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Select item 31241880
1.
Holistic services for people with advanced disease and chronic or refractory breathlessness: a mixed-methods evidence synthesis.
Editors
Maddocks M1, Brighton LJ1, Farquhar M2, Booth S1,3, Miller S1, Klass L1, Tunnard I1, Yi D1, Gao W1, Bajwah S1, Man WDC4,5, Higginson IJ1.

Source
Southampton (UK): NIHR Journals Library; 2019 Jun.
Health Services and Delivery Research.

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Excerpt
BACKGROUND:
Breathlessness is a common and distressing symptom of many advanced diseases, affecting around 2 million people in the UK. Breathlessness increases with disease progression and often becomes chronic or refractory. Breathlessness-triggered services that integrate holistic assessment and specialist palliative care input as part of a multiprofessional approach have been developed for this group, offering tailored interventions to support self-management and reduce distress.

OBJECTIVES:
The aim was to synthesise evidence on holistic breathlessness services for people with advanced disease and chronic or refractory breathlessness. The objectives were to describe the structure, organisation and delivery of services, determine clinical effectiveness, cost-effectiveness and acceptability, identify predictors of treatment response, and elicit stakeholders’ evidence-based priorities for clinical practice, policy and research.

DESIGN:
The mixed-methods evidence synthesis comprised three components: (1) a systematic review to determine the clinical effectiveness, cost-effectiveness and acceptability of holistic breathlessness services; (2) a secondary analysis of pooled individual data from three trials to determine predictors of clinical response; and (3) a transparent expert consultation (TEC), comprising a stakeholder workshop and an online consensus survey, to identify stakeholders’ priorities.

RESULTS:
Thirty-seven papers reporting on 18 holistic breathlessness services were included in the systematic review. Most studies enrolled people with thoracic cancer, were delivered over 4–6 weeks, and included breathing training, relaxation techniques and psychological support. Meta-analysis demonstrated significant reductions in the Numeric Rating Scale (NRS) distress due to breathlessness, significant reductions in the Hospital Anxiety and Depressions Scale (HADS) depression scores, and non-significant reductions in the Chronic Respiratory Disease Questionnaire (CRQ) mastery and HADS anxiety, favouring the intervention. Recipients valued education, self-management interventions, and expertise of the staff in breathlessness and person-centred care. Evidence for cost-effectiveness was limited and inconclusive. The responder analysis (n = 259) revealed baseline CRQ mastery and NRS distress to be strong predictors of the response to breathlessness services assessed by these same measures, and no significant influence from baseline breathlessness intensity, patient diagnosis, lung function, health status, anxiety or depression. The TEC elicited 34 priorities from stakeholders. Seven priorities received high agreement and consensus, reflecting stakeholders’ (n = 74) views that services should be person-centred and multiprofessional, share their breathlessness management skills with others, and recognise the roles and support needs of informal carers.

LIMITATIONS:
The evidence synthesis draws predominantly from UK services and may not be generalisable to other settings. Some meta-analyses were restricted by reporting biases and statistical heterogeneity.

CONCLUSIONS:
Despite heterogeneity in composition and delivery, holistic breathlessness services are highly valued by recipients and can lead to significant improvements in the distress caused by breathlessness and depression. Outcomes of improved mastery and reduced distress caused by breathlessness are not influenced by patient diagnosis, lung function or health status. Stakeholders highlighted the need for improved access to person-centred, multiprofessional breathlessness services and support for informal carers.

FUTURE WORK:
Our research suggests that key therapeutic components of holistic breathlessness services be considered in clinical practice and models of delivery and educational strategies to address stakeholders’ priorities tested.

STUDY REGISTRATION:
This study is registered as PROSPERO CRD42017057508.

FUNDING:
The National Institute for Health Research (NIHR) Health Services and Delivery programme. Matthew Maddocks, Wei Gao and Irene J Higginson are supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London; Matthew Maddocks is supported by a NIHR Career Development Fellowship (CDF-2017-009), William D-C Man is supported by the NIHR CLAHRC Northwest London and Irene J Higginson holds a NIHR Emeritus Senior Investigator Award.

Copyright © Queen’s Printer and Controller of HMSO 2019. This work was produced by Maddocks et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.

Sections
Plain English summary
Scientific summary
Chapter 1. Introduction
Chapter 2. Evidence synthesis methods
Chapter 3. Systematic review results
Chapter 4. Responder analysis results
Chapter 5. Transparent expert consultation results
Chapter 6. Discussion and conclusion
Acknowledgements
References
Appendix 1. The MEDLINE search strategy
Appendix 2. Schedule for stakeholder workshop
Appendix 3. The PRISMA flow chart
Appendix 4. Description of included services and studies
Appendix 5. Outcomes measured in controlled studies
Appendix 6. The QualSyst quality assessment: quantitative
Appendix 7. Risk of bias
Appendix 8. The QualSyst quality assessment: qualitative
Appendix 9. Mixed-methods quality assessment
Appendix 10. Quality assessment of economic evaluations
Appendix 11. Reporting quality
List of abbreviations
PMID: 31241880
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Holistic services for people with advanced disease and chronic or refractory breathlessness: a mixed-methods evidence synthesis
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Select item 31242036
2.
Arterioscler Thromb Vasc Biol. 2019 Jul;39(7):1402-1418. doi: 10.1161/ATVBAHA.118.312190. Epub 2019 May 9.
Intussusceptive Vascular Remodeling Precedes Pathological Neovascularization.
Ali Z1, Mukwaya A2, Biesemeier A3, Ntzouni M4, Ramsköld D5, Giatrellis S5, Mammadzada P6, Cao R7, Lennikov A2, Marass M8, Gerri C8, Hildesjö C9, Taylor M10, Deng Q11, Peebo B2, Del Peso L12,13, Kvanta A6, Sandberg R5, Schraermeyer U3, Andre H6, Steffensen JF14, Lagali N2, Cao Y7, Kele J11, Jensen LD1.
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Abstract
Objective- Pathological neovascularization is crucial for progression and morbidity of serious diseases such as cancer, diabetic retinopathy, and age-related macular degeneration. While mechanisms of ongoing pathological neovascularization have been extensively studied, the initiating pathological vascular remodeling (PVR) events, which precede neovascularization remains poorly understood. Here, we identify novel molecular and cellular mechanisms of preneovascular PVR, by using the adult choriocapillaris as a model. Approach and Results- Using hypoxia or forced overexpression of VEGF (vascular endothelial growth factor) in the subretinal space to induce PVR in zebrafish and rats respectively, and by analyzing choriocapillaris membranes adjacent to choroidal neovascular lesions from age-related macular degeneration patients, we show that the choriocapillaris undergo robust induction of vascular intussusception and permeability at preneovascular stages of PVR. This PVR response included endothelial cell proliferation, formation of endothelial luminal processes, extensive vesiculation and thickening of the endothelium, degradation of collagen fibers, and splitting of existing extravascular columns. RNA-sequencing established a role for endothelial tight junction disruption, cytoskeletal remodeling, vesicle- and cilium biogenesis in this process. Mechanistically, using genetic gain- and loss-of-function zebrafish models and analysis of primary human choriocapillaris endothelial cells, we determined that HIF (hypoxia-induced factor)-1α-VEGF-A-VEGFR2 signaling was important for hypoxia-induced PVR. Conclusions- Our findings reveal that PVR involving intussusception and splitting of extravascular columns, endothelial proliferation, vesiculation, fenestration, and thickening is induced before neovascularization, suggesting that identifying and targeting these processes may prevent development of advanced neovascular disease in the future. Visual Overview- An online visual overview is available for this article.

KEYWORDS:
choroidal neovascularization; hypoxia; intussusception; macular degeneration; zebrafish

PMID: 31242036 DOI: 10.1161/ATVBAHA.118.312190
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Select item 31240959
3.
Future Oncol. 2019 Jun 26. doi: 10.2217/fon-2018-0827. [Epub ahead of print]
A real-world study of socioeconomic factors with survival in adults aged 18-64 years with renal cell carcinoma.
Zhang SL1, Zhang ZY1, Liu ZJ2, Wang WR3, Li ZM1, Han B1, Wang X4, Wang LS1.
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Abstract
Aim: To evaluate the impact of socioeconomic factors (SEFs) on survival of renal cell carcinoma (RCC) patients. Materials & methods: RCC patients diagnosed between 2007 and 2015 were collected from the SEER database. The crude and multivariate Cox regression analysis was used to identify the independent prognostic factors and quantity the mortality risks for overall survival (OS). Results: Three SEFs including marital status, insurance status and median household income were identified as prognostic factors for OS. SEF-stage was built based on the three SEFs. Moreover, the SEF-stage 1 had superior OS than SEF-stage 2 within the respective American Joint Committee on Cancer stages. Conclusion: The SEF-stage was an independently prognostic factor for OS in RCC. Incorporation of SEF-stage into the American Joint Committee on Cancer staging system might be beneficial for better survival prediction and clinical management. However, further studies were needed to validate these findings in other populations.

KEYWORDS:
AJCC staging system; SEER; renal cell carcinoma; socioeconomic factors; survival

PMID: 31240959 DOI: 10.2217/fon-2018-0827
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Select item 31240949
4.
Future Oncol. 2019 Jun 26. doi: 10.2217/fon-2018-0772. [Epub ahead of print]
Systematic Review of adverse events reporting in clinical trials leading to approval of targeted therapy and immunotherapy.
Bossi P1, Botta L2, Bironzo P3, Sonetto C3, Musettini G4, Sbrana A4, Di Giannantonio V5, Locati LD5, Di Maio M6, Antonuzzo A4.
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Abstract
Aim: Reporting toxicities of targeted therapies (TTs) and immunotherapy in oncology requires special attention. Materials & methods: We identified TTs and immunotherapies approved by the US FDA for solid malignancies in the adult population. Publications were reviewed according to a 24-point score based on the Consolidated Standards of Reporting Trials guidance. Results: We identified 81 trials (>45,000 patients). The experimental drug was studied as single agent in 51% of the cases; setting of disease was mainly (95%) advanced/metastatic. Lowest scores in adverse event (AE) description regarded: reporting recurrent/late toxicities and duration of the AEs (>90%), time of occurrence and indication of all-grade AEs (>75%). Conclusions: Suboptimal reporting of AEs in trials leading to approval of TTs and immunotherapy was shown. Improving AE descriptions should be a priority in ongoing trials.

