1.
Int J Cancer. 2020 Mar 24. doi: 10.1002/ijc.32990. [Epub ahead of print]
Metabolic Factors Contribute to T-cell Inhibition in the Ovarian Cancer Ascites.
Abstract
Malignant ascites is one of the major clinical features of ovarian cancer, which serves as a carrier for the peritoneal dissemination of tumor cells and predicts a poor prognosis in patients. In the microenvironment of ovarian cancer ascites, anti-tumor immunity is suppressed, which enables the tumor cells to escape from immune surveillance. The metabolic factors, including hypoxia, nutrient deprivation, and accumulation of metabolic products, contribute to the immunosuppressive status of malignant ascites. The malignant ascites and ovarian solid tumors exhibit differential metabolic profiles. In this review, we have summarized the most recent findings on the interaction between immune cells and metabolic factors in the ovarian cancer ascites. The effects of metabolic factors on the anti-tumor functions of T-cells in the malignant ascites were analyzed. Finally, we have discussed the potential directions for future research in this field. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
T-cell; ascites; immunosuppression; metabolism; ovarian cancer
2.
Eur J Cancer. 2020 Mar 21;130:146-154. doi: 10.1016/j.ejca.2020.02.008. [Epub ahead of print]
Older versus younger adults with gastric cancer receiving perioperative treatment: Results from the CRITICS trial.
Slagter AE1, Tudela B2, van Amelsfoort RM1, Sikorska K3, van Sandick JW4, van de Velde CJH5, van Grieken NCT6, Lind P7, Nordsmark M8, Putter H9, Hulshof MCCM10, van Laarhoven HWM11, Grootscholten C12, Braak JPBM5, Meershoek-Klein Kranenbarg E5, Jansen EPM1, Cats A12, Verheij M13.
Abstract
AIM:
To evaluate treatment-related toxicity, treatment compliance, surgical complications and event-free survival (EFS) in older (≥70 years) versus younger (<70 years) adults who underwent perioperative treatment for gastric cancer.
METHODS:
In the CRITICS trial, 788 patients with resectable gastric cancer were randomised before start of any treatment and received preoperative chemotherapy (3 cycles of epirubicin, cisplatin or oxaliplatin and capecitabine), followed by surgery, followed by either postoperative chemotherapy or chemoradiotherapy (45Gy + cisplatin + capecitabine).
RESULTS:
172 (22%) patients were older adults. During preoperative chemotherapy, 131 (77%) older adults versus 380 (62%) younger adults experienced severe toxicity (p < 0.001); older adults received significantly lower relative dose intensities (RDIs) for all chemotherapeutic drugs. Equal proportions of older versus younger adults underwent curative surgery: 137 (80%) versus 499 (81%), with comparable postoperative complications and postoperative mortality. Postoperative therapy after curative surgery started in 87 (64%) older adults versus 391 (78%) younger adults (p < 0.001). Incidence of severe toxicity during postoperative chemotherapy was 22 (54%) in older adults versus 113 (59%) in younger adults (p = 0.541); older adults received significantly lower RDIs for all chemotherapeutic drugs. Severe toxicity rates for postoperative chemoradiotherapy were 22 (48%) older adults versus 89 (45%) for younger adults (p = 0.703), with comparable chemotherapy RDIs and radiotherapy dose. Two-year EFS was 53% for older adults versus 51% for younger adults.
CONCLUSION:
Perioperative treatment compliance, especially in the postoperative phase, was poorer in older adults compared with younger adults. As comparable proportions of patients underwent curative surgery, future studies should focus on neo-adjuvant treatment.
TRIAL REGISTRATION:
ClinicalTrials.gov identifier: NCT00407186. EudraCT number: 2006-00413032.
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
KEYWORDS:
Chemoradiotherapy; Chemotherapy; Older adults; Resectable gastric cancer
3.
Exerc Immunol Rev. 2020;26:24-42.
Exercise and the Kynurenine pathway: Current state of knowledge and results from a randomized cross-over study comparing acute effects of endurance and resistance training.
Joisten N1, Kummerhoff F1, Koliamitra C1, Schenk A1, Walzik D1, Hardt L1, Knoop A2, Thevis M2, Kiesl D3, Metcalfe AJ1, Bloch W1, Zimmer P1,4.
Abstract
INTRODUCTION:
The essential amino acid tryptophan (TRP) is primarily degraded through the kynurenine (KYN) pathway, which is dysregulated in several chronic diseases. KYN pathway metabolites have immune- and neuro-modulatory properties and are involved in th de novo synthesis of nicotinamide adenine dinucleotide (NAD+). Currently, little evidence exists demonstrating that physical exercise may influence this pathway. However, differences between acute and chronic stimuli as well as the influence of exercise modalities remain to be investigated. Here, we provide an overview of existing studies and present results of a randomized cross-over trial on acute effects of a single-bout of resistance and endurance exercise.
