Conventional dose versus dose escalated radiotherapy including high-dose-rate brachytherapy boost for patients with Gleason score 9–10 clinical localized prostate cancer

As several recent researches focus on the importance of Gleason 9–10, we examine the role of radiotherapy dose escalation in those patients. We analyzed 476 patients with Gleason score 9–10 prostate cancer treated with radiotherapy. Of them, 127 patients were treated with conventional-dose external beam radiotherapy (Conv RT) and 349 patients were treated with high-dose radiotherapy (HDRT; 249 patients received high-dose-rate brachytherapy boost + external beam radiotherapy [HDR boost] and 100 patients received intensity-modulated radiotherapy [IMRT]). We compared these treatment groups using multi-institutional retrospective data. The patients had a median follow-up period of 66.3 months. HDRT showed superior biochemical disease-free survival (bDFS) rate (85.2%; HDR boost 84.7% and IMRT 86.6%) to Conv RT (71.1%, p < 0.0001) at 5 years, with a hazard ratio of 0.448. There were borderline difference in prostate cancer-specific mortality (PCSM; 4.3% and 2.75%, p = 0.0581), and distant metastasis-free survival (DMFS; 94.4% and 89.6%, p = 0.0916) rates at 5-years between Conv RT and HDRT group. Dose escalated radiotherapy showed better bDFS, borderline improvement in PCSM, and equivocal outcome in DMFS in with clinically localized Gleason 9–10 prostate cancer.

ArthroRad trial: multicentric prospective and randomized single-blinded trial on the effect of low-dose radiotherapy for painful osteoarthritis depending on the dose—results after 3 months’ follow-up

Purpose Randomized comparison of the effect of radiotherapy on painful osteoarthritis (OA) applying a standard-dose vs. a very-low-dose regime Patients and methods Patients with OA of the hand and knee joints were included. Further inclusion criteria: symptoms for more than 3 months, favorable general health status, age above 40 years. Patients with prior local radiotherapy, trauma, rheumatoid arthritis, or vascular diseases were excluded. After randomization (every joint was randomized separately), the following protocols were applied: standard arm: total dose 3.0 Gy, single fractions of 0.5 Gy twice weekly; experimental arm: total dose 0.3 Gy, single fractions of 0.05 Gy twice weekly. The dosage was not known to the patients. The patients were examined 3 and 12 months after radiotherapy. Scores like VAS (visual analogue scale), KOOS-SF (the knee injugy and osteoarthritis outcome score), SF-SACRAH (short form score for the assessment and quantification of chronic rheumatic affections of the hands), and SF-12 (short form 12) were used. Results A total of 64 knees and 172 hands were randomized. 3.0 Gy was applied to 87 hands and 34 knees, 0.3 Gy was given to 85 hands and 30 knees. After 3 months, we observed good pain relief after 3 Gy and after 0.3 Gy, there was no statistically significant difference. Side effects were not recorded. The trial was closed prematurely due to slow recruitment. Conclusion We found favorable pain relief and a limited response in the functional and quality of life scores in both arms. The effect of low doses such as 0.3 Gy on pain is widely unknown. Further trials are necessary to compare a conventional dose to placebo and to further explore the effect of low doses on inflammatory disorders.

Effect of Flexible Half-dose Gonadotropin-releasing Hormone Antagonist Protocol on in Vitro Fertilization Outcome in Predicted Normal Responder: A Study Protocol for a Multicentered, Randomized, Non-inferiority, Parallel Controlled Trial

BackgroundGonadotropin-releasing hormone antagonists (GnRH-ant) are widely used in current in vitro fertilization-embryo transfer (IVF-ET), however, whether the lowest daily dose of GnRH-ant is individualized remains unknown. Due to the negative effect of GnRH-ant on endometrial receptivity, lessening the amount of GnRH-antagonists used during controlled ovarian stimulation may be helpful for embryo implantation. As such, a randomized controlled study is essential to validate the feasibility and efficacy of daily GnRH-ant dose reduction to 0.125 mg geared towards providing scientific evidence for guidance in clinical practice.MethodsIn total, 620 infertile women undergoing in vitro fertilization will be enrolled in the multicentered, randomized, parallel controlled trial. Based on a computer-generated random list, they will be randomly and equally subdivided into half-dose GnRH-ant group or conventional-dose GnRH-ant group. The primary outcome is ongoing pregnancy i.e., intrauterine pregnancy diagnosed by pelvic ultrasonography at more than 12 weeks of gestation accompanied by normal fetal heartbeats. Secondary outcomes include cycle cancellation, premature luteinizing hormone surge, positive pregnancy, embryo implantation rate, clinical pregnancy, early spontaneous abortion, and live birth. The intention-to-treat and per protocol analyses will be used to initially analyze the difference in ongoing pregnancy rate between the two groups, while the multiple imputation method was used to handle missing values in the data.DiscussionAt present, no randomized controlled trials (RCTs) have been performed on the use of the half-dose GnRH-ant protocol (0.125mg/d) to improve reproductive outcomes of IVF-ET in predicted normal responder, compared to conventional-dose GnRH-ant protocol (0.25mg/d). Half-dose GnRH-ant protocol might provide a suitable clinical solution for predicted normal responder undergoing IVF treatment. Thus, it is critical to conduct a well-designed RCT to evaluate the impact of a half-dose GnRH-ant protocol on the reproductive outcomes of IVF-ET in predicted normal responder.Trial registrationThis study was registered in the Chinese Clinical Trials Registry Platform on August 29, 2020. (chictr.org.cn; identifier: ChiCTR2000037629).

