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1
Clinical Trial J Clin Oncol
. 2019 Jul 10;37(20):1704-1712. doi: 10.1200/JCO.18.01182. Epub 2019 Feb 15.
Multicenter Trial of [ 18 F]fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Staging of Head and Neck Cancer and Negative Predictive Value and Surgical Impact in the N0 Neck: Results From ACRIN 6685
Val J Lowe 1, Fenghai Duan 2, Rathan M Subramaniam 3, JoRean D Sicks 2, Justin Romanoff 2, Twyla Bartel 4, Jian Q Michael Yu 5, Brian Nussenbaum 6, Jeremy Richmon 7, Charles D Arnold 8, David Cognetti 9, Brendan C Stack Jr 10
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PMID: 30768363 PMCID: PMC6638599 (available on 2020-07-10) DOI: 10.1200/JCO.18.01182
Free PMC article
Abstract
Purpose: The objective of this study was to determine the negative predictive value (NPV) of positron emission tomography (PET)/computed tomography (CT) for the clinically N0 neck on the basis of neck dissection.

Methods: Participants with newly diagnosed, first-time, head and neck squamous cell carcinoma (HNSCC) and at least one clinically N0 neck side for which dissection was planned were included. A total of 287 participants were prospectively enrolled from 23 American College of Radiology Imaging Network-qualified institutions. PET/CT was compared with findings at neck dissection.

Results: PET/CT scans and pathology findings were available for 270 N0 neck sides from 212 participants. For visual assessment, the NPV specific to the clinical-N0 sides was 0.868 (95% CI, 0.803 to 0.925). For dichotomized maximum standardized uptake value, the NPVs specific to the nodal basins were 0.940 (95% CI, 0.928 to 0.952) and 0.937 (95% CI, 0.925 to 0.949) at prespecified cutoffs of 2.5 and 3.5, respectively. The optimal cutoff maximum standardized uptake value was determined to be 1.8, with an NPV of 0.942 (95% CI, 0.930 to 0.953). The PET/CT-informed surgical treatment plan was changed in 51 of 237 participants (22%) compared with the PET/CT-blinded surgical plan. In 34 participants (14%), this led to planned dissection of additional nodal levels. In 12 participants (5%), this led to fewer planned dissected nodal levels. Negative PET/CT scans in N0 necks was true negative in 87% and false negative in 13%.

Conclusion: [18F]fluorodeoxyglucose-PET/CT has high NPV for the N0 neck in T2 to T4 HNSCC. The surgical treatment plans on the basis of PET/CT findings may be changed in approximately 22% of this group. These findings suggest that [18F]fluorodeoxyglucose-PET/CT may assist the clinician in deciding on the best therapy for the clinically N0 neck in HNSCC. Well-designed clinical trials should be performed to test the outcome of omitting neck dissection by using PET/CT.

Comment in
Positron Emission Tomography/Computed Tomography in Evaluation of the Clinically N0 Neck in Head and Neck Squamous Cell Carcinoma.
Ferris RL, Cramer JD, Branstetter Iv BF.
J Clin Oncol. 2019 Jul 10;37(20):1683-1685. doi: 10.1200/JCO.19.00544. Epub 2019 May 31.
PMID: 31150317 No abstract available.
Cited by 4 articles
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2
J Clin Oncol
. 2019 Jul 10;37(20):1753-1774. doi: 10.1200/JCO.18.01921. Epub 2019 Feb 27.
Management of the Neck in Squamous Cell Carcinoma of the Oral Cavity and Oropharynx: ASCO Clinical Practice Guideline
Shlomo A Koyfman 1, Nofisat Ismaila 2, Doug Crook 3, Anil D'Cruz 4, Cristina P Rodriguez 5, David J Sher 6, Damian Silbermins 7, Erich M Sturgis 8, Terance T Tsue 9, Jared Weiss 10, Sue S Yom 11, F Christopher Holsinger 12
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PMID: 30811281 PMCID: PMC7098829 DOI: 10.1200/JCO.18.01921
Free PMC article
Abstract
Purpose: The aim of the current work is to provide evidence-based recommendations to practicing physicians and others on the management of the neck in patients with squamous cell carcinoma of the oral cavity and oropharynx.

Methods: ASCO convened an Expert Panel of medical oncology, surgery, radiation oncology, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1990 through 2018. Outcomes of interest included survival, regional disease control, neck recurrence, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.

Results: The literature search identified 124 relevant studies to inform the evidence base for this guideline. Six clinical scenarios were devised; three for oral cavity cancer and three for oropharynx cancer, and recommendations were generated for each one.

Recommendations: For oral cavity cancers, clinical scenarios focused on the indications for and the hallmarks of a high-quality neck dissection, indications for postoperative radiotherapy or chemoradiotherapy, and whether radiotherapy alone is sufficient elective treatment of an undissected neck compared with high-quality neck dissection. For oropharynx cancers, clinical scenarios focused on hallmarks of a high-quality neck dissection, factors that would favor operative versus nonoperative primary management, and clarifying criteria for an incomplete response to definitive chemoradiation for which salvage neck dissection would be recommended. Consensus was reached and recommendations were made for all six clinical scenarios. Additional information is available at www.asco.org/head-neck-cancer-guidelines .

Conflict of interest statement
Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Comment in
ASCO Neck Dissection Guidelines Response Letter.
Schilling C, Lai SY, Chegini S, McGurk M.
J Oncol Pract. 2019 Oct;15(10):560-561. doi: 10.1200/JOP.19.00331. Epub 2019 Sep 12.
PMID: 31513477 No abstract available.
Cited by 2 articles3 figures
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3
Multicenter Study J Clin Oncol
. 2019 Jul 1;37(19):1666-1676. doi: 10.1200/JCO.18.01579. Epub 2019 May 17.
Perceptions of Patients With Breast and Colon Cancer of the Management of Cancer-Related Pain, Fatigue, and Emotional Distress in Community Oncology
Tenbroeck G Smith 1, Alyssa N Troeschel 1, Kathleen M Castro 2, Neeraj K Arora 3, Kevin Stein 4 5, Joseph Lipscomb 4, Otis W Brawley 1, Ryan M McCabe 6, Steven B Clauser 3, Elizabeth Ward 1
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PMID: 31100037 PMCID: PMC6804889 DOI: 10.1200/JCO.18.01579
Free PMC article
Abstract
Purpose: Pain, fatigue, and distress are common among patients with cancer but are often underassessed and undertreated. We examine the prevalence of pain, fatigue, and emotional distress among patients with cancer, as well as patient perceptions of the symptom care they received.

Patients and methods: Seventeen Commission on Cancer-accredited cancer centers across the United States sampled patients with local/regional breast (82%) or colon (18%) cancer. We received 2,487 completed surveys (61% response rate).

Results: Of patients, 76%, 78%, and 59% reported talking to a clinician about pain, fatigue, and distress, respectively, and 70%, 61%, and 54% reported receiving advice. Sixty-one percent of patients experienced pain, 74% fatigue, and 46% distress. Among those patients experiencing each symptom, 58% reported getting the help they wanted for pain, 40% for fatigue, and 45% for distress. Multilevel logistic regression models revealed that patients experiencing symptoms were significantly more likely to have talked about and received advice on coping with these symptoms. In addition, patients who were receiving or recently completed curative treatment reported more symptoms and better symptom care than did those who were further in time from curative treatment.

Conclusion: In our sample, 30% to 50% of patients with cancer in community cancer centers did not report discussing, getting advice, or receiving desired help for pain, fatigue, or emotional distress. This finding suggests that there is room for improvement in the management of these three common cancer-related symptoms. Higher proportions of talk and advice among those experiencing symptoms imply that many discussions may be patient initiated. Lower rates of talk and advice among those who are further in time from treatment suggest the need for more assessment among longer-term survivors, many of whom continue to experience these symptoms. These findings seem to be especially important given the high prevalence of these symptoms in our sample.

Cited by 2 articles1 figure
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4
Hum Pathol
. 2019 Dec;94:92-97. doi: 10.1016/j.humpath.2019.08.020. Epub 2019 Sep 5.
ADAM3A Copy Number Gains Occur in a Subset of Conjunctival Squamous Cell Carcinoma and Its High Grade Precursors
M Adelita Vizcaino 1, Abeer Z Tabbarah 2, Laura Asnaghi 3, Azza Maktabi 4, Allen O Eghrari 5, Divya Srikumaran 5, Charles G Eberhart 6, Fausto J Rodriguez 7
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PMID: 31493427 PMCID: PMC6917831 (available on 2020-12-01) DOI: 10.1016/j.humpath.2019.08.020
Free PMC article
Abstract
Conjunctival squamous cell carcinoma (cSCC) and its precursors are among the most frequent ocular surface neoplasms worldwide. Copy gain of 8p11.22 and ADAM3A overexpression have been recently identified in invasive cSCC. We sought to study copy number gains using fluorescent in situ hybridization (FISH) in cSCC and the spectrum of precursor lesions. A total of 54 cases conjunctival squamous intraepithelial neoplasia (CIN), carcinoma in situ (CIS), or cSCC were studied using FISH with an ADAM3A (8p11 locus) probe and a chromosome 8 (Chr 8) centromere reference probe. Eighty one percent (44/54) of the cases presented in men and 19% (10/54) in women. The age at presentation ranged from 12 to 94 years (mean 65.5 years). Severe CIN was diagnosed in 45% (24/54) of the cases, followed by CIS in 31% (17/54), moderate CIN in 15% (8/54), invasive cSCC in 7% (4/54), and mild CIN in 2% (1/54). Nine (of 54) (17%) cases harbored ADAM3A or Chr 8 gains, with one of these cases demonstrating high level amplification. All ADAM3A alterations were restricted to high-grade lesions, including 2/17 (12%) cCIS, 1/4 (24%) cSCC, 5/24 (20%) severe CIN and 1/8 (12%) moderate CIN. Monosomy 8 was detected in 2 (4%) cases. No ADAM3A alterations were detected in non-neoplastic controls. Gains of ADAM3A/chromosome 8 occur in a subset of cSCC and its precursors. Alterations were present in high-grade lesions, sparing non-neoplastic conjunctiva and absent in tested controls. Thus, the specificity of this alteration as a biomarker for ocular SCC deserves further study.

