Prospective Trial Research Articles

40 Gray in 5 Fractions for Salvage Reirradiation of Spine Lesions Previously Treated With Stereotactic Body Radiotherapy.

A retrospective single-center analysis of the safety and efficacy of reirradiation to 40 Gy in 5 fractions (reSBRT) in patients previously treated with stereotactic body radiotherapy to the spine was performed. We identified 102 consecutive patients treated with reSBRT for 105 lesions between 3/2013 and 8/2021. Sixty-three patients (61.8%) were treated to the same vertebral level, and 39 (38.2%) to overlapping immediately adjacent levels. Local control was defined as the absence of progression within the treated target volume. The probability of local progression was estimated using a cumulative incidence curve. Death without local progression was considered a competing risk. Most patients had extensive metastatic disease (54.9%) and were treated to the thoracic spine (53.8%). The most common regimen in the first course of stereotactic body radiotherapy was 27 Gy in 3 fractions, and the median time to reSBRT was 16.4 months. At the time of simulation, 44% of lesions had advanced epidural disease. Accordingly, 80% had myelogram simulations. Both the vertebral body and posterior elements were treated in 86% of lesions. At a median follow-up time of 13.2 months, local failure occurred in 10 lesions (9.5%). The 6- and 12-month cumulative incidences of local failure were 4.8% and 6%, respectively. Seven patients developed radiation-related neuropathy, and 1 patient developed myelopathy. The vertebral compression fracture rate was 16.7%. In patients with extensive disease involvement, reSBRT of spine metastases with 40 Gy in 5 fractions seems to be safe and effective. Prospective trials are needed to determine the optimal dose and fractionation in this clinical scenario.

Melatonin and melatonin receptor agonists in the treatment of nocturia: A systematic review.

Causes of nocturia may extend beyond primary bladder pathology and it has been commonly associated as a side effect of sleep disorders. This has led to the study of melatonin and melatonin receptor agonists as a primary treatment for nocturia hypothesized to be secondary to sleep disorders. We aim to systematically review the efficacy and reported safety of melatonin and melatonin receptor agonists in the treatment of nocturia. A search strategy of EMBASE and Pubmed/Medline databases was utilized to identify eligible studies. Two thousand and twenty-eight unique references were identified in concordance with the Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines for systematic reviews, of which nine papers met the inclusion criteria. The Cochrane Collaboration risk of bias criteria in the open label and nonplacebo studies was used to assess bias. The nine studies identified included 3 randomized double-blinded placebo-controlled trials, 2 randomized non-placebo trial, and 4 prospective open-label trials. Three utilized the melatonin-receptor agonist ramelteon (8 mg) and six utilized melatonin (four 2 mg extended release, two 2 mg normal release). Nocturia improved in 8 studies varying from moderate to low efficacy related to reduction in nocturia episodes. Five studies evaluated sleep parameters finding improvement in both nocturia and sleep quality. Male subjects represented 76.8% of 371 total subjects in prospective and randomized trials. Ramelteon and melatonin were both reported as well tolerated during nocturia treatment. A meta-analysis was not able to be performed due to the heterogeneity of bladder diagnoses. At this time, there is insufficient evidence to routinely recommend melatonin as an effective treatment for nocturia given the limitations of current clinical studies. Randomized placebo-controlled trials and prospective open label studies in non-neurogenic populations report a trend towards nocturia improvement with good tolerability and rare side effects. Therefore, further larger scale randomized trials with focused urologic diagnoses in well-characterized patient populations are warranted.

As how artificial intelligence is revolutionizing endoscopy.

