scholarly journals A Pilot Clinical Study on the Prognostic Relevance of Plasmatic Exosomes Levels in Oral Squamous Cell Carcinoma Patients

Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 429 ◽  
Author(s):  
Samuel Rodríguez Zorrilla ◽  
Mario Pérez-Sayans ◽  
Stefano Fais ◽  
Mariantonia Logozzi ◽  
Mercedes Gallas Torreira ◽  
...  

Background: To evaluate the relationship between the plasmatic CD63 and CAV1 positive exosome levels, in patients with OSCC before and after surgical treatment and to correlate it with their overall survival. Methods: A double-blind pilot study over 10 patients OSCC and T4 stage without distant metastases or local bone invasion has been performed. The average follow-up period was 37.64 months (34.3–40.84). We obtained 2 plasma tubes of 1 mL each before surgery and 7 days after surgery. Before performing the immunocapture-based analysis, EVs (Extracellular Vesicles) were isolated from the plasma and characterized with western blot analysis. Results: Mean values of CD63 positive plasmatic exosomes (EXO-CD63) after surgery decreased from 750.88 ± 286.67 to 541.71 ± 244.93 (p = 0.091). On the other hand, CAV-1 positive plasmatic exosomes (EXO-CAV-1) increased after surgery from 507 ± 483.39 to 1120.25 ± 1151.17 (p = 0.237). Patients with EXO-CD63 levels lower than the mean global value before the surgery had a survival of 36.04 months compared with the group with EXO-CD63 higher than the average who only survived 12.49 ± 1.67 months from the diagnosis, p = 0.225. When EXO-CAV-1 levels before surgery was lower than the average (813.94 ± 801.21) overall survival was 24.69 ± 22.23 months in contrast when it was higher that was only 11.64 months, p = 0.157. Patients with lower EXO-CD63 levels after surgery lived an average of 23.84 ± 23.9 months, while those with higher plasmatic levels of EXO-CD63 live 13.35 months, p = 0.808. When EXO-CAV-1 levels after surgery were lower, the average overall survival was 20.344 ± 15.40 months, in contrast when the EXO-CAV-1 levels were higher showing rather an estimate survival expectation of 1.64 months. Conclusions: Surgical treatment induced a dramatic reduction of the plasmatic levels of exosomes expressing CD63 as early as 1 week after resection. This first result suggests that the tumour mass is responsible of the high levels of circulating exosomes detected in cancer patients. At the same time point exosome expressing CAV-1 increased, possibly due to the inflammatory reaction immediately after surgery. Lastly, statistical analysis showed that lower levels of plasmatic exosomes both before and after surgery correlated with a better life expectancy of OSCC patients. Hopefully, this approach will prove useful in the clinical follow-up of cancer patients.

2020 ◽  
Vol 93 (1108) ◽  
pp. 20190353 ◽  
Author(s):  
Chiara Lucrezia Deantoni ◽  
Andrei Fodor ◽  
Cesare Cozzarini ◽  
Claudio Fiorino ◽  
Chiara Brombin ◽  
...  

Objective: To evaluate toxicity and clinical outcome in synchronous bone only oligometastatic (≤2 lesions) prostate cancer patients, simultaneously irradiated to prostate/prostatic bed, lymph nodes and bone metastases. Methods: From 2/2009 to 6/2015, 39 bone only prostate cancer patients underwent radiotherapy (RT) at “radical” doses to bone metastases (median 2 Gy equivalent dose, EQD2>40Gy, α/β = 1,5), nodes, and prostate/prostatic bed, within the same RT course, in association with androgen deprivation therapy (ADT). Biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were evaluated. Results: After a median follow-up of 46.5 (1.2–103.6) months, 5 patients died from disease progression, 10 experienced biochemical relapse, 19, still in ADT, presented undetectable prostate-specific antigen (PSA) at the last follow-up. Five patients who discontinued ADT after a median of 34 months (5.8–41) are free from biochemical relapse. The 4 year Kaplan–Meier estimates of biochemical relapse-free survival, clinical relapse-free survival, freedom from distant metastases and overall survival were 53.3%, 65.7%, 73.4% and 82.4% respectively. No Grade > 2 acute events and only two severe late urinary events were recorded, not due to the concomitant treatment of primary and metastatic disease. Conclusion: Our results suggest that “radical” and synchronous irradiation of primitive tumor and metastatic disease may be a valid approach in synchronous bone only prostate cancer patients, showing mild toxicity profile and promising survival results. Advances in knowledge: To the best of our knowledge, this is the first analysis of clinical outcome in synchronous bone-only metastasis (neither nodal nor visceral) patients at diagnosis, treated with radical RT to all disease, associated to ADT.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 79-79
Author(s):  
Kazuki Sudo ◽  
Takashi Taketa ◽  
Arlene M. Correa ◽  
Maria-Claudia Campagna ◽  
Roopma Wadhwa ◽  
...  