Keywords: ADAM3A; Conjunctiva; Conjunctival squamous intraepithelial neoplasia; Ocular surface carcinoma; Squamous cell carcinoma.

Copyright © 2019 Elsevier Inc. All rights reserved.

Conflict of interest statement
Conflicts of interest: None.

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5
Multicenter Study Cancer
. 2019 Dec 1;125(23):4224-4231. doi: 10.1002/cncr.32420. Epub 2019 Aug 13.
Association of Neurologic Deficits With Surgical Outcomes and Health-Related Quality of Life After Treatment for Metastatic Epidural Spinal Cord Compression
Ori Barzilai 1, Anne L Versteeg 2, C Rory Goodwin 3, Arjun Sahgal 4, Laurence D Rhines 5, Daniel M Sciubba 6, James M Schuster 7, Michael H Weber 8, Aron Lazary 9, Michael G Fehlings 10, Michelle J Clarke 11, Paul M Arnold 12, Stefano Boriani 13, Chetan Bettegowda 6, Ziya L Gokaslan 14, Charles G Fisher 15, Ilya Laufer 1, AOSpine Knowledge Forum Tumor
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PMID: 31410854 DOI: 10.1002/cncr.32420
Abstract
Background: A critical knowledge gap exists regarding the impact of neurologic deficits on surgical outcomes and health-related quality of life (HRQOL) for patients surgically treated for metastatic epidural spinal cord compression (MESCC).

Methods: This prospective, multicenter and international study analyzed the impact of the neurologic status on functional status, HRQOL, and postoperative survival. The collected data included the patient demographics, overall survival, American Spinal Injury Association (ASIA) impairment scale, Spinal Instability Neoplastic Score, treatment details and complications and HRQOL measures, including version 2 of the 36-Item Short Form Health Survey (SF-36v2) and version 2.0 of the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ2.0).

Results: A total of 239 patients surgically treated for spinal metastases were included. Six weeks after treatment, 99 of the 108 patients with a preoperative ASIA grade of E remained stable, 8 deteriorated to ASIA D, and 1 deteriorated to ASIA A. Of 55 patients with ASIA D, 27 improved to ASIA E, 27 remained stable and 1 deteriorated to ASIA C. Of 11 patients with ASIA A to C, 2 improved to ASIA E, 4 improved to ASIA D, and 5 remained stable. At the 6- and 12-week follow-up, better ASIA scores were associated with better scores on multiple SF-36v2 and SOSGOQ items. Postoperatively, patients with ASIA grades of A to D were more likely to have urinary tract infections and wound complications. Patients with a baseline ASIA grade of E or D survived significantly longer.

Conclusions: Patients with neurologic deficits due to MESCC have worse HRQOL and decreased overall survival. Nevertheless, surgery can result in stabilization or improvement of neurologic function which may translate into better HRQOL. Postoperative care and follow-up are challenging for patients with neurologic deficits because they experience more complications.

Keywords: health-related quality of life (HRQOL); neurologic deficit; spine; surgery; treatment; tumor.

© 2019 American Cancer Society.

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6
Cancer
. 2019 Dec 1;125(23):4252-4259. doi: 10.1002/cncr.32377. Epub 2019 Sep 10.
Type and Case Volume of Health Care Facility Influences Survival and Surgery Selection in Cases With Early-Stage Non-Small Cell Lung Cancer
Shidan Wang 1, Sunny Lai 1, Mitchell S von Itzstein 2, Lin Yang 1 3, Donghan M Yang 1, Xiaowei Zhan 1, Guanghua Xiao 1 4, Ethan A Halm 2 5, David E Gerber 2 5 6, Yang Xie 1 4 6
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PMID: 31503336 DOI: 10.1002/cncr.32377
Abstract
Background: With the expansion of non-small cell lung cancer (NSCLC) screening methods, the percentage of cases with early-stage NSCLC is anticipated to increase. Yet it remains unclear how the type and case volume of the health care facility at which treatment occurs may affect surgery selection and overall survival for cases with early-stage NSCLC.

Methods: A total of 332,175 cases with the American Joint Committee on Cancer (AJCC) TNM stage I and stage II NSCLC who were reported to the National Cancer Data Base (NCDB) by 1302 facilities were studied. Facility type was characterized in the NCDB as community cancer program (CCP), comprehensive community cancer program (CCCP), academic/research program (ARP), or integrated network cancer program (INCP). Each facility type was dichotomized further into high-volume or low-volume groups based on the case volume. Multivariate Cox proportional hazard models, the logistic regression model, and propensity score matching were used to evaluate differences in survival and surgery selection among facilities according to type and volume.

Results: Cases from ARPs were found to have the longest survival (median, 16.4 months) and highest surgery rate (74.8%), whereas those from CCPs had the shortest survival (median, 9.7 months) and the lowest surgery rate (60.8%). The difference persisted when adjusted by potential confounders. For cases treated at CCPs, CCCPs, and ARPs, high-volume facilities had better survival outcomes than low-volume facilities. In facilities with better survival outcomes, surgery was performed for a greater percentage of cases compared with facilities with worse outcomes.

Conclusions: For cases with early-stage NSCLC, both facility type and case volume influence surgery selection and clinical outcome. Higher surgery rates are observed in facilities with better survival outcomes.

Keywords: facility type; facility volume; lung cancer; prognosis; surgery selection.

© 2019 American Cancer Society.

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7
Multicenter Study Cancer
. 2019 Dec 1;125(23):4203-4209. doi: 10.1002/cncr.32440. Epub 2019 Sep 3.
Diagnostic Colonoscopy Completion After Abnormal Fecal Immunochemical Testing and Quality of Tests Used at 8 Federally Qualified Health Centers in Southern California: Opportunities for Improving Screening Outcomes
Balambal Bharti 1 2, Folasade Fola Popoola May 3 4, Jesse Nodora 1 2 5, María Elena Martínez 1 2 5, Karina Moyano 6, Shauntay L Davis 7, Christian B Ramers 1 8, Felipe Garcia-Bigley 8, Shawne O'Connell 9, Kevin Ronan 10, Melissa Barajas 11, Sheree Gordon 12, Giselle Diaz 13, Evelyn Ceja 14, Meghan Powers 15, Elva M Arredondo 16, Samir Gupta 1 2 17
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PMID: 31479529 PMCID: PMC7008958 (available on 2020-12-01) DOI: 10.1002/cncr.32440
Free PMC article
Abstract
Background: The effectiveness of colorectal cancer screening with fecal immunochemical tests (FITs) of stool blood depends on high rates of colonoscopy follow-up for abnormal FITs and the use of high-quality tests. This study characterized colonoscopy referral and completion among patients with abnormal FITs and the types of FITs implemented in a sample of Southern California Federally Qualified Health Centers (FQHCs).

Methods: FQHCs in San Diego, Imperial, and Los Angeles Counties were invited to define a cohort of ≥150 consecutive patients with abnormal FITs in 2015-2016 and to provide data on sex, insurance status, diagnostic colonoscopy referrals and completion within 6 months of abnormal FITs, and the types (brands) of FITs implemented. The primary outcomes were the proportions with colonoscopy referrals and completion for all patients at each FQHC and in aggregate.

Results: Eight FQHCs provided data for 1229 patients with abnormal FITs; 46% were male, and 20% were uninsured. Among patients with abnormal FITs, 89% (1091 of 1229; 95% confidence interval [CI], 0.87-0.91) had a colonoscopy referral, and 44% (539 of 1229; 95% CI, 0.41-0.47) had colonoscopy completion. Across FQHCs, the range for colonoscopy referral was 73% to 96%, and the range for completion was 18% to 57%. Six of the 8 FQHCs (75%) reported FIT brands with limited data to support their effectiveness.

Conclusions: In a sample of Southern California FQHCs, diagnostic colonoscopy completion after abnormal FITs was substantially below the nationally recommended benchmark to achieve 80% completion, and the use of FIT brands with limited data to support their effectiveness was high. These findings suggest a need for policies and multilevel interventions to promote diagnostic colonoscopy among individuals with abnormal FITs and the use of higher quality FITs.

Keywords: Federally Qualified Health Center; Hispanic; abnormal fecal immunochemical test (FIT); colorectal cancer; screening.

© 2019 American Cancer Society.

Conflict of interest statement
Conflict of Interest Statement

The Authors have no relevant conflicts of interest to disclose.

Comment in
Low rates of diagnostic colonoscopy in Federally Qualified Health Centers: A persistent problem that must be addressed to achieve the promise of colorectal cancer screening.
Myers RE.
Cancer. 2019 Dec 1;125(23):4134-4135. doi: 10.1002/cncr.32438. Epub 2019 Sep 3.
PMID: 31479509 No abstract available.
Cited by 1 article
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8
J Cancer Surviv
. 2019 Oct;13(5):749-758. doi: 10.1007/s11764-019-00794-6. Epub 2019 Jul 24.
Unmet Needs of Family Cancer Caregivers Predict Quality of Life in Long-Term Cancer Survivorship
Youngmee Kim 1, Charles S Carver 2
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PMID: 31342303 PMCID: PMC6832821 (available on 2020-10-01) DOI: 10.1007/s11764-019-00794-6
Free PMC article
Abstract
Purpose: To identify demographic and caregiving characteristics associated with caregivers' unmet needs and to examine associations of caregivers' unmet needs with their quality of life at 2 years and 5 years since their patients' initial diagnosis.

