Future Oncol. 2019 Oct 25. doi: 10.2217/fon-2019-0365. [Epub ahead of print]
Relationship of single nucleotide polymorphisms and haplotype interaction of mitochondrial unfolded protein response pathway genes with head and neck cancer.
Ahmed MW1, Mahjabeen I1, Gul S1, Khursheed A1, Mehmood A1, Kayani MA1.
Author information
1
Cancer Genetics & Epigenetics Lab, Department of Biosciences, COMSATS University Islamabad, Park Road Tarlai Kalan, Islamabad Pakistan.
Abstract
Aim: In this study, we evaluated the effect of selected polymorphisms of mitochondrial unfolded protein response (UPRmt) pathway in 500 head and neck cancer (HNC) patients and 500 healthy controls from Pakistan. Materials & methods: The experiments were conducted using tetra-ARMS PCR followed by DNA sequencing. Results: Multivariate analysis showed that AA genotype of rs3782116 showed fivefold, GG genotype of rs6598072 approximately twofold and CC genotype of rs4946936 and TT genotype of rs12212067 showed twofold increased risk of HNC. Furthermore, haplotype analysis showed that certain haplotypes of UPRmt pathway single nucleotide polymorphisms have significant association with increased HNC risk. Conclusion: These results show that genetic aberrations in UPRmt pathway genes have association with increased HNC risk and can be an indicator of advance clinical outcome especially invasion and metastasis.

KEYWORDS:
HNC; UPRmt mechanism; clinical outcome; haplotype analysis; metastasis

PMID: 31651195 DOI: 10.2217/fon-2019-0365
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22.
Future Oncol. 2019 Oct 25. doi: 10.2217/fon-2019-0279. [Epub ahead of print]
Efficacy of immune checkpoint inhibitors in cancer patients of different ages: a meta-analysis.
Li J1, Gu J1.
Author information
1
College of Pharmacy, Southwest Minzu University, No.16 South 4th Section, 1st Ring Road, Chengdu, Sichuan 610041, PR China.
Abstract
Aim: We conducted an up-to-date meta-analysis of randomized controlled trials (RCTs) to compare the immune checkpoint inhibitors (ICIs) in different age groups. Methods: The relevant RCTs in cancer patients receiving ICIs were searched and the systematic evaluation was performed. PubMed, MEDLINE and EMBASE were searched for studies published till January 2019. Results: A total of 27 RCTs included 17,546 patients were available for this meta-analysis. ICIs significantly improved overall survival (OS) and progression-free survival (PFS) in both of the younger (<65 years) and the older cancer patients (≥65 years). No significantly prolonged OS and PFS was observed among patients older than 75 years. Conclusion: ICIs could not significantly improve OS and PFS compared with controls in cancer patients aged over 75 years.

KEYWORDS:
age; immune checkpoint inhibitors; meta-analysis; overall survival; progression-free survival

PMID: 31650854 DOI: 10.2217/fon-2019-0279
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Select item 31650851
23.
Future Oncol. 2019 Oct 25. doi: 10.2217/fon-2019-0319. [Epub ahead of print]
Interaction of 22 risk SNPs with Helicobacter pylori infection and risk of gastric cardia adenocarcinoma.
Xiao FK1, Yang JX1,2, Li XM1,3, Zhao XK1, Zheng PY2, Wang LD1.
Author information
1
Henan Key Laboratory for Esophageal Cancer Research of the First Affiliated Hospital, Zhengzhou University, Zhengzhou, Henan 450052, PR China.
2
Department of Gastroenterology, the Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, PR China.
3
Department of Pathology, Women & Infants Hospital of Zhengzhou, Zhengzhou, Henan 450012, PR China.
Abstract
Aim: To determine the prevalence of Helicobacter pylori infection and correlation between H. pylori infection and single nucleotide polymorphism (SNPs) identified in gastric cardia adenocarcinoma (GCA) patients. Methods: A case control study was performed. 22 risks of GCA-related SNPs were identified by genotyping assay and the relationship between susceptibility loci for GCA and H. pylori infection was further analyzed. Results: Helicobacter pylori infection was associated with GCA significantly (odds ratio: 1.40; 95% CI: 1.29-1.53 p < 0.01). Five GCA risk SNPs had their genotypes significantly different between H. pylori positive patients and H. pylori negative patients. Conclusion: The interaction between SNPs susceptibility loci and H. pylori infection is associated with an increased risk of GCA.