KEYWORDS:
Systematic Review; immunotherapy; targeted treatments; toxicities

PMID: 31240949 DOI: 10.2217/fon-2018-0772
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Select item 31240403
5.
Curr Oncol Rep. 2019 Jun 25;21(8):70. doi: 10.1007/s11912-019-0815-1.
Radiomics: an Introductory Guide to What It May Foretell.
Nougaret S1,2, Tibermacine H3,4, Tardieu M3,4, Sala E5.
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Abstract
PURPOSE OF REVIEW:
To briefly review the radiomics concept, its applications, and challenges in oncology in the era of precision medicine.

RECENT FINDINGS:
Over the last 5 years, more than 500 studies have evaluated the role of radiomics to predict tumor diagnosis, genetic pattern, tumor response to therapy, and survival in multiple cancers. This new post-processing method is aimed at extracting multiple quantitative features from the image and converting them into mineable data. Radiomics models developed have shown promising results and may play a role in the near future in the daily patient management especially to assess tumor heterogeneity acting as a whole tumor virtual biopsy. For now, radiomics is limited by its lack of standardization; future challenges will be to provide robust and reproducible metrics extracted from large multicenter databases.

KEYWORDS:
CT; Cancer; MRI; PET/CT; Radiomics; Texture

PMID: 31240403 DOI: 10.1007/s11912-019-0815-1
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Select item 31240271
6.
JCO Precis Oncol. 2019;3. doi: 10.1200/po.18.00176. Epub 2019 Jan 22.
Duality of purpose: Participant and parent understanding of the purpose of genomic tumor profiling research among children and young adults with solid tumors.
Marron JM1,2,3,4,5, Cronin AM3, DuBois SG1,2, Glade-Bender J6, Kim A7, Crompton BD1,2, Meyer SC1, Janeway KA1,2, Mack JW1,2,3.
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Abstract
PURPOSE:
Increasing use of genomic tumor profiling may blur the line between research and clinical care. We aimed to describe research participants' perspectives on the purpose of genomic tumor profiling research in pediatric oncology.

METHODS:
We surveyed 45 participants (response rate 85%) in a pilot study of genomic profiling in pediatric solid tumors at four academic cancer centers following return of sequencing results. We defined understanding according to a one-item ("basic") definition (recognizing that the primary purpose was not to improve the patient's treatment) and a four-item ("comprehensive") definition (primary purpose was not to improve patient's treatment; primary purpose was to improve treatment of future patients; there may not be direct medical benefit; most likely result of participation was not increased likelihood of cure).

RESULTS:
Sixty-eight percent of respondents (30/44) demonstrated basic understanding of the study purpose; 55% (24/44) demonstrated comprehensive understanding. Understanding was more frequently seen in those with higher education and greater genetic knowledge according to basic (81% vs 50%, p=0.05; and 82% vs 46%, p=0.03, respectively) and comprehensive definitions (73% vs 28%, p=0.01; 71% vs 23%, p=0.01). Ninety-three percent of respondents who believed the primary purpose was to improve the patient's care simultaneously stated that the research also aimed to benefit future patients.

CONCLUSIONS:
Most participants in pediatric tumor profiling research understand that the primary goal of this research is to improve care for future patients, but many express dual goals when participating in sequencing research. Some populations demonstrate increased rates of misunderstanding. Nuanced participant views suggest further work is needed to assess and improve participant understanding, particularly as tumor sequencing moves beyond research into clinical practice.

KEYWORDS:
cancer; ethics; genomics; molecular profiling; patient perspectives; pediatric oncology; therapeutic misconception

PMID: 31240271 DOI: 10.1200/po.18.00176
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Select item 31240208
7.
Biomed Res Int. 2019 May 22;2019:2741598. doi: 10.1155/2019/2741598. eCollection 2019.
Development of an Empirically Calibrated Model of Esophageal Squamous Cell Carcinoma in High-Risk Regions.
Wang Z1, Zhang Q2, Wu B3.
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Abstract
OBJECTIVE:
This study constructs, calibrates, and verifies a mathematical simulation model designed to project the natural history of ESCC and is intended to serve as a platform for testing the benefits and cost-effectiveness of primary and secondary ESCC prevention alternatives.

METHODS:
The mathematical model illustrates the natural history of ESCC as a sequence of transitions among health states, including the primary health states (e.g., normal mucosa, precancerous lesions, and undetected and detected cancer). Using established calibration approaches, the parameter sets related to progression rates between health states were optimized to lead the model outputs to match the observed data (specifically, the prevalence of precancerous lesions and incidence of ESCC from the published literature in Chinese high-risk regions). As illustrative examples of clinical and policy application, the calibrated and validated model retrospectively simulate the potential benefit of two reported ESCC screening programs.

RESULTS:
Nearly 1,000 good-fitting parameter sets were identified from 1,000,000 simulated sets. Model outcomes had sufficient calibration fit to the calibration targets. Additionally, the verification analyses showed reasonable external consistency between the model-predicted effectiveness of ESCC screening and the reported data from clinical trials.

CONCLUSIONS:
This parameterized mathematical model offers a tool for future research investigating benefits, costs, and cost-effectiveness related to ESCC prevention and treatment.

PMID: 31240208 PMCID: PMC6556290 DOI: 10.1155/2019/2741598
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Select item 31239842
8.
J Oncol. 2019 May 23;2019:9014607. doi: 10.1155/2019/9014607. eCollection 2019.
Γδ T Cell-Based Immunotherapy in Melanoma: State of the Art.
Toia F1, Di Stefano AB1, Meraviglia S2, Lo Presti E2, Pirrello R1, Rinaldi G3, Fulfaro F3, Dieli F2, Cordova A1.
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Abstract
Metastatic melanoma is still associated with a poor prognosis, and there is increasing interest in immunotherapy alone or in combination with other adjuvant therapies. Γδ T lymphocytes play a pivot role in the immune response against cancer, but while γδ-based immunotherapy is already a clinical reality for several solid tumors, data on melanoma are still limited and fragmented. This systematic review presents preclinical and clinical evidence for a role of γδ T lymphocytes in immunotherapeutic strategies for advanced melanoma and discusses research state of the art and future perspectives. Current strategies focus on in vivo stimulation, and ex vivo adoptive therapy and vaccination; results are promising, but further studies are needed to better investigate the interactions in tumoral microenvironment and to improve clinical efficacy of immunotherapeutic protocols.

PMID: 31239842 PMCID: PMC6556315 DOI: 10.1155/2019/9014607
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Select item 31239542
9.
Br J Cancer. 2019 Jun 26. doi: 10.1038/s41416-019-0497-3. [Epub ahead of print]
Targeting CXCL12/CXCR4 and myeloid cells to improve the therapeutic ratio in patient-derived cervical cancer models treated with radio-chemotherapy.
Lecavalier-Barsoum M1, Chaudary N2, Han K2,3,4, Pintilie M2,5, Hill RP2,3,6, Milosevic M7,8,9.
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Abstract
BACKGROUND:
The CXCL12/CXCR4 chemokine pathway is involved in cervical cancer pathogenesis and radiation treatment (RT) response. We previously reported that radiochemotherapy (RTCT) and concurrent administration of the CXCR4 inhibitor plerixafor improved primary tumour response. The aims of this study were to determine optimal sequencing of RTCT and plerixafor, the mechanisms responsible for improved response and the effect of plerixafor on late intestinal toxicity.

METHODS:
Orthotopic cervical cancer xenografts were treated with RTCT (30 Gy in 2 Gy fractions and cisplatin) with or without concurrent, adjuvant or continuous plerixafor. The endpoints were growth delay and molecular and immune cell changes at the end of treatment. Late intestinal toxicity was assessed by histologic examination of the rectum 90 days after a single 20 Gy fraction.

RESULTS:
RTCT increased CXCL12/CXCR4 signalling and the intratumoral accumulation of myeloid cells; the addition of plerixafor mitigated these effects. All of the RTCT and plerixafor arms showed prolonged tumour growth delay compared to RTCT alone, with the adjuvant arm showing the greatest improvement. Plerixafor also reduced late intestinal toxicity.

CONCLUSION:
Adding Plerixafor to RTCT blunts treatment-induced increases in CXCL12/CXCR4 signalling, improves primary tumour response and reduces intestinal side effects. This combination warrants testing in future clinical trials.

PMID: 31239542 DOI: 10.1038/s41416-019-0497-3
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Select item 31239068
10.
Semin Oncol. 2019 Jun 17. pii: S0093-7754(19)30044-2. doi: 10.1053/j.seminoncol.2019.03.002. [Epub ahead of print]
Invasive lobular breast cancer: A review of pathogenesis, diagnosis, management, and future directions of early stage disease.
Thomas M1, Kelly ED2, Abraham J1, Kruse M3.
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Abstract
Invasive lobular carcinoma (ILC) is the second most common type of invasive breast cancer after invasive ductal carcinoma (IDC). Invasive lobular carcinoma has unique clinical, pathologic, and radiographic features which suggest that it is a distinct clinical entity; however, it is treated with the same treatment paradigms as IDC. Information regarding the specific treatment of ILC, including response to standard therapy, is sparse. Neoadjuvant treatment considerations are of great importance in this space as ILC is often found at a locally advanced stage. In this review, we summarize the classic features of ILC and the available data regarding efficacy of both endocrine therapy and chemotherapy in curative treatment of breast cancer.