Methods: Family cancer caregivers completed prospective longitudinal surveys at 2 years (T1) and 5 years (T2) post diagnosis. Demographic and caregiving characteristics were measured at T1. Unmet needs and quality of life were measured at T1 and T2.

Results: Younger and spousal caregivers reported greater unmet needs (B > 2.03, p < .05). Independent of demographic characteristics, caregivers' perception that providing care to their relative with cancer was overwhelming was consistently associated with unfulfillment of their needs in various domains, concurrently and prospectively (B > 2.50, p < .05), across the long-term survivorship phases.

Conclusions: Findings highlight the contribution of earlier subjective caregiving stress to family caregivers' needs not being met both currently and years later, which, in turn, related to poorer quality of life across different family caregivership trajectories. Findings suggest identifying at-risk subgroups of family caregivers based on demographics and assessing caregiving stress as a priority in psycho-oncology research and clinical practices.

Implications for cancer survivors: Family caregivers' quality of life is affected by cancer survivors' illness trajectory many years after the initial cancer diagnosis, so are the caregivers' needs. Cancer survivorship care plan should take careful consideration of the nuanced long-term contributions of caregivers' unmet needs to their specific aspects of quality of life.

Keywords: Bereavement; Caregivers; Long-term cancer care; Long-term survivorship trajectory; Quality of life; Unmet needs.

Conflict of interest statement
Conflict of Interest

None of the authors have financial conflict of interest to disclose. Authors do not have a financial relationship with the organization that sponsored the research, authorship, etc. Authors have full control of all primary data and agree to allow the journal to review the data if requested.

Cited by 1 article
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9
Review J Natl Cancer Inst
. 2019 May 1;111(5):442-448. doi: 10.1093/jnci/djy232.
Personalized Risk-Stratified Cancer Follow-Up Care: Its Potential for Healthier Survivors, Happier Clinicians, and Lower Costs
Deborah K Mayer 1 2, Catherine M Alfano 3
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PMID: 30726949 PMCID: PMC6804411 DOI: 10.1093/jnci/djy232
Free PMC article
Abstract
The growth in the number of cancer survivors in the face of projected health-care workforce shortages will challenge the US health-care system in delivering follow-up care. New methods of delivering follow-up care are needed that address the ongoing needs of survivors without overwhelming already overflowing oncology clinics or shuttling all follow-up patients to primary care providers. One potential solution, proposed for over a decade, lies in adopting a personalized approach to care in which survivors are triaged or risk-stratified to distinct care pathways based on the complexity of their needs and the types of providers their care requires. Although other approaches may emerge, we advocate for development, testing, and implementation of a risk-stratified approach as a means to address this problem. This commentary reviews what is needed to shift to a risk-stratified approach in delivering survivorship care in the United States.

© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Comment in
Improving care for cancer survivors: Experts say the oncology community must provide new surveillance methods and more personalized follow-up for the rapidly increasing numbers of cancer survivors.
Printz C.
Cancer. 2019 Nov 15;125(22):3905-3907. doi: 10.1002/cncr.32588.
PMID: 31661564 No abstract available.
Cited by 4 articles2 figures
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10
Hum Pathol
. 2019 Dec;94:16-22. doi: 10.1016/j.humpath.2019.10.004. Epub 2019 Oct 27.
Pathological Risk Factors for Metastatic Disease at Presentation in Testicular Seminomas With Focus on the Recent pT Changes in AJCC TNM Eighth Edition
Glenda Scandura 1, Thomas Wagner 2, Luis Beltran 3, Constantine Alifrangis 4, Jonathan Shamash 4, Daniel M Berney 5
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PMID: 31666197 DOI: 10.1016/j.humpath.2019.10.004
Abstract
Management of clinical stage (CS) 1 testicular seminoma is controversial. Treatment choice is based on a number of pathological risk factors. However, they have been inconsistently associated with risk of metastatic disease. The eighth edition of the American Joint Committee on Cancer Tumor-Node-Metastasis staging system has separated pT1a and pT1b tumors according to a 3-cm size cutoff and upstaged invasion of hilar soft tissue and epididymis as pT2. We investigated pathological predictors of metastatic disease at presentation in 332 testicular seminomas. Age, tumor size, invasion of vessels, hilar soft tissue, rete testis, epididymis, spermatic cord, tunica vaginalis and tumor at spermatic cord margin were assessed and correlated with CS at presentation. A total of 290 (87%) tumors were CS 1; 42 (13%) were CS 2/3. Median patient age of CS 1 was 36 years (20-81); that of CS 2/3 was 36 years (26-63). Mean tumor size of CS 1 was 38 mm (5-95 mm); that of CS 2/3 was 54 mm (8-95 mm). On univariate analysis, lymphovascular invasion (P = .044), epididymal invasion (P = .009) and tumor size (P = .0001) were associated with higher CS. On multivariate analysis, tumor size (P = .0001) and epididymis invasion (P = .023) remained significant. Optimal tumor size cutoff was 4.25 cm. We conclude that tumor size and epididymal invasion are the strongest predictors of metastatic disease at presentation. The results validate changes in American Joint Committee on Cancer Tumor-Node-Metastasis staging eighth edition but suggest a tumor size of 4 cm as better cutoff value.

Keywords: Epididymis invasion; Seminoma; Staging; TNM classification; Testicular germ cell tumors; Tumor size.

Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.

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11
J Community Health
. 2019 Jun;44(3):451-462. doi: 10.1007/s10900-018-00612-7.
The Association Between Perceived Stress and Hypertension Among Asian Americans: Does Social Support and Social Network Make a Difference?
Xiaoxiao Lu 1, Hee-Soon Juon 2, Xin He 3, Cher M Dallal 3, Ming Qi Wang 4, Sunmin Lee 3
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PMID: 30604222 PMCID: PMC6504578 DOI: 10.1007/s10900-018-00612-7
Free PMC article
Abstract
Prior research suggests that stress plays role in the etiology and progression of hypertension. To lend a more accurate depiction of the underlying mechanisms between stress and hypertension, this study aims to assess the associations between perceived stress and hypertension across varying levels of social support and social network among Asian Americans. We conducted a cross-sectional study using data on 530 Chinese, Korean and Vietnamese Americans recruited from a liver cancer prevention program in the Washington D.C.-Baltimore metropolitan area. Hypertension prevalence was 29.1%. Individuals with high perceived stress were 61% more likely to have hypertension compared to those with low levels of perceived stress (odds ratio 1.61, 95% confidence interval 1.15, 2.46). There was no evidence that social support and social network acted as effect modifiers. Social support had a direct beneficial effect on hypertension, irrespective of whether individuals were under stress. The relationship between perceived stress and hypertension was modified by gender and ethnicity whereby a significant positive association was only observed among male or Chinese participants. Our study highlights the importance of understanding the associations between stress, social support, and hypertension among Asian American subgroups. Findings from the study can be used to develop future stress management interventions, and incorporate culturally and linguistically appropriate strategies into community outreach and education to decrease hypertension risk within the Asian population.

Keywords: Asian American; Hypertension; Social network; Social support; Stress.

Conflict of interest statement
Conflict of interest

Xiaoxiao Lu, Hee-Soon Juon, Xin He, Cher M Dallal , Ming Qi Wang, and Sunmin Lee declare that they have no conflict of interest.

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12
Retraction of Publication Am J Cancer Res
. 2020 May 1;10(5):1630. eCollection 2020.
Volasertib Suppresses the Growth of Human Hepatocellular Carcinoma in vitro and in vivo [Retraction]
No authors listed
PMID: 32509401
Abstract
[This retracts the article on p. 2476 in vol. 6, PMID: 27904765.].

AJCR Copyright © 2020.

Retraction of
Volasertib suppresses the growth of human hepatocellular carcinoma in vitro and in vivo.
Zheng DW, Xue YQ, Li Y, Di JM, Qiu JG, Zhang WJ, Jiang QW, Yang Y, Chen Y, Wei MN, Huang JR, Wang K, Wei X, Shi Z.
Am J Cancer Res. 2016 Nov 1;6(11):2476-2488. eCollection 2016.
PMID: 27904765 Free PMC article. Retracted.
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13
Eur Urol Oncol
. 2019 Feb;2(1):21-27. doi: 10.1016/j.euo.2018.06.005. Epub 2018 Jul 6.
Frailty and Greater Health Care Resource Utilization Following Major Urologic Oncology Surgery
Benjamin L Taylor 1, Leilei Xia 2, Thomas J Guzzo 2, Douglas S Scherr 3, Jim C Hu 3
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PMID: 30929842 DOI: 10.1016/j.euo.2018.06.005
Abstract
Background: In the setting of value-based care, it is critical to improve our understanding of surgical risk and greater health care resource utilization (HRU) as it relates to frailty.

Objective: To evaluate the impact of frailty on HRU and surgical morbidity in urologic oncology surgery using the five-item frailty index.

Design, setting, and participants: A retrospective cohort study was conducted using subjects from the 2012-2016 American College of Surgeons National Surgical Quality Improvement Program who underwent radical cystectomy or minimally invasive or open radical prostatectomy, radical nephrectomy, or partial nephrectomy.