METHODS:
24 healthy male adults conducted both an acute endurance exercise (EE) and resistance exercise (RE) session. Blood samples were collected before, immediately after and one hour after cessation of each exercise session. Outcomes comprised serum levels of TRP, KYN, kynurenic acid (KA), quinolinic acid (QA) and calculated ratios. Gene expression of the enzymes indoleamine 2,3 dioxygenase (IDO) 1 and kynurenine aminotransferase (KAT) 4 was measured in peripheral blood mononuclear cells (PBMCs). Moreover, serum concentrations of the potential KYN pathway mediators interleukin (IL)-6 and cortisol were determined. Finally, we investigated baseline correlations between immune cell subsets, potential mediators and initial KYN pathway activation outcomes.
RESULTS:
The KYN/TRP ratio correlated positively with IL-6 and CD56bright NK-cells and negatively with CD56dim NKcells. Expression of IDO1 in PBMCs correlated positively with IL-6, regulatory T-cells and CD56bright NK-cells, whereas negative correlations to cytotoxic T-cells and CD56dim NKcells were revealed. A significant time effect on KYN/TRP ratio was detected for RE. Regarding KA and KA/KYN ratio, an increase after exercise followed by a decrease at the follow- up measurement was revealed in EE. KAT4 expression also increased after exercise in EE. Moreover, elevated QA levels were observed after the EE session.
CONCLUSIONS:
In contrast to chronic exercise interventions, single-bouts of endurance exercise provoke acute alterations on KYN pathway outcomes in humans. Our results indicate that EE induces stronger alterations than RE. Enhanced conversion of KYN to both, KA and QA suggest a peripheral KYN clearance, thereby preventing pathological accumulation within the CNS. Future acute and chronic exercise studies are needed to examine the role of NAD+ synthesis starting with TRP and the interplay between KYN pathway activation and mid- to long-term immunological modulations.
Copyright © 2020 International Society of Exercise and Immunology. All rights reserved.
KEYWORDS:
Endurance exercise; Exercise; Immune system; Kynurenine pathway; Resistance exercise
4.
PLoS One. 2019 Dec 20;14(12):e0226570. doi: 10.1371/journal.pone.0226570. eCollection 2019.
Luminescent and fluorescent triple reporter plasmid constructs for Wnt, Hedgehog and Notch pathway.
Abstract
Tracking the activity of signalling pathways is a fundamental method for basic science, as well as in cancer- and pharmaceutical research. The developmental pathways Wnt, Hedgehog and Notch are frequently deregulated in cancers and represent a valuable target for the discovery of novel anticancer compounds. Here we present reporter systems for tracking activity of these pathways by using specific promoter elements driving the expression of either sensitive luciferases or fluorescent proteins. A high level of sensitivity was obtained using the luciferase reporter genes for firefly (FLuc), secreted Gaussia (GLuc) and synthetic NanoLuc (NLuc). As fluorescent reporter proteins, mTurqouise2, tdTomato and iRFP720 were chosen. Specificity of pathway activity was validated by co-transfection with pathway activating genes, showing significant response to induction. In addition, multi-gene plasmids were cloned, allowing the detection of all three pathways by one vector. By using the multi-gene vector 3P-Luc (wnt-NLuc, hedgehog-FLuc, Notch-GLuc), we could unambiguously demonstrate the crosstalk between pathways, while excluding cross reactivity of luciferase substrates. First studies with synthetic compounds confirmed the applicability of the system for future drug screening approaches.
- PMID:
- 31860685
- PMCID:
- PMC6924688
- DOI:
- 10.1371/journal.pone.0226570
- [Indexed for MEDLINE]
5.
Future Oncol. 2019 Nov;15(31):3547-3554. doi: 10.2217/fon-2019-0115. Epub 2019 Oct 30.
A Phase I/Ib trial of Ad-REIC in liver cancer: study protocol.
Oyama A1, Shiraha H1, Uchida D1, Iwamuro M2, Kato H1, Takaki A1, Ikeda F1, Onishi H1, Yasunaka T1, Takeuchi Y1, Wada N1, Iwasaki Y1, Sakata M1, Okada H1, Kumon H3.