Copyright © 2019 Elsevier Inc. All rights reserved.

PMID: 31239068 DOI: 10.1053/j.seminoncol.2019.03.002
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Select item 31238988
11.
J Immunother Cancer. 2019 Jun 25;7(1):159. doi: 10.1186/s40425-019-0636-7.
Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials.
Lv JW1, Li JY1, Luo LN2, Wang ZX3, Chen YP4.
Author information
Abstract
Recent phase 1-2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), however head-to-head comparison among these regimens is lacking. We aimed to comprehensively compare the efficacy and safety of different anti-PD-1 drugs, standard chemotherapy, and their combination therapy in RM-NPC. Adverse event (AE) and objective response rate (ORR) were assessed. The pooled incidence rates of grade 1-5/3-5 AEs were 74.1%/29.6, 54.2%/17.4, 92.3%/24.5, 96.8%/16.1, 91.2%/42.8, and 100%/87.9% for pembrolizumab, nivolumab, JS001, camrelizumab, chemotherapy and camrelizumab+chemotherapy, respectively, which suggested that nivolumab and pembrolizumab exhibited the optimal safety regarding grade 1-5 AEs whereas camrelizumab and nivolumab regarding grade 3-5 AEs. As second- or later-line therapy, ORR was higher with camrelizumab (34.1%), followed by pembrolizumab (26.3%), JS001 (23.3%), and nivolumab (19.0%); whereas ORR with first-line nivolumab reached 40%. Additionally, first-line camrelizumab+chemotherapy achieved a dramatically higher ORR than that with chemotherapy alone (90.9% vs. 64.1%). Pooled ORR was 28.4 and 17.4% for PD-L1-positive and PD-L1-negative patients, respectively (P = 0.11). Here, we represent preliminary evidence for the comparative safety and efficacy of existing anti-PD-1 agents with/without chemotherapy in RM-NPC, which indicated that camrelizumab has the least toxicity profile and merits future investigation. Our findings might provide insights into the future design of immunotherapy trials in RM-NPC.

KEYWORDS:
Anti-PD-1; Chemotherapy; Combination therapy; Efficacy; Nasopharyngeal carcinoma; Predictive biomarker; Safety profiles

PMID: 31238988 DOI: 10.1186/s40425-019-0636-7
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Select item 31238738
12.
Future Oncol. 2019 Jun 26. doi: 10.2217/fon-2018-0888. [Epub ahead of print]
Cause-specific death assessment of patients with stage I small-cell lung cancer: a competing risk analysis.
Liu J1,2,3,4, Zhou H1,2,3,4, Zhang Y1,2,3, Fang W1,2,3, Yang Y1,2,3, Hong S1,2,3, Chen G1,2,3, Zhao S1,2,3, Chen X1,2,3, Zhang Z1,2,3, Xian W4, Shen J4, Huang Y1,2,3, Zhao H1,2,3, Zhang L1,2,3.
Author information
Abstract
Aim: Stage I small-cell lung cancer (SCLC) is a potentially curable disease that needs timely and multidisciplinary management. The aim of this study was to evaluate the probability of cause-specific mortality for patients with stage I SCLC. Material & methods: We identified patients in the SEER database and constructed a proportional subdistribution hazard model to evaluate cancer-specific mortality. A nomogram was built based on Fine and Gray competing risk regression model. Results: A total of 864 stage I SCLC patients were identified. The 5-year cumulative incidence of SCLC-specific mortality was 56.2%, while that for other causes of death was 17.3%. The c-index for the prognostic prediction model was 0.66. Besides, the nomogram was well calibrated. Conclusion: Our nomogram might serve as a reference for clinicians when evaluating the prognosis of stage I SCLC.

KEYWORDS:
SCLC; SEER; cancer-specific death; competing risk nomogram

PMID: 31238738 DOI: 10.2217/fon-2018-0888
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Select item 31238721
13.
Future Oncol. 2019 Jun 26. doi: 10.2217/fon-2019-0010. [Epub ahead of print]
Utilization of tumor genomics in clinical practice: an international survey among ASCO members.
Barroso-Sousa R1,2, Guo H3, Srivastava P4, James T5, Birch W6, Siu LL7, Tew WP8, Tolaney SM1.
Author information
Abstract
Aim: To identify patterns of use and barriers to tumor genomic testing among oncologists. Methods: We surveyed American Society of Clinical Oncology physician members about their use of genomic testing. Results: Among 11,900 members surveyed, a total of 1000 responded to the survey (participation rate, 8.4%). A total of 75% of the respondents included in the analysis reported ordering tests for at least 1-10% of their patients. Practice setting (academic vs community) was only a determinant in the ordering frequency in North America. Regardless of location, academic oncologists were more likely to prescribe medicine in the context of a clinical trial. Access to clinical trials and costs associated with testing were the barriers identified worldwide. Conclusion: There is substantial variation in the use of genomic tools according to region and practice setting; yet, the barriers are similar worldwide.

KEYWORDS:
genomics; next-generation sequencing; oncology; precision medicine

PMID: 31238721 DOI: 10.2217/fon-2019-0010
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Select item 31238718
14.
Future Oncol. 2019 Jun 26. doi: 10.2217/fon-2019-0168. [Epub ahead of print]
The day after De-ESCALaTE and RTOG 1016 trials results.
Orlandi E1, Licitra L2,3.
Author information
KEYWORDS:
cetuximab; chemotherapy; cisplatin; deintensification; oropharyngeal carcinoma; radiotherapy

PMID: 31238718 DOI: 10.2217/fon-2019-0168
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Select item 31238634
15.
Zhonghua Wei Chang Wai Ke Za Zhi. 2019 Jun 25;22(6):550-559. doi: 10.3760/cma.j.issn.1671-0274.2019.06.008.
["Watch and wait" strategy after neoadjuvant therapy for rectal cancer: status survey of perceptions, attitudes and treatment selection in Chinese surgeons].
[Article in Chinese; Abstract available in Chinese from the publisher]
Sun TT1, Wang L, Yao YF, Peng YF, Zhao J, Zhan TC, Leng JH, Wang HY, Chen N, Chen PJ, Li YJ, Zhang X, Liu XZ, Zhang Y, Wu AW.
Author information
Abstract
Objective: To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher's exact test for categorical variables. Results: Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions: Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.

KEYWORDS:
"Watch and wait" approach; Clinical complete response; Neoadjuvant chemoradiation; Rectal neoplasms

PMID: 31238634 DOI: 10.3760/cma.j.issn.1671-0274.2019.06.008
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Select item 31238263
16.
J Reprod Immunol. 2019 Jun 18;133:37-42. doi: 10.1016/j.jri.2019.06.001. [Epub ahead of print]
Treatment with intravenous immunoglobulin in patients with recurrent pregnancy loss: An update.
Christiansen OB1, Kolte AM2, Krog MC2, Nielsen HS2, Egerup P3.
Author information
Abstract
Intravenous immunoglobulin (IVIg) has a documented clinical effect in many autoimmune diseases and has so far been tested in >10 randomised controlled trials (RCTs) in women with recurrent pregnancy loss (RPL). The results of the RCTs have, however, been very divergent. In meta-analyses of all trials, no significant impact on live birth rate has been reported. In contrast, in sensitivity analyses, IVIg significantly increased live birth rates when initiated prior to conception and it had a borderline significant therapeutic effect in women with secondary RPL. Higher dosages of IVIg and serological signs of autoimmunity in the treated patients tended to increase the success rate after treatment. A follow-up study of patients from our recent RCT also supports a significant therapeutic effect in patients who had received IVIg before conception. The lessons learned from the published trials and meta-analyses should be incorporated in the design of future RCTs of IVIg in the treatment of RPL.

Copyright © 2019. Published by Elsevier B.V.

KEYWORDS:
Immunomodulation; Intravenous immunoglobulin; Recurrent Miscarriage; Recurrent pregnancy loss

PMID: 31238263 DOI: 10.1016/j.jri.2019.06.001
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Select item 31237445
17.
Future Oncol. 2019 Jun 25. doi: 10.2217/fon-2019-0064. [Epub ahead of print]
Management of distal ureter and bladder cuff at the time of nephroureterectomy: surgical techniques and predictors of outcome.
Attalla K1, Patnaik S1, Vellos T1, Mehrazin R1.
Author information
Abstract
Open radical nephroureterectomy (NU) with removal of the ureter and bladder cuff is the 'gold standard' in the treatment of high-grade urothelial cancers of the upper urinary tract. A salient issue is the management of the distal ureter and bladder cuff at time of surgery. Which technique confers superior oncologic benefit is of particular interest since this disease process is notoriously plagued with high intravesical recurrence rates. Although open radical NU is the 'gold standard', the maturation of minimally invasive surgery formidably challenges approaches considered 'gold standard'. We thus sought to critically review the literature comparing perioperative and oncologic outcomes in the approaches used to manage the distal ureter and bladder cuff in patients undergoing radical NU.