Outcome measurements and statistical analysis: Multivariable logistic regression was performed to determine the association between frailty index and any increase in HRU, which was defined as prolonged length of stay greater than the 75th percentile, discharge to continued care, or unplanned readmission within 30 d.

Results and limitations: In the overall cohort of 92 999 subjects and within each surgery type, increasing frailty score was associated with significant stepwise increases in HRU. Logistic regression adjusting for patient demographics revealed statistically significant odds ratios of 1.2 (95% confidence interval [CI] 1.2-1.3; p<0.001), 1.5 (95% CI 1.4-1.6; p<0.001), and 2.0 (95% CI 1.8-2.1; p<0.001) at frailty indices of 1, 2, and ≥3, respectively, for increased HRU relative to no frailty. In subanalyses, each categorical increase in frailty index was independently associated with prolonged length of stay, more discharges to continued care, and unplanned readmission. Increasing frailty score was associated with increasing rates of any complication and serious complications within each surgery type. The analysis is limited by the retrospective design and available data within a large hospital-based database.

Conclusions: Frailty in major urologic oncology surgery is associated with greater HRU and surgical morbidity.

Patient summary: We assessed the impact of frailty on greater health care resource utilization and complications after major urologic cancer surgery in a large US population. With each increase in a frailty score, there was an increase in the likelihood of having complications, prolonged hospital stay, more discharges to continued care, and unplanned readmissions within 30 d.

Keywords: Complications; Frailty; Oncology; Resource utilization; Surgery.

Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Cited by 2 articles
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14
Am J Cancer Res
. 2020 May 1;10(5):1321-1343. eCollection 2020.
Prolactin and Androgen R1881 Induce Pro-Survival carboxypeptidase-D and EDD E3 Ligase in Triple-Negative and HER2+ Breast Cancer
Tyler M MacDonald 1, Lynn N Thomas 1, Aurinjoy Gupta 1, Penelope J Barnes 2 3, Catherine Kl Too 1
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PMID: 32509382
Abstract
Plasma membrane carboxypeptidase-D (CPD) hydrolyzes C-terminal arginine (Arg) from extracellular substrates, and Arg is converted into nitric oxide (NO) in the cell. CPD is upregulated by prolactin (PRL) and androgens in breast cancer (BCa) cells, increasing NO production to promote cell survival. EDD E3 ubiquitin ligase, upregulated by PRL/androgens, is implicated in TORC1 signaling. This study investigated CPD and EDD in triple-negative (TNBC) and HER2+ BCa. Kaplan-Meier analysis showed a negative correlation between CPD or EDD mRNA expression in TNBC patients and relapse-free survival. Immunohistochemistry showed that benign and malignant breast tissues stained abundantly for the PRL receptor (PRLR) and androgen receptor (AR). CPD and EDD staining were elevated in TNBC and HER2+ tumors as compared to benign tissues. In TNBC/HER2+ cell lines, CPD and EDD protein expression were upregulated by PRL or synthetic androgen methyltrienolone (R1881) at 3-6 h. PRL/R1881-induced CPD in TNBC and HER2+ cells increased intracellular NO production, which was abolished by PRLR antagonist ∆1-9-G129R-hPRL and AR antagonist flutamide. In turn, treatment with NO increased viability and decreased apoptosis in Arg-deprived TNBC cells. Cell viability and apoptosis were also affected in HER2+ cells with CPD knockdown. Lastly, EDD knockdown decreased PRL/R1881-induced phosphorylation of initiation factor 4E binding protein-1 and decreased 4E release in TNBC cells. In summary, PRL/R1881-induced CPD promotes TNBC/HER2+ cell survival through production of NO, and EDD promotes TNBC cell survival by TORC1 activation. This study implicates CPD and EDD as useful therapeutic targets for TNBC/HER2+ tumors, and suggests that PRLR and AR blockade are also beneficial to these patients.

Keywords: EDD E3 ligase; Prolactin; androgen; breast cancer; carboxypeptidase-D; cell survival.

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15
Am J Cancer Res
. 2020 May 1;10(5):1477-1517. eCollection 2020.
Incidence and Prognosis of Liver Metastasis at Diagnosis: A Pan-Cancer Population-Based Study
Shuncong Wang 1, Yuanbo Feng 1, Johan Swinnen 1, Raymond Oyen 1, Yue Li 2, Yicheng Ni 1
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PMID: 32509393
Abstract
Metastasis is a major cause of cancer-related death and liver metastasis (LM) is a distinct type for its relatively good prognosis after timely treatment for selected patients. However, a generalizable estimation of incidence and prognosis of LM is lacking. Cancer patients with known LM status in the Surveillance, Epidemiology and End Results database were enrolled in the present study. The incidence and prognosis of LM were calculated by primary cancer type and clinicopathological factors. Among 1,630,725 cases, 105,329 (6.46%) cases present LM at diagnosis, with a median survival of 4 months. LM presents at diagnosis in 39.96% of pancreatic cancer, 16.00% of colorectal cancer (CRC) and 12.68% of lung cancer. Of all LM cases, 25.58% originated from lung cancer, with 24.76% from CRC and 17.55% from pancreatic cancer. LM originated from small intestine cancer shows the best prognosis (median survival: 30 months), followed by testis cancer (25 months) and breast cancer (15 months). Subgroup analyses demonstrated disparities in incidence and prognosis of LM, with higher incidence and poorer prognosis in the older population, African American, male, and patients with inferior socioeconomic status. The current study provides a generalizable data resource for the epidemiology of LM, which may help tailor screening protocol, design clinical trials and estimate disease burden.

Keywords: Metastasis; SEER; epidemiology; liver.

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16
Am J Cancer Res
. 2020 May 1;10(5):1366-1383. eCollection 2020.
Overexpression of COX7RP Promotes Tumor Growth and Metastasis by Inducing ROS Production in Hepatocellular Carcinoma Cells
Guihu Wang 1 2, Branimir Popovic 3 4, Junyan Tao 3 4, An Jiang 1 2
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PMID: 32509385
Abstract
Cumulative evidence has indicated that mitochondrial respiration dysfunction plays important roles in tumorigenesis. However, the role of COX7RP, a critical regulator in the formation of mitochondrial respiratory supercomplex that has been suggested to be over-expressed in hepatocellular carcinoma (HCC) by our bioinformatic analysis of TCGA data, in tumor progression remains largely unclear. In this study, we found that COX7RP is frequently over-expressed in HCC mainly due to the down-regulation of miR-130a-3p and predicts poor prognosis of HCC patients. Functional experiments revealed that COX7RP promoted both growth and metastasis of HCC through induction of cell cycle progression and epithelial to mesenchymal transition (EMT), and suppression of cell apoptosis. Mechanistically, increased generation of reactive oxygen species (ROS) and subsequently activated nuclear transcription factor-κB (NF-κB) signaling was found to contribute to the promotion of HCC cell growth and metastasis by COX7RP. Collectively, COX7RP plays a critical oncogenic role in hepatocellular carcinogenesis, supporting COX7RP as a novel prognostic factor and therapeutic target in HCC.

Keywords: COX7A2L; HCC; growth; metastasis; reactive oxygen species.

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17
Review Am J Cancer Res
. 2020 May 1;10(5):1278-1293. eCollection 2020.
The Role of Mitochondrial Dynamics in Human Cancers
Yawen Ma 1 2, Lihua Wang 1 2, Renbing Jia 1 2
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PMID: 32509379
Abstract
Mitochondria are crucial cellular organelles. Under extracellular stimulations, mitochondria undergo constant fusion and fission dynamics to meet different cellular demands. Mitochondrial dynamics is regulated by specialized proteins and lipids. Dysregulated mitochondrial dynamics has been linked to the initiation and progression of diverse human cancers, affecting aspects such as cancer metastasis, drug resistance and cancer stem cell survival, suggesting that targeting mitochondrial dynamics is a potential therapeutic strategy. In the present review, we summarize the molecular mechanisms underlying fusion and fission dynamics and discuss the effects of mitochondrial dynamics on the development of human cancers.

Keywords: Mitochondrial dynamics; cancer stem cells; human cancers; lipids.

AJCR Copyright © 2020.

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18
Am J Cancer Res
. 2020 May 1;10(5):1416-1428. eCollection 2020.
Aberrant USP11 Expression Regulates NF90 to Promote Proliferation and Metastasis in Hepatocellular Carcinoma
Changmao Zhang 1, Chengrong Xie 1, Xiaomin Wang 1, Yayu Huang 2, Shaoyang Gao 3, Jing Lu 1, Yuyan Lu 1, Sheng Zhang 3
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PMID: 32509388
Abstract
Growing evidence indicates that deubiquitinase ubiquitin-specific protease 11 (USP11) plays an important role in cellular function by regulating the stability of its substrates. USP11 is dysregulated in many types of cancer and involved in tumor development and progression. We previously showed that USP11 was upregulated in hepatocellular carcinoma (HCC) and promoted HCC cell invasion and metastasis potency. However, the mechanism underlying the role of USP11 in HCC cell metastasis and its function in cell proliferation remain unknown. Here, CCK-8, soft agar assays and nude mouse models showed that USP11 was essential for HCC cells survival and proliferation in vitro and in vivo. Results form mass spectrometry, co-immunoprecipitation, and ubiquitination assays demonstrated that USP11 interacted with nuclear factor 90 (NF90) and promoted its deubiquitination, thereby stabilizing it in HCC cells. Moreover, the effect of USP11 on promoting HCC cells proliferation and metastasis was dependent on NF90, and USP11 expression was positively correlated with NF90 expression in human HCC tissues, as demonstrated via immunohistochemistry. Collectively, the present findings indicated that USP11 binded to and deubiquitinated NF90, thereby stabilizing the protein expression level and promoting HCC cell proliferation and metastasis. NF90 was identified as an important downstream target of USP11. Dysregulated signaling of this novel USP11/NF90 axis might promote HCC proliferation and metastasis, and the axis could be a potential therapeutic target in HCC.

