondents reported "far too many" or "somewhat too many" residency positions for the actual job needs in the U.S.ConclusionAfter training, residency graduates place higher value on factors in residency that can directly improve job procurement. This finding is more common among more recent graduates, potentially a result of the perception of a tightening job market with too many radiation oncologists in training.



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Late Toxicity and Outcomes Following Radiation Therapy for Chest Wall Sarcomas in Pediatric Patients

Publication date: Available online 26 April 2017
Source:Practical Radiation Oncology
Author(s): John T. Lucas, Israel Fernandez-Pineda, Christopher L. Tinkle, Michael W. Bishop, Sue C. Kaste, Rajiv Heda, Andrew M. Davidoff, Matthew J. Krasin
PurposeTo investigate the contribution of radiotherapy to acute and late toxicity in pediatric chest wall sarcoma patients and evaluate dosimetric correlates of higher incidence toxicities such as scoliosis, and pneumonitis.Methods/MaterialsThe data from 23 consecutively treated pediatric patients with chest wall sarcomas of various histologies (desmoid, Ewing, rhabdomyosarcoma, non-rhabdomyosarcoma-soft tissue sarcomas (NRSTS) were reviewed to evaluate the relationship between end-organ radiation dose, clinical factors, and the risk of subsequent late effects (scoliosis, pneumonitis). Cobb angles were used to quantify the extent of scoliosis. Doses to the spine and lung were calculated from the radiation treatment plan.ResultsThe range of scoliosis identified on follow-up imaging ranged from −47.6 to 64 degrees (median 2.95°). No relationship was identified between either radiation dose to the ipsilateral or contralateral vertebral body or tumor size and the degree or direction of scoliosis. The extent of surgical resection and number and location of resected ribs affected the extent of scoliosis. The dominant predictor of extent of scoliosis at long-term follow-up was the extent of scoliosis following surgical resection. Radiation pneumonitis was uncommon and was not correlated with mean dose or volume of lung receiving 24Gy. However, one of three surviving patients who received whole pleural surface radiotherapy developed significant restrictive lung disease.ConclusionsAcute and late radiotherapy associated toxicities in pediatric chest wall sarcoma patients are modest. The degree of scoliosis following resection is a function of the extent of resection and of the number and location of ribs resected, and the degree of scoliosis at the last follow-up visit is a function of the extent of scoliosis following surgery. Differential radiotherapy dose across the vertebral body does not increase the degree of scoliosis. Severe restrictive pulmonary disease is a late complication of survivors after whole pleural surface radiotherapy.SummaryWe evaluated 23 pediatric patients with chest wall sarcoma on a prospective trial for acute and late toxicities related to multimodality care, with particular emphasis on restrictive pulmonary disease and scoliosis. Disease control was comparable to that in prior series, with distant failure being the most common progression event. Restrictive pulmonary disease was uncommon but seemed to be compounded by multimodality therapy. We observed a substantial effect of the extent of surgical resection and the number and location of ribs resected on the risk of postoperative scoliosis. The greatest predictor of continued scoliosis was the extent of scoliosis prior to radiotherapy.



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Post-Operative Stereotactic Radiosurgery for Resected Brain Metastases: A Comparison of Outcomes for Large Resection Cavities

Publication date: Available online 26 April 2017
Source:Practical Radiation Oncology
Author(s): Jim Zhong, Matthew J. Ferris, Jeffrey Switchenko, Robert H. Press, Zachary Buchwald, Jeffrey J. Olson, Bree R. Eaton, Walter J. Curran, Hui-Kuo G. Shu, Ian R. Crocker, Kirtesh R. Patel
PurposeAlthough historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed post-operative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and post-operative SRS are lacking. Here we compare outcomes in patients with large brain metastases > 4 cm to those with smaller metastases ≤ 4 cm treated with surgical resection followed by SRS to the resection cavity.Methods and materialsConsecutive patients with brain metastases treated at our institution with surgical resection and post-operative SRS were retrospectively reviewed. Patients were stratified into ≤ 4 cm and > 4 cm cohorts based on pre-operative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the two cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up.ResultsA total of 117 consecutive cases were identified. Of these patients, 90 (77%) had pre-operative tumors ≤ 4 cm, and 27 (23%) > 4 cm in greatest dimension. The only significant baseline difference between the two groups was a higher proportion of patients who underwent gross total resection in the ≤ 4 cm compared to the > 4 cm cohort, 76% vs. 48%, respectively (p<0.01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤ 4 cm and > 4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all p>0.05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size.ConclusionsBrain metastases > 4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review.



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Radiation Oncology Residency Selection: A Post-Graduate Evaluation of Factor Importance and Survey of Variables Associated with Job Securement

Publication date: Available online 26 April 2017
Source:Practical Radiation Oncology
Author(s): Jeffrey V. Brower, Stanley L. Liauw, Abhinav V. Reddy, Daniel W. Golden
BackgroundMedical students often choose to pursue a career in Radiation Oncology with limited meaningful exposure to the field. We previously identified factors which were most influential to an applicant's rank list order. Here we sought to assess if residency graduates had differing views regarding those factors. We also polled recent graduates' attitudes of the current job market.Material and MethodsAn anonymous, internet-based survey was developed and distributed to graduates of radiation oncology residencies from 2003–06 and 2012–15 to assess the importance of factors with regard to residency selection, training, and job securement and attitudes toward the job market within the United States.ResultsResponses were received from 198 of 848 (23%) of those invited to participate. The respondents were divided into two cohorts for analysis, an "early" cohort (2001–09) and a "contemporary" cohort (2010–16) Respondents recalled "quality of clinical training," "perceived happiness of residents," and "sense of community among faculty and residents" as the three most important factors influencing the rank list; post-residency the most valued factors of the residency experience were "quality of clinical training," "geographic location," and "faculty mentorship." Factors that were assigned the greatest differential value in hindsight to influence the rank list included "faculty mentorship," "willingness of faculty to call employer," and "quality of alumni base." 64% of respondents reported the job market to be difficult or very difficult. This perception was more common among contemporary graduates (p<0.05). 60% of respondents reported "far too many" or "somewhat too many" residency positions for the actual job needs in the U.S.ConclusionAfter training, residency graduates place higher value on factors in residency that can directly improve job procurement. This finding is more common among more recent graduates, potentially a result of the perception of a tightening job market with too many radiation oncologists in training.



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