KEYWORDS:
distal ureter and bladder cuff; radical nephroureterectomy; upper tract urothelial carcinoma

PMID: 31237445 DOI: 10.2217/fon-2019-0064
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Select item 31237444
18.
Future Oncol. 2019 Jun 25. doi: 10.2217/fon-2018-0861. [Epub ahead of print]
Bladder cancer mortality after a diagnosis of nonmuscle-invasive bladder carcinoma.
Abdel-Rahman O1,2.
Author information
Abstract
Aim: To assess mortality from bladder cancer following a diagnosis of nonmuscle-invasive bladder cancer. Materials & methods: This is a SEER registry-based study. The risk of death from bladder cancer was compared with that of the general population. Cox proportional model was performed to calculate the hazard ratio (HR) for death according to baseline characteristics. Results: The bladder cancer-specific mortality at 20 years was 11%; and it was higher for black patients compared with white patients (adjusted HR: 1.711 [95% CI: 1.564-1.872]; p  <  0.0001); additionally, it was higher for patients older than 70 years old compared with younger patients (adjusted HR: 2.005 [95% CI: 1.916-2.099]; p  < 0 .0001). The risk of bladder cancer mortality increased after diagnosis of a recurrent bladder cancer (both nonmuscle-invasive and muscle-invasive; adjusted HR: 6.97 [95% CI: 6.56-7.40]; p  < 0 .0001). Conclusion: Important predictors for death from bladder cancer following a diagnosis of nonmuscle-invasive bladder cancer include older age at diagnosis and black race.

KEYWORDS:
NMIBC; bladder cancer; mortality; nonmuscle-invasive bladder cancer; urothelial carcinoma

PMID: 31237444 DOI: 10.2217/fon-2018-0861
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Select item 31237441
19.
Future Oncol. 2019 Jun 25. doi: 10.2217/fon-2019-0068. [Epub ahead of print]
Clinical implications of mismatch repair deficiency in prostate cancer.
Sedhom R1, Antonarakis ES1.
Author information
Abstract
Immune checkpoint blockade holds great promise in the treatment of solid tumors but has not yet been approved for use in advanced prostate cancer. This is largely due to the relatively modest response in clinical trials in unselected patients and the lack of available biomarkers to predict clinical benefit. Germline and somatic mismatch repair (MMR) gene deficiencies are more prevalent than previously thought, especially in the metastatic setting, in patients with high-grade Gleason scores and in patients with variant histologies. An early signal suggests that patients with deficiency in MMR may respond well to immunotherapy. Both germline and somatic genetic testing are recommended, yet questions remain on the best modality for testing given lack of standardization and false-negative results in patients with complex genomic structural rearrangements. Expanded panels, such as next generation sequencing may increase the sensitivity without compromising specificity. Future studies are still needed to explore the relationships of hypermutation, tumor mutational burden, tumor-infiltrating lymphocytes and microsatellite instability-H status as predictors of response to immunotherapy. The drivers of variable response is largely unknown, and a more mature understanding of the mechanisms of resistance in deficiencies in MMR tumors may help to more precisely inform use of immunotherapy in prostate cancer.

KEYWORDS:
germline mutations; immunotherapy; mismatch repair defects; prostate cancer; somatic mutations

PMID: 31237441 DOI: 10.2217/fon-2019-0068
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Select item 31237166
20.
Future Oncol. 2019 Jun 25. doi: 10.2217/fon-2019-0063. [Epub ahead of print]
Preoperative high c-reactive protein/albumin ratio is a poor prognostic factor of oral squamous cell carcinoma.
Wang Q1, Song X1, Zhao Y2, He Q1, Shi M1, Xu P1, Ni S1, Chen Y1, Lin J3, Zhang L1.
Author information
Abstract
Aim: To explore whether c-reactive protein/albumin (CRP/Alb) ratio is a poor prognostic factor for patients with oral squamous cell carcinoma (OSCC). Patients & methods: Receiver-operating characteristic analysis was performed to evaluate the optimal cut-off value of CRP/Alb ratio in 240 patients with OSCC. The Kaplan-Meier method was used to plot the overall survival and disease-free survival curves. Cox proportional hazards model was used to implement univariate and multivariate analyses. Results: Preoperative high CRP/Alb ratio was associated with age, advanced stage, lymphatic metastasis, platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio (all p < 0.05). Elevated CRP/Alb ratio independently predicts worse overall survival and disease-free survival of patients with OSCC. Conclusion: Preoperative high CRP/Alb ratio was a poor independent prognostic marker of OSCC.

KEYWORDS:
AUC; CRP/Alb; DFS; NLR; OS; PLR; ROS; marker; oral squamous cell carcinoma; prognosis

PMID: 31237166 DOI: 10.2217/fon-2019-0063
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Select item 31237152
21.
Future Oncol. 2019 Jun 25. doi: 10.2217/fon-2018-0868. [Epub ahead of print]
Anti-PD-1 versus anti-PD-L1 therapy in patients with pretreated advanced non-small-cell lung cancer: a meta-analysis.
Tartarone A1, Roviello G2, Lerose R3, Roudi R4, Aieta M1, Zoppoli P5.
Author information
Abstract
Aim: At present three immune checkpoint inhibitors (ICIs), two anti-PD-1 (nivolumab and pembrolizumab) and one anti-PD-L1 (atezolizumab) can be used in pretreated non-small-cell lung cancer patients. The aim of this meta-analysis is an indirect comparison between anti-PD-1 and anti-PD-L1 inhibitors. Methods: Seven studies (>4000 patients) were considered. Results: Considering the overall survival ICIs showed very robust efficacy over docetaxel, while in terms of progression-free survival the therapy with ICIs is slightly favored. Anti-PD-1 gives a more significant benefit than anti-PD-L1; however, excluding the KEYNOTE 010 trial that enrolled only PD-L1-positive patients, the subgroup difference remains only in terms of progression-free survival. Conclusion: This meta-analysis confirms the superiority of ICIs over docetaxel in pretreated non-small-cell lung cancer patients and would indicate a slight benefit from anti-PD-1 than from anti-PD-L1 inhibitors, always keeping in mind the possible biases of this indirect comparison.

KEYWORDS:
atezolizumab; avelumab; checkpoint inhibitors; immunotherapy; meta-analysis; nivolumab; non-small-cell lung cancer; pembrolizumab

PMID: 31237152 DOI: 10.2217/fon-2018-0868
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Select item 31237146
22.
Future Oncol. 2019 Jun 25. doi: 10.2217/fon-2018-0669. [Epub ahead of print]
Prognostic impact of tumor-associated macrophage infiltration in esophageal cancer: a meta-analysis.
Li J1, Xie Y1, Wang X1, Li F1,2, Li S1, Li M1, Peng H1, Yang L1, Liu C1, Pang L1, Zou H1, Zhao J1, Qi Y1, Cao Y1, Hu J1.
Author information
Abstract
Aim: To provide clarity surrounding the association between tumor-associated macrophages (TAMs) and esophageal cancer prognosis. Materials & methods: Several databases were searched. The meta-analysis was conducted by using software Stata 12.0 and Revman. Results: 16 studies were included in this analysis (2292 samples). CD68+ TAM density was not associated with overall survival (OS; hazard ratio [HR]: 0.88, 95% CI: 0.67-1.15; p = 0.33) and disease-free survival (HR: 1.25, 95% CI: 0.66-2.35; p = 0.49). M2-like TAMs were associated with poor overall survival (HR: 1.47, 95% CI: 1.10-1.98; p = 0.01), Tumor, Node, Metastasis staging and vessel metastasis. Conclusion: CD68+ TAM density is not associated with esophageal cancer progression, while CD163+ M2-like TAMs is a potential risk factor.

KEYWORDS:
TAMs; clinicopathological significance; esophageal cancer; meta-analysis; tumor-associated macrophages

PMID: 31237146 DOI: 10.2217/fon-2018-0669
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Select item 31237145
23.
Future Oncol. 2019 Jun 25. doi: 10.2217/fon-2019-0170. [Epub ahead of print]
Excess of second tumors in denosumab-treated patients: a metabolic hypothesis.
Tovazzi V1, Dalla Volta A2, Pedersini R1, Amoroso V1, Berruti A1.
Author information
KEYWORDS:
denosumab; hyperparathyroidism; hypocalcemia; second malignancies

PMID: 31237145 DOI: 10.2217/fon-2019-0170
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Select item 31236388
24.
World J Clin Cases. 2019 Jun 6;7(11):1242-1252. doi: 10.12998/wjcc.v7.i11.1242.
Radiation therapy for extrahepatic bile duct cancer: Current evidences and future perspectives.
Koo T1, Park HJ2, Kim K3.
Author information
Abstract
Extrahepatic bile duct cancer (EBDC) is a rare malignancy that involves neoplastic changes extending from both hepatic ducts to the common bile duct. The treatment of choice is surgical resection, but the predominant pattern of initial treatment failure is locoregional recurrence. Accordingly, adjuvant radiotherapy has been administered after surgical resection based on these rationales. At this time, there is minimal evidence supporting adjuvant radiotherapy, because there have been no phase III trials evaluating its benefit. Relatively small retrospective studies have tried to compare outcomes associated with EBDC treated with or without radiotherapy. We aimed to review studies investigating adjuvant radiotherapy for resected EBDC. Because less than one-third of EBDC cases are amenable to curative resection at diagnosis, other locoregional treatment modalities need to be considered, including radiotherapy. The next aim of this review was to summarize reports of definitive radiotherapy for unresectable EBDC. Patients with advanced EBDC often experience biliary obstruction, which can lead to jaundice and progress to death. Biliary stent insertion is an important palliative procedure, but stents are prone to occlusion after subsequent ingrowth of the EBDC. Radiotherapy can be effective for maintaining the patency of inserted stents. We also reviewed the benefit of palliative radiotherapy combined with the biliary stent insertion. Lastly, we discuss the existing gaps in the evidence supporting radiotherapy in the management of EBDC.

