Yaowen Zhang

Background/Purpose: Analyse the outcomes of stages I–III inoperable endometrial cancer (IEC) patients treated with external-beam-irradiation (EBRT) and 3D-image-guided-brachytherapy (IGBT). Material and Methods: Medical records of IEC patients receiving EBRT + IGBT in eight European and one Canadian centres (2004–2019) were examined, including: pelvic ± para-aortic EBRT and lymph node boost; anaesthetic procedure, applicators, BT-planning imaging, clinical target volume (CTV), brachytherapy schedule, and EQD2 to the CTV_{(α/β=4.5Gy)} and D2 cm³_(α/β=3Gy) for organs at risk. Complications are evaluated using CTCAEv4 scores. The 2- and 5-year survival probability according to stages was estimated (cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS)). Statistics: descriptive analysis and the Kaplan–Meier method. Results: 103 patients (stages: I-44, II-14, III-44) were included. Median follow-up: 28 months (7–170). All patients received pelvic ± para-aortic EBRT. Median D90-EQD2_(α/β=4.5) to the CTV:73.3 Gy (44.6–132.7), 69.9 Gy (44.7–87.9 and 75.2 Gy (55.1–97) in stages I, II, and III, respectively. Thirty patients presented relapse (stages: 10-I, 3-II, 17-III): 24 uterine (stages: 7-I, 3-II, 14-III), 15 nodal (stages: 4-I, 1-II, 10-III), and 23 distant (stages: 6-I, 2-II, 15-III). Five year CSS was 71.2% (stages: 82%-I-II and 56%-III) and DFS, LRFS, LRRFS, and DMFS were 55.5%, 59%, 72%, and 67.2%, respectively. Late G3-G4 complications (crude): 1.3% small bowel, 2.5% rectum, and 5% bladder. Conclusion: In stages I–III of the IEC, EBRT + IGBT offer good 2- and 5-year CSS of 88.7% and 71.2%, respectively, with the best outcomes in stages I–II. Prospective studies are needed to determine how better outcomes can be achieved.

Background: Mortality of the older adult population suffering from COVID-19 has been increasing at an alarming rate, and people older than 76 years of age reported 18% mortality. Mainly, the EU and USA exhibited a greater fatality rate due to lack of selective immunization and anti-SARS Co-V-2 therapeutics. Very limited reports are available to delineate the impact of COVID-19 on the geriatric population and the failures of aminoquinoline therapy. Methods: We performed a substantial literature review in the PubMed/Medline databases to extract the information pertaining to the COVID-19 impact on the geriatric population and recent failures of aminoquinoline therapy in COVID-19 patients of EU, China, USA and the requirement of vaccination. Results and Discussions: Both parental strains and mutant variants of SARS Co-V-2 can induce severe respiratory complications, multiorgan failure, and clotting abnormalities in older adults due to low immunocompetence. Aminoquinoline derivatives, such as chloroquine (CQ) and hydroxychloroquine (HCQ), are preferred primarily for COVID-19 treatment, but several controversies are being reported for its usage worldwide. In this review, we have provided the effects of COVID-19 on the geriatric population of EU and an overview of the mechanism of action of aminoquinolines. Furthermore, CQ and HCQ are not the preferred choice of drugs if the COVID-19 patients already have existing co-morbid conditions viz., diabetes mellitus and hypertension. Conclusion: A new advent of COVID-19 vaccines, such as nucleic acid-based (DNA/mRNA) vaccines, protein subunit vaccines, viral vector vaccines, and inactivated vaccines, have been developed for treating SARS-CoV-2 infection after the failure of aminoquinoline therapy in EU, China, and USA patients. However, some of the vaccines are yet to be examined against mutant strains of SARS CoV-2 that originated in the UK, Nigeria, South Africa, Brazil, and India.

Purpose: To evaluate the preliminary results of the use of 68 Gy EQD2_{(α/β=3 Gy)} as a dose limit to the lowest dose in the most exposed 2 cm³ of the vagina in order to reduce G2 late vaginal problems in postoperative endometrial carcinoma (EC). Methods: From November 2016 to October 2019, 69 postoperative EC patients receiving vaginal brachytherapy (VBT) ± external beam radiotherapy (EBRT) were prospectively analyzed. The median EBRT dose was 45 Gy (range: 44–50.4 Gy), 1.8−2 Gy/day, 5 fractions(Fr)/week. VBT was administered with the following schedule: 1Fr of 7 Gy after EBRT and 2 daily Fr × 7.5 Gy in exclusive VBT. The dose was prescribed at 0.5 cm from the applicator surface with an active length of 2.5 cm; 56 patients were treated with vaginal cylinders (49–3.5 cm, 6–3 cm, and 1–2.5 cm) and 13 with the colpostat technique. The overall VBT dose was adjusted to meet the vaginal restriction of < 68 Gy EQD2_{(α/β=3 Gy)} at 2 cm³. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum, and the objective LENT-SOMA criteria for vagina. Results: With a median follow-up of 31.0 months, no vaginal-cuff recurrences were found. Late toxicity: only 1G1(1.4%) rectal toxicity; 21G1(30.4%) and 3G2(4.3%) vaginal complications. Only one (1.4%) of 3 G2 manifested as vaginal shortening. Conclusions: In postoperative EC patients treated with VBT, only one developed G2 vaginal stenosis with the use of 68 Gy EQD2_{(α/β=3 Gy)} as a dose constraint. These preliminary results seem to indicate the value of this dose limit for reducing G2 vaginal stenosis. Nonetheless, these findings should be confirmed in a larger number of patients with longer follow-up.