With incessant advances in information technology and its implications in all domains of our lives, artificial intelligence (AI) has emerged as a requirement for improved machine performance. This brings forth the query of how this can benefit endoscopists and improve both diagnostic and therapeutic endoscopy in each part of the gastrointestinal tract. Additionally, it also raises the question of the recent benefits and clinical usefulness of this new technology in daily endoscopic practice. There are two main categories of AI systems: computer-assisted detection (CADe) for lesion detection and computer-assisted diagnosis (CADx) for optical biopsy and lesion characterization. Quality assurance is the next step in the complete monitoring of high-quality colonoscopies. In all cases, computer-aided endoscopy is used, as the overall results rely on the physician. Video capsule endoscopy is a unique example in which a computer operates a device, stores multiple images, and performs an accurate diagnosis. While there are many expectations, we need to standardize and assess various software packages. It is important for healthcare providers to support this new development and make its use an obligation in daily clinical practice. In summary, AI represents a breakthrough in digestive endoscopy. Screening for gastric and colonic cancer detection should be improved, particularly outside expert centers. Prospective and multicenter trials are mandatory before introducing new software into clinical practice.

Cancer biology in diabetes update: Focusing on antidiabetic drugs.

The association of type 2 diabetes with certain cancer risk has been of great interest for years. However, the effect of diabetic medications on cancer development is not fully understood. Prospective clinical trials have not elucidated the long-term influence of hypoglycemic drugs on cancer incidence and the safety for cancer-bearing patients with diabetes, whereas numerous preclinical studies have shown that antidiabetic drugs could have an impact on carcinogenesis processes beyond the glycemic control effect. Because there is no evidence of the safety profile of antidiabetic agents on cancer biology, careful consideration would be required when prescribing any medicines to patients with diabetes and existing tumor. In this review, we discuss the potential influence of each diabetes therapy in cancer 'initiation', 'promotion' and 'progression'.

Cost-utility analysis and impact on the environment of videoconference in pressure injury. A randomized controlled trial in individuals with spinal cord injury

Study designA prospective randomized controlled trial (RCT) in persons with spinal cord injury (SCI) and ongoing pressure injury (PI).ObjectivesThe main aim was to perform a cost-utility analysis (CUA) alongside the RCT comparing regular care to regular care with additional videoconference consultations. Secondary aims were to assess costs and greenhouse gas emission related to transportation in the two study groups.SettingTwo spinal cord units in Norway.MethodsParticipants were allocated to a regular care group (RCG) and a regular care group with additional videoconference (VCG), in a 1-year follow-up between 2016 and 2018. Costs were prospectively collected, and health-related quality of life (HRQoL) data were collected at baseline and 12 months. The outcome was quality-adjusted life years (QALYs), derived from the EQ-5D-5L questionnaire. Results are reported as incremental cost-effectiveness ratio (ICER), expressed as the cost per additional QALY gained. Transportation related costs and environmental emissions were compared by t-tests.ResultsThere were 56 participants included, 28 in each group. Of these 27 in the VCG and 26 in the RCG completed. Three participants died. The mean cost per patient was € 8819 in the VCG and € 3607 in the RCG, with 0.1 QALYs gained in the VCG. No significant differences were identified regarding HRQoL or secondary outcomes.ConclusionThe VCG costs € 5212 more for an additional 0.1 QALYs, giving an ICER of € 52,120 per QALY. No significant differences were found regarding transportation-related costs, or emission of greenhouse gases.Trial registrationwww.ClinicalTrials.gov; NCT02800915, TeleSCIpi. CRISTIN.no. https://app.cristin.no/projects/show.jsf?id=545284. Sunnaas Rehabilitation hospital’s web page, available at https://www.sunnaas.no/fag-og-forskning/fagstoff/sar.

HOW DOES VITAMIN D SUPPLEMENTATION CHANGE THE OUTCOME FOR MOTHER AND CHILD?

