Evidence-Based Dose Planning Aims and Dose Prescription in Image-Guided Brachytherapy Combined With Radiochemotherapy in Locally Advanced Cervical Cancer.

Vaginal dose-surface maps in cervical cancer brachytherapy: Methodology and preliminary results on correlation with morbidity.

Objective The study aims to investigate if a relationship exists between vaginal doses and vaginal stenosis (VS) using posterior–inferior border of symphysis (PIBS) points and the International Commission on Radiation Units-Rectum (ICRU-R) point evaluation system for definitive radio(chemo)therapy in locally advanced cervical cancer. Methods and Materials From a vaginal dose study in China, 351 patients were prospectively assessed. For every reference point of the PIBS system and ICRU-R point was calculated for all BT and summed with EBRT. Pearson’s chi-square test and Student’s unpaired t-test compared variables with and without vaginal stenosis (VS) G ≥2. The risk factors were assessed for VS G ≥2 in multi- and univariate analyses through Cox proportional hazards model followed by a dose–effect curve construction. The VS morbidity rate was compared via the log-rank test using the median vaginal reference length (VRL). Results The patients (38-month median follow-up) had 21.3% three-year actuarial estimate for VS G ≥2. Compared to G <2 patients, VS G ≥2 patients received higher doses to PIBS points except for PIBS − 2 and had significantly shorter VRL. VRL (HR = 1.765, P = 0.038), total EBRT and BT ICRU-R point dose (HR = 1.017, p = 0.003) were risk factors for VS. With VRL >4.6 cm, the 3-year actuarial estimate was 12.8% vs. 29.6% for VRL ≤4.6 cm. According to the model curve, the risks were 21, 30, and 39% at 75, 85, and 95 Gy, respectively (ICRU-R point dose). Conclusions PIBS system point doses correlated with late vaginal toxicity. VRL combined with both EBRT and BT dose to the ICRU-R point contribute to VS risk.

https://www.frontiersin.org/articles/10.3389/fonc.2022.840144/pdf

Using New Vaginal Doses Evaluation System to Assess the Dose–Effect Relationship for Vaginal Stenosis After Definitive Radio(Chemo)Therapy for Cervical Cancer

Modulators of the sphingosine-1-phosphate receptor (S1PR) have been proposed as a promising strategy for treating stroke. However, the detailed mechanisms and the potential translational value of S1PR modulators for intracerebral hemorrhage (ICH) therapy warrant exploration. Using collagenase VII-S-induced ICH in the left striatum of mice, we investigated the effects of siponimod on cellular and molecular immunoinflammatory responses in the hemorrhagic brain in the presence or absence of anti-CD3 monoclonal antibodies (Abs). We also assessed the severity of short- and long-term brain injury and evaluated the efficacy of siponimod in long-term neurologic function. Siponimod treatment significantly decreased brain lesion volume and brain water content on day 3 and the volume of the residual lesion and brain atrophy on day 28. It also inhibited neuronal degeneration on day 3 and improved long-term neurologic function. These protective effects may be associated with a reduction in the expression of lymphotactin (XCL1) and T-helper 1 (Th1)-type cytokines (interleukin 1β and interferon-γ). It may also be associated with inhibition of neutrophil and lymphocyte infiltration and alleviation of T lymphocyte activation in perihematomal tissues on day 3. However, siponimod did not affect the infiltration of natural killer cells (NK) or the activation of CD3-negative immunocytes in perihematomal tissues. Furthermore, it did not influence the activation or proliferation of microglia or astrocytes around the hematoma on day 3. Siponimod appears to have a profound impact on infiltration and activation of T lymphocytes after ICH. The effects of neutralized anti-CD3 Abs-induced T-lymphocyte tolerance on siponimod immunomodulation further confirmed that siponimod alleviated the cellular and molecular Th1 response in the hemorrhagic brain. This study provides preclinical evidence that encourages future investigation of immunomodulators, including siponimod, which target the lymphocyte-related immunoinflammatory reaction in ICH therapy. 

Lymphocyte-Related Immunomodulatory Therapy with Siponimod (BAF-312) Improves Outcomes in Mice with Acute Intracerebral Hemorrhage

Dose at posterior-inferior border of symphysis point: A predictor for vaginal stricture in cervical cancer.