79 Background: For local-regional E-EGJ cancer patients, the preferred therapy is chemoradiation (CTRT) followed by surgery (TMT). Following TMT, esophagogastroduodenoscopy (EGD) and imaging studies are routinely performed but the literature lacks guidance for an evidence-based surveillance strategy. Methods: Between 2000 and 2010, 579 patients with local-regional E-EGJ cancer underwent TMT. We reviewed the patterns of relapse over time. Local-regional relapse was classified as regional or luminal-only. Overall survival was estimated by the Kaplan-Meier method. Results: For 579 patients, the median follow-up time was 57.4 months (95% confidence interval [CI]: 51.5-63.3 months). First relapses were as follows: 199 patients (34.4%) with distant metastases and 33 (5.7%) with local-regional relapse (of these only 10 [or 1.7% of 579] had a luminal-only relapse). 3 out of 33 patients underwent salvage surgery and survived >2 years from relapse. Sixteen out of 33 patients received CTRT and only 4 survived >2 years. Therefore, 7 (21% of patients with local-regional relapse or 1.2% of 579 patients) survived >2 years. For the 33 patients with local-regional relapse, the median overall survival from relapse was 15.3 months (95% CI: 11.0-19.6). Conclusions: After TMT therapy, local-regional relapses are uncommon (<6%) and luminal-only relapses are even rare (<2%). 91% of local-regional relapses occur within 3 years of surgery. Only 7 (1.2% of 579) patients survived > 2 years despite therapy. These data can contribute to an evidence-based surveillance strategy for E-EGJ cancer patients after TMT. Supported by UTMDACC and generous donors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Chieh Ho ◽  
Yuan-Chun Lai ◽  
Hsuan-Yu Lin ◽  
Ming-Hui Ko ◽  
Sheng-Hung Wang ◽  
...  

AbstractWe aimed to determine the prognostic significance of cardiac dose and hematological immunity parameters in esophageal cancer patients after concurrent chemoradiotherapy (CCRT). During 2010–2015, we identified 101 newly diagnosed esophageal squamous cell cancer patients who had completed definitive CCRT. Patients' clinical, dosimetric, and hematological data, including absolute neutrophil count, absolute lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR), at baseline, during, and post-CCRT were analyzed. Cox proportional hazards were calculated to identify potential risk factors for overall survival (OS). Median OS was 13 months (95% confidence interval [CI]: 10.38–15.63). Univariate analysis revealed that male sex, poor performance status, advanced nodal stage, higher percentage of heart receiving 10 Gy (heart V10), and higher NLR (baseline and follow-up) were significantly associated with worse OS. In multivariate analysis, performance status (ECOG 0 & 1 vs. 2; hazard ratio [HR] 3.12, 95% CI 1.30–7.48), heart V10 (> 84% vs. ≤ 84%; HR 2.24, 95% CI 1.26–3.95), baseline NLR (> 3.56 vs. ≤ 3.56; HR 2.36, 95% CI 1.39–4.00), and follow-up NLR (> 7.4 vs. ≤ 7.4; HR 1.95, 95% CI 1.12–3.41) correlated with worse OS. Volume of low cardiac dose and NLR (baseline and follow-up) were associated with worse patient survival.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7046-7046
Author(s):  
Ruben A. Mesa ◽  
Stephen T. Oh ◽  
Aaron Thomas Gerds ◽  
Vikas Gupta ◽  
John V. Catalano ◽  
...  