Long Term and Low Dose Mifepristone in The Treatment of Uterine Leiomyoma

To explore the long-term effect of low-dose mifepristone in the treatment of uterine leiomyoma. Methods: 90 cases of hysteromyoma treated in our hospital from December 2018 to May 2019 were randomly divided into control group and observation group, 45 cases in each group. The control group was treated with conventional dose (25mg / D) of mifepristone, and the observation group with low dose (12.5mg / D) of mifepristone. The uterine volume, uterine fibroid volume, hormone level, therapeutic effect and adverse reactions were compared between the two groups. Results: After treatment, the volume of uterus and hysteromyoma in the two groups decreased significantly, but there was no significant difference between the observation group and the control group (P > 0.05); the level of E2, P, FSH in the two groups decreased, but there was no significant difference between the observation group and the control group (P > 0.05); the treatment effect of the observation group and the control group was no significant difference (P > 0.05); the adverse reactions of nausea, anorexia, hot flashes and fatigue in the observation group The birth rate was significantly lower than that of the control group (P < 0.05). Conclusion: Low dose mifepristone can also effectively reduce the level of estrogen and progesterone in patients with uterine leiomyoma, reduce the volume of leiomyoma, reduce the incidence of adverse reactions, with high safety, which is worthy of clinical application.

Prognostic factors in elderly patients with T1 glottic cancer treated with radiotherapy

The aim of the study was the evaluation of the effectiveness of radiotherapy in elderly T1 glottic cancer patients and prognostic factors with particular focus on comorbidities. Five-year overall survival, disease-specific survival, and local control rates were 63%, 92%, and 93%, respectively. Multivariate analysis showed that the following factors had statistically significant impact on local relapse risk and cancer death risk: diabetes, underweight, and fraction dose of 2 Gy. High number of comorbidities, high CCI, and underweight negatively influenced overall survival. A retrospective analysis was performed in a group of 131 T1N0M0 glottic cancer patients aged 70 and above treated with irradiation at the National Institute of Oncology in Cracow between 1977 and 2007. In the analyzed group men prevailed (92%) of mean age of 74 years. Each patient was diagnosed with at least one comorbidity with the following comorbid conditions being most frequent: hypertension, ischemic heart disease, and chronic obstructive pulmonary disease. In the studied group, the effect of comorbidities on overall survival was evaluated using Charlson Comorbidity Index (CCI). Twenty five (19%) patients showed underweight. All patients were irradiated once daily, 5 days a week, to a total dose of 60–70 Gy with a fraction dose of 2 or 2.5 Gy. Radiotherapy is an effective treatment modality in elderly T1 glottic cancer patients. Diabetes as comorbidity, underweight, and conventional dose fractionation decrease the probability of curative effect of radiotherapy in this group of patients, while high number of comorbidities diminishes the probability of long-term survival.

Comparing the Efficacy of Double Dose Hepatitis B Vaccine with Conventional Dose Hepatitis B Vaccine in CLD Patients

Aim: To compare the efficacy of double dose hepatitis B vaccine with conventional dose hepatitis B vaccine in hepatitis C related chronic liver disease patients. Study design: Interventional study (randomized controlled clinical trial) Place and duration of study: Outpatient Department of Medicine, Services Hospital, Lahore from 12th August 2019 to 12th February 2020. Methodology: One hundred and ten patients of both male and female age group 30 to 70 years diagnosed with chronic liver disease on the basis of changed liver echo texture on ultrasound were included. Patients were divided into two groups, each group having 55 patients. One group was given double dose (2ml) while the other was given conventional dose (1ml). Both groups were compared for efficacy in terms of prevention of CLD. Results: The mean age of conventional group was 33.8±9.6 years while 33.7±9.1 years in the double dose group with male predominance (69.10%). Hypo-responsiveness was detected in 23.6% and 32.7% of conventional low dose group and double dose group respectively. There were gender variations in mean Anti-HBs levels. It was 129.80±70.53 mIU/mL in males and 113.26±75.57 mIU/mL in female patients (P= 0.039). Mean titers of anti-HBs in conventional dose group and high dose group were 127.82±67.59 mIU/mL and 121.56±77.00 mIU/mL, respectively (P= 0.52). Conclusion: Double dose hepatitis B vaccination in chronic HCV infected patients efficiently increases the response rate and hence protection against chronic hepatitis B. Keywords: Double dose hepatitis B vaccine, conventional hepatitis B vaccine, chronic hepatitis.

Demonstration of the FLASH Effect Within the Spread-out Bragg Peak After Abdominal Irradiation of Mice

Purpose The effects of FLASH-level dose rates delivered at the spread-out Bragg peak (SOBP) on normal tissue damage in mice were investigated. Materials and Methods Fifty nontumor-bearing mice received abdominal irradiation, 30 at FLASH dose rates (100 Gy/s) and 20 at conventional dose rates (0.1 Gy/s). Total dose values ranged from 10 to 19 Gy, delivered in a single spot by a synchrocyclotron proton therapy system. Centered on the abdomen, the collimated field delivered was an 11-mm diameter circle with a water-equivalent depth of 2.4 cm from entrance to distal 80% dose. A ridge filter was used to provide dose uniformity over the full 2.4-cm range. The spatial distribution was identical for both the FLASH and conventional deliveries. Results Overall survival and individual mouse weights were tracked for 21 days after the exposure date, and LD50 values were compared for the FLASH and conventional dose rate groups. Mice exposed to FLASH dose rates had a higher LD50 value as compared with mice exposed to conventional dose rates, with a dose-dependent improvement in survivability of 10% to 20%. The FLASH cohort also showed greater or equal percent population survival for each day of the study. Conclusion These results are preliminary confirmation of the potential for the combination of the advantages of the Bragg peak with the normal tissue sparing benefits of FLASH treatments. This experiment also confirms that pulsed synchrocyclotrons can be used for the purpose of FLASH research and treatment.