Keywords: Hepatocellular carcinoma; metastasis; nuclear factor 90; proliferation; ubiquitin-specific protease 11.

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19
Am J Cancer Res
. 2020 May 1;10(5):1534-1547. eCollection 2020.
Identification of a Transcriptomic Signature With Excellent Survival Prediction for Squamous Cell Carcinoma of the Cervix
John J Wallbillich 1 2 3, Paul Mh Tran 1, Shan Bai 1, Lynn Kh Tran 1, Ashok K Sharma 1, Sharad A Ghamande 2, Jin-Xiong She 1 2
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PMID: 32509396
Abstract
Survival for patients with newly diagnosed cervical cancer has not significantly improved over the past several decades. We sought to identify a clinically relevant set of prognostic genes for squamous cell carcinoma of the cervix (SCCC), the most common cervical cancer subtype. Using RNA-sequencing data and survival data from 203 patients in The Cancer Genome Atlas (TCGA), we conducted a series of analyses using different decile cutoffs for gene expression to identify genes that could indicate large and consistent survival differences across different decile cutoffs of gene expression. Those analyses identified 42 high-risk genes. A patient's survivability could be estimated by simply counting the number of high-risk genes with extremely high expression (above the 90th percentile) or estimating a transcriptomic risk score (TRS) using a machine learning algorithm with 9 of the 42 genes. On multivariate analysis, the significant predictors of mortality included high TRS (HR = 44.8), stage IV (HR = 28.1), intermediate TRS (HR = 4.75), and positive lymph node status (HR = 2.92). Approximately 18% of earlier-stage patients were identified as a poor-prognosis subgroup with high TRS. In patients with SCCC, transcriptomic risk appears to better predict survival than clinical prognostic factors, including stage.

Keywords: Cervical cancer; RNA; TCGA; gene expression; prognostic biomarker; squamous cell carcinoma; transcriptomic risk.

AJCR Copyright © 2020.

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20
Review Am J Cancer Res
. 2020 May 1;10(5):1568-1591. eCollection 2020.
Breast Cancer in Low-Middle Income Countries: Abnormality in Splicing and Lack of Targeted Treatment Options
Flavia Zita Francies 1, Rodney Hull 1, Richard Khanyile 1, Zodwa Dlamini 1
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PMID: 32509398
Abstract
Breast cancer is a common malignancy among women worldwide. Regardless of the economic status of a country, breast cancer poses a burden in prevention, diagnosis and treatment. Developed countries such as the U.S. have high incidence and mortality rates of breast cancer. Although low incidence rates are observed in developing countries, the mortality rate is on the rise implying that low- to middle-income countries lack the resources for preventative screening for early detection and adequate treatment resources. The differences in incidence between countries can be attributed to changes in exposure to environmental risk factors, behaviour and lifestyle factors of the different population groups. Genomic modifications are an important factor that significantly alters the risk profile of breast tumourigenesis. The incidence of early-onset breast cancer is increasing and evidence shows that early onset of breast cancer is far more aggressive than late onset of the disease; possibly due to the difference in genetic alterations or tumour biology. Alternative splicing is a pivotal factor in the progressions of breast cancer. It plays a significant role in tumour prognosis, survival and drug resistance; hence, it offers a valuable option as a therapeutic target. In this review, the differences in breast cancer incidence and mortality rates in developed countries will be compared to low- to middle-income countries. The review will also discuss environmental and lifestyle risk factors, and the underlying molecular mechanisms, genetic variations or mutations and alternative splicing that may contribute to the development and novel drug targets for breast cancer.

Keywords: BRCA; Breast cancer; ER; HER2; aberrant splicing; family history.

AJCR Copyright © 2020.

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None.

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21
Am J Cancer Res
. 2020 May 1;10(5):1384-1399. eCollection 2020.
Inhibiting ULK1 Kinase Decreases Autophagy and Cell Viability in High-Grade Serous Ovarian Cancer Spheroids
Bipradeb Singha 1 2, Jeremi Laski 1 2, Yudith Ramos Valdés 1, Elaine Liu 1, Gabriel E DiMattia 1 3 4, Trevor G Shepherd 1 2 5 4
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PMID: 32509386
Abstract
Metastasis in high-grade serous ovarian cancer (HGSOC) occurs through an unconventional route that involves exfoliation of cancer cells from primary tumors and peritoneal dissemination via multicellular clusters or spheroids. Previously, we demonstrated autophagy induction in HGSOC spheroids grown in vitro and in spheroids collected from ovarian cancer patient ascites; thus, we speculate that autophagy may contribute to spheroid cell survival and overall disease progression. Hence, in this study we sought to evaluate whether ULK1 (unc-51-like kinase-1), a serine-threonine kinase critical for stress-induced autophagy, is important for autophagy regulation in HGSOC spheroids. We demonstrate that HGSOC spheroids have increased ULK1 protein expression that parallels autophagy activation. ULK1 knockdown increased p62 accumulation and decreased LC3-II/I ratio in HGSOC spheroids. In addition, knocking down ATG13, a protein that regulates ULK1 activity via complex formation, phenocopied our ULK1 knockdown results. HGSOC spheroids were blocked in autophagic flux due to ULK1 and ATG13 knockdown as determined by an mCherry-eGFP-LC3B fluorescence reporter. These observations were recapitulated when HGSOC spheroids were treated with an ULK1 kinase inhibitor, MRT68921. Autophagy regulation in normal human fallopian tube epithelial FT190 cells, however, may bypass ULK1, since MRT68921 reduced viability in HGSOC spheroids but not in FT190 cells. Interestingly, ULK1 mRNA expression is negatively correlated with patient survival among stage III and stage IV serous ovarian cancer patients. As we observed using established HGSOC cell lines, cultured spheroids using our new, patient-derived HGSOC cells were also sensitive to ULK1 inhibition and demonstrated reduced cell viability to MRT68921 treatment. These results demonstrate the importance of ULK1 for autophagy induction in HGSOC spheroids and therefore justifies further evaluation of MRT68921, and other novel ULK1 inhibitors, as potential therapeutics against metastatic HGSOC.

Keywords: Autophagy; MRT68921; ULK1; high-grade serous ovarian cancer; spheroids.

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22
Am J Cancer Res
. 2020 May 1;10(5):1455-1466. eCollection 2020.
BAP1 Maintains Chromosome Stability by Stabilizing DIDO1 in Renal Cell Carcinoma
Jiantao Xiao 1, Ruhan Zhang 2, Jingtao Peng 3, Zhonghua Yang 1
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PMID: 32509391
Abstract
BRCA1-associated protein 1 (BAP1) is a member of the ubiquitin C-terminal hydrolase family of deubiquitinating enzymes and is implicated in transcriptional regulation. The BAP1 gene is mutated in 5%-15% of patients with clear cell renal cell carcinoma (ccRCC), the most common form of renal cancer, which suggests that BAP1 is a tumor suppressor. However, whether BAP1 influences the progression of ccRCC tumors expressing wildtype (WT) BAP1 is unclear. Here, we identified DIDO1 as a bona fide substrate for BAP1. DIDO1 is a component of the centrosome proteins and plays an essential role in spindle assembly. BAP1 binds to DIDO1 and stabilizes DIDO1 through de-ubiquitination. BAP1 contributes to chromosome stability partially via DIDO1. A positive correlation was identified between BAP1 and DIDO1 expression in ccRCC tissues. Downregulation of both BAP1-loss and DIDO1 protein expression in ccRCC was associated with adverse clinicopathological features. This study revealed a novel mechanism involving BAP1 in the regulation of DIDO1 stability, and the results also provide insight into the relationship between BAP1 mutations and chromosome instability in ccRCC.

Keywords: BAP1; DIDO1; chromosome instability; clear cell renal cell carcinoma; de-ubiquitination.

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23
Am J Cancer Res
. 2020 May 1;10(5):1548-1567. eCollection 2020.
SLC25A18 Has Prognostic Value in Colorectal Cancer and Represses Warburg Effect and Cell Proliferation via Wnt Signaling
Li Liang 1, Yanjie Chen 2, Yiyi Yu 1, Weiyu Pan 3, Yuehong Cui 1, Xiaojing Xu 1, Ke Peng 1, Mengling Liu 1, Khalid Rashid 1, Yingyong Hou 3, Tianshu Liu 1
Affiliations expand
PMID: 32509397
Abstract
Colorectal cancer (CRC) is a common malignant tumor worldwide. The solute carrier family 25 member 18 (SLC25A18) transports glutamate across the inner mitochondrial membrane and involves some non-tumor diseases, yet little is known about its role in malignancy. Here, we studied the function and mechanism of SLC25A18 in CRC. We conducted a bioinformatic analysis of the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to identify the correlation of SLC25A18 expression with clinic-pathological characteristics. Function experiments were implemented to estimate the variation of aerobic glycolysis and cell proliferation due to in vitro and in vivo up- or down-regulation of SLC25A18. Immunohistochemical staining of SLC25A18 was performed on a tissue microarray of 106 patients with primary or metastatic CRC to evaluate its predictive and prognostic value. SLC25A18 expression was low in the CRC samples and was negatively correlated with stage, age and serum carcinoembryonic antigen levels. High expression of SLC25A18 indicated longer disease-free survival time after surgery. Exogenous overexpression of SLC25A18 decreased glucose consumption, lactate production, intracellular ATP concentration and cell proliferation and abrogated expression of CTNNB1, PKM2, LDHA and MYC. Inhibition of Wnt/β-catenin restored SLC25A18-repressed cellular activities. SLC25A18 clinically predicted a longer survival time after surgery or medicine treatment. These results showed that increased SLC25A18 expression inhibits Warburg effect and cell proliferation via Wnt/β-catenin cascade, and suggest a better prognosis after treatment.