Background: To evaluate whether EQD2_{(α/β = 3Gy)} at 2 cm³ of the most exposed area of the vagina is related to late vaginal toxicity in postoperative endometrial cancer (PEC) patients (p) treated with exclusive brachytherapy (BT). Methods: From 2014 to 2017, 43p were included in this study. BT was administered: 3-fractions of 6Gy in 37p and 2-fractions of 7.5Gy in 6p. The dose was prescribed at a depth of 5 mm from the applicator surface with dose-point optimization based on distance. The active treatment length was 2.5 cm. CTV-D90 and the dose to the most exposed 2 cm³ of the vagina was calculated for each patient. Late toxicity of the bladder and rectum was assessed using Radiation Therapy Oncology Group (RTOG) criteria, and vaginal toxicity by objective Late Effects Normal Tissue Task Force (LENT)-Subjective, Objective, Management, Analytic (SOMA) (LENT-SOMA) criteria. Statistics: frequency tables, mean, median, range, standard deviation, and box plot. Results: The median follow-up was 51 months (12–68). 20 p (46.5%) and 2 p (4.7%) developed G1 and G2 vaginal complications, respectively. Only 1/2 p-G2 receiving EQD2_{(α/β = 3Gy)} at 2 cm³ >68Gy presented vaginal shortening and 18/20 p-G1 received doses < 68Gy. Conclusions: PECp receiving exclusive brachytherapy with doses < 68Gy EQD2_{(α/β = 3Gy)} at 2 cm² of the vagina presented only G0–G1 vaginal toxicity, except for one with bleeding telangiectasias. Larger prospective studies are necessary to confirm the present results.

To analyse the possible relationship between the EQD2(α/β=3Gy) at 2 cm3 of the vagina and late toxicity in vaginal-cuff-brachytherapy (VBT) after external-beam-irradiation (EBRT) for postoperative endometrial carcinoma (EC). From 2014 to 2016, 62 postoperative EC patients were treated with EBRT + VBT. The median EBRT dose was 45 Gy (44 Gy-50.4 Gy). VBT involved a single 7 Gy dose. Toxicity was prospectively evaluated using the RTOG score for the rectum and bladder and the objective LENT-SOMA criteria for the vagina. EQD2(α/β = 3Gy) at 2 cm3 of the most exposed part of the vagina was calculated by the sum of the EBRT + VBT dose. Statistics: Boxplot, Student's t and Chi-square tests and ROC curves. Mean follow-up: 39.2 months (15-68). Late toxicity: bladder:0 patient; rectum:2 patients-G1; Vagina: 26 patients-17G1, 9G2; median EQD2(α/β=3Gy) at 2 cm3 in G0-G1 patients was 70.4 Gy(SD2.36), being 72.5 Gy(SD2.94) for G2p. The boxplot suggested a cut-point identifying the absence of G2: 100 % of G2p received >68 Gy, ROC curves showed an area under the curve of 0.72 (sensitivity of 1 and specificity of 0.15). Doses >68 Gy EQD2(α/β=3Gy) at 2 cm3 to the most exposed area of the vagina were associated with late G2 vaginal toxicity in postoperative EC patients treated with EBRT + VBT suggesting a very good dose limit to eliminate the risk of G2 late toxicity. The specificity obtained indicates the need for prospective analyses.

Purpose To determine whether brachytherapy with a single hypofractionated dose of 7 Gy provides the similar vaginal-cuff relapses and safety profile in terms of complications compared to schedules of 2 or 3 fractions of lower doses in patients treated previously with external beam irradiation in postoperative endometrial carcinoma. Methods/material From June 2003 to December 2016, 325 patients were treated with 3 different schedules of high-dose-rate brachytherapy after external beam irradiation for postoperative endometrial carcinoma. The patients were divided into 3 groups: Group-1: 125 patients were treated with 3 fractions of 4–6 Gy per fraction (3 fractions/week) between 2003 and 2008; Group-2: 93 patients were treated with 2 consecutive daily fractions of 5–6 Gy between 2008 and 2011; Group-3: 107 patients received a single fraction of 7 Gy between 2011 and 2016. Bladder and rectum complications were assessed using RTOG scores and with the objective scores of LENT-SOMA for the vagina. Statistics: the chi-square test. Results The mean follow-up of Groups 1, 2 and 3 was 95, 67 and 51 months, respectively. Three patients in Group-1, 2 in Group-2, 1 in Group-3 developed vaginal-cuff relapse (p = 0.68). No differences were found in late toxicity among the three groups. Conclusions One single dose of 7 Gy is safe and effective and may be the best treatment schedule with a similar incidence of vaginal-cuff relapses, complications and patient comfort with less hospital attendance.