Introduction: Pregnancy represents a period in which rapid bodily changes occur, which include a wide range of physiological interactions occurring in both the mother and the developing foetus. The role of vitamin D3 metabolism within pregnancy is an over-shadowed but very important aspect for the normal and healthy muscoskeletal development of the foetus and for the various alternative functions associated with vitamin D3 for the pregnant female. The purpose: To provide a detailed understanding ofhe current status of vitamin D3 and the role it has within pregnancy and to identify the efficacy and the wide range of effects that vitamin D3 has for both the mother and foetus. Materials and methods: We conducted a review of the available literature at PubMed, Google Scholar, and Science Direct, which included observational studies, prospective and controlled trials, reports and guidelines for appropriate dosages of vitamin D3 to be used within pregnant females. Results and Discussion: Our review of the scientific literature showed evidence of the benefits of vitamin D3 within pregnant women and the effect, if any, on the numerous physiological processes taking place within both the mother and the foetus. We found data indicating that vitamin D3 can prove to be very important in preventingreeclampsia, gestational diabetes and congenital malformations of the foetus. Conclusion: The administration of vitamin D3 may be a potential technique to prevent complications to the mother and the developing foetus both during and after pregnancy, either solely or as a combined therapy.

Use of wearable technology in cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source: a systematic review.

Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring. We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised. A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting. Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder.

Does Adenoid Hypertrophy Affect Hemoglobin and Erythropoietin Levels in Children?

Objective: Adenoid hypertrophy restricts the nasal airflow by obstructing the choanae posteriorly and may lead to chronic hypoxia. The present study mainly aims to compare pre- and postoperative erythropoietin (EPO) and hemoglobin (Hgb) levels in children undergoing adenoidectomy. Methods: Between 2021 September and 2022 August, 61 children who performed adenoidectomy in the ENT clinic included in this prospective clinical trial. The pre- and postoperative third months EPO and Hgb values of children were compared. Results: The mean age of the children undergoing adenoidectomy was 5.7±3.4 (range, 3-9 years). Twenty-seven of the subjects were men and 34 were women. The mean EPO values of the adenoid hypertrophy patients preoperatively and at postoperative third months were 13.7±2.4 Mu/mL and 10.8±1.6 Mu/mL, respectively. The decrease in mean EPO value was significant (p = 0.031). The mean Hgb levels of the subjects preoperatively and at postoperative 3rd months were 12.1±2.4 g/dL and 11.9±1.6 g/dL, respectively. When pre- and postoperative 3rd month mean Hgb values compared, the difference was not significant (p = 0.721). Conclusions: According to these outcomes, grade 4 adenoid hypertrophy is associated with significantly increased EPO values compared to post-operative values in children. To validate these results further prospective studies with larger sample sizes are required.

(022) Penile Implant Reservoir Placement: The Current Utilized Various Techniques and the Associated Outcome: Systematic Review and Meta-Analysis