KEYWORDS:
gastric cardia adenocarcinoma; helicobacter pylori infection; single nucleotide polymorphism

PMID: 31650851 DOI: 10.2217/fon-2019-0319
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Select item 31650850
24.
Future Oncol. 2019 Oct 25. doi: 10.2217/fon-2019-0381. [Epub ahead of print]
Apoptosis induction effect of Apocynum venetum polyphenol on human U87 glioma cells via NF-κB pathway.
Zeng S1, Zhao X2, Xu LS1, Yang D1, Chen L1, Xu MH1.
Author information
1
Department of Neurosurgery, Daping Hospital, Army Medical University, Chongqing 400042, PR China.
2
Chongqing Collaborative Innovation Center for Functional Food, Chongqing University of Education, Chongqing 400067, PR China.
Abstract
Aim: Apocynum venetum polyphenol (AVP) was used in in vitro glioma cells culture to prove the growth inhibitory effect of AVP on human U87 glioma cells via NF-κB pathway. Materials & methods: The MTT assay, DAPI morphology, quantitative PCR and western blot experiments were used for determination in vitro. Results & conclusion: AVP can also induce U87 cancer cells apoptosis illustrated by DAPI morphology. AVP could enhance the mRNA and protein expression of IκB-α, TNF-α, TRAIL, caspase-3 and caspase-9 in U87 cancer cells and reduce those of NF-κBp65, cIAP-1, cIAP-2, TGF-β2, CyclinD1, VEGF and IL-8. After ammonium pyrrolidine dithiocarbamate (PDTC) treatment, the NF-κBp65 expression was reduced in U87 cells, and AVP could raise these effects. The results of HPLC indicate that AVP mainly contains six constituents. The growth inhibitory effects of AVP on U87 glioma cells are predominantly from these natural active constituents.

KEYWORDS:
Apocynum venetum; NF-κB; U87 cells; apoptosis; polyphenol

PMID: 31650850 DOI: 10.2217/fon-2019-0381
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Select item 31650847
25.
Future Oncol. 2019 Oct 25. doi: 10.2217/fon-2019-0461. [Epub ahead of print]
Photobiomodulation for the palliation of oral mucositis in cancer patients: the future is here.
Zadik Y1.
Author information
1
Department of Oral Medicine, Oral & Maxillofacial Center, Medical Corps, Israel Defense Forces; & Oral Medicine Clinic for Hematologic & Oncologic Patients, Department of Oral Medicine, Sedation & Maxillofacial Imaging, Hebrew University-Hadassah School of Dental Medicine, Jerusalem 9112102, Israel.
KEYWORDS:
cancer; guidelines; laser; low level laser therapy; oral medicine; oral mucositis; oral oncology; pain; photobiomodulation

PMID: 31650847 DOI: 10.2217/fon-2019-0461
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Select item 31650845
26.
Future Oncol. 2019 Oct 25. doi: 10.2217/fon-2019-0523. [Epub ahead of print]
Perspectives of lung cancer control and molecular prevention.
Davidson DD1, Cheng L1.
Author information
1
Department of Pathology & Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, IN 46202, USA.
KEYWORDS:
biomarker; carcinogenesis; lung; molecular prevention; precision genomics; screening and cancer control

PMID: 31650845 DOI: 10.2217/fon-2019-0523
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Select item 31650705
27.
Cancer Med. 2019 Oct 24. doi: 10.1002/cam4.2603. [Epub ahead of print]
Real-world health utility scores and toxicities to tyrosine kinase inhibitors in epidermal growth factor receptor mutated advanced non-small cell lung cancer.
Jiang SX1,2, Walton RN3, Hueniken K1, Baek J1,2, McCartney A1, Labbé C4, Smith E1,2, Chan SWS1,2, Chen R1,2, Brown C1, Patel D1, Liang M1, Eng L1,2, Sacher A1,2, Bradbury P1,2, Leighl NB1,2, Shepherd FA1,2, Xu W5, Liu G1,2,5,6, Hurry M3, O'Kane GM1,2.
Author information
1
Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada.
2
Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
3
AstraZeneca Canada, Mississauga, ON, Canada.
4
Insitut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada.
5
Biostatistics, Princess Margaret Cancer Centre and Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
6
Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Abstract
BACKGROUND:
As the treatment landscape in patients with non-small cell lung cancer (NSCLC) harboring mutations in the epidermal growth factor receptor (EGFRm) continues to evolve, real-world health utility scores (HUS) become increasingly important for economic analyses.

METHODS:
In an observational cohort study, questionnaires were completed in EGFRm NSCLC outpatients, to include demographics, EQ-5D-based HUS and patient-reported toxicity and symptoms. Clinical and radiologic characteristics together with outcomes were extracted from chart review. The impact of health states, treatment type, toxicities, and clinical variables on HUS were evaluated.