Abstract
This study will assess the safety and efficacy of the administration of adenoviral vector expressing the human-reduced expression in immortalized cells (Ad-REIC) to a liver tumor in patients with hepatocellular carcinoma (HCC) or liver metastasis of pancreatic cancer. A Phase I clinical study of Ad-REIC administration to a liver tumor in a patient with HCC or liver metastasis of pancreatic cancer will be conducted. The study is a single-arm, prospective, nonrandomized, noncomparative, open-label, single-center trial performed in Okayama University Hospital, Okayama, Japan. Ad-REIC will be injected into the liver tumor under ultrasound guidance. Ad-REIC administration will be repeated a total of three-times every 2 weeks. The primary end point is the dose-limiting toxicity and incidence of adverse events. The secondary end points are the objective response rate and disease control rate. This study aims to expand the indication of Ad-REIC by assessing its safety and efficacy in patients with HCC or liver metastasis of pancreatic cancer.
KEYWORDS:
DKK-3; gene therapy; hepatic cancer; liver metastasis; pancreatic ductal adenocarcinoma; prognosis; targeted treatment
6.
Future Oncol. 2019 Nov;15(31):3597-3608. doi: 10.2217/fon-2019-0233. Epub 2019 Oct 29.
Journal retractions in oncology: a bibliometric study.
Abstract
Aim: To investigate secular trends in article retractions in the oncology literature, particularly relating to cancer treatments and data available to patients. Methods: A bibliometric analysis of article retractions from PubMed in the period 2000-2018. Results: Analysis shows that article lifetime - that is the time period from initial publication to ultimate retraction - has decreased in recent years. It also shows that the retraction rate has also increased over the same period. Furthermore, over 20% of retracted oncology publications analyzed in this study relate to treatment-relevant topics such as clinical trials and studies in the anticancer properties of supplements. Conclusion: The causes and context of these trends are discussed and reference made to the dangers of scientific misconduct in oncology.
KEYWORDS:
article retractions; oncology retractions; patient information; pseudoscience; science publishing; scientific fraud; scientific misconduct
7.
Future Oncol. 2019 Nov;15(31):3633-3646. doi: 10.2217/fon-2019-0279. Epub 2019 Oct 25.
Efficacy of immune checkpoint inhibitors in cancer patients of different ages: a meta-analysis.
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
8.
Future Oncol. 2019 Nov;15(31):3579-3585. doi: 10.2217/fon-2019-0319. Epub 2019 Oct 25.
Interaction of 22 risk SNPs with Helicobacter pylori infection and risk of gastric cardia adenocarcinoma.
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
9.
Future Oncol. 2019 Nov;15(31):3527-3530. doi: 10.2217/fon-2019-0523. Epub 2019 Oct 25.
Perspectives of lung cancer control and molecular prevention.
KEYWORDS:
biomarker; carcinogenesis; lung; molecular prevention; precision genomics; screening and cancer control
10.
Cancer Biother Radiopharm. 2019 Nov;34(9):597-603. doi: 10.1089/cbr.2019.3049. Epub 2019 Oct 23.
Melanoma-Targeting Property of Y-90-Labeled Lactam-Cyclized α-Melanocyte-Stimulating Hormone Peptide.
Abstract
Purpose: The purpose of this study was to evaluate melanoma-targeting property of 90Y-DOTA-GGNle-CycMSHhex to facilitate its potential therapeutic application. Materials and Methods: DOTA-GGNle-CycMSHhex was synthesized and readily labeled with 90Y in 0.25 M NH4Ac-buffered solution to generate 90Y-DOTA-GGNle-CycMSHhex. The specific receptor binding, internalization, and efflux of 90Y-DOTA-GGNle-CycMSHhex were determined on B16/F10 murine melanoma cells. The biodistribution property of 90Y-DOTA-GGNle-CycMSHhex was examined on B16/F10 melanoma-bearing C57 mice. Results: 90Y-DOTA-GGNle-CycMSHhex displayed receptor-specific binding, rapid internalization, and prolonged efflux on B16/F10 melanoma cells. 90Y-DOTA-GGNle-CycMSHhex exhibited high uptake and prolonged retention in melanoma, and fast urinary clearance on B16/F10 melanoma-bearing C57 mice. The B16/F10 tumor uptake was 20.73% ± 7.99%, 19.93% ± 5.73%, 14.8% ± 4.61%, and 6.69% ± 1.85% ID/g at 0.5, 2, 4, and 24 h postinjection, respectively. Conclusions: 90Y-DOTA-GGNle-CycMSHhex displayed melanocortin-1 receptor (MC1R) targeting and specificity on B16/F10 melanoma cells and tumors. The favorable melanoma-targeting property and fast urinary clearance of 90Y-DOTA-GGNle-CycMSHhex warranted its evaluation for melanoma therapy in future studies.