Abstract Introduction Many innovations in the field of inflatable penile prosthesis (IPP) has been emerged. Since the introduction of the IPP, reservoir positioning in the space of Retzius (SOR) was considered the classical approach that had been utilized for many years. However, in certain group of patients, reservoir insertion in such space might be difficult or even risky. As a result, many alternatives for the reservoir placement outside the SOR has emerged with the intent of safe and reliable reservoir placement. Objective To conduct a systematic review for the studies evaluating the outcomes of different techniques used for IPP reservoir placement to look for possible superiority of any approach over others. Methods A systemic review was performed utilizing (PRISMA) statement. The PubMed and Google scholar were used to look for articles published up to January 2023. Original articles reporting different techniques for IPP reservoir placement and evaluating the associated outcomes were included. Data regarding study design, sample size, approach of reservoir placement, surgical technique, device type and reported outcomes (infection rate, bladder/bowel/vascular injury, reservoir herniation, mechanical failure, auto-inflation, reservoir palpability and patients’ satisfaction) were collected. Pooled proportion was calculated and included in the meta-analysis. The Newcastle-Ottawa scale was used for assessing the quality of the studies. Results A total of 23 articles meeting the inclusion criteria, all were retrospective reviews. 11 compared more than one technique for reservoir placement whereas 12 described a single technique. In total, techniques for 6 main different reservoir locations has been reported, including SOR (7 studies), submuscular/subrectus (6 studies), Lateral retroperitoneal (1 study), subcutaneous (1 study), sub external oblique (1 study) and intraperitoneal (1 study). Another 7 modifications have been described for the SOR technique (traditional SOR, accessing SOR using blunt scissor in post-prostatectomy patients, accessing SOR using blunt scissor in virgin cases, dilating SOR using catheter balloon, accessing SOR under direct vision, accessing SOR through external oblique fascia incision, and the addition of The Tubing Hitch&Lasso, Intussusception Anchor technique (THALIA)). Another 6 modifications for the submuscular/subrectus approach have been described (posterior to transversalis fascia (PTF), anterior to transversalis fascia (ATF), high submuscular, subrectus using counter incision, subrectus with the addition of THALIA, low submuscular with trans-fascial-fixation (TFF)). None of the studies have proven the superiority of one technique over others, with most of the techniques has comparable intra-operative and post-operative outcomes (table 1). The addition of anchoring step (THALIA or TFF) resulted in neglected risk of reservoir herniation, however, related studies has small sample size with no comparison groups. Meta-analysis for the studies of SOR (n=7) and submuscular/subrectus (n=6) groups showed a statistically significant difference only in the herniation rates (figure 1). 10 studies were of strong quality (8 stars) while the remaining 13 studies were of poor quality. Conclusions Modest evidence suggests a comparable favorable outcome of various approaches used for IPP reservoir placement. The lack of enough prospective trials, short term follow up, and diversity in the techniques prescribed prevent the ability to build strong evidence. For the purpose of supporting the superiority of any technique, further prospective studies on a larger number of patients with long-term follow up are needed to reach a solid verdict. Disclosure No.

(273) Influences of Oral Dehydroepiandrosterone (DHEA) Administration on Hormonal Profile, Menopausal Clinical Symptoms and Sexual Function in Early Postmenopausal Symptomatic Women

Abstract Introduction Dehydroepiandrosterone (DHEA) and its sulfate (DHEAs) are steroid hormones secreted by the adrenal glands. The aging process is associated with decreased levels of DHEA and DHEAs, which are the initial causes of many age-related changes. Objective We aimed to evaluate the effects of oral administration of DHEA (50mg/day) on hormonal profile, menopausal clinical symptoms and sexual function in early postmenopausal symptomatic Caucasian women at baseline and after 2, 4 and 6 months of treatment. Methods For our prospective clinical trial, 42 symptomatic early postmenopausal women (50–55±3.5 years) were selected. Participants were divided into two groups. The study group (n-22) received oral DHEA 50mg/day for 6 months and the control group (n-20) received placebo. Serum levels of DHEA, DHEAs, androstenedione (A4), allopregnanolone (3α,5α- THP), progesterone (P4), 17OH progesterone (17OHP), cortisol, testosterone (T), dihydrotestosterone (DHT), estrone (E1), estradiol (E2), SHBG, LH, FSH and β-Endorphin were determined at baseline and after 2, 4 and 6 months of treatment. The results of the Menopause Rating Scale (MRS) and the McCoy Female Sexuality Questionnaire (MFSQ) were evaluated before and after the treatment. Results During the treatment period in the study group, a progressive increase in serum levels of DHEA, DHEAs, A4, T, DHT, E2, E1, 3α,5α-THP and β-Endorphin were observed. P4 and 17OHP levels showed only a slight increase. By the 4th month of treatment and final data, a decrease in cortisol levels was observed. LH and FSH levels gradually decreased. SHBG levels remained constant. After 6 months of treatment, assessing the results of the MRS in the DHEA group showed a progressive improvement of menopausal symptoms. The results of the McCoy questionnaire were also improved in the study group. Conclusions DHEA administration had a significant effect on certain endocrine parameters in early postmenopausal symptomatic Caucasian women, was associated with improvements of menopausal physical symptoms, sexual function and psycho-emotional parameters. Our findings support the hypothesis that administration of DHEA in symptomatic postmenopausal women restores both androgenic and estrogenic milieu and reduces most of the clinical symptoms caused by the changes of these environments during postmenopausal period. On this basis we can assume, that DHEA may be considered as a potentially effective medication for MHT. However, conducting further, more specific clinical trials are needed. Disclosure No.