RESULTS:
Between 2014 and 2018, a total of 260 patients completed 994 encounters. Across treatment groups, patients with disease progression had lower HUS compared to controlled disease (0.771 vs 0.803; P = .01). Patients predominantly received gefitinib as the first-line EGFR tyrosine kinase inhibitor (TKI) (n = 157, mean-HUS = 0.798), whereas osimertinib (n = 62, mean-HUS = 0.806) and chemotherapy (n = 38, mean-HUS = 0.721) were more likely used in subsequent treatment lines. In longitudinal analysis, TKIs retained high HUS (>0.78) compared to chemotherapy (HUS < 0.74). There were no differences between the frequency or severity of toxicity scores in patients receiving gefitinib compared to osimertinib; however, TKI therapy resulted in fewer toxicities than chemotherapy (P < .05), with the exception of worse diarrhea and skin rash (P < .001). Severity in toxicities inversely correlated with HUS (P < .001). Clinico-demographic factors significantly affecting HUS included age, Eastern Cooperative Oncology Group Performance Score (ECOG PS), disease state, treatment group, and metastatic burden.

CONCLUSIONS:
In a real-world EGFRm population, patients treated with gefitinib or osimertinib had similar HUS and toxicities, scores which were superior to chemotherapy. Health utility scores inversely correlated with patient-reported toxicity scores. In the era of targeted therapies, future economic analyses should incorporate real-world HUS.

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

KEYWORDS:
EGFR mutation; health economics; health utility scores; lung cancer; real-world

PMID: 31650705 DOI: 10.1002/cam4.2603
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Select item 31650266
28.
Eur Radiol. 2019 Oct 24. doi: 10.1007/s00330-019-06500-5. [Epub ahead of print]
Nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: clinical outcomes and patterns of failure among subsets of 8th AJCC stage IVa.
Huang CL1, Guo R1, Li JY1, Xu C1, Mao YP1, Tian L2, Lin AH3, Sun Y1, Ma J1, Tang LL4.
Author information
1
Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China.
2
Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangzhou, 510060, People's Republic of China.
3
Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, People's Republic of China.
4
Department of Radiation Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, 651 Dongfeng Road East, Guangzhou, 510060, People's Republic of China. tangll@sysucc.org.cn.
Abstract
OBJECTIVES:
The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma (NPC) merged T4N0-2 and T1-4N3 to create stage IVa. In the present study, we aimed to assess the difference in clinical outcomes and patterns of failure between 8th AJCC T4N0-2 and T1-4N3 NPC patients treated with intensity-modulated radiotherapy (IMRT).

METHODS:
We included 3107 patients with stage IVa NPC disease (1871 with T4N0-2 and 1236 with T1-4N3) according to the 8th AJCC staging system. Overall survival (OS) was the primary endpoint. The clinical outcomes between T4N0-2 and T1-4N3 patients were compared.

RESULTS:
T1-4N3 patients had significantly worse 3-year OS (84.1% vs. 89.2%; p < 0.001) and distant metastasis-free survival (DMFS; 78.3% vs. 85.9%; p < 0.001), but better local relapse-free survival (LRFS; 94.9% vs. 92.2%; p = 0.003), as compared with T4N0-2 patients. Multivariate analysis showed that T1-4N3 was still an independent adverse prognostic factor for both DMFS (hazard ratio [HR] = 1.517, 95% confidence interval [CI] = 1.274-1.806, p < 0.001) and OS (HR = 1.315, 95% CI = 1.100-1.572, p = 0.003), whereas T4N0-2 was an independent adverse prognostic factor for LRFS (HR = 1.581, 95% CI = 1.158-2.158, p = 0.004).

CONCLUSIONS:
In terms of the OS, T4N0-2 patients had better prognosis compared with T1-4N3 patients, and the patterns of failure differed between T4N0-2 and T1-4N3 patients. We believe that future modifications of the AJCC/UICC staging system should separate T4N0-2 from T1-4N3.

KEY POINTS:
• In nasopharyngeal carcinoma, T4N0-2 patients tended to develop local relapse, whereas T1-4N3 patients were more likely to develop distant metastasis. • In terms of overall survival, T4N0-2 patients had better prognosis than T1-4N3 patients. • T4N0-2 should be separated from T1-4N3 in the UICC/AJCC staging system.

KEYWORDS:
Intensity-modulated radiotherapy; Nasopharyngeal carcinoma; Prognosis; Stage; Treatment failure

PMID: 31650266 DOI: 10.1007/s00330-019-06500-5
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29.
J Med Imaging Radiat Sci. 2019 Oct 21. pii: S1939-8654(19)30501-6. doi: 10.1016/j.jmir.2019.09.002. [Epub ahead of print]
Preparing for Artificial Intelligence: Systems-Level Implications for the Medical Imaging and Radiation Therapy Professions.
French J1, Chen L2.
Author information
1
Cancer Strategy & Capital Redevelopment, British Columbia Cancer Agency, Vancouver, British Columbia, Canada. Electronic address: jfrench2@bccancer.bc.ca.
2
Cancer Strategy & Capital Redevelopment, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Abstract
Innovations in artificial intelligence (AI) are driving a new industrial revolution, and as a result, the medical radiation sciences is experiencing transformational, open, beneficial, yet disruptive changes. Many studies have already been published on specific frontline examples where AI will improve cancer care, but discussions of how AI will change the medical radiation sciences and its associated professions at the systems level have been comparatively sparse. In this article, the system-level implications of AI on the medical radiation sciences are discussed, and recommendations are made on how professionals in this field may need to adapt in preparation for a future where AI will be an integral part of the health care system at all levels.