KEYWORDS:
90Y-DOTA-GGNle-CycMSHhex; melanocortin-1 receptor; melanoma therapy
- PMID:
- 31644317
- PMCID:
- PMC6856944
- [Available on 2020-11-01]
- DOI:
- 10.1089/cbr.2019.3049
- [Indexed for MEDLINE]
11.
BMC Pulm Med. 2019 Oct 15;19(1):177. doi: 10.1186/s12890-019-0951-2.
Combined pulmonary fibrosis and emphysema and idiopathic pulmonary fibrosis in non-small cell lung cancer: impact on survival and acute exacerbation.
Moon SW1, Park MS1, Kim YS1, Jang J1, Lee JH2, Lee CT2, Chung JH3, Shim HS4, Lee KW3, Kim SS5, Lee SH6, Yoon HI7.
Abstract
BACKGROUND:
In non-small cell lung cancer (NSCLC) patients, concomitant idiopathic pulmonary fibrosis (IPF) and emphysema (CPFE) are independently related to poor survival. CPFE is a condition with features of both pulmonary fibrosis and emphysema. Here, we evaluated the effect of CPFE and IPF alone on the outcomes of NSCLC patients.
PATIENTS AND METHODS:
We retrospectively evaluated 283 patients with CPFE or IPF who were diagnosed with NSCLC between November 2003 and February 2018 at two tertiary care hospitals in South Korea. Patients were classified into CPFE and IPF groups according to chest computed tomography findings.
RESULTS:
One-hundred-and-seven patients (37.8%; mean age: 70.1 years; men 97.2%) had CPFE. Compared with IPF patients, CPFE patients had a heavier smoking history; lower diffusing capacity of carbon monoxide (78.0% vs 64.8%, p < 0.001), and lower forced expiratory volume in 1 s. Of all patients with NSCLC, 71.7% overall died during the follow-up period; 71.6% died in the CPFE group and 72.0% in the IPF group. Multivariate logistic regression analysis showed that CPFE (odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.09-4.69; P = 0.029) was significantly correlated with acute exacerbations (AEs). In a Cox proportional hazards analysis, stage > III NSCLC, higher Eastern Cooperative Oncology Group performance status, and higher gender-age-physiology index score was related to higher mortality. However, CPFE was not related to a higher mortality rate in univariate (hazard ratio [HR]: 1.00; 95% CI: 0.75-1.32, P = 0.972) or multivariate analysis (HR: 0.89; 95% CI: 0.66-1.21, P = 0.466).
CONCLUSIONS:
AE risk, but not all-cause mortality, was higher in patients with CPFE and NSCLC than in those with IPF and NSCLC. Physicians should be aware of the exaggerated risk of AE in patients with concomitant CPFE and NSCLC.
KEYWORDS:
Acute exacerbation; Combined pulmonary fibrosis and emphysema (CPFE); Idiopathic pulmonary fibrosis; Mortality; Non-small cell lung cancer
- PMID:
- 31615505
- PMCID:
- PMC6792261
- DOI:
- 10.1186/s12890-019-0951-2
- [Indexed for MEDLINE]
12.
Future Oncol. 2019 Nov;15(31):3565-3578. doi: 10.2217/fon-2019-0193. Epub 2019 Sep 20.
The role of obinutuzumab in the management of follicular lymphoma.
Abstract
The outcomes for follicular lymphoma (FL) have improved significantly in recent years. This has been driven by an improved understanding of the pathobiology of FL and the development of therapeutic anti-CD20 antibodies. Combining rituximab with chemotherapy, coupled with its use as maintenance therapy, has contributed to significant improvements in disease control and progression-free survival. However, FL remains incurable and almost all patients invariably relapse. Therefore, there remains a need to develop novel therapeutic options and optimize existing regimens. Obinutuzumab (a first-in-class, glycoengineered, humanized type 2 anti-CD20 antibody) has been evaluated in a number of clinical trials. In this review, we will summarize the evaluable results of clinical trials investigating the efficacy of obinutuzumab in the treatment of FL.
KEYWORDS:
clinical trials; drug development; follicular lymphoma; immunotherapy
13.
Future Oncol. 2019 Nov;15(31):3609-3617. doi: 10.2217/fon-2019-0377. Epub 2019 Sep 13.
Predicting lymph node metastasis in early gastric cancer patients: development and validation of a model.
