The Feasibility and Safety of Induction Chemotherapy Followed by Definitive Chemoradiation in Patients with Locally Advanced Cervical Cancer: A Single-Arm Phase II Clinical Trial.

BACKGROUND: The present study aimed at investigating the feasibility and safety of induction chemotherapy followed by definitive chemoradiation (dCRT) in patients with locally advanced cervical cancer. MATERIALS AND METHODS: In this single-arm clinical trial, patients with cervical cancer (stages IB3-IVA) received a median four cycles of induction chemotherapy (paclitaxel and carboplatin, every three weeks) followed by dCRT (which consisted of the whole pelvis at the dose of 45-50 Gy along with weekly cisplatin (40 mg/m2) followed by intracavitary brachytherapy at the total dose of 80-90 Gy). Primary end point was local control at three months, which was assessed by gynecologic examination and pelvic MRI. The secondary outcome of the study was treatment-related toxicity. RESULTS: Seventy-four patients with the mean age of 51.6 ± 9.5 years were included. The most frequent (51.4%) disease stage was IIB. Complete and partial clinical responses were observed in 60.8% and 14.9% of patients, respectively. The frequency of progressive disease and stable disease were 14.9% and 9.5%, respectively. Grade II and III neutropenia (during neoadjuvant chemotherapy were 13.5% and 2.7%, respectively; these figures during chemoradiation were 29.7% and 13.5%, respectively. A treatment interruption was observed for 60.8% (45 cases) of patients during chemoradiation and 31.1% during  induction chemotherapy. DISCUSSION AND CONCLUSION: Induction chemotherapy followed by chemoradiation is feasible in patients with locally advanced cervical cancer; however, the toxicity should be managed properly to avoid delayed e treatment. More than three quarters of the patients achieved complete or partial clinical response within a three-month follow-up.

Evaluation of Mucosamin Effect on Treating Radiation Induced Oral Mucositis during and after Radiotherapy amongst Patients with Oral Cavity Squamous Cell Carcinoma.

BACKGROUND: Oral mucositis is a serious complication radiation therapy for cancer. This is a major complication during radiation therapy of the head and neck tumors in approximately all patients. Therefore, this study was conducted to evaluate the effect of Mucosamin on treatment of radiation induced oral mucositis during and after radiotherapy amongst patients with oral cavity squamous cell carcinoma. MATERIALS AND METHODS: In this prospective clinical trial, eligible patients who referred to radiation oncology department of Namazi Hospital, Shiraz, Iran from Jan 2018 till Jan 2019 were evaluated. The cases with confirmed pathologic diagnosis of squamous cell carcinoma of the oral cavity underwent 6,000 cGy radiation therapy and were randomly divided into two groups: 1- Intervention group; Mucosamin spray for 3-4 times a day (n = 40); 2 - Control group; standard medications (3 times a day) (n = 40). Oral mucositis was evaluated weekly based on RTOG scoring scale. Grade of mucositis was recorded during treatment and after radiation therapy. RESULTS: A total of 80 patients were divided in two groups of Mucosamin and control. From week 3 until the end of radiotherapy (week 6) and after radiotherapy (week 8), there was a significant difference in the severity of oral mucositis between the Mucosamin and the control groups (P <0.05). CONCLUSION: The results of this study showed that Mucosamin spray was able to significantly improved radiation-induced oral mucositis in patients with oral squamous cell carcinoma.
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Exosomal noncoding RNAs: key players in glioblastoma drug resistance.

Glioma, as one of the most severe human malignancies, is defined as the Central Nervous System's (CNS) tumors. Glioblastoma (GBM) in this regard, is the most malignant type of gliomas. There are multiple therapeutic strategies to cure GBM, for which chemotherapy is often the first-line treatment. Still, various cellular processes, such as uncontrolled proliferation, invasion and metastasis, may disturb the treatment efficacy. Drug resistance is another process in this way, which can also cause undesirable effects. Thereupon, identifying the mechanisms, involved in developing drug resistance and the relevant mechanisms can be very helpful in GBM management. The discovery of exosomal non-coding RNAs (ncRNAs), RNA molecules that can be transferred between the cells and different tissues using the exosomes, was a milestone in this regard. It has been revealed that the key exosomal ncRNAs, including circular RNAs, microRNAs, and long ncRNAs, are able to modulate GBM drug resistance through different signaling pathways or by affecting regulatory proteins and their corresponding genes. Nowadays, researchers are trying to overcome the limitations of chemotherapy by targeting these RNA molecules. Accordingly, this review aims to clarify the substantial roles of exosomal ncRNAs in GBM drug resistance and involved mechanisms.

Efficacy and Feasibility of Adding Induction Chemotherapy to Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer: A Phase II Clinical Trial.

