Complete Rate Research Articles

Effect of neoadjuvant concurrent three-dimensional conformal chemoradiotherapy with conventional two-dimensional chemoradiotherapy in locally advanced rectal cancer

Background: Rectal carcinoma is a prevalent clinical condition, and treatment hinges on factors like tumor specifics, staging, grading, and histopathological characteristics. While surgery remains the primary treatment, neoadjuvant chemoradiotherapy, particularly using 3D-CRT, has proven effective in reducing local recurrence rates for locally advanced cases. Alternatively, 2D-RT is considered for neoadjuvant treatment. This study aimed to compare the impact of neoadjuvant concurrent three-dimensional conformal chemoradiotherapy with conventional two-dimensional chemoradiotherapy in the context of locally advanced rectal cancer. Methods: In this multicentre quasi-experimental study, 60 patients with biopsy-proven adenocarcinoma and clinically confirmed locally advanced rectal cancer, were divided into Group A (receiving oral capecitabine with three-dimensional conformal radiotherapy) and Group B (receiving the same capecitabine dose with 50 Gy two-dimensional radiotherapy). After surgery within 6-12 weeks, outcomes were analysed. Results: After neoadjuvant chemoradiotherapy, clinical complete response rates were 16.7% in Group A and 10.0% in Group B, with a higher pathological complete response in Group A (10.0% vs. 3.3%). Tumor downsizing occurred in 83.3% of Group A and 73.3% of Group B, and sphincter-sparing surgery was achieved in 73.3% of Group A and 56.7% of Group B. Grade 2 toxicities included anemia (10.0% vs. 13.3%), leucopenia (13.3% vs. 20.0%), diarrhoea (10.0% vs. 16.7%), proctitis (13.3% vs. 40.0%), and urinary toxicity (10.0% vs. 20.0%). Grade-1 toxicities were nausea (20.0% vs. 40.0%), vomiting (20.0% vs. 36.7%), mucositis (56.7% vs. 60.0%), hand-foot syndrome (33.3% vs. 40.0%), and urinary toxicity (43.3% vs. 56.67%), with significant proctitis in Group A (p=0.012). Other toxicities showed non-significant p-values (>0.05). Conclusions: Tumour response was not statistically significant between the patients of concurrent 3D-CRT and 2D-RT Arms. But the patients of 3D-CRT arm showed better response arithmetically. Also, there was an observable significant reduction of toxicities (lower gastrointestinal) in the 3D-CRT arm.

Efficacy and safety of solifenacin combined with biofeedback in children with overactive bladder

BackgroundOveractive bladder is a common chronic urological disorder in children, liable to impact normal social activities, disrupt sleep and even impair self-esteem. We aimed to evaluate the efficacy and safety of solifenacin combined with biofeedback for paediatric overactive bladder.MethodForty-five children with overactive bladder were enrolled and divided into three groups: 15 patients in Group A were treated with solifenacin, 15 cases in Group B with biofeedback, and the other 15 patients in Group C with the combination of solifenacin plus biofeedback. Each group was subdivided into the non-urge incontinence (non-UI) and urge incontinence (UI) groups. The remission rates were compared among the three groups at 2, 4, 8 and 12 weeks from the beginning of treatment. The side effects of solifenacin were recorded and followed up.ResultAfter 2 weeks since initial treatment, the complete response rates were 33.3% (5/15), 20.0% (3/15), and 53.3% (8/15) in the three groups. At 4 weeks, the complete remission rates were 46.7% (7/15), 33.3% (5/15), and 60.0% (9/15) respectively. Moreover, the complete remission rates of the UI groups were higher than the non-UI groups (p < 0.05). At 8 weeks, the complete response rates were 53.3% (8/15), 40.0% (6/15), and 67.7% (10/15). At 12 weeks, the complete response rates were 67.8% (10/15), 60.0% (9/15), and 86.7% (13/15). The complete response rates were higher and urodynamic parameters were improved obviously in group C than the other two groups (p < 0.05) during the follow-ups. The median voiding frequency decreased and median functional bladder capacity increased obviously in Group C after 4 weeks (p < 0.05). Dry mouth was observed in 2 patients (4.4%). 2 patients experienced constipation (4.4%), and neither case was severe. The symptoms of these four patients had relieved by reducing the dose of solifenacin.ConclusionSolifenacin combined with biofeedback had good efficacy and compliance for children experiencing overactive bladder. It took only 2 weeks to achieve the complete response rate over 50%, especially for the improvement of UI symptoms.

Safety and effectiveness assessment of the surpass evolve (SEASE): a post-market international multicenter study

BackgroundFlow diverters are the first-line treatment for specific intracranial aneurysms (iA). Surpass Evolve (SE) is a new-generation 64-wire flow diverter with a high braid angle. Current literature on the SE...

FRED X flow diverter for the treatment of intracranial aneurysms: Two-center experience and mini-review of the literature.