Keywords: SLC25A18; Warburg effect; Wnt/β-catenin; cell proliferation; colorectal cancer; survival.

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24
Am J Cancer Res
. 2020 May 1;10(5):1356-1365. eCollection 2020.
A Novel, Small Peptide With Activity Against Human Pancreatic Cancer
Michael R Kozlowski 1, Roni E Kozlowski 2
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PMID: 32509384
Abstract
KTH-222 is a novel, 8-amino acid length peptide. It is derived from a motif identified in a group of peptides that are related to atrial natriuretic peptide and that are able to inhibit cancer cell growth. We report here that KTH-222 inhibits the attachment, proliferation, and development of an invasive morphology in cultured human pancreatic tumor cells (MIA PaCa-2 and HPAC). At a biochemical level, it inhibits tubulin polymerization which may underlie these cellular effects. We further report that KTH-222 reduces the rate of tumor growth and prolongs survival in mice implanted with MIA PaCa-2 cells. In this model system, KTH-222 is more effective than gemcitabine, a drug commonly used in the treatment of pancreatic cancer. Furthermore, KTH-222 does not decrease the rate of weight gain in the treated mice, suggesting the absence of gross toxicity. These activities of KTH-222 suggest that it may be useful in the treatment of pancreatic cancer.

Keywords: Pancreatic cancer; atrial natriuretic peptide; chemotherapy; small peptide.

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25
Am J Cancer Res
. 2020 May 1;10(5):1518-1521. eCollection 2020.
Should Patients Stop Their Radiotherapy or Chemotherapy During the COVID-19 Pandemic
Bin Huang 1 2, Jian Zhu 2, Xiong-Ying Wu 3, Xu-Hui Gao 2
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PMID: 32509394
Abstract
In the previous stage, there were too many patients with Corona virus disease 2019 (COVID-19) in Wuhan. Ordinary people, patients, even doctors, had a great sense of desperate. On the one hand, almost all doctors participated in the treatment of patients of COVID-19. On the other hand, the government restricted residents to go out, and the sick people were also afraid of being infected with COVID-19 when seeking medical treatment. Whether cancer patients seek medical treatment or not has become a contradiction for a long time. Our Viewpoint paper is to provide a positive signal to doctors and patients that patients with in the middle or advanced stage of cancer can receive radiotherapy and/or chemotherapy normally under protective measures.

Keywords: COVID-19; Radiotherapy; chemotherapy.

AJCR Copyright © 2020.

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26
Am J Cancer Res
. 2020 May 1;10(5):1608-1629. eCollection 2020.
MLL5α Activates AR/NDRG1 Signaling to Suppress Prostate Cancer Progression
Yongjun Quan 1 2, Yun Cui 1, Wasilijiang Wahafu 1, Yuexin Liu 2, Hao Ping 2, Xiaodong Zhang 1
Affiliations expand
PMID: 32509400
Abstract
Prostate cancer (PCa) is one of the most prevalent malignancies in men. However, the molecular mechanism controlling the transformation of androgen-dependent PCa (ADPC) to castration-resistant PCa (CRPC) is largely unknown. Androgen receptor (AR) signaling has been reported to play a key role in this process; thus, searching for the novel AR co-activator is important for identifying the mechanism underlying PCa progression. In this study, we focused on the function of mixed lineage leukemia-5α (MLL5α), an epigenetic regulator that exhibits aberrant expression in PCa. MLL5α was the primary expressed form of MLL5 protein in PCa cells and it significantly suppressed proliferation, invasion, and migration in PCa cell lines. Upon stimulation with dihydrotestosterone (DHT), knockdown of MLL5α significantly suppressed N-myc downstream regulated gene 1 (NDRG1) and Kallikrein-related peptidase 3 (KLK3) expression. MLL5α directly bound with AR on the androgen response elements (AREs) and recruited H3K4me3 to the promoters of NDRG1 and KLK3. Downregulation of NDRG1 partially restored the cell invasion and migration suppressed by MLL5α. As evaluated by the proliferation of PCa cells, overexpression of MLL5α synergistically promoted sensitivity to enzalutamide (ENZ) treatment. In PCa patients, MLL5α expression was lower in the high Gleason score (GS) (GS > 7) group than in the low GS (GS < 7) group. In conclusion, suppression of AR/NDRG1 signaling via androgen deprivation therapy (ADT) may be a potential mechanism of CRPC progression. MLL5α significantly suppressed PCa progression by promoting AR/NDRG1 signaling, indicating that regulating MLL5α expression may be a potential treatment approach for patients with advanced PCa.

Keywords: AR; MLL5α; NDRG1; Prostate cancer; enzalutamide; histone methylation.

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27
Am J Cancer Res
. 2020 May 1;10(5):1442-1454. eCollection 2020.
NQO1 Is a Determinant for Cellular Sensitivity to Anti-Tumor Agent Napabucasin
Gaigai Guo 1, Zhouyong Gao 2, Mengsha Tong 1 3, Dongdong Zhan 1 4, Guangshun Wang 2, Yi Wang 1 2, Jun Qin 1 2
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PMID: 32509390
Abstract
Napabucasin (NAPA) is thought to be a potent cancer stemness inhibitor in different types of cancer cell lines. While it has shown promising activity in early phase clinical trials, two recent phase III NAPA clinical trials failed to meet the primary endpoint of overall survival. The reason for the failure is not clear, but a possible way to revive the clinical trial is to stratify patients with biomarkers that could predict NAPA response. Here, we report the identification of NAD(P)H dehydrogenase 1 (NQO1) as a major determinant of NAPA efficacy. A proteomic profiling of cancer cell lines revealed that NQO1 abundance is negatively correlated with IC50; in vitro assays showed that NAPA is a substrate for NQO1, which mediates the generation of ROS that leads to cell death. Furthermore, activation of an NQO1 transcription factor NRF2 by chemicals, including an FDA approved drug, can increase the NAPA cytotoxicity. Our findings suggest a potential use of NQO1 expression as a companion diagnostic test to identify patients in future NAPA trials and a combination strategy to expand the application of NAPA-based regimens for cancer therapy.

Keywords: NQO1; NRF2; Napabucasin; ROS; proteomics.

AJCR Copyright © 2020.

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28
Am J Cancer Res
. 2020 May 1;10(5):1400-1415. eCollection 2020.
CLIC4 Regulates Radioresistance of Nasopharyngeal Carcinoma by iNOS After γ-Rays but Not Carbon Ions Irradiation
Lin Zhu 1, Qianping Chen 1, Longshan Zhang 2, Songling Hu 1, Wang Zheng 1, Chen Wang 1, Yang Bai 1, Yan Pan 1, Teruaki Konishi 3, Jian Guan 2, Chunlin Shao 1
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PMID: 32509387
Abstract
Nasopharyngeal carcinoma (NPC) is a major health problem in the East and Southeast Asia, and the intensity modulated radiotherapy (IMRT) is the current preferred treatment method of NPC, but radioresistance-induced residual and recurrent tumors are the main cause of treatment failure. Till now, the mechanism of radioresistance and prognostic biomarkers of NPC are still unrevealed. In this study, we collected clinical NPC samples and established radioresistant NPC-R cell lines by irradiating NPC cells with fractionation doses of γ-rays. Using genechip assay between radioresistance and radiosensitive clinical samples and TMT assay between NPC and NPC-R cells, differential expressed genes were examined and the potential biomarker of radioresistance was screened. Immunohistochemical assay of NPC clinical specimens showed that CLIC4 was significantly up-regulated in radioresistance tumor tissues. In vitro studies confirmed that up-regulation of CLIC4 gene enhanced radioresistance in comparison with the alterations of intracellular oxidative metabolism of reactive oxygen species (ROS) and nitric oxide (NO) in an opposite way. Correspondingly, inhibition of CLIC4 sensitized NPC cells to irradiation and decreased nuclear translocation of iNOS and intracellular level of NO in NPC cells. Interestingly, the capacity for DNA repair had no difference between NPC and NPC-R cells. Moreover, because of great interests in using carbon ion irradiation to treat NPC effectively, we demonstrated that, after carbon ion irradiation, NPC-R and NPC cells had similar survival even under the status of up- or down-regulation of CLIC4. Conclusively, CLIC4 contributes to radioresistance of NPC to γ-rays but not carbon ions by regulating intracellular oxidative metabolism of nuclear translocation of iNOS.

Keywords: CLIC4; Nasopharyngeal carcinoma; iNOS; ionizing radiation; oxidative stress.