Abstract
Aim: To develop and validate a model to predict possibility of lymph node metastasis (LNM) in early gastric cancer. Materials & methods: An LNM prediction model was developed by logistic regression based on the demographics or characteristics of the tumor (N = 746) and then internally and externally validated (N = 126). Results: Four variables, lymphovascular invasion, differentiated types, diameter of tumor and T stage were screened into the model. The area under the receiver-operating characteristic curve of the model was 0.861 (95% CI: 0.851-0.864) in internal validation and 0.911 (95% CI: 0.848-0.974) in the validation set. Conclusion: The model shows excellent discrimination and calibration performance, and is potential to be a useful clinical model to predict the risk of LNM in early gastric cancer.
KEYWORDS:
early gastric cancer; lymph node metastasis; nomogram; predictive model
14.
Future Oncol. 2019 Nov;15(31):3531-3545. doi: 10.2217/fon-2019-0373. Epub 2019 Sep 13.
Glasdegib plus intensive/nonintensive chemotherapy in untreated acute myeloid leukemia: BRIGHT AML 1019 Phase III trials.
Cortes JE1, Dombret H2, Merchant A3, Tauchi T4, DiRienzo CG5, Sleight B5, Zhang X5, Leip EP5, Shaik N5, Bell T5, Chan G5, Sekeres MA6.
Abstract
Glasdegib, an oral Hedgehog pathway inhibitor, has been associated with significantly improved survival when combined with low-dose cytarabine in patients with untreated acute myeloid leukemia (AML) who were unsuitable for intensive chemotherapy, when compared with low-dose cytarabine alone. BRIGHT AML 1019 (NCT03416179) comprises two independently powered Phase III, randomized (1:1), double-blind global trials evaluating oral glasdegib 100 mg once daily or placebo plus one of two standard chemotherapy regimens in adults with untreated AML. The intensive trial combines glasdegib/placebo with cytarabine and daunorubicin (7 + 3), while the nonintensive trial combines glasdegib/placebo with azacitidine. The primary end point of both studies is overall survival. Secondary end points include response, time to and duration of response, event-free survival, safety, patient-reported outcomes and pharmacokinetics. Trial registration number: ClinicalTrials.gov identifier: NCT03416179.
KEYWORDS:
Hedgehog signaling pathway; acute myeloid leukemia; glasdegib; intensive chemotherapy; myelodysplastic syndrome; nonintensive chemotherapy; smoothened inhibitor
15.
Future Oncol. 2019 Nov;15(31):3555-3563. doi: 10.2217/fon-2019-0380. Epub 2019 Sep 9.
GENESIS: Phase III trial evaluating BL-8040 + G-CSF to mobilize hematopoietic cells for autologous transplant in myeloma.
Abstract
Effective hematopoietic cell transplantation relies upon collecting adequate numbers of CD34+ hematopoietic stem cells, typically from peripheral blood. A minimum of ≥2 × 106 CD34+ cells/kg are necessary, while transplants of ≥5-6 × 106 CD34+ cells/kg are associated with improved hematopoietic recovery. Granulocyte colony stimulating factor (G-CSF) remains the gold standard for hematopoietic stem cell mobilization. However, in randomized trials for autologous-hematopoietic cell transplantation in multiple myeloma, approximately 45% of patients remain unable to optimally mobilize with G-CSF alone despite multiple injections and apheresis days. Therefore, reducing mobilization failures remains an unmet need. The study objective is to evaluate the superiority of one dose of BL-8040 plus G-CSF over placebo plus G-CSF to mobilize ≥6.0 × 106 CD34+ cells/kg in up to two apheresis days. ClinicalTrials.gov: NCT03246529.
KEYWORDS:
CXCR4/SDF-1 signaling; apheresis; autologous hematopoietic cell transplantation; multiple myeloma; stem cell mobilization
16.
Future Oncol. 2019 Nov;15(31):3587-3596. doi: 10.2217/fon-2019-0406. Epub 2019 Sep 4.
Automated extraction of treatment patterns from social media posts: an exploratory analysis in renal cell carcinoma.
Abstract
Aim: The use of health-related social media forums by patients is increasing and the size of these forums creates a rich record of patient opinions and experiences, including treatment histories. This study aimed to understand the possibility of extracting treatment patterns in an automated manner for patients with renal cell carcinoma, using natural language processing, rule-based decisions, and machine learning. Patients & methods: Obtained results were compared with those from published observational studies. Results: 42 comparisons across seven therapies, three lines of treatment, and two-time periods were made; 37 of the social media estimates fell within the variation seen across the published studies. Conclusion: This exploratory work shows that estimating treatment patterns from social media is possible and generates results within the variation seen in published studies, although further development and validation of the approach is needed.
KEYWORDS:
natural language processing; oncology; social-media; treatment patterns
17.