Copyright © 2019. Published by Elsevier Inc.

KEYWORDS:
AI; Artificial intelligence; disruptive technology; medical radiation sciences; radiation oncology; radiation therapy; systems

PMID: 31648963 DOI: 10.1016/j.jmir.2019.09.002
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30.
Int J Radiat Oncol Biol Phys. 2019 Oct 19. pii: S0360-3016(19)33873-8. doi: 10.1016/j.ijrobp.2019.10.005. [Epub ahead of print]
Aligning requirements of training and assessment in radiation treatment planning in the era of competency-based medical education.
Moideen N1, de Metz C2, Kalyvas M2, Soleas E3, Egan R4, Dalgarno N5.
Author information
1
Department of Oncology Queen's University, Kingston Health Sciences Centre, Cancer Centre of Southeastern Ontario at Kingston Health Sciences Centre, 25 King Street West Kingston, ON K7L 5P9. Electronic address: Nikitha.Moideen@kingstonhsc.ca.
2
Department of Oncology Queen's University, Kingston Health Sciences Centre.
3
Queen's University Faculty of Education, Educational Consultant, Office of Professional Development and Educational Scholarship.
4
Queen's University Faculty of Health Sciences, Office of Health Sciences Education.
5
Queen's University Faculty of Health Sciences, Director of Educational Scholarship in the Office of Professional Development and Educational Scholarship.
Abstract
PURPOSE:
Radiation treatment planning (RTP) is a unique skill that requires interdisciplinary collaboration among radiation oncologists (ROs), dosimetrists, and medical physicists (MP) to train and assess residents. With the adoption of competency-based medical education (CBME) in Canada, it is essential residency program curricula focuses on developing competencies in RTP to facilitate entrustment. Our study investigates how radiation oncology team members' perspectives on RTP education align with requirements of the CBME approach, and its implications for improving residency training.

METHODS:
This qualitative research study took place in the department of oncology at one mid-size academic institution. Through convenience sampling, focus groups were conducted with ROs (n=11), dosimetrists (n=7), MPs (n=7), and residents (n=7). Thematic design was adopted to analyze the transcripts through open coding resulting in three overarching themes.

RESULTS:
The results identified existing strengths and weaknesses of the residency program, and future opportunities to redesign the curriculum and assessment process within a CBME model. Three overarching themes emerged from the analysis: (1) the strengths of RTP in the CBME environment; (2) challenges of RTP in CBME; and (3) opportunities for change. Stakeholders were optimistic CBME will help enrich resident learning with the increased frequency and quality of competency-based assessments. Participants suggested building a library of cases and developing computer based learning resources so as to provide a safe environment to develop skills in contouring, dosimetry, and plan evaluation, in accordance with CBME training.

CONCLUSION:
This study identified future opportunities to redesign the RTP curriculum and assessment process within a CBME model. The need for innovative teaching and learning strategies including case libraries, computer-based learning and quality assessments were highlighted in designing an innovative RTP planning curriculum.

Copyright © 2019 Elsevier Inc. All rights reserved.

PMID: 31647968 DOI: 10.1016/j.ijrobp.2019.10.005
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31.
J Comput Biol. 2019 Oct 24. doi: 10.1089/cmb.2019.0152. [Epub ahead of print]
Integrated Analysis of mRNA-miRNA-lncRNA ceRNA Network in Human HR+/Her-2- Breast Cancer and Triple Negative Breast Cancer.
Jia X1, Shi Y1, Zhu Y1, Meng W1, He L1, Jia Y1, Tong Z1.
Author information
1
Department of Breast Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer; Key Laboratory of Cancer Prevention and Therapy, Tianjin; Tianjin's Clinical Research Center for Cancer; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, People's Republic of China.
KEYWORDS:
TCGA; breast cancer; ceRNA; lncRNA; miRNA