Efficacy of 5-fluorouracil (5-FU) and low molecular weight heparin (LMWH) in high-risk pediatric retinal detachment; randomized clinical trial

BackgroundPediatric rhegmatogenous retinal detachments (PRRDs) are complex, rare occurrences and are often related to trauma or congenital abnormalities. Children often do not recognize or report symptoms of retinal detachment. Thus at presentation, PRRD is typically advanced often with macular involvement, proliferative vitreoretinopathy (PVR), chronic duration, and poor visual acuity. Because 5-FU and LMWH are effective in different aspects in the PVR process, it was believed that a syngergistic approach to the prevention of PVR would be advantageous.MethodsAfter informed consent, children under 14 years of age with high-risk PRRD underwent pars plana vitrectomy and silicone oil injection with scleral buckle divided into 2 groups in prospective randomized trial. Group A received intraoperative infusion of 5-FU (200 µg/ml) and LMWH (5 IU/ml), group B received infusion of normal saline. Primary outcome was occurrence of recurrent PRRD within 12 weeks, secondary outcomes were occurrence of PVR, best corrected visual acuity (BCVA), number and timing of secondary procedures within 12 weeks.ResultsThe study included 42 eyes of 41 patients, 21 in group A and 21 in group B, the duration of PRRD ranged from 0.5 to 7 months in group A and 0.25-5 months in group B.The rate of recurrent PRRD was higher in group B 33% compared to 19% in group A (p = 0.292). The mean timing of occurrence of recurrent PRRD was 9.5 ± 5 weeks in group A compared to 2.86 ± 2.41 weeks in group B (p = 0.042), more patients in group B ended up with more advanced PVR (p = 0.038), BCVA was hand movement (HM) only in all cases preoperatively and improved to HM-0.3 Snellen in group A compared to light perception (PL)-0.1Snellen in group B (p = 0.035), there was no difference in any of secondary procedures but with later timing in group A 9.71 ± 3.73 weeks than in group B 4.0 ± 2.83 weeks (p = 0.042).ConclusionThis study concluded that the use of the 5-FU and LMWH combination in high risk PRRD resulted in lower rate of postoperative PVR, later recurrence of PRRD and better final BCVA.Trial registration numberRegistry: clinicaltrials.gov PRS NCT06166914 date of initial release 4/12/2023. Unique Protocol ID: 9,163,209 date 21/10/2021. Retrospectively registered

Next-Generation Screening for Colorectal Cancer, an Incremental Approach to a Global Disease.

New screening tests for early detection of colorectal cancer and its precursors are rapidly emerging with the focus on noninvasive tests which can be used in both structured opportunistic and population-based organized screening programs. Novel technologies are identifying new combinations of promising markers. Conducting large prospective clinical trials of efficacy requires very large numbers of subjects constituting intended-use populations. These trials are often preceded by studies using smaller numbers of "convenience" samples to derive panels of relevant markers and algorithms to combine them and define what constitutes a positive test. The article by Gagrat and colleagues in this issue reports results from one such study designed to yield a "next-generation" multitargeted (mt-sDNA) stool test. This report exemplifies the advantages and limitations of this approach. See related article by Gagrat et al., p. 119.

Abstract IA015: Is salpingectomy as effective as bilateral salpingo-oophorectomy in preventing ovarian, fallopian tube, and peritoneal cancer? Let’s prove it!

Abstract IA015: Is salpingectomy as effective as bilateral salpingo-oophorectomy in preventing ovarian, fallopian tube, and peritoneal cancer? Let’s prove it!