KEYWORDS:
Adjuvant radiotherapy; Biliary stent; Definitive radiotherapy; Extrahepatic bile duct cancer; Palliative radiotherapy; Patterns of failure

PMID: 31236388 PMCID: PMC6580339 DOI: 10.12998/wjcc.v7.i11.1242
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Conflict of interest statement
Publication type
Select item 31236113
25.
Stem Cells Int. 2019 May 19;2019:2079742. doi: 10.1155/2019/2079742. eCollection 2019.
Pancreatic Ductal Organoids React Kras Dependent to the Removal of Tumor Suppressive Roadblocks.
Perkhofer L1, Engler M1, Gout J1, Arnold F1, Morawe M1, Breunig M1, Seufferlein T1, Kleger A1, Frappart PO1.
Author information
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is still the Achilles heel in modern oncology, with an increasing incidence accompanied by a persisting high mortality. The developmental process of PDAC is thought to be stepwise via precursor lesions and sequential accumulation of mutations. Thereby, current sequencing studies recapitulate this genetic heterogeneity in PDAC and show besides a handful of driver mutations (KRAS, TP53) a plethora of passenger mutations that allow to define subtypes. However, modeling the mutations of interest and their effects is still challenging. Interestingly, organoids have the potential to recapitulate in vitro, the in vivo characteristics of the tissue they originate from. Here, we could establish and develop tools allowing us to isolate, culture, and genetically modify ductal mouse organoids. Transferred to known effectors in the IPMN-PDAC sequence, we could reveal significantly increased proliferative and self-renewal capacities for PTEN and RNF43 deficiency in the context of oncogenic KRASG12D in mouse pancreatic organoids. Overall, we were able to obtain promising data centering ductal organoids in the focus of future PDAC research.

PMID: 31236113 PMCID: PMC6545725 DOI: 10.1155/2019/2079742
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Select item 31235702
26.
Sci Rep. 2019 Jun 24;9(1):9142. doi: 10.1038/s41598-019-45161-8.
Vitamin D receptors (VDR), hydroxylases CYP27B1 and CYP24A1 and retinoid-related orphan receptors (ROR) level in human uveal tract and ocular melanoma with different melanization levels.
Markiewicz A1, Brożyna AA2, Podgórska E3, Elas M3, Urbańska K3, Jetten AM4, Slominski AT5,6, Jóźwicki W7,8, Orłowska-Heitzman J9, Dyduch G9, Romanowska-Dixon B10.
Author information
Abstract
In recent years, a significant number of studies have investigated the preventive role of vitamin D in a number of different neoplasms. In this study, we analyze various components of the vitamin D signaling pathways in the human uveal tract and uveal melanoma, including analysis of the expression of vitamin D receptors (VDR), the activating and inactivating hydroxylases, respectively, CYP27B1 and CYP24A1, and the retinoic acid-related orphan receptors (ROR) α (RORα) and γ (RORγ) in these tissues. We further analyzed the expression of VDR, CYP27B1, CYP24A1, and ROR in relation to melanin levels, clinical stage and prognosis. Our study indicated that the uveal melanoma melanin level inversely correlated with VDR expression. We further showed that vitamin D is metabolized in uveal melanoma. This is significant because until now there has been no paper published, that would describe presence of VDR, hydroxylases CYP27B1 and CYP24A1, and RORα and RORγ in the human uveal tract and uveal melanomas. The outcomes of our research can contribute to the development of new diagnostic and therapeutic methods in uveal tract disorders, especially in uveal melanoma. The presented associations between vitamin D signaling elements and uveal melanoma in comparison to uveal tract encourage future clinical research with larger patients' population.

PMID: 31235702 DOI: 10.1038/s41598-019-45161-8
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Select item 31234813
27.
BMC Cancer. 2019 Jun 24;19(1):616. doi: 10.1186/s12885-019-5776-0.
Achieving a timely diagnosis for teenagers and young adults with cancer: the ACE "too young to get cancer?" study.
Dommett RM1,2, Pring H1, Cargill J1, Beynon P1, Cameron A1, Cox R2, Nechowska A1, Wint A3, Stevens MCG4,5.
Author information
Abstract
BACKGROUND:
Time to diagnosis (TTD) concerns teenagers and young adults (TYA) with cancer and may affect outcome.

METHODS:
Healthcare records from 105 TYA in a regional cancer service were assessed to document events from 1st symptom to treatment start. Detailed pathway construction was possible for 104 patients and allowed a multidisciplinary panel review of each pathway with assessment of good practice and lessons for the future.

RESULTS:
1st presentation was to primary care in 86, and 93% consulted in primary care before diagnosis. Routes to Diagnosis were 45% via urgent 2 Week Wait pathways and 38% as emergency referrals. Total Interval (time from 1st presentation to treatment start) was median 63 (range 1-559) days, varying within/between diagnoses. Patient interval (time from 1st symptom to 1st presentation) was longest for lymphoma, carcinoma and bone tumour (medians: 9, 12, 20 days). Overall, time in primary care was short (median 3, range 0-537 days) compared to secondary care (median 29, range 0-195 days) and longest for lymphoma, carcinoma, brain/CNS (medians: 10, 15, 16 days). Specialist Care interval (time from 1st specialist visit to treatment start) was longest for bone, brain/CNS, lymphoma, carcinoma (medians: 30, 33, 36, 48 days). 40% pathways were rated as showing good/best practice but 16% were less than satisfactory. Continued safety-netting/support was identified from primary care but analysis suggested opportunities for improvement in transition through secondary care.

CONCLUSIONS:
Previous reports of prolonged TTD have focused on delay in referral from primary care but this study suggests that this might be reduced by optimising management in secondary care.

KEYWORDS:
Primary care; Routes to diagnosis; Secondary care; TYA; Time to diagnosis

PMID: 31234813 DOI: 10.1186/s12885-019-5776-0
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Select item 31234645
28.
Future Oncol. 2019 Jun 25. doi: 10.2217/fon-2019-0243. [Epub ahead of print]
Ramucirumab and paclitaxel in patients with gastric cancer and prior trastuzumab: subgroup analysis from RAINBOW study.
De Vita F1, Borg C2, Farina G3, Geva R4, Carton I5, Cuku H6, Wei R7, Muro K8.
Author information
Abstract
Aim: This subgroup analysis of the RAINBOW study evaluated the efficacy and safety of ramucirumab in patients with gastric cancer/gastroesophageal junction adenocarcinoma who received prior trastuzumab therapy. Patients & methods: Of adult patients enrolled in the RAINBOW study, 39 had received prior trastuzumab therapy. Of these, 20 patients were treated with ramucirumab plus paclitaxel and 19 patients with placebo plus paclitaxel within the RAINBOW trial. Results: Overall survival was longer with ramucirumab plus paclitaxel (11.4 months; 95% CI: 7.0-17.9) versus placebo plus paclitaxel (7.0 months; 95% CI: 3.4-14.6), hazard ratio: 0.68 (0.33-1.41); p = 0.30. Longer progression-free survival, higher objective response were observed in ramucirumab combination group. Conclusion: Ramucirumab plus paclitaxel demonstrated efficacy benefits with manageable safety profile in a subgroup of patients pretreated with trastuzumab. Clinical trial registration number: NCT01170663.

KEYWORDS:
gastric cancer; HER-2 inhibitor; VEGFR-2 inhibitor; prior trastuzumab; ramucirumab plus paclitaxel; targeted therapy

PMID: 31234645 DOI: 10.2217/fon-2019-0243
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Select item 31101211
29.
Transplant Proc. 2019 May;51(4):1263-1267. doi: 10.1016/j.transproceed.2019.04.007.
Lung Transplantation in Hungary From Cardiac Surgeons' Perspective.
Fazekas L1, Ghimessy Á2, Gieszer B2, Radeczky P2, Mészáros L2, Török K2, Bogyó L2, Hartyánszky I3, Pólos M3, Daróczi L3, Agócs L2, Kocsis Á2, Bartók T4, Dancs T4, Tóth KK4, Schönauer N4, Madurka I4, Elek J4, Döme B5, Rényi-Vámos F2, Lang G2, Farkas A2.
Author information
Abstract
Thoracic organ transplantation made a fresh start in Hungary with the first double lung transplant in December 2015. This major leap in Hungarian transplantation was preceded by almost 10 years of preparation, new infrastructure development, and structural changes not only at the organizational level but in human resources as well. In the following years, until recently, altogether 47 lung transplants were performed on 24 men and 23 women. The underlying pathologies were as follows: chronic obstructive pulmonary disease, 25; cystic fibrosis, 11; idiopathic pulmonary fibrosis, 7; as well as other diseases, including bronchiectasis, eosinophilic granuloma, lymphangioleiomyomatosis, and primary pulmonary hypertension in 4 cases. The youngest recipient was 13 and the oldest was 65 years old. Overall survival rates at 30 days and at 1 year were 96% and 82%, respectively. No patients were lost in the cystic fibrosis and other diseases group, whereas the 1-year survival rates of the chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis groups were 73% and 71%, respectively. The results show the robustness and viability of the program, although there is still opportunity for further improvement. In this short paper, we summarize the fields of possible further cooperation of thoracic and cardiac teams as well as future challenges facing the new Hungarian lung transplant program.

Copyright © 2019 Elsevier Inc. All rights reserved.

PMID: 31101211 DOI: 10.1016/j.transproceed.2019.04.007
[Indexed for MEDLINE]
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Select item 31054547
30.
Zhonghua Wei Chang Wai Ke Za Zhi. 2019 Apr 25;22(4):336-341. doi: 10.3760/cma.j.issn.1671-0274.2019.04.005.
[Fudan experience of neoadjuvant treatment for rectal cancer].
[Article in Chinese; Abstract available in Chinese from the publisher]
Zhang J1, Shen LJ, Wan JF, Yang LF, Zhu J, Zhang Z.
Author information
Abstract
Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. Fudan University Shanghai Cancer Center has carried out multiple series of studies to explore the optimization of the neoadjuvant therapy since 2005. On the one hand, the "addition" method refers to a higher intensity treatment at the neoadjuvant stage to obtain better tumor regression. On the other hand, the "subtraction" method reduces some unnecessary treatment from the current triad of surgery, radiotherapy and chemotherapy to improve the quality of life of patients. However, locally advanced rectal cancer is associated with great heterogeneity, and therefore, any single treatment mode will not be optimal for all. Notably, the treatment decision-making should be based on clinical presentations, imaging findings, and molecular biology to precisely stratify patients. Besides, the scheme should be dynamically adjusted according to the therapeutic response, so as to realize the dual goals of prolonging patients' life and improving their quality of life. Meanwhile, the treatment decision-making for target population under the guidance of biomarker should be dynamically and self-adaptively adjusted based on the therapeutic effect. This approach will become the future development direction and objective for the precise medical treatment for rectal cancer.