PMID: 31647320 DOI: 10.1089/cmb.2019.0152
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32.
J Peripher Nerv Syst. 2019 Oct;24 Suppl 2:S6-S12. doi: 10.1111/jns.12337.
Chemotherapy-induced peripheral neurotoxicity: A multifaceted, still unsolved issue.
Cavaletti G1, Alberti P1, Argyriou AA2, Lustberg M3, Staff NP4, Tamburin S5; Toxic Neuropathy Consortium of the Peripheral Nerve Society.
Author information
1
Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
2
Department of Neurology, "Saint Andrew's" State General Hospital of Patras, Patras, Greece.
3
Department of Internal Medicine, Division of Medical Oncology, The Ohio State University Medical Center, Columbus, Ohio.
4
Department of Neurology, Mayo Clinic, Rochester, Minnesota.
5
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Abstract
Chemotherapy-induced peripheral neurotoxicity (CIPN) is a potentially dose-limiting side effect of several commonly used cytotoxic chemotherapy agents. The main pharmacological classes that may cause CIPN include classical anticancer drugs, as well as the recently introduced immune checkpoint inhibitors and antibody drug conjugates. The absence of a complete knowledge of CIPN pathophysiology is only one of the several unsolved issues related to CIPN. Among some of the most relevant aspects of CIPN deserving further attention include the real number of patients exposed to the risk of CIPN, the long-term impact on cancer survivors' quality of life due to incomplete recovery from CIPN, the economic burden related to acute and chronic CIPN, and the different perspective and education of the healthcare specialists in charge of managing patients with CIPN. Overall, CIPN remains a very challenging area of research as there are still several unresolved issues to be addressed in the future. In this special issue, the multifaceted profile of CIPN will be presented, with particular emphasis on bolstering the need to develop more optimized outcome measures than the existing ones to accurately evaluate the extent of CIPN, but also to ascertain the differences in the incidence, risk factors, clinical phenotype, and management of CIPN, according to the most commonly used neurotoxic chemotherapy classes. Perspectives for future research to pursue in order to cover the gaps in knowledge in the CIPN field will also be discussed.

© 2019 Peripheral Nerve Society.

KEYWORDS:
adult; chemotherapy; children; economic costs; neurotoxicity

PMID: 31647155 DOI: 10.1111/jns.12337
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Select item 31646903
33.
Future Oncol. 2019 Oct;15(30):3451-3456. doi: 10.2217/fon-2019-0292.
Prediagnostic BMI and thyroid cancer incidence in the PLCO trial.
Abdel-Rahman O1,2.
Author information
1
Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada.
2
Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Abstract
Aim: To assess the correlation between prediagnostic BMI and thyroid cancer risk within the prostate, lung, colorectal and ovary (PLCO) trial. Methods: PLCO trial participants without a history of thyroid cancer before study enrollment who have complete information about prediagnostic BMI were included. Multivariable Cox regression analyses were conducted to assess the impact of prediagnostic BMI on thyroid cancer risk. Results: Higher BMI at the time of the study enrollment was associated with a higher thyroid cancer risk (hazard ratio: 1.046; p < 0.01). Furthermore, compared with a normal to normal prediagnostic BMI trajectory, both normal to overweight as well as normal to obese trajectories were associated with a higher thyroid cancer risk (p = 0.04 and p = 0.03, respectively). Conclusion: Higher BMI at the time of study entry as well as an increasing prediagnostic BMI trajectory are associated with a higher thyroid cancer risk.

KEYWORDS:
BMI; incidence; risk factor; thyroid cancer

PMID: 31646903 DOI: 10.2217/fon-2019-0292
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34.
J BUON. 2019 Jul-Aug;24(4):1619-1625.
Is stereotactic body radiotherapy an alternative to surgery in early stage non small cell lung cancer?
Yaprak G1, Ozan Seseogullari O, Dogan Akaslan B, Isik N.
Author information
1
1Dr Lutfi Kirdar Kartal Training and Research Hospital, Department of Radiation Oncology, Istanbul, Turkey.
Abstract
PURPOSE:
To determine local control and overall survival of patients with medically inoperable early-stage non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy.

METHODS:
Included were a total of 52 patients (7;13% females and 45;87% males) with medically inoperable early-stage NSCLC and who were treated with stereotactic ablative body radiotherapy (SBRT) by a CyberKnife robotic radiotherapy machine between 2009 and 2017. Depending on tumor size and location, median 45 Gy (30-60) were delivered in median 3 fractions (3-5) to Planning Target Volume. As regards the tumor-tracking system; X-Sight lung tracking system was used in 43 (83%) patients, gold fiducials in 4 (8%) patients, and X-Sight spine tracking system in 5 (9%) patients.

RESULTS:
The median age of patients was 67 years (54-86). Tumor was staged as cT1 in 38 (73%) patients and cT2 in 14 (27%) patients. Median follow up was found to be 23 months (10-84 months). Median survival time was 38 months and, 1-3-5 year survival rates were respectively 94%-53%-33.6%. Locoregional recurrence occurred in 8 (15%) patients and recurrence was local only in 4 (8%) patients, while it was regional only in 3 (6%) and distant only in 12 (23%) patients. During follow up, local, regional and distant recurrence was detected in 27 (52%) cases and median progression free survival was found to be 25 months. 1-3-5 year progression free survival was 71.2%-39%-26%, respectively. Grade 3 toxicity was observed in only one patient; no grade 4-5 toxicity was observed.

