scholarly journals The Clinical Impact of MicroRNA-21 in Low Rectal Cancer Treated with High-Dose Chemoradiotherapy in the Organ Preserving Setting

2020 ◽  
Vol 2 (4) ◽  
pp. 378-384
Author(s):  
Caroline Brenner Thomsen ◽  
Rikke Fredslund Andersen ◽  
Lars Henrik Jensen ◽  
Anders Jakobsen ◽  
Torben Frøstrup Hansen

Background: Organ preservation in the treatment of rectal cancer has seen an increase in interest. Clinical complete response (cCR) after high-dose chemoradiotherapy (CRT) allows for non-surgical management (NSM), but the selection of patients is challenging and standard clinical staging insufficient. MicroRNA-21-5p (miR-21) is ubiquitously upregulated in cancer and has been associated with treatment response in rectal cancer treated with standard preoperative CRT. The aim of the present study was to investigate this association in low rectal cancer treated in the NSM setting. Methods: Forty-eight patients from our single-arm phase II trial (NCT00952926) were eligible for analysis. All patients had resectable T2 or T3, N0–N1 low adenocarcinoma and received intensity-modulated radiotherapy plus brachytherapy boost and oral tegafur–uracil. Patients with cCR six weeks after end of treatment assessed by clinical examination, magnetic resonance imaging, and biopsy, were referred to observation and close follow-up. The miR expression in the diagnostic biopsies was measured by qPCR. The relationship between miR-21 expression and cCR was assessed using the Wilcoxon rank-sum test. Results: Thirty-eight patients had cCR after treatment and were allocated to observation while 10 patients had incomplete response and underwent surgery. MicroRNA-21 was successfully analyzed in all samples. The median tumor expression of miR-21 was significantly higher in patients with incomplete response than in those with cCR, 24.3 (95% confidence interval (CI) 17.1–36.8) and 16.6 (95% CI 13.9–21.1), respectively, p = 0.03. Conclusions: The present study adds to the evidence of the clinical impact of miR-21 in rectal cancer treated with CRT. The findings are comparable with results seen in patients treated in the standard preoperative setting and may assist in the selection of patients for an organ preserving approach.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16120-e16120
Author(s):  
Torben Hansen ◽  
Caroline Brenner Thomsen ◽  
Rikke Fredslund Andersen ◽  
Lars Henrik Jensen ◽  
Anders Kristian Moeller Jakobsen

e16120 Background: Neoadjuvant chemoradiotherapy (CRT) in curatively intended doses may result in clinical complete response (cCR) in selected patients, allowing for non-surgical management (NSM) of patients with low rectal cancers. MicroRNA-21-5p (miR-21), ubiquitous upregulated in cancer, has been associated with treatment response in rectal cancers treated with standard preoperative CRT. The aim of the present study was to investigate this association in low rectal cancers treated in the NSM setting. Methods: Forty eight patients from our single-arm phase II trial (NCT00952926) were available for analyses. All patients had resectable, T2 or T3, N0–N1, low adenocarcinomas and received 65Gy (intensity-modulated radiotherapy plus brachytherapy boost) and oral tegafur-uracil. Patients with cCR 6 weeks after treatment (clinical examination, magnetic-resonance imaging and biopsy) were referred to observation and followed closely. The miR expression, in the diagnostic biopsies, was measured by qPCR in 20 µl reactions using TaqMan MicroRNA Assays. The protocol using custom RT and preamplification pools was followed. The miR-193a-5p, -27a and –let7g were used for normalization based on previous recommendations from our group. The relationship between miR-21 expression and cCR was assessed using the Wilcoxon rank-sum tests. Results: Thirty-eight patients achieved cCR after treatment and were followed in observation while 10 patients proceeded to surgery due to a non-cCR. MicroRNA-21 was successfully analyzed in all samples. The median tumor expression of miR-21 in patients proceeding to surgery was significantly higher compared to patients achieving cCR, 24.3 (95% confidence interval (CI) 17.1-36.8) and 16.6 (95% CI 13.9-21.1), p = 0.02, respectively. Conclusions: The present results support a clinical impact of miR-21 in rectal cancer treated with CRT, comparable with results seen in patients treated in the standard preoperative setting, and may assist in the selection of patients for an organ preserving approach.