Clin Lung Cancer. 2019 Nov;20(6):461-468.e2. doi: 10.1016/j.cllc.2019.05.015. Epub 2019 Jul 4.
Predictors of Respiratory Decline Following Stereotactic Ablative Radiotherapy to Multiple Lung Tumors.
Abstract
INTRODUCTION:
Stereotactic ablative radiotherapy (SABR) is highly effective at controlling early stage primary lung cancer and lung metastases. Although previous studies have suggested that treating multiple lung tumors with SABR is safe, post-treatment changes in respiratory function have not been analyzed in detail.
PATIENTS AND METHODS:
We retrospectively identified patients with 2 or more primary lung cancers or lung metastases treated with SABR and analyzed clinical outcomes and predictors of toxicity. We defined a composite respiratory decline endpoint to include increased oxygen requirement, increased dyspnea scale, or death from respiratory failure not owing to disease progression.
RESULTS:
A total of 86 patients treated with SABR to 203 lung tumors were analyzed. A total of 21.8% and 41.8% of patients developed composite respiratory decline at 2 and 4 years, respectively. When accounting for intrathoracic disease progression, 12.7% of patients developed composite respiratory decline at 2 years. Of the patients, 7.9% experienced grade 2 or greater radiation pneumonitis. No patient- or treatment-related factor predicted development of respiratory decline. The median overall survival was 46.9 months, and the median progression-free survival was 14.8 months. The cumulative incidence of local failure was 9.7% at 2 years.
CONCLUSION:
Although our results confirm that SABR is an effective treatment modality for patients with multiple lung tumors, we observed a high rate of respiratory decline after treatment, which may be owing to a combination of treatment and disease effects. Future studies may help to determine ways to avoid pulmonary toxicity from SABR.
Copyright © 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
Dyspnea; Lung metastases; Radiation therapy; Synchronous primary lung cancer; Toxicity
18.
Clin Lung Cancer. 2019 Nov;20(6):477-483. doi: 10.1016/j.cllc.2019.06.005. Epub 2019 Jun 14.
A Population-Based Study of Incidence and Survival of 1588 Thymic Malignancies: Results From the California Cancer Registry.
Abstract
BACKGROUND:
Thymic malignancies are rare and there are limited contemporary population-based epidemiological studies for this uncommon cancer.
PATIENTS AND METHODS:
Adults aged 20 years and older diagnosed with thymic malignancies between 1988 and 2015 were identified from the California Cancer Registry (n = 1588). Trends in age-adjusted incidence rates were examined overall and according to race/ethnicity, and the proportion diagnosed according to stage was evaluated over time. Cox proportional hazards regression was used to estimate hazard ratios (HRs) for overall survival (OS), and Fine and Gray competing risks regression for cause-specific survival (CSS).
RESULTS:
Age-adjusted incidence increased on average 2.08% per year over the study period (95% confidence interval [CI], 1.30%-2.86%; P < .0001), with an incidence of 0.277 cases per 100,000 in 2015. Incidence was highest among Asian/Pacific Islander and non-Hispanic black individuals. The proportion of unknown stage at diagnosis declined as localized diagnoses increased over time. Compared with patients with thymoma, those with thymic carcinoma had significantly worse OS (HR, 1.63; 95% CI, 1.33-2.01; P < .0001) and CSS (subdistribution HR, 2.99; 95% CI, 2.29-3.91; P < .0001). Advanced stage at diagnosis was also associated with worse survival. Surgical intervention was associated with better prognosis for patients with localized (HR, 0.08; 95% CI, 0.02-0.30; P = .0002) or regional disease (HR, 0.14; 95% CI, 0.06-0.34; P < .0001).
CONCLUSION:
Thymic malignancy incidence is increasing in California. There was incidence variation across race/ethnicity, which warrants future study. These findings provide contemporary insight into the incidence and prognostic factors of thymic malignancies.
Copyright © 2019 Elsevier Inc. All rights reserved.
KEYWORDS:
California; Cancer registry; Epidemiology; Thymic carcinoma; Thymoma
19.
Clin Mol Hepatol. 2019 Jun;25(2):190-198. doi: 10.3350/cmh.2018.0087. Epub 2019 Mar 22.
Evaluation of bioenergetic and mitochondrial function in liver transplantation.
Abstract
BACKGROUND/AIMS:
We measured changes in mitochondrial function and bioenergetics that occur during ischemia/ reperfusion in fresh liver samples of patients undergoing liver transplantation. These variations correlated with markers of liver function and clinical outcome. Ischemia/reperfusion injury related to liver transplantation affects mitochondrial function and bioenergetics. Experimental studies were conducted to identify the role of bioenergetics and mitochondrial dysfunction. To the best of our knowledge, no investigation of these two factors' impacts on liver transplantation has been performed.