7046 Background: Momelotinib (MMB) is a potent JAK1, JAK2 and ACVR1 inhibitor with clinical activity against the hallmark features of myelofibrosis (MF), namely anemia, constitutional symptoms and splenomegaly, across the continuum of JAKi naïve or previously JAKi treated intermediate/high risk MF patients as demonstrated in the previously conducted Phase 3 SIMPLIFY-1 & -2 clinical trials (S1, S2). S1 enrolled JAKi-naïve patients with MF (n = 432) double-blind randomized 1:1 to MMB or ruxolitinib (RUX). S2 enrolled patients with MF with hematological toxicity during prior RUX therapy (n = 156) randomized 2:1 to open-label MMB or best available therapy (BAT; consisting of RUX in 88% of patients). In both trials, following the 24-week randomized treatment (RT) period, patients could continue MMB (MMB→MMB) and those randomized to RUX/BAT could cross-over to MMB (RUX/BAT→MMB) for extended treatment (ET). Previously published data from the SIMPLIFY studies demonstrate robust overall survival (OS) for MMB-treated patients in S1 and S2 (median not reached and 34.3 months, respectively) with a maximum follow up of approximately 5 years and median of 2.9 years in S1 and 2.3 years in S2. Methods: OS data for patients receiving MMB in S1 and S2 are reported here for subgroups defined by Week 24 (W24) transfusion independence (TI) responders vs non-responders, and also other efficacy endpoints. Survival was estimated using KM analysis with descriptive log-rank tests for comparison applied (all p-values are descriptive). Results: As previously reported, W24 TI rates were higher in the MMB arms of S1 (67% vs 49%) and S2 (43% vs 21%). In S1, W24 TI responders in the MMB group show an OS advantage, with median OS not reached and 3-year survival of 80% (HR = 0.30; p = 0.0001) compared to MMB TI non-responders. Similarly in S2, W24 TI responders in the MMB group show a trend toward better OS compared to TI non-responders (HR = 0.57; p = 0.0652). The HRs in S1 for MMB responders vs non-responders for W24 SRR and TSS were 0.59 (p = 0.0904) and 0.65 (p = 0.1657), respectively. Alternative analyses using OS defined from W24 demonstrated consistent results. Conclusions: These new analyses suggest JAKi naïve patients receiving MMB who maintain or achieve TI at W24 have favorable OS compared to MMB TI non-responders, with a similar trend observed in S2. These findings are consistent with anemia and transfusion dependency being key predictors of shortened OS in MF and suggest that TI response at W24 may become a surrogate for clinical benefit, supporting the clinical relevance of MMB’s differentiated pro-erythropoietic ACVR1 inhibition. Clinical trial information: NCT01969838.


2019 ◽  
Vol 23 (62) ◽  
pp. 1-94 ◽  
Author(s):  
Mark T Drayson ◽  
Stella Bowcock ◽  
Tim Planche ◽  
Gulnaz Iqbal ◽  
Guy Pratt ◽  
...  