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29
JCO Glob Oncol
. 2020 May;6:752-760. doi: 10.1200/GO.20.00156.
Mortality and Advanced Support Requirement for Patients With Cancer With COVID-19: A Mathematical Dynamic Model for Latin America
Alejandro Ruiz-Patiño 1 2, Oscar Arrieta 3, Luis E Pino 4, Christian Rolfo 5, Luisa Ricaurte 1 2, Gonzalo Recondo 6, Zyanya-Lucia Zatarain-Barron 3, Luis Corrales 7, Claudio Martín 8, Feliciano Barrón 3, Carlos Vargas 1 2 9, Hernán Carranza 1 2 9, Jorge Otero 1 2 9, July Rodriguez 1 2, Carolina Sotelo 1 2, Lucia Viola 10, Alessandro Russo 5 11, Rafael Rosell 12 13, Andrés F Cardona 1 2 9
Affiliations expand
PMID: 32469610 PMCID: PMC7268899 DOI: 10.1200/GO.20.00156
Free PMC article
Abstract
Purpose: In the midst of a global pandemic, evidence suggests that similar to other severe respiratory viral infections, patients with cancer are at higher risk of becoming infected by COVID-19 and have a poorer prognosis.

Methods: We have modeled the mortality and the intensive care unit (ICU) requirement for the care of patients with cancer infected with COVID-19 in Latin America. A dynamic multistate Markov model was constructed. Transition probabilities were estimated on the basis of published reports for cumulative probability of complications. Basic reproductive number (R0) values were modeled with R using the EpiEstim package. Estimations of days of ICU requirement and absolute mortality were calculated by imputing number of cumulative cases in the Markov model.

Results: Estimated median time of ICU requirement was 12.7 days, median time to mortality was 16.3 days after infection, and median time to severe event was 8.1 days. Peak ICU occupancy for patients with cancer was calculated at 16 days after infection. Deterministic sensitivity analysis revealed an interval for mortality between 18.5% and 30.4%. With the actual incidence tendency, Latin America would be expected to lose approximately 111,725 patients with cancer to SARS-CoV-2 (range, 87,116-143,154 patients) by the 60th day since the start of the outbreak. Losses calculated vary between < 1% to 17.6% of all patients with cancer in the region.

Conclusion: Cancer-related cases and deaths attributable to SARS-CoV-2 will put a great strain on health care systems in Latin America. Early implementation of interventions on the basis of data given by disease modeling could mitigate both infections and deaths among patients with cancer.

Conflict of interest statement
Oscar Arrieta
Honoraria: AstraZeneca, Merck Sharp & Dohme, Roche

Consulting or Advisory Role: Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Pfizer

Research Funding: AstraZeneca (Inst), Roche (Inst), Merck Sharp & Dohme (Inst)

Luis E. Pino
Consulting or Advisory Role: AstraZeneca

Speakers’ Bureau: Roche

Travel, Accommodations, Expenses: MSD Oncology

Christian Rolfo
Consulting or Advisory Role: Mylan, Archer Biosciences, Oncopass, Inivata, Merck Serono

Speakers’ Bureau: Novartis, MSD, Boehringer Ingelheim, Guardant Health, AstraZeneca

Research Funding: Pfizer

Travel, Accommodations, Expenses: AstraZeneca

Uncompensated Relationships: OncoDNA, Biomark, Guardant Health,

Gonzalo Recondo
Consulting or Advisory Role: Roche, Amgen, Pfizer

Travel, Accommodations, Expenses: AstraZeneca, Pfizer

Luis Corrales
Consulting or Advisory Role: AstraZeneca, Roche, MSD Oncology, Pfizer

Speakers’ Bureau: Roche, AstraZeneca, MSD Oncology

Research Funding: Roche

Travel, Accommodations, Expenses: Roche, AstraZeneca, MSD Oncology

Claudio Martín
Consulting or Advisory Role: MSD Oncology, Boehringer Ingelheim, AstraZeneca, Bristol Myers Squibb, Pfizer, Roche

Speakers’ Bureau: Bristol Myers Squibb, Roche, Boehringer Ingelheim, Pfizer, MSD Oncology, AstraZeneca

Feliciano Barrón
Speakers’ Bureau: AstraZeneca

Travel, Accommodations, Expenses: AstraZeneca

Carlos Vargas
Honoraria: Roche, Novartis Institutes for BioMedical Research

Consulting or Advisory Role: Roche, Pfizer, MSD, Bristol Myers Squibb

Speakers’ Bureau: Roche

Travel, Accommodations, Expenses: Roche

Hernán Carranza
Consulting or Advisory Role: Roche, Amgen, Pfizer

Speakers’ Bureau: Roche

Travel, Accommodations, Expenses: Roche, Merck

Jorge Otero
Consulting or Advisory Role: AstraZeneca

Speakers’ Bureau: AstraZeneca

Travel, Accommodations, Expenses: AstraZeneca

July Rodriguez
Speakers’ Bureau: Bayer AG, AstraZeneca

Carolina Sotelo
Travel, Accommodations, Expenses: American Association for Cancer Research

Lucia Viola
Consulting or Advisory Role: AstraZeneca

Travel, Accommodations, Expenses: Mundipharma, Boehringer Ingelheim, AstraZeneca

Andrés F. Cardona
Honoraria: Bristol Myers Squibb, Roche, Boehringer Ingelheim, AbbVie, Merck Sharp & Dohme, Celldex

Consulting or Advisory Role: Roche, Merck Sharp & Dohme, Novartis, AstraZeneca, Bristol-Myers Squibb, Foundation Medicine, Boehringer Ingelheim, Foundation for Clinical and Applied Cancer Research

Speakers’ Bureau: Merck Sharp & Dohme, Roche, Bristol Myers Squibb, Novartis, Foundation for Clinical and Applied Cancer Research, Foundation Medicine

Travel, Accommodations, Expenses: Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Boehringer Ingelheim, Foundation Medicine

No other potential conflicts of interest were reported.

21 references3 figures
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30
Am J Cancer Res
. 2020 May 1;10(5):1344-1355. eCollection 2020.
Predicting Long-Term Multicategory Cause of Death in Patients With Prostate Cancer: Random Forest Versus Multinomial Model
Jianwei Wang 1, Fei Deng 2, Fuqing Zeng 3, Andrew J Shanahan 4, Wei Vivian Li 5, Lanjing Zhang 6 7 8 9
Affiliations expand
PMID: 32509383
Abstract
The majority of patients with prostate cancer die of non-cancer causes of death (COD). It is thus important to accurately predict multi-category COD in these patients. Random forest (RF), a popular machine learning model, has been shown useful for predicting binary cancer-specific deaths. However, its accuracy for predicting multi-category COD in cancer patients is unclear. We included patients in Surveillance, Epidemiology, and End Results-18 cancer registry-program with prostate cancer diagnosed in 2004 (followed-up through 2016). They were randomly divided into training and testing sets with equal sizes. We evaluated prediction accuracies of RF and conventional statistical/multinomial models for 6-category COD by data-encoding types using the 2-fold cross-validation approach. Among 49,864 prostate cancer patients, 29,611 (59.4%) were alive at the end of follow-up, and 5,448 (10.9%) died of cardiovascular disease, 4,607 (9.2%) of prostate cancer, 3,681 (7.4%) of non-prostate cancer, 717 (1.4%) of infection, and 5,800 (11.6%) of other causes. We predicted 6-category COD among these patients with a mean accuracy of 59.1% (n=240, 95% CI, 58.7%-59.4%) in RF models with one-hot encoding, and 50.4% (95% CI, 49.7%-51.0%) in multinomial models. Tumor characteristics, prostate-specific antigen level, and diagnosis confirmation-method were important in RF and multinomial models. In RF models, no statistical differences were found between the accuracies of training versus cross-validation phases, and those of categorical versus one-hot encoding. We here report that RF models can outperform multinomial logistic models (absolute accuracy-difference, 8.7%) in predicting long-term 6-category COD among prostate cancer patients, while pathology diagnosis itself and tumor pathology remain important factors.

Keywords: Prostate cancer; cause-specific mortality; machine learning; prediction; prognosis.

AJCR Copyright © 2020.

Conflict of interest statement
None.

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31
Am J Cancer Res
. 2020 May 1;10(5):1522-1533. eCollection 2020.
Current Statuses of Molecular Targeted and Immune Checkpoint Therapies in Hepatocellular Carcinoma
Deqiang Kong 1, Chen Liu 1, Xiaolong Miao 1, Yao Wang 2, Xianfeng Ding 2, Weihua Gong 1
Affiliations expand
PMID: 32509395
Abstract
Treatment of advanced hepatocellular carcinoma (HCC) still confronts great challenges due to high rate of therapeutic resistance. The emergence of systemic treatment with molecular targeted and immune checkpoint therapies has brought novel approaches towards patients with advanced HCC. However, sorafenib, as the first approved systemic treatment in 2007, only increased overall survival by three months in advanced HCC patients. Afterwards, little progress has been made for molecular targeted agents. Only four molecular drugs are empirically used in clinical practice. Lenvatinib acts as a first-line drug, whereas regorafenib, ramucirumab, and cabozantinib are defined as second-line drugs. Nevertheless, clinical findings reveal that overall survival remains unchanged. Albeit immunotherapy-based approaches are currently considered promising therapeutic strategies for advanced HCC, a minority of patients could benefit from them. These beneficiaries are to be accordingly identified. Combined immunotherapies with matched molecular targeted treatments would be a novel breakthrough. Herein, we summarize the current statuses of immunotherapies and molecular targeted drug therapies, and mainly identify clinically feasible chemoimmunotherapeutic strategies.

Keywords: Hepatocellular carcinoma; chemoimmunotherapy; immunotherapy; molecular targeted therapy.

AJCR Copyright © 2020.

Conflict of interest statement
None.