PURPOSE: Currently, neoadjuvant chemoradiation (CRT) followed by total mesorectal resection is considered the standard of care for treating locally advanced rectal cancer. This study aimed to investigate the efficacy and feasibility of adding induction chemotherapy to neoadjuvant CRT in locally advanced rectal cancer. METHODS: This phase-II clinical trial included 54 patients with newly diagnosed, locally advanced (clinical T3-4 and/or N1-2, M0) rectal cancer. All patients were treated with 3 cycles of preoperative chemotherapy using the XELOX (capecitabine + oxaliplatin) regimen before and after a concurrent standard long course of CRT (45-50.4 Gy) followed by standard radical surgery. Pathologic complete response (PCR) rate and toxicity were the primary and secondary endpoints, respectively. RESULTS: The study participants included 37 males and 17 females, with a median age of 59 years (range, 20-80 years). Twenty-nine patients (54%) had clinical stage-II disease, and 25 patients (46%) had clinical stage-III disease. Larger tumor size (P = 0.006) and distal rectal location (P = 0.009) showed lower PCR compared to smaller tumor size and upper rectal location. Pathologic examinations showed significant tumor regression (6.1 ± 2.7 cm vs. 1.9 ± 1.8 cm, P < 0.001) with 10 PCRs (18.5%) compared to before the intervention. The surgical margin was free of cancer in 52 patients (96.3%). Treatment-related toxicities were easily tolerated, and all patients completed their planned treatment without interruption. Grade III and IV toxicities were infrequent. CONCLUSION: The addition of induction chemotherapy to neoadjuvant CRT is an effective and well-tolerated treatment approach in patients with rectal cancer.

Insufficient lymph node assessment in gastric adenocarcinoma.

BACKGROUND: This study aimed to investigate the sufficient (≥ 16) lymph node assessment in 449 patients with gastric adenocarcinoma and literature review. METHODS: Four hundred and forty-nine patients with pathologically confirmed locoregional invasive gastric adenocarcinoma from 2004 to 2013 were included. A standard surgical resection was performed for all the patients with (n = 16) or without (n = 433) neoadjuvant treatment. RESULTS: In this study, 301 men and 148 women with a median age of 58 (range 21-88) years were included. The median total numbers of examined lymph nodes were 9 (range 0-55). Ninety-five patients (21.2%) had adequate (≥ 16) lymph node examination, and 70 patients (15.6%) had no examined lymph nodes. In univariate analysis, total or near total gastrectomy (P <  0.001), advanced node stage (P < 0.001), primary tumor size > 6 cm (P < 0.001), and the presence of perineural invasion (P = 0.039) were associated with more average number of examined lymph nodes. On multivariate analysis, node stage (P < 0.001) and type of surgery (P = 0.008) were independent predictive factors. CONCLUSION: In this study, approximately one in five patients with gastric adenocarcinoma had sufficient lymph node assessment. More studies are suggested for identifying a true inadequate lymph node dissection from insufficient lymph node assessment.

High-dose-rate brachytherapy in treatment of non-melanoma skin cancer of head and neck region: preliminary results of a prospective single institution study.

PURPOSE: Skin cancers are the most common human malignancy with increasing incidence. Currently, surgery is standard of care treatment for non-melanoma skin cancers. However, brachytherapy is a growing modality in the management of skin cancers. Therefore, we aimed to assess the outcome of patients with non-melanoma skin cancers treated by high-dose-rate (HDR) brachytherapy with surface mold technique. MATERIAL AND METHODS: In this prospective study, we recruited patients with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin who were candidates for definitive or adjuvant brachytherapy during 2013-2014. Alginate was used for making the individualized surface molds for each patient. Patients were treated with afterloading radionuclide HDR brachytherapy machine, with a total dose of 30-52 Gy in 10-13 fractions. Participants were followed for 2 years for radiation toxicity, cosmetic results, and local failures. RESULTS: A total of 60 patients (66.7% male; median age, 71 years) were included, of which 42 (70.0%) underwent definitive radiotherapy. Seventy-five percent of lesions were BCC. The mean total dose was 39.6 ± 5.4 Gy. Of patients in definitive group, 40/42 (95.2%) experienced complete clinical response after 3 months. The recurrence rate was 2/18 (11.11%) and 1/42 (2.38%) in adjuvant and definitive groups, respectively. The percentage of grade 3-4 acute (3-month post-treatment) and late toxicities (2 years post-treatment) was 6.7% and 0%, respectively. The cosmetic results were good/excellent in 96.2% of patients after 2 years of follow-up. CONCLUSIONS: With appropriate patient selection and choosing as lowest dose per fraction as possible, HDR brachytherapy with customized surface molds yields good oncological and cosmetic results for the treatment of localized skin BCC and SCC.

High-dose-rate intraluminal brachytherapy prior to external radiochemotherapy in locally advanced esophageal cancer: preliminary results.

PURPOSE: Dysphagia is a common initial presentation in locally advanced esophageal cancer and negatively impacts patient quality of life and treatment compliance. To induce fast relief of dysphagia in patients with potentially operable esophageal cancer high-dose-rate (HDR) brachytherapy was applied prior to definitive radiochemotherapy. MATERIAL AND METHODS: In this single arm phase II clinical trial between 2013 to 2014 twenty patients with locally advanced esophageal cancer (17 squamous cell and 3 adenocarcinoma) were treated with upfront 10 Gy HDR brachytherapy, followed by 50.4 Gy external beam radiotherapy (EBRT) and concurrent chemotherapy with cisplatin/5-fluorouracil. RESULTS: Tumor response, as measured by endoscopy and/or computed tomography scan, revealed complete remission in 16 and partial response in 4 patients (overall response rate 100%). Improvement of dysphagia was induced by brachytherapy within a few days and maintained up to the end of treatment in 80% of patients. No differences in either response rate or dysphagia resolution were found between squamous cell and adenocarcinoma histology. The grade 2 and 3 acute pancytopenia or bicytopenia reported in 4 patients, while sub-acute adverse effects with painful ulceration was seen in five patients, occurring after a median of 2 months. A perforation developed in one patient during the procedure of brachytherapy that resolved successfully with immediate surgery. CONCLUSIONS: Brachytherapy before EBRT was a safe and effective procedure to induce rapid and durable relief from dysphagia, especially when combined with EBRT.