METHODS:
This was a prospective study of 28 patients who underwent liver transplantation. We measured parameters of mitochondrial function and bioenergetics in biopsies performed during the procedure.
RESULTS:
We observed a statistically significant reduction in mitochondrial membrane potential, an increase in lag phase, and decreases in mitochondrial respiration and adenosine triphosphate content (P<0.010). Higher postoperative aminotransferase peaks correlated with worse mitochondrial function; mitochondrial respiration correlated with arterial lactate (P<0.010).
CONCLUSION:
There is a relationship between mitochondrial function and ischemia/reperfusion injury. The future use of these clinical markers as prognostic factors may allow early identification of post-transplant liver failure and may indicate the need to perform a new transplant.
KEYWORDS:
Adenosine triphosphate (ATP); Ischemia; Liver extracts; Liver transplantation; Mitochondria
20.
Thorac Cancer. 2019 Apr;10(4):585-586. doi: 10.1111/1759-7714.13012. Epub 2019 Feb 28.
Immunotherapy in non-small cell lung cancer: The past, the present, and the future.
- PMID:
- 30821103
- PMCID:
- PMC6449275
- DOI:
- 10.1111/1759-7714.13012
- [Indexed for MEDLINE]
21.
Clin Oncol (R Coll Radiol). 2019 Apr;31(4):232-241. doi: 10.1016/j.clon.2019.01.006. Epub 2019 Feb 2.
Clinical Outcomes and Prognostic Features of Angiosarcoma: Significance of Prior Radiation Therapy.
Abstract
AIMS:
Angiosarcoma is a rare and aggressive malignancy with a poor prognosis. There is limited literature describing prognostic factors and guidelines for treatment. We aim to describe outcomes in angiosarcoma, including the impact of patient-, tumour- and treatment-related factors on prognosis.
MATERIALS AND METHODS:
Patients with non-metastatic angiosarcoma diagnosed between 2008 and 2017 were retrospectively reviewed. Univariable and multivariable Cox proportional hazards methods were used to evaluate factors associated with locoregional recurrence, distant failure and overall survival. The Kaplan-Meier method and log-rank statistics were used to compare outcomes among patients with and without a history of prior radiation therapy.
RESULTS:
The cohort included 65 patients. The median age at diagnosis was 68 years (35-93). Nineteen patients had a history of receiving prior radiation therapy at the anatomic location of their angiosarcoma. Treatment modalities included surgery (n = 19), surgery + radiation therapy (n = 12), surgery + chemotherapy (n = 8), chemotherapy + radiation therapy (n = 7) and all three modalities (n = 14). The median follow-up was 18 (2-192) months. The 2-year locoregional control, distant control and overall survival were 61.8, 63.6 and 58.9%, respectively. On multivariable analysis, a history of previous radiation therapy was associated with inferior outcomes with respect to locoregional recurrence (hazard ratio 89.67, 95% confidence interval 8.45-951.07, P < 0.001), distant failure (hazard failure 3.74, 95% confidence interval 1.57-8.91, P = 0.003) and overall survival (hazard ratio 3.89, 95% confidence interval 1.56-9.60, P = 0.003). In patients with primary angiosarcoma, the rates of locoregional control, distant control and overall survival were 72.4, 73.4 and 65.1%, respectively, compared with 31.9, 41.1 and 45.1% in patients with radiation therapy-induced angiosarcoma (P = 0.001).
CONCLUSION:
Angiosarcomas that arise as a result of previous radiation therapy have worse outcomes compared with primary angiosarcomas. Although selection bias and compromise of clinical care in radiation therapy-induced angiosarcoma are partially to blame, differences in genomic profiles of the tumours need to be characterised to evaluate the underlying biological differences, as this may guide future treatment management. This study adds to the existing body of literature on angiosarcoma. Results from the current study are presented alongside previously published data to further characterise outcomes and prognostic factors on this rare and aggressive malignancy.
Copyright © 2019 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
KEYWORDS:
Angiosarcoma; primary angiosarcoma; radiation therapy; secondary angiosarcoma
22.
Curr Treat Options Oncol. 2019 Feb 4;20(1):9. doi: 10.1007/s11864-019-0605-x.
Blastic Plasmacytoid Dendritic Cell Neoplasm.