CONCLUSION:
A high local control rate with no major toxicity was obtained by SBRT in the patients with medically inoperable early-stage NSCLC. In the near future, SBRT may be an alternative that has growing evidence to support comparable outcomes in selected stage I patients.

PMID: 31646817
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Select item 31646092
35.
Oncoimmunology. 2019 Jul 25;8(11):e1644109. doi: 10.1080/2162402X.2019.1644109. eCollection 2019.
Immune checkpoint inhibitors in mCRPC - rationales, challenges and perspectives.
Taghizadeh H1,2, Marhold M1,2, Tomasich E1,2, Udovica S1,2, Merchant A1,2, Krainer M1,2.
Author information
1
Department of Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria.
2
Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna, Austria.
Abstract
The advancement of immune-therapeutics in cancer treatment has proven to be promising in various malignant diseases. However, in castration resistant prostate cancer (mCRPC) major Phase III trials have been unexpectedly disappointing. To contribute to a broader understanding of the role and use of immune-therapeutics in mCRPC, we conducted a systematic review. We searched the websites ClinicalTrials.gov, PubMed and ASCO Meeting Library for clinical trials employing immune checkpoint inhibitors in mCRPC. This article not only describes the rationale of individual trials, but it also summarizes the current status of the field and sheds light on strategies for future success.

© 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.

KEYWORDS:
T lymphocytes; checkpoint inhibitors; immunotherapy; mCRPC; vaccines

PMID: 31646092 PMCID: PMC6791446 DOI: 10.1080/2162402X.2019.1644109
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Select item 31646087
36.
Oncoimmunology. 2019 Jul 18;8(11):e1638212. doi: 10.1080/2162402X.2019.1638212. eCollection 2019.
Trial watch: dendritic cell vaccination for cancer immunotherapy.
Sprooten J1, Ceusters J2, Coosemans A2,3, Agostinis P1,4, De Vleeschouwer S5,6, Zitvogel L7,8,9,10, Kroemer G11,12,13,14,15, Galluzzi L16,17,18,19, Garg AD1.
Author information
1
Cell Death Research & Therapy (CDRT) unit, Department of Cellular & Molecular Medicine, KU Leuven, Leuven, Belgium.
2
Department of Oncology, Laboratory of Tumor Immunology and Immunotherapy, ImmunOvar Research Group, KU Leuven, Leuven Cancer Institute, Leuven, Belgium.
3
Department of Gynecology and Obstetrics, UZ Leuven, Leuven, Belgium.
4
Center for Cancer Biology (CCB), VIB, Leuven, Belgium.
5
Research Group Experimental Neurosurgery and Neuroanatomy, KU Leuven, Leuven, Belgium.
6
Department of Neurosurgery, UZ Leuven, Leuven, Belgium.
7
Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.
8
INSERM, Villejuif, France.
9
Center of Clinical Investigations in Biotherapies of Cancer (CICBT) 1428, Villejuif, France.
10
Université Paris Sud/Paris XI, Le Kremlin-Bicêtre, France.
11
Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.
12
Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.
13
Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
14
Suzhou Institute for Systems Medicine, Chinese Academy of Sciences, Suzhou, China.
15
Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.
16
Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
17
Sandra and Edward Meyer Cancer Center, New York, NY, USA.
18
Department of Dermatology, Yale School of Medicine, New Haven, CT, USA.
19
Université de Paris Descartes, Paris, France.
Abstract
Dendritic- cells (DCs) have received considerable attention as potential targets for the development of anticancer vaccines. DC-based anticancer vaccination relies on patient-derived DCs pulsed with a source of tumor-associated antigens (TAAs) in the context of standardized maturation-cocktails, followed by their reinfusion. Extensive evidence has confirmed that DC-based vaccines can generate TAA-specific, cytotoxic T cells. Nonetheless, clinical efficacy of DC-based vaccines remains suboptimal, reflecting the widespread immunosuppression within tumors. Thus, clinical interest is being refocused on DC-based vaccines as combinatorial partners for T cell-targeting immunotherapies. Here, we summarize the most recent preclinical/clinical development of anticancer DC vaccination and discuss future perspectives for DC-based vaccines in immuno-oncology.

© 2019 Taylor & Francis Group, LLC.