(207) Premature Ejaculation and Varicocele, are they Associated? Systematic Review

Abstract Introduction Premature ejaculation (PE) is one of the most common sexual disorders that negatively impacts couple’s satisfaction. Varicocele on the other hand is a highly prevalent condition affecting men population. A higher incidence of PE is observed among patients with varicocele, which incited several authors to evaluate the possible correlation between varicocele and PE. Others went beyond that to investigate whether varicocele repair can lead to an improvement in PE. Objective To systematically review the literature for all the studies exploring the relationship between PE and varicocele. Methods A systemic review was performed utilizing (PRISMA) statement. The PubMed, Google scholar and Scopus databases were used to look for articles published up to June 2023 using the appropriate keywords. Articles reporting an association between the presence of varicocele and PE and exploring changes in ejaculation latency time after varicocele correction were included. Data including study design, sample size, varicocele details, PE diagnostic method, outcome measured and tools used to measure it were collected. The Newcastle-Ottawa scale was used for assessing the quality of the included studies. Results A total of eight studies were identified, two of them were retrospective and six were prospective. Intravaginal ejaculation latency time (IELT) was used as a diagnostic tool for PE in 5 studies, Premature Ejaculation Diagnostic Tool (PEDT) in 1 study, Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores in 1 study, and subjective assessment in 2 studies. Two studies looked for the prevalence of PE among patients with and without varicocele. Both studies showed a significantly higher frequency of PE among varicocele patients. Whereas six studies evaluated the improvement in ejaculatory function after varicocelectomy; five of them revealed a statistically significant improvement. Quality check: only one study was of strong quality while the remaining 7 studies were of fair quality. Conclusions Limited evidence suggests the presence of positive relation between varicocele and PE. The small number of studies and patients, lack of enough prospective clinical trials, short term follow up, heterogenous study design and absence or diversity in the diagnostic tools used prevent our ability to build strong evidence. For the purpose of supporting the relation and validate it, further prospective studies on a larger number of patients with long-term follow up are needed to reach a solid verdict. Disclosure No.

Auto-segmentation of neck nodal metastases using self-distilled masked image transformer on longitudinal MR images.

Auto-segmentation promises greater speed and lower inter-reader variability than manual segmentations in radiation oncology clinical practice. This study aims to implement and evaluate the accuracy of the auto-segmentation algorithm, "Masked Image modeling using the vision Transformers (SMIT)," for neck nodal metastases on longitudinal T2-weighted (T2w) MR images in oropharyngeal squamous cell carcinoma (OPSCC) patients. This prospective clinical trial study included 123 human papillomaviruses (HPV-positive [+]) related OSPCC patients who received concurrent chemoradiotherapy. T2w MR images were acquired on 3 T at pre-treatment (Tx), week 0, and intra-Tx weeks (1-3). Manual delineations of metastatic neck nodes from 123 OPSCC patients were used for the SMIT auto-segmentation, and total tumor volumes were calculated. Standard statistical analyses compared contour volumes from SMIT vs manual segmentation (Wilcoxon signed-rank test [WSRT]), and Spearman's rank correlation coefficients (ρ) were computed. Segmentation accuracy was evaluated on the test data set using the dice similarity coefficient (DSC) metric value. P-values <0.05 were considered significant. No significant difference in manual and SMIT delineated tumor volume at pre-Tx (8.68 ± 7.15 vs 8.38 ± 7.01 cm3, P = 0.26 [WSRT]), and the Bland-Altman method established the limits of agreement as -1.71 to 2.31 cm3, with a mean difference of 0.30 cm3. SMIT model and manually delineated tumor volume estimates were highly correlated (ρ = 0.84-0.96, P < 0.001). The mean DSC metric values were 0.86, 0.85, 0.77, and 0.79 at the pre-Tx and intra-Tx weeks (1-3), respectively. The SMIT algorithm provides sufficient segmentation accuracy for oncological applications in HPV+ OPSCC. First evaluation of auto-segmentation with SMIT using longitudinal T2w MRI in HPV+ OPSCC.