Background Myeloma causes profound immunodeficiency and recurrent serious infections. There are approximately 5500 new UK cases of myeloma per annum, and one-quarter of patients will have a serious infection within 3 months of diagnosis. Newly diagnosed patients may benefit from antibiotic prophylaxis to prevent infection. However, the use of prophylaxis has not been established in myeloma and may be associated with health-care-associated infections (HCAIs), such as Clostridium difficile. There is a need to assess the benefits and cost-effectiveness of the use of antibacterial prophylaxis against any risks in a double-blind, placebo-controlled, randomised clinical trial. Objectives To assess the risks, benefits and cost-effectiveness of prophylactic levofloxacin in newly diagnosed symptomatic myeloma patients. Design Multicentre, randomised, double-blind, placebo-controlled trial. A central telephone randomisation service used a minimisation computer algorithm to allocate treatments in a 1 : 1 ratio. Setting A total of 93 NHS hospitals throughout England, Northern Ireland and Wales. Participants A total of 977 patients with newly diagnosed symptomatic myeloma. Intervention Patients were randomised to receive levofloxacin or placebo tablets for 12 weeks at the start of antimyeloma treatment. Treatment allocation was blinded and balanced by centre, estimated glomerular filtration rate and intention to give high-dose chemotherapy with autologous stem cell transplantation. Follow-up was at 4-week intervals up to 16 weeks, with a further follow-up at 1 year. Main outcome measures The primary outcome was to assess the number of febrile episodes (or deaths) in the first 12 weeks from randomisation. Secondary outcomes included number of deaths and infection-related deaths, days in hospital, carriage and invasive infections, response to antimyeloma treatment and its relation to infection, quality of life and overall survival within the first 12 weeks and beyond. Results In total, 977 patients were randomised (levofloxacin, n = 489; placebo, n = 488). A total of 134 (27%) events (febrile episodes, n = 119; deaths, n = 15) occurred in the placebo arm and 95 (19%) events (febrile episodes, n = 91; deaths, n = 4) occurred in the levofloxacin arm; the hazard ratio for time to first event (febrile episode or death) within the first 12 weeks was 0.66 (95% confidence interval 0.51 to 0.86; p = 0.002). Levofloxacin also reduced other infections (144 infections from 116 patients) compared with placebo (179 infections from 133 patients; p-trend of 0.06). There was no difference in new acquisitions of C. difficile, methicillin-resistant Staphylococcus aureus and extended-spectrum beta-lactamase Gram-negative organisms when assessed up to 16 weeks. Levofloxacin produced slightly higher quality-adjusted life-year gains over 16 weeks, but had associated higher costs for health resource use. With a median follow-up of 52 weeks, there was no significant difference in overall survival (p = 0.94). Limitations Short duration of prophylactic antibiotics and cost-effectiveness. Conclusions During the 12 weeks from new diagnosis, the addition of prophylactic levofloxacin to active myeloma treatment significantly reduced febrile episodes and deaths without increasing HCAIs or carriage. Future work should aim to establish the optimal duration of antibiotic prophylaxis and should involve the laboratory investigation of immunity, inflammation and disease activity on stored samples funded by the TEAMM (Tackling Early Morbidity and Mortality in Myeloma) National Institute for Health Research Efficacy and Mechanism Evaluation grant (reference number 14/24/04). Trial registration Current Controlled Trials ISRCTN51731976. Funding details This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 62. See the NIHR Journals Library website for further project information.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5506-5506
Author(s):  
Paolo Zola ◽  
Giovannino Ciccone ◽  
Elisa Piovano ◽  
Luca Fuso ◽  
Elena Peirano ◽  
...  

5506 Background: Intensive follow-up in cancer patients, which absorbs a lot of health system resources and can be a source of increased stress for patients, are often proposed on the assumption that an early recognition of relapse will translate in better outcomes. In endometrial cancer few randomized controlled trials were conducted to assess the role of a reduced number of the scheduled visits and of different settings of the follow-up, but did not investigate the contribution of routine serum, cytological or imaging follow-up investigations in improving overall survival or quality of life. The TOTEM study was planned to compare an intensive (INT) vs minimalist (MIN) 5- year follow-up regimen in endometrial cancer patients in terms of overall survival (OS). Methods: Patients surgically treated for endometrial cancer, in complete clinical remission confirmed by imaging, FIGO stage I-IV, were stratified by center and in low (LoR) or high (HiR) risk of recurrence and then randomized to INT or MIN hospital-based follow-up regimens. The main study hypothesis was to demonstrate an improvement from 75% to 80% (expected hazard ratio, HR = 0.78) of the 5-year OS with the INT regimen. Secondary objectives were to compare relapse free survival (RFS), health-related quality of life (HRQL) assessed at baseline, at 6 and 12 months and then yearly (with the SF-12 Physical and Mental Health Summary Scale) and costs. Results: 1884 patients were randomized in 42 centers between 2008 and 2018, and 1847 patients were available for the final analysis (60% LoR). Compliance with the follow-up scheduled visits was 75.3%, similar between INT (74.7%) and MIN (75.9%) arms, whereas the mean number of recorded exams (laboratory or imaging) was markedly higher in the INT than in the MIN arms (9.7 vs 2.9, p < 0.0001). After a median follow-up of 66 months, the overall 5-year OS was 91.3%, 90.6% in the INT and 91.9% in the MIN arms, respectively (HR = 1.12, 95%CI 0.85-1.48, p = 0.429). Comparing the INT vs MIN arms, the 5-year OS were 94.1% and 96.8% (HR = 1.48, 0.92-2.37, p = 0.104) in the LoR and 85.3% and 84.7% (HR = 0.96, 0.68-1.36, p = 0.814) in the HiR group. No relevant differences emerged in RFS between INT and MIN regimens, (HR = 1.13, 0.87-1.48, p = 0.365). At the time of the relapse most women were asymptomatic (146/228, 64.0%), with a tendency of higher proportions in the INT than in the MIN arm, both in the LoR group (78.8% vs 61.1%, p = 0.070) and in the HiR one (64% vs 60%, p = 0.754). HRQL was available only for a subgroup of patients (50% at baseline) and did not differ between arms. Conclusions: Intensive follow-up in endometrial cancer treated patients showed a weak and uncertain advantage in detecting earlier asymptomatic relapses but did not improve OS, even in HiR patients, nor influenced HRQL. Frequent routine use of imaging and laboratory exams in these patients should be discouraged. Clinical trial information: NCT00916708.