Abstract
While there is a high initial response rate with standard chemotherapeutic regimens for blastic plasmacytoid dendritic cell neoplasm (BPDCN), the responses are typically not durable and this remains a very aggressive disease with generally poor outcomes. For this reason, the standard approach for eligible patients has been high-dose induction chemotherapy preferably with acute lymphoblastic leukemia (ALL)-based regimens followed by consolidation with allogeneic hematopoietic stem cell transplantation (alloHSCT). Unfortunately, many patients with this disease are elderly and/or frail and cannot tolerate this therapy, and the low-dose regimens being used in this population are generally not as effective. However, this paradigm may be changing with the advent of newer targeted therapies, particularly the exploitation of CD123. SL-401 has shown very promising results with manageable toxicities and durable responses and appears to be a viable option for elderly or frail patients who are not eligible for transplant. The other CD123-directed therapies, especially chimeric antigen receptor-therapy (CAR-T), may also give promising results in trials that are currently underway. CAR-T has shown promise in a number of other hematologic malignancies, and toxicities have become more manageable as its use is becoming more widespread. While SL-401 has shown potential to provide durable responses even without transplant, we do not yet know whether it will be effective as a means to avoid transplant in patients who are otherwise eligible. All transplant-eligible patients should undergo alloHSCT consolidation given the current available data indicating this is the optimal approach to achieve a long-term remission. Once the CD123-directed therapies are established as standard regimens, future studies may be designed to investigate whether these therapies can be utilized without the use of transplant. Furthermore, combination therapy using anti-CD123 agents with high-dose induction chemotherapy or other low-dose regimens for elderly/frail patients should be investigated. Given the promising results in early clinical trials, it appears CD123 is the most viable target for BPDCN, and future studies should continue to exploit its expression on BPDCN cells.
KEYWORDS:
BPDCN; Bone marrow transplant; CD123; Leukemia; SL-401; Venetoclax
23.
Curr Treat Options Oncol. 2019 Jan 24;20(1):7. doi: 10.1007/s11864-019-0607-8.
Targeted Therapy and Immunotherapy for Melanoma in Japan.
Abstract
Melanoma has several clinically and pathologically distinguishable subtypes, which also differ genetically. Mutation patterns vary among different melanoma subtypes, and efficacy of immune-checkpoint inhibitors differs depending on the subtype of melanoma. In spite of the recent revolution of systemic therapies for advanced melanoma, access to innovative agents is still restricted in many countries. This review article aimed to describe the epidemiology and current status of systemic therapies for melanoma in Japan, where melanoma is rare, but access to innovative agents is available. Acral and mucosal melanomas, which are common in Asian populations, predominantly occur in sun-protected areas and share several biological features. Both the melanomas harbor KIT mutation in approximately 15% of the cases; BRAF or NRAS mutation is found in approximately 10-15% of acral melanoma, but these mutations are less frequent in mucosal melanoma. Combined use of BRAF and MEK inhibitors is one of the standards of care for patients with advanced BRAF-mutant melanoma. In patients with melanoma harboring KIT mutation in exon 11 or 13, KIT inhibitors can be a treatment option; however, none of them have been approved in Japan. Immune-checkpoint inhibitors are expected to be less effective against acral and mucosal melanomas because their somatic mutation burden is lower than those in non-acral cutaneous melanomas. A recently completed phase II trial of nivolumab and ipilimumab combination therapy in 30 Japanese patients with melanoma, including seven with acral and 12 with mucosal melanoma, demonstrated an objective response rate of 43%. Regarding oncolytic viruses, canerpaturev (C-REV, also known as HF10) and talimogene laherparepvec (T-VEC) are currently under review in early phase trials. In the adjuvant setting, dabrafenib plus trametinb combination, nivolumab monotherapy, and pembrolizumab monotherapy were approved in July, August, and December 2018 in Japan, respectively. However, most of the adjuvant phase III trials excluded patients with mucosal melanoma. A phase III trial of adjuvant therapy with locoregional interferon (IFN)-β versus surgery alone is ongoing in Japan (JCOG1309, J-FERON), in which IFN-β is injected directly into the site of the primary tumor postoperatively, so that it would be drained through the untreated lymphatic route to the regional node basin. After the recent approval of these new agents, the JCOG1309 trial will be revised to focus on patients with stage II disease. In conclusion, acral and mucosal melanomas have been treated based on the available medical evidence for the treatment of non-acral cutaneous melanomas. Considering the differences in genetic backgrounds and therapeutic efficacy of immunotherapy, specialized therapeutic strategies for these subtypes of melanoma should be established in the future.
KEYWORDS:
Acral; Asian; Immunotherapy; Melanoma; Mucosal; Targeted therapy
- PMID:
- 30675668
- PMCID:
- PMC6344396
- DOI:
- 10.1007/s11864-019-0607-8
- [Indexed for MEDLINE]
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