Clinical Outcomes in Patients With DLBCL Treated With R-CHOP According to Radiotherapy and Interim PET Response.

Interim positron emission tomography/computed tomography (PET/CT) scan is a valuable tool for assessing the early metabolic response to chemotherapy in diffuse large B-cell lymphoma (DLBCL). Although radiotherapy is an effective treatment for lymphoma, especially for local tumor control, the role of consolidative radiotherapy in diffuse large B-cell lymphoma (DLBCL) remains controversial. This study analyzed the clinical outcomes of patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), stratified by interim PET response and the administration of radiotherapy. We conducted a retrospective review of 107 patients with DLBCL treated with R-CHOP chemotherapy between January 2012 and December 2016. Overall survival (OS), recurrence-free survival (RFS), and freedom from disease progression (FFDP) were calculated using the Kaplan-Meier method and compared using the log-rank test. Forty-six patients were included in this analysis, with a median follow-up time of 65.9 months (range=4.7-125.3 months). The metabolic CR (mCR) group exhibited superior OS, RFS, and FFDP compared with the metabolic PR (mPR) group (p=0.003, p=0.001, and p=0.008, respectively). The 1-, 2-, and 5-year FFDP were 92.97%, 89.3%, and 85.6%, respectively, in the mCR group and 78.6%, 61.9%, and 44.2%, respectively, in the mPR group. In subgroup analysis, the FFDP of the mPR group without radiotherapy was significantly lower than that of the other groups (mCR with/without radiotherapy and mPR with radiotherapy, p=0.001). Consolidative radiation therapy using interim PET can benefit patients who do not achieve mCR. Further well-controlled prospective randomized trials are required.

The Survival Outcomes of the Metastatic Nonclear Cell Renal Cell Carcinoma in the Immunotherapy Era: Princess Margaret Cancer Centre Experience.

Immunotherapy (IO) with or without targeted therapy (TT) is the standard treatment for patients with metastatic clear cell renal cell carcinoma (RCC). The evidence supporting their use in metastatic nonclear cell renal cell carcinoma (nccRCC) subtypes is based on small prospective trials and retrospective analyses. Here, we report survival outcomes for patients with metastatic nccRCC treated with IO and/or TT at the Princess Margaret Cancer Centre, Toronto, ON, Canada. Demographics, disease characteristics, and survival outcomes were collected retrospectively. Overall (OS), progression-free survival (PFS), and objective response rates (ORR) were calculated. We identified 69 patients with metastatic nccRCC treated with IO and/or TT as the first-line treatment, and 36 (52.1%) patients as the second-line treatment. Median OS of the first line IO recipients (n = 12) and non-IO recipients (n = 57) was not reached (NR) and 17.2 months (95% confidence interval (95% CI): 7.3-27.0; P = 0.23), respectively. Median PFS of first-line IO recipients and non-IO recipients was NR and 4.7 months (95% CI: 3.7-5.6; P = 0.019), respectively. The ORR of IO recipients versus non-IO recipients was 50% versus 12.3% (P = 0.007). Median OS of the second-line IO recipients (n = 8) and non-IO recipients (n = 28) was NR and 6.3 months (95% CI: 3.2-9.3; P = 0.003), respectively. Median PFS of second-line IO recipients and non-IO recipients was 4.8 months (95% CI: 2.7-6.8) and 2.8 months (95% CI: 1.8-3.7; P = 0.014), respectively. ORR of IO recipients and non-IO recipients was 37.5% and 3.5%, respectively; P = 0.028. While the number of patients included in our retrospective review was small, our analysis suggested that patients with nccRCC have improved survival outcomes with IO treatment. Validation of prospective dataset is required before widespread clinical utilization.