KEYWORDS:
Antigen cross-presentation; DAMPs; TLR signaling; clinical trial; immune checkpoint blockers; plasmacytoid dendritic cells; tumor-infiltrating lymphocytes

PMID: 31646087 PMCID: PMC6791419 [Available on 2020-07-18] DOI: 10.1080/2162402X.2019.1638212
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37.
Ecancermedicalscience. 2019 Aug 6;13:957. doi: 10.3332/ecancer.2019.957. eCollection 2019.
Early toxicity and treatment outcomes of extended field-intensity modulated radiotherapy for cervical cancer patients with para-aortic nodal metastasis.
Gupta M1, Chopra S2, Kunder S1, Dheera A3, Sampathirao D3, Engineer R1, Ghosh J4, Gurram L1, Mahantshetty U1, Gupta S4, Shrivastava S1.
Author information
1
Department of Radiation Oncology, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai, India.
2
Department of Radiation Oncology, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Homi Bhabha National Institute, Kharghar, Navi Mumbai, India.
3
Department of Medical Physics, Tata Memorial Hospital, Tata Memorial Centre, Homi Bhabha National Institute, Parel, Mumbai, India.
4
Department of Medical Oncology, Advanced Centre for Treatment Research and Education in Cancer, Tata Memorial Centre, Homi Bhabha National Institute, Kharghar, Navi Mumbai, India.
Abstract
OBJECTIVE:
Extended-field radiotherapy (EFRT) with concurrent chemotherapy represents standard treatment in cervical cancer patients with para-aortic lymph nodal (PALN) metastasis. While EFRT with Intensity Modulated RT (IMRT) has been demonstrated to reduce toxicities, the dose thresholds for minimizing acute toxicity is not clear. The present study was undertaken to report the early toxicity with extended-field intensity-modulated radiotherapy (EF-IMRT) for carcinoma of the cervix in our cohort of patients and determine dose-volume parameters that predict ≥grade II haematological toxicity and diarrhoea.

METHODOLOGY:
This was a retrospective study of consecutive cervical cancer patients with PALN metastasis treated with EF-IMRT. Patients received rotational IMRT +/- neoadjuvant chemotherapy (NACT) and/or concurrent chemotherapy (45-50 Gy/25#/5 weeks) followed by high-dose rate brachytherapy. Acute haematological and gastrointestinal toxicity (diarrhoea and vomiting) was correlated with doses received by bowel and marrow. Receiver operator characteristics curves were used for deriving thresholds that predict for increased toxicity and tested on univariate and multivariate analysis. Finally, disease free and overall survival (DFS and OS) was calculated.

RESULTS:
A total of 43 patients were included. One-fourth of the patients (11/43) received NACT and 88% received concurrent chemotherapy. Within the upfront EF-IMRT cohort, 22.6% and 9.7% patients developed grade ≥III haematological (HT) and gastrointestinal (GI) toxicity respectively, with an increase in HT (≥ grade III HT =67%) in patients receiving NACT (p = 0.007). In the entire cohort bone marrow Volume receiving 10 Gy (V10>) 90% correlated with an increase in ≥ grade III HT (p = 0.05). No dose volume thresholds could be validated for GI toxicity. The OS and DFS at 2 years was 56% and 54%, respectively.

CONCLUSION:
EF-IMRT is a feasible option for cervical cancer patients with PALN involvement and is associated with acceptable grade III toxicity. Future studies need to focus on minimizing HT toxicity.

© the authors; licensee ecancermedicalscience.

KEYWORDS:
EFRT; IMRT; PALN; cervical cancer; toxicity

PMID: 31645885 PMCID: PMC6759319 DOI: 10.3332/ecancer.2019.957
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38.
Ecancermedicalscience. 2019 Jul 31;13:956. doi: 10.3332/ecancer.2019.956. eCollection 2019.
Effect of radiation dose to the periventricular zone and subventricular zone on survival in anaplastic gliomas.
Valiyaveettil D1, Malik M1, Joseph DM2.
Author information
1
Department of Radiation Oncology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad 500082, India.
2
Department of Radiation Oncology, All India Institute of Medical Sciences, Rishikesh 249203, India.
Abstract
PURPOSE:
Evidence suggests a correlation of subventricular zone (SVZ) irradiation on survival. Most of the data have been analysed in glioblastoma patients. The aim of this study is to analyse the dose to the subventricular and periventricular zone and its outcomes in anaplastic gliomas.

MATERIALS AND METHODS:
A retrospective analysis of patients with anaplastic gliomas were admitted for post-chemoradiation from January 2010 to June 2016 was done from treatment records. SVZ was contoured as 5 mm expansion along the lateral margin of the lateral ventricles, and PVZ was contoured as 5 mm lateral expansion adjacent to ventricles. Dosimetric data were collected from the treatment planning system.

RESULTS:
Ninety-five patients were included in the analysis. The median age was 35 years. Two- and five-year overall survival (OS) for the entire group was 84% and 54.2%, respectively. Two- and five-year progression-free survival (PFS) was 79.8% and 50.6%, respectively. Patients receiving <54 Gy to the i/l SVZ showed a significantly better PFS and OS. 5-Year OS was 72.6% in this group compared to 37% for the group receiving ≥54 Gy (p = 0.01). Five-year PFS was 69.9% in this group compared to 31.9% for the group receiving ≥54 Gy (p = 0.02). However, this was not significant in multivariate analysis.