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32
Review Am J Cancer Res
. 2020 May 1;10(5):1294-1307. eCollection 2020.
Chronic Stress-Induced Immune Dysregulation in Cancer: Implications for Initiation, Progression, Metastasis, and Treatment
Leyi Zhang 1 2, Jun Pan 1 2, Wuzhen Chen 1 2, Jinxin Jiang 1 2, Jian Huang 1 2
Affiliations expand
PMID: 32509380
Abstract
Psychological stress is a well-accepted risk factor in cancer initiation and progression. The explosive growth of psychoneuroimmunology research in the past decade has yielded an unprecedented wealth of information about the critical role of chronic stress in the immune dysfunction that influences tumor behaviors, which presents insights to mitigate distress and improve prognosis in cancer patients. Chronic stress exacerbates inflammation and causes a metabolism disorder, making it difficult for the organisms to maintain homeostasis and increasing its susceptibility to cancer. The shifted differentiation and redistribution of the immune system induced by chronic stress fail to combat cancer efficiently. Chronic stress increases the tumor-educated immune suppressive cells and impairs the cytotoxicity of cellular immunity, thereby promoting lymphatic metastasis and hematogenous metastasis. In addition, the efficacy of existing cancer therapies is undermined because chronic stress prevents the immune system from responding properly. Emerging stress-reduction measures have been administered to assist cancer patients to cope with the adverse effects of chronic stress. Here we systematically review the current molecular, cellular, physiological mechanisms about stress-mediated immune responses in the enhancement of tumor initiation and progression, remodeling of tumor microenvironment and impairment of anti-tumor treatment. We also summarize the potential clinically applicable stress-oriented strategies towards cancer and discuss briefly where important knowledge gaps remain.

Keywords: Tumor immunology; anti-cancer therapy; biobehavioral sciences; psychological distress; tumor microenvironment.

AJCR Copyright © 2020.

Conflict of interest statement
None.

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33
Am J Cancer Res
. 2020 May 1;10(5):1592-1607. eCollection 2020.
Examining Factors Underlying Geographic Disparities in Early-Onset Colorectal Cancer Survival Among Men in the United States
Charles R Rogers 1, Justin X Moore 2 3, Fares Qeadan 1, Lily Y Gu 1, Matthew S Huntington 1, Andreana N Holowatyj 4 5 6
Affiliations expand
PMID: 32509399
Abstract
Background: Despite overall incidence reduction in colorectal cancer (CRC) the past 32 years, unexplained incidence and mortality rates have increased significantly in younger adults ages 20-49. To improve understanding of sex-specific differences among this population, we aimed to determine the variance in early-onset CRC (EOCRC) survival among US men diagnosed with CRC before age 50, while considering individual- and county-level CRC outcome determinants. Methods: Hotspots (i.e., counties with high EOCRC mortality rates) were derived from Centers for Disease Control and Prevention data from 1999-2017, and linked to SEER data for men aged 15-49 years with CRC. Cox proportional hazards models were used to compare CRC-specific survival probability and hazard in hotspots versus non-significant counties. A generalized R2 was used to estimate the total variance in EOCRC survival explained by clinicodemographic and county-level determinants. Results: We identified 232 hotspot counties for EOCRC-214 (92%) of which were in the South. In hotspots, 1,009 men were diagnosed with EOCRC and 31,438 in non-significant counties. After adjusting for age, race, tumor stage and grade, surgery, chemotherapy, radiation therapy, and marital status, men residing in hotspot counties had higher hazard of CRC-specific death (HR 1.24, 95% CI, 1.12-1.36). Individual/county-level factors explained nearly 35% of the variation in survival, and adult smoking served as the strongest county-level determinant of EOCRC survival. Conclusion: Distinct geographic patterns of EOCRC were predominantly located in the southern US. Survival after EOCRC diagnosis was significantly worse among men residing in hotspot counties.

Keywords: Colorectal cancer; SEER; early-onset; racial disparities; smoking.

AJCR Copyright © 2020.

Conflict of interest statement
None.

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34
Am J Cancer Res
. 2020 May 1;10(5):1429-1441. eCollection 2020.
Combined Effects of Mesenchymal Stem Cells Carrying Cytosine Deaminase Gene With 5-fluorocytosine and Temozolomide in Orthotopic Glioma Model
Da-Young Chang 1, Jin-Hwa Jung 2, Andrew Aujin Kim 3, Subash Marasini 2, Young Jun Lee 2, Sun Ha Paek 4, Sung-Soo Kim 1, Haeyoung Suh-Kim 1 2
Affiliations expand
PMID: 32509389
Abstract
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor, and current standard therapy provides modest improvements in progression-free and overall survival of patients. Innate tumor resistance and presence of the blood-brain barrier (BBB) require the development of multi-modal therapeutic regimens. Previously, cytosine deaminase (CD)-expressing mesenchymal stem cells (MSC/CD) were found to exhibit anticancer activity with a wide therapeutic index by converting 5-fluorocytosine (5-FC), a nontoxic prodrug into 5-fluorouracil (5-FU), a potent anticancer drug. In this study, we evaluated the efficacy of MSC/CD in a multi-modal combination regimen with temozolomide (TMZ). Cell viability test, cell cycle, and normalized isobologram analyses were performed. In vivo anticancer effects were tested in a mouse orthotopic glioma model. TMZ and MSC/CD with 5-FC synergistically interacted and suppressed U87 glioma cell line growth in vitro. Combined treatment with TMZ and 5-FU increased cell cycle arrest and DNA breakage. In an orthotopic xenograft mouse model, treatment with TMZ alone suppressed tumor growth; however, this effect was more intense with MSC/CD transplantation followed by the sequential treatment with 5-FC and TMZ. Therefore, we propose that sequential treatment with 5-FC and MSC/CD can be used in patients with GBM during the immediate postoperative period to sensitize tumors to subsequent adjuvant chemo- and radiotherapy.

Keywords: 5-fluorocytosine; Mesenchymal stem cells; cytosine deaminase; glioma; temozolomide.

AJCR Copyright © 2020.

Conflict of interest statement
None.

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35
Am J Cancer Res
. 2020 May 1;10(5):1467-1476. eCollection 2020.
Preventive Effect of Celecoxib in Sorafenib-Related Hand-Foot Syndrome in Hepatocellular Carcinoma Patients, a Single-Center, Open-Label, Randomized, Controlled Clinical Phase III Trial
Jian-Cong Chen 1 2, Jun-Cheng Wang 1 3, Yang-Xun Pan 1 3, Min-Jiang Yi 1 3, Jin-Bin Chen 1 3, Xiao-Hui Wang 1 3, Yi-Zhen Fu 1 3, Yao-Jun Zhang 1 3, Li Xu 1 3, Min-Shan Chen 1 3, Rong-Xin Zhang 3 4, Zhong-Guo Zhou 1 3
Affiliations expand
PMID: 32509392
Abstract
Skin toxicity, especially hand-foot syndrome (HFS), is one of the most common sorafenib-induced adverse events (AEs) in hepatocellular carcinoma (HCC) patients, leading to treatment interruption and failure. Mucocutaneous inflammation may cause HFS; therefore, we investigated whether celecoxib can alleviate HFS, improve patients' quality of life and increase survival when administered in conjunction with active therapy. Our randomized, open-label study prospectively enrolled 116 advanced HCC patients receiving sorafenib as targeted therapy from July 2015 to July 2016. All patients were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib with or without celecoxib. Sorafenib-related AEs were recorded, Survival was compared between the two groups. Compared to the Sorafenib group, the SoraCele group had lower incidence rates of ≥ grade 2 and grade 3 HFS (63.8% vs 29.3%, P < 0.001; 19.0% vs 3.4%, P = 0.008, respectively), hair loss, rash and abdominal pain. Kaplan-Meier analysis revealed a lower risk of ≥ grade 2 HFS (HR, 0.384; P = 0.002) and a lower dose reduction/interruption rate (46.6% to 15.5%, P < 0.001) in the SoraCele group. Cox proportional hazards regression analysis demonstrated that celecoxib was the only independent predictive factor of developing ≥ grade 2 HFS (HR, 0.414; P = 0.004). Longer progression-free survival (PFS) was also observed in the SoraCele group (P = 0.039), although overall survival was not prolonged (P = 0.305). These results suggest that sorafenib + Celecoxib administration alleviated sorafenib-related skin toxicity. Longer PFS was achieved in clinical practice, although overall survival was not prolonged (ClinicalTrials.gov: NCT02961998).

Keywords: Hand-foot syndrome; celecoxib; hepatocellular carcinoma; sorafenib.

AJCR Copyright © 2020.

Conflict of interest statement
None.

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Review Am J Cancer Res
. 2020 May 1;10(5):1308-1320. eCollection 2020.
Immune Battle at the Premalignant Stage of Colorectal Cancer: Focus on Immune Cell Compositions, Functions and Cytokine Products
Guanglin Cui 1 2
Affiliations expand
PMID: 32509381
Abstract
It is now widely accepted that most human cancers, including colorectal cancers (CRCs), develop from premalignant lesions through a long-term multistep process. Host immunity is a key determinant that maintains most premalignant lesions in a stable state via immunosurveillance. However, premalignant cells use diverse strategies to escape host immunosurveillance. A switch in the immune function from immunosurveillance to immunosuppression facilitates the progression of premalignant lesions to established CRCs. This review summarizes the recent progress in understanding alterations in the immune landscape, including immune cell compositions, functions and cytokine products, in the premalignant stage of CRC and provides an updated discussion on its translational significance along the colorectal adenoma-carcinoma sequence.

Keywords: Colorectum; cytokine; immune cell; immunity; premalignant lesion.

AJCR Copyright © 2020.

Conflict of interest statement
None.

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