KEYWORDS:
Chemoradiotherapy; Neoadjuvant therapy; Rectal neoplasms

PMID: 31054547 DOI: 10.3760/cma.j.issn.1671-0274.2019.04.005
[Indexed for MEDLINE]
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Select item 30886871
31.
J Immunol Res. 2019 Feb 11;2019:4516041. doi: 10.1155/2019/4516041. eCollection 2019.
Immunoglobulin Gamma-Like Therapeutic Bispecific Antibody Formats for Tumor Therapy.
Chen S1, Li L1,2, Zhang F1, Wang Y1, Hu Y1, Zhao L1.
Author information
Abstract
Bispecific antibodies (BsAbs) are a sort of dual functional proteins with specific binding to two distinct targets, which have become a focus of interest in antibody engineering and drug development research and have a promising future for wide applications in cancer immunotherapy and autoimmune disease. The key of clinical application and commercial-scale manufacturing of BsAbs is the amenability to assembly and purification of desired heterodimers. Advances in genetic engineering technology had resulted in the development of diverse BsAbs. Multiple recombinant strategies have been used to solve the mispairing problem between light and heavy chains, as well as to enforce accurate dimerization of heterologous heavy chains. There are 23 platforms available to generate 62 BsAbs which can be further divided into IgG-like ones and fragment-based ones, and more than 50 molecules are undergoing clinical trials currently. BsAbs with IgG-like architecture exhibit superior advantages in structure (similar to natural antibodies), pharmacokinetics, half-life, FcR-mediated function, and biological activity. This review considers various IgG-like BsAb generation approaches, summarizes the clinical applications of promising new BsAbs, and describes the mechanism of BsAbs in tumor therapy.

PMID: 30886871 PMCID: PMC6388348 DOI: 10.1155/2019/4516041
[Indexed for MEDLINE] Free PMC Article
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Select item 30791774
32.
Expert Rev Gastroenterol Hepatol. 2019 Apr;13(4):285-291. doi: 10.1080/17474124.2019.1573143. Epub 2019 Feb 4.
Oxaliplatin in perioperative chemotherapy for gastric and gastroesophageal junction (GEJ) adenocarcinoma.
Fritsch R1,2,3, Hoeppner J2,4,5.
Author information
Abstract
Platinum-based chemotherapy remains standard-of-care for gastric and gastroesophageal junction (GEJ) adenocarcinoma. For locally advanced resectable disease, perioperative treatment with cisplatin-based doublet or triplet chemotherapy regimens had been the predominant approach in Europe and the US, based on pivotal phase III trials including the MAGIC study. Results from more recent landmark studies including the German FLOT4 and the Asian CLASSIC trials have, however, triggered a shift from cisplatin towards oxaliplatin-based chemotherapy protocols in the perioperative setting. Areas covered: This drug profile summarizes current state-of-the-art of perioperative and adjuvant treatment for locally advanced resectable gastric/GEJ cancers with a special focus on the increasingly predominant role of oxaliplatin over cisplatin in this setting. We review pharmacology, clinical efficacy, and safety profile of oxaliplatin and oxaliplatin combination regimens. We highlight recent advances and ongoing developments in the field. Expert opinion: While the adoption of oxaliplatin-containing combination regimens for perioperative therapy of gastric/GEJ cancers represents a significant step ahead, many pivotal questions remain unanswered. At the sample time, the evolution of molecular subtyping and immunotherapy is likely to dramatically change clinical practice in the foreseeable future.

KEYWORDS:
Perioperative chemotherapy; efficacy; esophageal cancer; gastric cancer; gastroesophageal junction adenocarcinoma; oxaliplatin; safety

PMID: 30791774 DOI: 10.1080/17474124.2019.1573143
[Indexed for MEDLINE]
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Select item 30685385
33.
EBioMedicine. 2019 Feb;40:733-742. doi: 10.1016/j.ebiom.2019.01.027. Epub 2019 Jan 24.
Low TREM1 expression in whole blood predicts anti-TNF response in inflammatory bowel disease.
Verstockt B1, Verstockt S2, Dehairs J3, Ballet V4, Blevi H5, Wollants WJ5, Breynaert C6, Van Assche G1, Vermeire S1, Ferrante M7.
Author information
Abstract
BACKGROUND:
With the changed therapeutic armamentarium for Crohn's disease (CD) and ulcerative colitis (UC), biomarkers predicting treatment response are urgently needed. We studied whole blood and mucosal expression of genes previously reported to predict outcome to anti-TNF therapy, and investigated if the signature was specific for anti-TNF agents.

METHODS:
We prospectively included 54 active IBD patients (24CD, 30UC) initiating anti-TNF therapy, as well as 22 CD patients initiating ustekinumab and 51 patients initiating vedolizumab (25CD, 26UC). Whole blood expression of OSM, TREM1, TNF and TNFR2 was measured prior to start of therapy using qPCR, and mucosal gene expression in inflamed biopsies using RNA-sequencing. Response was defined as endoscopic remission (SES-CD ≤ 2 at week 24 for CD and Mayo endoscopic sub-score ≤ 1 at week 10 for UC).

FINDINGS:
Baseline whole blood TREM1 was downregulated in future anti-TNF responders, both in UC (FC = 0.53, p = .001) and CD (FC = 0.66, p = .007), as well as in the complete cohort (FC = 0.67, p < .001). Receiver operator characteristic statistics showed an area under the curve (AUC) of 0.78 (p = .001). A similar accuracy could be achieved with mucosal TREM1 (AUC 0.77, p = .003), which outperformed the accuracy of serum TREM1 (AUC 0.58, p = .31). Although differentially expressed in tissue, OSM, TNF and TNFR2 were not differentially expressed in whole blood. The TREM1 predictive signal was anti-TNF specific, as no changes were seen in ustekinumab and vedolizumab treated patients.

INTERPRETATION:
We identified low TREM-1 as a specific biomarker for anti-TNF induced endoscopic remission. These results can aid in the selection of therapy in biologic-naïve patients.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

KEYWORDS:
Adalimumab; Anti-TNF; Biomarker; Endoscopic remission; IBD; Infliximab; Personalised medicine; TREM1

PMID: 30685385 PMCID: PMC6413341 DOI: 10.1016/j.ebiom.2019.01.027
[Indexed for MEDLINE] Free PMC Article
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Select item 30339147
34.
Oncol Nurs Forum. 2018 Nov 1;45(6):683-685. doi: 10.1188/18.ONF.683-685.
What Is the Rural Cultural Perspective?
LeBaron VT1.
Author information
Abstract
An article by Lally et al. (2018) in the current issue describes the process of collecting end-user feedback from a sample of rural Nebraskan women with breast cancer regarding a web-based, psychosocial distress management program, CaringGuidance™. The current article uses that study to inform discussion on future work in the realm of interventions for rural cancer survivors.

KEYWORDS:
acceptability; feasibility; online focus groups; psychosocial interventions; rural breast cancer survivors

PMID: 30339147 DOI: 10.1188/18.ONF.683-685
[Indexed for MEDLINE]
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Select item 30337268
35.
Clin Lung Cancer. 2019 Jan;20(1):e107-e114. doi: 10.1016/j.cllc.2018.09.014. Epub 2018 Sep 24.
Lymph Node Size Predicts for Asymptomatic Brain Metastases in Patients With Non-small-cell Lung Cancer at Diagnosis.
Rice SR1, Molitoris JK1, Vyfhuis MAL1, Edelman MJ2, Burrows WM3, Feliciano J4, Nichols EM1, Suntharalingam M1, Donahue J3, Carr SR3, Friedberg J3, Badiyan S1, Simone CB 2nd1, Feigenberg SJ5, Mohindra P6.
Author information
Abstract
BACKGROUND:
We questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non-small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases.

MATERIALS AND METHODS:
A retrospective analysis of 193 consecutive, treatment-naïve patients with NSCLC diagnosed between January 2010 and August 2015 was performed. Exclusion criteria included no brain MRI staging, symptomatic brain metastases, or stage IV based on extracranial disease. Univariate and multivariate logistic regression was performed.

RESULTS:
The patient characteristics include median age of 65 years (range, 36-90 years), 51% adenocarcinoma/36% squamous carcinoma, and pre-MRI stage grouping of 31% I, 22% II, 34% IIIA, and 13% IIIB. The overall prevalence of brain metastases was 5.7% (n = 11). One (2.4%) stage IA and 1 (5.6%) stage IB patient had asymptomatic brain metastases at diagnosis, both were adenocarcinomas. On univariate analysis, increasing lymph nodal stage (P = .02), lymph nodal size > 2 cm (P = .009), multi-lymph nodal N1/N2 station involvement (P = .027), and overall stage (P = .005) were associated with asymptomatic brain metastases. On multivariate analysis, increasing lymph nodal size remained significant (odds ratio, 1.545; P = .009).

CONCLUSION:
Our series shows a 5.7% rate of asymptomatic brain metastasis for patients with stage I to III NSCLC. Increasing lymph nodal size was the only predictor of asymptomatic brain metastases, suggesting over-utilization of MRI in early-stage disease, especially in lymph node-negative patients with NSCLC. Future efforts will explore the utility of baseline MRI in lymph node-positive stage II and all stage IIIA patients.

Published by Elsevier Inc.