The posterior-inferior border of symphysis (PIBS) point system is a novel vaginal dose-reporting method and is a simple and reliable method proposed by the Medical University of Vienna proposed for both external-beam radiotherapy (EBRT) and brachytherapy (BT). In this multicenter study, we sought to first evaluate the vaginal radiation dose in Chinese cervical cancer patients according to the PIBS point system and then to analyze the factors influencing the dose distribution. We collected data from the medical records of 936 cervical cancer patients who underwent concurrent radiochemotherapy at 13 different institutions in China. Radiation doses at points A, PIBS+ 2 cm, PIBS and PIBS-2 cm, International Commission on Radiation Units (ICRU)-R and ICRU-B were measured. The median total doses in EQD2α/β = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 82.5 (52.7–392.1) Gy, 56.2 (51.4–82.1) Gy and 2.6 (0.9–7.4) Gy, respectively. The median total doses in EQD2α/β = 3 at ICRU-R and ICRU-B were 77.5 (54.8–132.4) Gy and 79.9 (60.7–133.7) Gy, respectively. The mean vaginal reference length (VRL) was 4.6 ± 1.0 cm (median, 4.5 cm). In patients with VRL ≤4.5 cm, the mean total doses in EQD2α/β = 3 at points PIBS+ 2 cm, PIBS and PIBS-2 cm were 128.5, 60.7 and 0.8 Gy, respectively. In patients with VRL > 4.5 cm, the mean total doses at these three points were 68.9, 0.5 and 54.5 Gy, respectively. Classification of patients revealed significant differences (P < 0.05) between these two groups. With the PIBS point system, Chinese patients with a shorter VRL of < 4.5 cm received higher radiation doses at the PIBS+ 2 cm, PIBS and PIBS-2 cm points than European and American patients. Further studies are required to establish the dose–effect relationships with these points as references. The study was registered as a clinical trial (NCT03257475) on August 22, 2017.

/pdf/vaginal-dose-of-radical-radiotherapy-for-cervical-cancer-in-1jkmalmq6a.pdf

Vaginal dose of radical radiotherapy for cervical cancer in China: a multicenter study

Acute intracerebral hemorrhage (ICH) is a devastating type of stroke worldwide. Neuronal destruction involved in the brain damage process caused by ICH includes a primary injury formed by the mass effect of the hematoma and a secondary injury induced by the degradation products of a blood clot. Additionally, factors in the coagulation cascade and complement activation process also contribute to secondary brain injury by promoting the disruption of the blood-brain barrier and neuronal cell degeneration by enhancing the inflammatory response, oxidative stress, etc. Although treatment options for direct damage are limited, various strategies have been proposed to treat secondary injury post-ICH. Perihematomal edema (PHE) is a potential surrogate marker for secondary injury and may contribute to poor outcomes after ICH. Therefore, it is essential to investigate the underlying pathological mechanism, evolution, and potential therapeutic strategies to treat PHE. Here, we review the pathophysiology and imaging characteristics of PHE at different stages after acute ICH. As illustrated in preclinical and clinical studies, we discussed the merits and limitations of varying PHE quantification protocols, including absolute PHE volume, relative PHE volume, and extension distance calculated with images and other techniques. Importantly, this review summarizes the factors that affect PHE by focusing on traditional variables, the cerebral venous drainage system, and the brain lymphatic drainage system. Finally, to facilitate translational research, we analyze why the relationship between PHE and the functional outcome of ICH is currently controversial. We also emphasize promising therapeutic approaches that modulate multiple targets to alleviate PHE and promote neurologic recovery after acute ICH.

https://downloads.hindawi.com/journals/omcl/2022/3948921.pdf

Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

Adjuvant chemoradiotherapy (CRT) has been shown to reduce the risk of recurrence for patients with risk factors after radical hysterectomy (RH). Early initiated CRT could result in superior oncological outcomes. Here, we aimed to compare the survival outcome of intermediate- or high-risk cervical cancer (CC) patients who, received adjuvant CRT between minimally invasive surgery (MIS) and open surgery.Data on stage IB1-IIA2 patients who underwent RH and postoperative CRT in our institution, from 2014 to 2017, were retrospectively collected. Patients with high or intermediate-risk factors who met the Sedlis criteria received sequential chemoradiation (SCRT). According to the surgical approaches, the enrolled patients were divided into MIS and open surgery groups. Then, the disease-free survival (DFS), overall survival (OS), and prognostic factors were analyzed.Among 129 enrolled CC patients, 68 received open surgery and 61 received MIS. The median time interval from surgery to chemotherapy and to radiotherapy was shorter in the MIS group (7 days vs. 8 days, P=0.014; 28 days vs. 35, P<0.001). Three-year DFS and OS were similar in both groups (85.2% vs. 89.7%, P=0.274; 89.9% vs. 98.5%, P=0.499). Further, sub-analysis indicated that the DFS and OS in intermediate/high-risk groups had no significant difference. Cox-multivariate analyses found that tumor size >4 cm and time interval from surgery to radiotherapy beyond 7 weeks were adverse independent prognostic factors for DFS.Based on the population we studied, for early-stage (IB1-IIA2) CC patients with intermediate- or high-risk factors who received postoperative SCRT, although the difference was not significant, the DFS and OS in the MIS group were slightly lower than the ORH group, and tumor size >4 cm and delayed adjuvant radiotherapy beyond 7 weeks were risk factors for recurrence. 

/pdf/the-impacts-of-minimally-invasive-surgery-on-intermediate-or-3opnlpkm.pdf

Ya-li Wang

Papers

Vaginal dose of radical radiotherapy for cervical cancer in China: a multicenter study

Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage

Using New Vaginal Doses Evaluation System to Assess the Dose–Effect Relationship for Vaginal Stenosis After Definitive Radio(Chemo)Therapy for Cervical Cancer

The impacts of minimally invasive surgery on intermediate- or high-risk cervical cancer patients received adjuvant radiotherapy