The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy

ObjectiveTo explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer. MethodsEighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology. ResultsIDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176–10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234–11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis. ConclusionIDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.

Eligibility criteria for using menopausal hormone therapy in breast cancer survivors: a safety report based on a systematic review and meta-analysis.

Menopause hormone therapy (MHT) effectively alleviates menopausal symptoms. However, it is generally not recommended for breast cancer survivors, although the scientific evidence is scarce. This study aimed to establish eligibility criteria for use of the MHT in breast cancer survivors based on a systematic review and meta-analysis of the literature. We conducted exhaustive literature searches until June 2022 in MEDLINE, The Cochrane Library, and EMBASE, using a tailored strategy with a combination of controlled vocabulary and search terms related to breast cancer survivors and MHT. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and assessed the risk of bias using the Cochrane and Risk of Bias in Non-randomized Studies - of Interventions tools. The quality of the evidence was graded according to grading quality of evidence and strength of recommendations criteria (A, high; B, moderate; C, low; and D, very low). We categorized MHT use into four levels: category 1 (no restrictions on use), category 2 (the benefits outweigh the risks), category 3 (the risks generally outweigh the benefits), and category 4 (MHT should not be used). A total of 12 studies met the eligibility criteria. Analysis of the three randomized clinical trials using combined MHT or tibolone revealed no significant differences concerning tumor recurrence (relative risk [RR], 1.46; 95% CI, 0.99-2.24). A combined analysis of randomized clinical trials, prospective, and retrospective trials found no elevated risk of recurrence (RR, 0.85; 95% CI, 0.54-1.33) or death (RR, 0.91; 95% CI, 0.38-2.19). The eligibility criteria for patients with hormone receptor (HR)-positive tumors fell into categories 3B and 3C for combined MHT or estrogen alone and 4A for tibolone. For HR-negative tumors, the category was 2B and 2C. Our findings suggest that MHT could be a viable treatment alternative for breast cancer survivors experiencing menopausal symptoms, especially those with HR-negative tumors. Personalized management is recommended for each peri/postmenopausal woman facing a diminished quality of life because of menopause symptoms. Further randomized trials are needed before considering changes to current standards of care.

Comparative analysis of post-operative rehabilitation approaches for medial patellar luxation in small-breed dogs

Background and Aim: Electrical stimulation (ES) and light amplification by stimulated emission of radiation (LASER) therapy are frequently used in post-operative rehabilitation; however, there is currently insufficient research comparing their effectiveness. This study aimed to assess the effectiveness of post-operative rehabilitation following medial patellar luxation (MPL) surgical correction by comparing ES and LASER therapy when combined with exercise. This was compared with a control group that consisted solely of post-operative home exercise implemented by the owner. Materials and Methods: We conducted a prospective clinical trial on dogs that had undergone surgical treatment for MPL. The dogs were categorized into the following three groups: The control group, which did not participate in any post-operative rehabilitation program; the ES group, which received post-operative rehabilitation involving ES therapy; and the LASER group, which underwent post-operative rehabilitation featuring LASER therapy. Results: There were no significant differences among the groups regarding the evaluation parameters, including lameness score, pain score, thigh muscle circumference, and range of motion. Although there may have been a difference in pain score in some groups, it could be attributed to the pre-operative condition of patients. These results aligned with the owner questionnaires’ canine brief pain inventory assessments, showing no significant differences between treatment groups. Conclusion: Post-operative rehabilitation for MPL correction may enhance limb usage, joint function, muscle mass, and pain relief. However, the duration and level of post-operative pain may influence the necessity for rehabilitation. In addition, ES and LASER therapy offer similar pain-relieving effects after MPL surgery; therefore, the choice between these methods depends on the availability of equipment and veterinarian preferences. Keywords: electrical stimulation, light amplification by stimulated emission of radiation therapy, medial patellar luxation, post-operative management, rehabilitation.