KEYWORDS:
Asymptomatic; Brain metastases; MRI; NSCLC; Staging

PMID: 30337268 DOI: 10.1016/j.cllc.2018.09.014
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36.
Clin Lung Cancer. 2019 Jan;20(1):37-42. doi: 10.1016/j.cllc.2018.09.002. Epub 2018 Sep 8.
Predictors of Distant Failure After Stereotactic Body Radiation Therapy for Stages I to IIA Non-Small-Cell Lung Cancer.
Miller CJ1, Martin B1, Stang K1, Hutten R1, Alite F2, Small C1, Emami B1, Harkenrider MM3.
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Abstract
PURPOSE:
The use of stereotactic body radiation therapy (SBRT) has emerged as an effective treatment modality for patients with early-stage non-small-cell lung cancer (NSCLC), with excellent local control rates. Despite this, there is a predominant pattern of distant failure. We sought to identify factors that help predict which patients with stages I to IIA NSCLC treated with SBRT are at highest risk of distant failure, so that we may utilize these factors in the future to help determine which patients may benefit from the addition of systemic therapies.

PATIENTS AND METHODS:
We retrospectively reviewed 292 patients treated with SBRT for early stage NSCLC from 2006 to 2016 at 2 institutions. Patients were classified by T stage, tumor size, location and histology, pretreatment positron emission tomography/computed tomography (PET/CT) standardized uptake value (SUV), smoking status, and age. The primary endpoint of the study was distant failure. We aimed to analyze if patient characteristics could be identified that predicted for distant failure through the use of competing risk analysis.

RESULTS:
The median follow-up was 21.9 months. The median dose of radiation and fractionation delivered was 50 Gy (range, 45-65 Gy) in 5 fractions (range, 3-13 fractions). The median patient age was 72.8 years (interquartile range, 65.4-79.7 years). The 2-year distant failure was 22.0%, and overall survival at 2 years was found to be 61.0%. For every 1-year increase in patient age, the hazard of distant failure at any given time was 3% lower (hazard ratio, 0.97; 95% confidence interval, 0.94-0.99; P = .04). None of the remaining characteristics emerged as significant risk factors for distant failure on univariable or multivariable analysis.

CONCLUSIONS:
Overall, our cohort had distant failure and survival rates comparable with what has been described in the literature. Although we were unable to identify factors outside of age that correlated to risk of distant failure, this topic warrants further investigation, as distant failure is the primary pattern of failure with SBRT when used as the primary management for early-stage NSCLC. Additional molecular studies are needed to further inform on the role of systemic therapy in patients with early-stage NSCLC to improve clinical outcomes.

Published by Elsevier Inc.

KEYWORDS:
Distant failure; NSCLC; Patterns of failure; Radiation therapy; SBRT

PMID: 30279109 DOI: 10.1016/j.cllc.2018.09.002
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37.
Clin Lung Cancer. 2018 Nov;19(6):531-543. doi: 10.1016/j.cllc.2018.08.011. Epub 2018 Aug 22.
First-line Chemotherapy Responsiveness and Patterns of Metastatic Spread Identify Clinical Syndromes Present Within Advanced KRAS Mutant Non-Small-cell Lung Cancer With Different Prognostic Significance.
Iams WT1, Yu H2, Shyr Y3, Patil T4, Horn L5, McCoach C6, Kelly K7, Doebele RC4, Camidge DR8.
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Abstract
BACKGROUND:
Unsuccessful KRAS-specific treatment approaches in non-small-cell lung cancer (NSCLC) might reflect underlying disease heterogeneity. We sought to define clinical "syndromes" within advanced KRAS mutant NSCLC to improve future clinical trials and create a clinical framework for future molecular development.

PATIENTS AND METHODS:
To test a series of a priori hypotheses regarding KRAS-mutant NSCLC clinical syndromes, we conducted a multi-institutional retrospective medical record review. Survival probabilities were estimated using the Kaplan-Meier model. Between-group differences were assessed using the log-rank test. Multivariate Cox regression analyses and Wilcoxon rank sum testing were used to assess progression-free survival and overall survival (OS) differences.

RESULTS:
Among 218 patients with advanced KRAS-mutant NSCLC, OS and progression-free survival with first-line chemotherapy did not differ by intrathoracic versus extrathoracic spread, smoking intensity, or the specific KRAS mutation. Metastatic disease at diagnosis resulted in significantly worse OS than recurrent, unresectable disease (median OS, 14.6 vs. 40.9 months; P = .001). Among the patients with metastatic disease at diagnosis, nonscalp, soft tissue metastases (syndrome X; 6% of cases; 95% confidence interval [CI], 2.5%-10.1%) signified a poor prognosis (median OS, 7.5 vs. 15.9 months for the controls; P = .021). The response to first-line chemotherapy (syndrome Y; 41% of cases; 95% CI, 32.3%-50.6%) signified a good prognosis (median OS, 26.7 vs. 11.9 months; P = .002). The overlap between these 2 syndromes was minimal (2 of 111). Multivariate analysis confirmed these observations. The hazard ratio for death for syndromes X and Y was 2.64 (95% CI, 1.13-6.14) and 0.45 (95% CI, 0.28-0.76), respectively.

CONCLUSION:
Chemotherapy-responsive disease and nonscalp, soft tissue spread might represent distinct clinical syndromes within KRAS-mutant NSCLC. The molecular biology underlying this heterogeneity warrants future studies.

Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS:
Chemotherapy-responsive; KRAS clinical syndromes; Metastatic; NSCLC; Soft tissue metastasis

PMID: 30197261 PMCID: PMC6204301 [Available on 2019-11-01] DOI: 10.1016/j.cllc.2018.08.011
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38.
Lung Cancer. 2018 Aug;122:214-219. doi: 10.1016/j.lungcan.2018.06.025. Epub 2018 Jun 19.
Association between hospital volume and mortality of patients with metastatic non-small cell lung cancer.
Goyal G1, Kommalapati A2, Bartley AC3, Gunderson TM3, Adjei AA4, Go RS5.
Author information
Abstract
BACKGROUND:
Prior studies have shown superior surgical outcomes of stage I-III non-small cell lung cancer (NSCLC) in centers with higher patient volumes. However, there is a lack of such information in stage IV NSCLC.

PATIENTS AND METHODS:
This is a retrospective study of stage IV NSCLC patients diagnosed between 2004 and 2014 using the National Cancer Data Base (NCDB). We classified the total number of patients treated at facilities into quartiles: quartile 1 (Q1): ≤23; quartile 2 (Q2): 24-36, quartile 3 (Q3): 37-55, and quartile 4 (Q4): ≥56 cases/year. Cox regression was used to assess whether risk of death differed between quartiles after adjusting for demographics, insurance type, Charlson-Deyo score, and type of therapy received.

RESULTS:
There were 338, 445 patients with stage IV NSCLC treated at 1326 facilities. We included the patients who received any form of therapy in the survival analysis. The unadjusted median overall survival by facility volume was: Q1: 6 months, Q2: 6 months, Q3: 7 months, and Q4: 8 months (p < .001). Multivariable analysis showed that facility volume was independent predictor of all-cause mortality. Compared with patients treated at Q4 facilities, patients treated at lower-quartile facilities had a small but significantly higher risk of death (Q3 hazard ratio [HR], 1.05 [95%CI, 1.04-1.06]; Q2 HR, 1.12 [95%CI, 1.11-1.14]; Q1 HR, 1.11 [95%CI, 1.10-1.12]).

CONCLUSIONS:
Patients who were treated for stage IV NSCLC at highest-volume facilities had less risk of all-cause mortality compared with those who were treated at lower-volume facilities. Although the survival advantage of being treated at highest-volume facilities appeared small, the results of this study suggest differences in cancer care delivery models among various facilities, and may become more relevant in the future era of personalized treatment of stage IV NSCLC.

Copyright © 2018 Elsevier B.V. All rights reserved.

KEYWORDS:
Hospital volumes; Lung cancer; NCDB; Overall survival

PMID: 30032834 DOI: 10.1016/j.lungcan.2018.06.025
[Indexed for MEDLINE]
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39.
Bioessays. 2018 Aug;40(8):e1800050. doi: 10.1002/bies.201800050. Epub 2018 Jun 4.
Understanding Immune Tolerance of Cancer: Re-Purposing Insights from Fetal Allografts and Microbes.
Barnet MB1,2,3, Blinman P4,5, Cooper W5,6,7, Boyer MJ3,5, Kao S3,5, Goodnow CC1.
Author information
Abstract
Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations. The treatment of cancer with immune checkpoint inhibitors aims to reverse the progression to tolerance of cancer, and achieve an immunogenic, rather than tolerogenic, homeostasis. Broadening the efficacy and durability of checkpoint inhibitors focuses on reversing tolerance and stimulating immunogenicity in the cancer, host, and environment. Two examples of important physiological states of tolerance that may inform tolerance of cancer are microbial infection and placental reproduction. These states of tolerance result from bilateral shaping of host and non-self, akin to immunoediting in cancer, and offer reliable models to study the immune tolerance paradigm.

© 2018 WILEY Periodicals, Inc.

KEYWORDS:
cancer; immune checkpoints; immune tolerance; immunotherapy

PMID: 29869436 DOI: 10.1002/bies.201800050
[Indexed for MEDLINE]
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40.
Clin Lung Cancer. 2018 Nov;19(6):e815-e821. doi: 10.1016/j.cllc.2018.04.007. Epub 2018 May 5.
Timing of Thoracic Radiation Therapy With Chemotherapy in Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Current Practice Patterns.
Farrell MJ1, Yahya JB1, Degnin C1, Chen Y1, Holland JM1, Henderson MA1, Jaboin JJ1, Harkenrider MM2, Thomas CR Jr1, Mitin T3.
Author information
Abstract
INTRODUCTION:
For limited-stage small-cell lung cancer (LS-SCLC), National Comprehensive Cancer Network guidelines recommend that thoracic radiotherapy (TRT) be delivered concurrently with chemotherapy and early in the regimen, with cycle 1 or 2. Evidence is conflicting regarding the benefit of early timing of TRT. A Korean randomized trial did not see a survival difference between early (cycle 1) and late (cycle 3) TRT. Current United States (US) practice patterns are unknown.