Author(s):  
A.P. Voznyuk ◽  
◽  
S.I. Anisimov ◽  
S.Y. Anisimova ◽  
L.L. Arutyunyan ◽  
...  

Purpose. To evaluate the efficacy and safety of femtolaser-assisted phacoemulsification in glaucomatous eyes in the long-term follow-up. Materials and methods. A retrospective analysis of the results of the surgical treatment of patients with combined cataract and glaucoma pathology was analyzed. The patients were divided into groups depending on the method of surgical intervention: 1) phacoemulsification with femtolaser support (26 eyes, 23 patients); 2) phacoemulsification (36 eyes, 30 patients); Results. Before surgery, there were no statistically significant differences in IOP and corneal hysteresis (СН) between groups 1 and 2. The mean values of IOP cc, IOP g and СН of group 1 before surgery were 22.7±6.1 mm Hg, 20.9±6.9 mm Hg, 8.5±1.6 mm Hg; 2 group – 22.9±8.7 mm Hg, 21.6±8.9 mm Hg, 8.9±1.6 mm Hg respectively. Average values of IOP cc, IOP g and CН 5 years after the surgical treatment in group 1 were 15.3±1.2 mm Hg, 14.4±3.4 mm Hg, 9.6±4.2 mm Hg; in group 2 – 18.0±4.2 mm Hg, 16.1±4.2 mm Hg, 8.8±2.2 mm Hg respectively. In both groups, stabilization of IOP and CH indices was noted, which remained throughout the entire observation period, which shows the normalization of the biomechanical properties of the corneoscleral membrane of the eye in the long-term postoperative period. Conclusion. Femtolaser accompaniment of phacoemulsification is an effective and safe method of cataract surgery for combined pathology. Key words: femtolaser, cataract, glaucoma, phacoemulsification.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
C. Eichler ◽  
C. Baucks ◽  
J. Üner ◽  
C. Pahmeyer ◽  
D. Ratiu ◽  
...  

Introduction. Literature shows platelet-rich plasma (PRP) to improve overall outcomes in orthopedics, dermatology, ophthalmology, gynecology, and plastic surgery. Data on oncological patients is very limited. Only one publication is available on PRP in breast cancer patients. This work evaluated PRP in sentinel node biopsy procedures for breast cancer patients in terms of complication rates and oncological short-term follow-up. Methods. The evaluated PRP was ACP®, i.e., autologous conditioned plasma by Arthrex®. Between 2015 and 2018, 163 patients were offered to receive an ACP®/PRP injection in their lymph node biopsy site. Recruitment resulted in an approximate one-to-one ratio for analysis. Endpoints were major (revision) and minor (seroma, hematoma, and infection) complications rates as well as distant metastases, local recurrence, and overall survival. Median follow-up was 30 months. Results. Complication rates and oncological follow-up showed PRP to be applicable to use in a sentinel node biopsy scenario in breast cancer patients. There were 0 revisions in the ACP®/PRP group and 1.2% revisions in the control group (not significant). Oncological follow-up showed zero (0) distant metastases and local recurrences as well as a 100% 30-month overall survival. Conclusions. This is the first analysis of ACP®/PRP used in breast cancer patients in a sentinel node biopsy setting worldwide. PRP does not seem to increase rates of local recurrence within this 30-month follow-up time frame. Also, trend towards decreasing complication rates could be shown.


2011 ◽  
Vol 65 (Suppl 1) ◽  
pp. A56-A57
Author(s):  
E. Bastiaannet ◽  
S. van de Velde ◽  
W. van de Water ◽  
M. Ernst ◽  
A. Voogd ◽  
...  

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