CONCLUSION:
Increased dose to the ipsilateral SVZ does not correlate with improved survival in anaplastic gliomas. There is conflicting evidence regarding the benefit of irradiating the stem cell zones. Future studies should focus on optimizing doses to these areas to reduce detriment in neurocognition.

© the authors; licensee ecancermedicalscience.

KEYWORDS:
anaplastic gliomas; neurocognition; periventricular zone; subventricular zone

PMID: 31645884 PMCID: PMC6759320 DOI: 10.3332/ecancer.2019.956
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39.
Cancer Gene Ther. 2019 Oct 23. doi: 10.1038/s41417-019-0143-5. [Epub ahead of print]
Identification of genes of four malignant tumors and a novel prediction model development based on PPI data and support vector machines.
Li M1, Wang P2, Zhang N3, Guo L4, Feng YM1,4.
Author information
1
Department of Biomedical Engineering, Tianjin Key Lab of BME Measurement, Tianjin University, Tianjin, PR China.
2
Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, PR China. wangping@tjmuch.com.
3
Department of Biomedical Engineering, Tianjin Key Lab of BME Measurement, Tianjin University, Tianjin, PR China. zhni@tju.edu.cn.
4
Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, PR China.
Abstract
Triple-negative breast cancer (TNBC), colon adenocarcinoma (COAD), ovarian cancer (OV), and glioblastoma multiforme (GBM) are common malignant tumors, in which significant challenges are still faced in early diagnosis, treatment, and prognosis. Therefore, further identification of genes related to those malignant tumors is of great significance for the improvement of management of the diseases. The database of the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository was used as the data source of gene expression profiles in this study. Malignant tumors genes were selected using a feature selection algorithm of maximal relevance and minimal redundancy (mRMR) and the protein-protein interaction (PPI) network. And finally selected 20 genes as potential related genes. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the potential related genes, and different tumor-specific genes and similarities and differences between network modules and pathways were analyzed. Further, using the potential cancer-related genes found above in this study as features, a support vector machine (SVM) model was developed to predict high-risk malignant tumors. As a result, the prediction accuracy reached more than 85%, indicating that such a model can effectively predict the four types of malignant tumors. It is demonstrated that such genes found above in this study indeed play important roles in the differentiation of the four types of malignant tumors, providing basis for future experimental biological validation and shedding some light on the understanding of new molecular mechanisms related to the four types of tumors.

PMID: 31645679 DOI: 10.1038/s41417-019-0143-5
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40.
Expert Opin Investig Drugs. 2019 Oct;28(10):917-930. doi: 10.1080/13543784.2019.1657825. Epub 2019 Aug 29.
Acetyl-CoA carboxylase (ACC) as a therapeutic target for metabolic syndrome and recent developments in ACC1/2 inhibitors.
Chen L1, Duan Y1, Wei H1, Ning H1, Bi C1, Zhao Y2, Qin Y3, Li Y1.
Author information
1
Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College & Chinese Academy of Medical Sciences , Tianjin , China.
2
School of Pharmacy and Bioengineering, Chongqing University of Technology , Chongqing , China.
3
Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
Abstract
Introduction: Acetyl-CoA Carboxylase (ACC) is an essential rate-limiting enzyme in fatty acid metabolism. For many years, ACC inhibitors have gained great attention for developing therapeutics for various human diseases including microbial infections, metabolic syndrome, obesity, diabetes, and cancer. Areas covered: We present a comprehensive review and update of ACC inhibitors. We look at the current advance of ACC inhibitors in clinical studies and the implications in drug discovery. We searched ScienceDirect ( https://www.sciencedirect.com/ ), ACS ( https://pubs.acs.org/ ), Wiley ( https://onlinelibrary.wiley.com/ ), NCBI ( https://www.ncbi.nlm.nih.gov/ ) and World Health Organization ( https://www.who.int/ ). The keywords used were Acetyl-CoA Carboxylase, lipid, inhibitors and metabolic syndrome. All documents were published before June 2019. Expert opinion: The key regulatory role of ACC in fatty acid synthesis and oxidation pathways makes it an attractive target for various metabolic diseases. In particular, the combination of ACC inhibitors with other drugs is a new strategy for the treatment of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Expanding the clinical indications for ACC inhibitors will be one of the hot directions in the future. It is also worth looking forward to exploring safe and efficient inhibitors that act on the BC domain of ACC.

KEYWORDS:
Acetyl-CoA carboxylase; inhibitors; lipid; metabolic syndrome

PMID: 31430206 DOI: 10.1080/13543784.2019.1657825