2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Jessica A. Smith ◽  
Aaron T. Wild ◽  
Aatur Singhi ◽  
Siva P. Raman ◽  
Haoming Qiu ◽  
...  

Purpose. To assess for differences in clinical, radiologic, and pathologic outcomes between patients with stage II-III rectal adenocarcinoma treated neoadjuvantly with conventional external beam radiotherapy (3D conformal radiotherapy (3DRT) or intensity-modulated radiotherapy (IMRT)) versus high-dose-rate endorectal brachytherapy (EBT).Methods. Patients undergoing neoadjuvant EBT received 4 consecutive daily 6.5 Gy fractions without chemotherapy, while those undergoing 3DRT or IMRT received 28 daily 1.8 Gy fractions with concurrent 5-fluorouracil. Data was collected prospectively for 7 EBT patients and retrospectively for 25 historical 3DRT/IMRT controls.Results. Time to surgery was less for EBT compared to 3DRT and IMRT (P<0.001). There was a trend towards higher rate of pathologic CR for EBT (P=0.06). Rates of margin and lymph node positivity at resection were similar for all groups. Acute toxicity was less for EBT compared to 3DRT and IMRT (P=0.025). Overall and progression-free survival were noninferior for EBT. On MRI, EBT achieved similar complete response rate and reduction in tumor volume as 3DRT and IMRT. Histopathologic comparison showed that EBT resulted in more localized treatment effects and fewer serosal adhesions.Conclusions. EBT offers several practical benefits over conventional radiotherapy techniques and appears to be at least as effective against low rectal cancer as measured by short-term outcomes.


2021 ◽  
Author(s):  
Zekun Wang ◽  
Wenyang Liu ◽  
Jianghu Zhang ◽  
Xuesong Chen ◽  
Jingbo Wang ◽  
...  

Abstract Background There is sparse research reporting effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This phase Ⅱ trial was conducted to provide the direct evidence for the current practice of prescribing antiemetic in patients with LA-HNSCC receiving CCRT.Methods Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m² every 3 weeks for two cycles. All patients were given orally aprepitant 125 mg once on d1, then 80mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8mg on d2-5. The primary endpoint was complete response (CR). Pursuant to δ=0.2 and α=0.05, the expected CR rate was 80%. Results A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years old, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% CI: 72.1-94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9-96.1) and 89.2% (95% CI: 74.6-97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3-84.7). The emesis-free response and nausea-free response in overall phase were 88.4% (95% CI: 74.9-96.1) and 60.5% (95% CI: 44.4-75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1-2. There was no grade 4 or 5 treatment-related adverse event with antiemetic usage. Conclusion The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving radiotherapy and concomitant high-dose cisplatin chemotherapy. Randomised phase 3 studies are required to further define the potential role of NK1RA in chemoradiotherapy setting.Trial registration: ClinicalTrials.gov, number NCT03572829. Registered 28 June 2018, https://clinicaltrials.gov/ct2/show/NCT03572829?term=NCT03572829&draw=2&rank=1.


2021 ◽  
Vol 28 (6) ◽  
pp. 5084-5100
Author(s):  
Antonio Gómez Caamaño ◽  
Ana M. García Vicente ◽  
Pablo Maroto ◽  
Alfredo Rodríguez Antolín ◽  
Julián Sanz ◽  
...  

This review presents challenges and recommendations on different aspects related to the management of patients with localized muscle-invasive bladder cancer (MIBC), which were discussed by a group of experts of a Spanish Oncology Genitourinary (SOGUG) Working Group within the framework of the Genitourinary Alliance project (12GU). It is necessary to clearly define which patients are candidates for radical cystectomy and which are candidates for undergoing bladder-sparing procedures. In older patients, it is necessary to include a geriatric assessment and evaluation of comorbidities. The pathological report should include a classification of the histopathological variant of MIBC, particularly the identification of subtypes with prognostic, molecular and therapeutic implications. Improvement of clinical staging, better definition of prognostic groups based on molecular subtypes, and identification of biomarkers potentially associated with maximum benefit from neoadjuvant chemotherapy are areas for further research. A current challenge in the management of MIBC is improving the selection of patients likely to be candidates for immunotherapy with checkpoint inhibitors in the neoadjuvant setting. Optimization of FDG-PET/CT reliability in staging of MIBC and the selection of patients is necessary, as well as the design of prospective studies aimed to compare the value of different imaging techniques in parallel.


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