MATERIALS AND METHODS:
We surveyed US radiation oncologists using an institutional review board-approved online questionnaire. Questions covered treatment recommendations, self-rated knowledge of trials, and demographics.

RESULTS:
We received 309 responses from radiation oncologists. Ninety-eight percent recommend concurrent chemoradiotherapy over sequential. Seventy-one percent recommend starting TRT in cycle 1 of chemotherapy, and 25% recommend starting in cycle 2. In actual practice, TRT is started most commonly in cycle 2 (48%) and cycle 1 (44%). One-half of respondents (54%) believe starting in cycle 1 improves survival compared with starting in cycle 3. Knowledge of the Korean trial was associated with flexibility in delaying TRT to cycle 2 or 3 (P = .02). Over one-third (38%) treat based on pre-chemotherapy volume.

CONCLUSION:
US radiation oncologists strongly align with National Comprehensive Cancer Network guidelines, which recommend early concurrent chemoradiotherapy. Nearly three-quarters of respondents prefer starting TRT with cycle 1 of chemotherapy. However, knowledge of a trial supporting a later start was associated with flexibility in delaying TRT. Treating based on pre-chemotherapy volume-endorsed by over one-third of respondents-may add unnecessary toxicity. This survey can inform development of future trials.

Copyright © 2018 Elsevier Inc. All rights reserved.

KEYWORDS:
Chemoradiotherapy; Combined-modality therapy; Questionnaire; Radiotherapy; Target volume

PMID: 29857969 DOI: 10.1016/j.cllc.2018.04.007
[Indexed for MEDLINE]
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Select item 29637868
41.
Anticancer Agents Med Chem. 2018;18(9):1220-1227. doi: 10.2174/1871520618666180411110036.
Translational Research: A Future Strategy for Managing Squamous Cell Carcinoma of the Head and Neck?
Caponigro F1, Ionna F2, Scarpati GDV3, Longo F2, Addeo R4, Manzo R5, Muto P6, Pisconti S1, Leopaldi L7, Perri F3.
Author information
Abstract
BACKGROUND:
Squamous Cell Carcinoma of the Head and Neck (SCCHN) are neoplasms arising from the epithelium of the first aero-digestive tract. They are very heterogeneous both clinically and biologically. Classic and well acknowledged risk factors are alcohol and tobacco consumption and other forms of smokeless tobacco assumption, although lately the incidence of Human Papilloma Virus (HPV)-related SCCHN is rapidly increasing. HPV-related tumors are very different from their alcohol and tobacco-associated counterpart, as they show strong chemo and radio sensitivity and thus can often be treated with conservative treatment strategies. Moreover, peculiar biologic features characterize HPV-related tumors, such as wild type TP53, low expression of Epidermal Growth Factor Receptor (EGFR), wild type CCND1 and high expression of P16. In contrast, alcohol and tobacco related SCCHN show opposite features, together with higher number of chromosomal and genetic abnormalities, conferring them chemo and radio resistance.

METHODS:
We have performed a narrative review of the PubMed database with the aim to study the mutational landscape of SCCHN.

RESULTS:
Several lines of evidence support the existence of at least two genetically different types of SCCHN, one virus-related and the other alcohol and/or tobacco-related, characterized by both clinical and biological opposite features. Virus related SCCHN are very chemo and radiosensitive, so suitable for organ preserving strategy, which in the near future may be induction chemotherapy followed by association of chemotherapy and underpowered radiotherapy. Alcohol and tobacco related SCCHN are themselves strongly heterogeneous and can be divided in different entities on the basis of the "Driver" genetic aberration, responsible for carcinogenesis. The most frequently mutated genes in alcohol and tobacco-related SCCHN are TP53, NOTCH1, CCND1, CDKN2A, EGFR and PI3KCA.

CONCLUSIONS:
Virus-related SCCHN can be managed with chemo-radiotherapy. Alcohol and tobacco-related tumors should be further characterized on the basis of their "Driver Mutations" in order to select effective targeted therapies.

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

KEYWORDS:
Translational research; human papilloma virus (HPV); neoplasms; squamous cell carcinoma; tobacco related SCCHN; virusrelated SCCHN.

PMID: 29637868 DOI: 10.2174/1871520618666180411110036
[Indexed for MEDLINE]
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42.
Sci Rep. 2017 Oct 3;7(1):12574. doi: 10.1038/s41598-017-13006-x.
Cancer-associated fibroblasts support vascular growth through mechanical force.
Sewell-Loftin MK1,2, Bayer SVH3,2, Crist E1, Hughes T1, Joison SM4, Longmore GD3,5,2, George SC6.
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Abstract
The role of cancer-associated fibroblasts (CAFs) as regulators of tumor progression, specifically vascular growth, has only recently been described. CAFs are thought to be more mechanically active but how this trait may alter the tumor microenvironment is poorly understood. We hypothesized that enhanced mechanical activity of CAFs, as regulated by the Rho/ROCK pathway, contributes to increased blood vessel growth. Using a 3D in vitro tissue model of vasculogenesis, we observed increased vascularization in the presence of breast cancer CAFs compared to normal breast fibroblasts. Further studies indicated this phenomenon was not simply a result of enhanced soluble signaling factors, including vascular endothelial growth factor (VEGF), and that CAFs generated significantly larger deformations in 3D gels compared to normal fibroblasts. Inhibition of the mechanotransductive pathways abrogated the ability of CAFs to deform the matrix and suppressed vascularization. Finally, utilizing magnetic microbeads to mechanically stimulate mechanically-inhibited CAFs showed partial rescue of vascularization. Our studies demonstrate enhanced mechanical activity of CAFs may play a crucial and previously unappreciated role in the formation of tumor-associated vasculature which could possibly offer potential novel targets in future anti-cancer therapies.

PMID: 28974764 PMCID: PMC5626692 DOI: 10.1038/s41598-017-13006-x
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43.
Eur Urol Focus. 2017 Apr;3(2-3):240-242. doi: 10.1016/j.euf.2016.08.013. Epub 2016 Sep 13.
Toward the future of the functional imaging of advanced prostate cancer.
Schiavina R1, Bianchi L2, Borghesi M1, Sabbatini R3, Brunocilla E1.
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Abstract
BS and CT are routinely used to assess the presence of metastases in advanced PCa patients. New imaging modalities such as PET and WB-MRI have the potential to replace previous imaging techniques allowing to earlier shift to more adequate therapies.

Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Comment on
Rationale for Modernising Imaging in Advanced Prostate Cancer. [Eur Urol Focus. 2017]
PMID: 28753788 DOI: 10.1016/j.euf.2016.08.013
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44.
Future Oncol. 2017 Jun;13(13):1135-1136. doi: 10.2217/fon-2017-0103. Epub 2017 Jun 26.
Letter in reply: Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases.
Reyes A1, Marti J1, Marfa S2, Jimenez W2,3, Reichenbach V2, Pelegrina A1, Fondevila C1, Valdecasas JC1, Fuster J1.
Author information
Abstract
In response to: S Sabour. Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases; rule of thumb.

Comment on
Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases; rule of thumb. [Future Oncol. 2017]
PMID: 28650245 DOI: 10.2217/fon-2017-0103
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45.
Future Oncol. 2017 Jun;13(13):1133-1134. doi: 10.2217/fon-2017-0035. Epub 2017 Jun 26.
Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases; rule of thumb.
Sabour S1,2.
Author information
Abstract
Response to: Reyes A, Marti J, Marfà S et al. Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases. Future Oncol. 13(10), 875-882 (2017).

KEYWORDS:
biomarker; colorectal cancer; liver metastases; outcomes research; prognosis; proteomic analysis

Comment in
Letter in reply: Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases. [Future Oncol. 2017]
Comment on
Prognostic prediction by liver tissue proteomic profiling in patients with colorectal liver metastases. [Future Oncol. 2017]
PMID: 28650211 DOI: 10.2217/fon-2017-0035
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Select item 27325275
46.
J Cancer Educ. 2018 Feb;33(1):109-115. doi: 10.1007/s13187-016-1063-9.
Bringing Cancer Prevention Research Competencies to the Classroom.
Yates MS1, Chang S2, Lee HY2, Faupel-Badger J3, Cameron C4.
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Abstract
The field of cancer prevention incorporates research all along the spectrum from basic science studies at the laboratory bench to epidemiology, behavioral sciences, and clinical studies, with the convergence of evidence from these different approaches aimed at implementing public health interventions that reduce the burden of this disease. Due to the necessity of multiple disciplines interacting in order to achieve a public health outcome, traditional discipline-specific training may not be adequately preparing the cancer prevention research workforce. We propose that cancer prevention researchers establish defined professional competencies which will allow them to shape the future directions of the field as well as to collaborate effectively in multidisciplinary teams, disseminate new findings beyond their own scientific circles, and advocate for their implementation for the public good. We previously proposed that these core competencies focus on knowledge of issues in other research fields, interdisciplinary communication, and leadership/teamwork. Here, we describe the reorganization of an existing course to incorporate activities deliberately designed to foster these competencies. We provide details about the course structure, student feedback, and ideas for future versions of this course. We hope this framework will be useful to others who are engaged in the collective effort to develop leaders in the field of cancer prevention research.

KEYWORDS:
Cancer prevention; Research competencies; Research education; Research training

PMID: 27325275 PMCID: PMC5173449 DOI: 10.1007/s13187-016-1063-9
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