The flow re-direction endoluminal device (FRED) is a safe and effective treatment option for intracranial aneurysms. The novel FRED X features an antithrombotic surface coating ("X Technology") on an otherwise unmodified stent design. This two-center study evaluates the clinical safety and efficacy of FRED X and compares it to the literature. Consecutive patients treated between 2020 and 2023 were retrospectively reviewed for aneurysm characteristics, procedural details and complications, and angiographic outcomes. A mini-review of the literature for FRED X clinical trials was performed and results were pooled using a random effects model. Thirty-four patients (mean age 56 years) were treated for 34 aneurysms. The mean aneurysm size was 7.7 ± 5.0 mm, 7 (21%) were ruptured, 6 (18%) were recurrent after previous treatment, 11 (32.3%) were located in the posterior circulation, and 4 (12.5%) had non-saccular morphology. All procedures were technically successful and no balloon angioplasty was required. There was 1 (2.9%) symptomatic complication (a transient ischemic attack) and no procedural morbidity or mortality. Technical asymptomatic events included 1 procedural stent occlusion that was reopened with thrombectomy and 3 cases of vasospasm. Complete and adequate occlusion rates were 68% (19/28) and 89% (25/28) at a mean follow-up time of 6 months, respectively. The results of this study are comparable to previous FRED X studies. The results demonstrate a high feasibility and procedural safety of the FRED X with adequate mid-term occlusion rates. Long-term and comparative studies are needed to evaluate the full potential of the FRED X.

Salvage lung resection after immunotherapy is feasible and safe

ObjectivesPatients with non–small cell lung cancer treated with immunotherapy and modern chemoradiation regimens show improved progression-free and overall survival. However, patients with limited oligo-progression represent a potential population in which local therapy such as surgery may have a potential role as salvage treatment. The objectives of our study were to evaluate the feasibility and safety of salvage lung resection after immunotherapy in patients with non–small cell lung cancer. MethodsThe National Cancer Database was queried for patients diagnosed and treated for non–small cell lung cancer stage I to IV, from 2013 to 2020. Patients who underwent surgery as salvage after immunotherapy were defined as undergoing surgery >5 months from the initiation of immunotherapy. As a sensitivity analysis, patients who underwent surgery as salvage after chemoradiation were also analyzed in a similar fashion. Surgical outcomes such as type of surgery, complete resection (R0) rates, and complete pathologic response rates were determined for feasibility. Length of stay, 30-day readmission rates, and 30-day mortality rates were determined and overall survivals were estimated with Kaplan-Meier analysis to evaluate for safety. ResultsOf the 934,093 patients diagnosed with non–small cell lung cancer stage I to IV from 2013 to 2020, 164 patients received immunotherapy and after 5 months underwent surgery. Lobectomy was the most commonly performed operation (74%) and pneumonectomy was required in 9% (n = 15). R0 resection was achieved in 89% (n = 146) and of these patients, 23% (n = 37) had complete pathologic response. Median length of stay was 4 days, 30-day readmission was 5%, and 30-day mortality was 0.6%. In our sensitivity analysis of chemoradiation patients (n = 445), the above data were similar to previously reported cohort studies of patients undergoing chemoradiation and subsequently salvage surgery. ConclusionsLung resection after immunotherapy appears to be a feasible salvage treatment option, with lobectomy being most common and with high R0 resection rates. Low patient morbidity and mortality rates also suggest the safety of this approach. Salvage surgery may be considered in patients who have oligo-progression after immunotherapy within the context of a comprehensive multidisciplinary treatment plan.

From standard therapies to monoclonal antibodies and immune checkpoint inhibitors - an update for reconstructive surgeons on common oncological cases.

Malignancies represent a persisting worldwide health burden. Tumor treatment is commonly based on surgical and/or non-surgical therapies. In the recent decade, novel non-surgical treatment strategies involving monoclonal antibodies (mAB) and immune checkpoint inhibitors (ICI) have been successfully incorporated into standard treatment algorithms. Such emerging therapy concepts have demonstrated improved complete remission rates and prolonged progression-free survival compared to conventional chemotherapies. However, the in-toto surgical tumor resection followed by reconstructive surgery oftentimes remains the only curative therapy. Breast cancer (BC), skin cancer (SC), head and neck cancer (HNC), and sarcoma amongst other cancer entities commonly require reconstructive surgery to restore form, aesthetics, and functionality. Understanding the basic principles, strengths, and limitations of mAB and ICI as (neo-) adjuvant therapies and treatment alternatives for resectable or unresectable tumors is paramount for optimized surgical therapy planning. Yet, there is a scarcity of studies that condense the current body of literature on mAB and ICI for BC, SC, HNC, and sarcoma. This knowledge gap may result in suboptimal treatment planning, ultimately impairing patient outcomes. Herein, we aim to summarize the current translational endeavors focusing on mAB and ICI. This line of research may serve as an evidence-based fundament to guide targeted therapy and optimize interdisciplinary anti-cancer strategies.

Mycophenolate mofetil vs. cyclophosphamide-based induction regimens for lupus nephritis: Outcomes at a tertiary care centre in Lahore, Pakistan.

To compare the efficacy of mycophenolate mofetil with intravenous cyclophosphamideas induction therapy in lupus nephritis. The observational, prospecrive, cohort study was conducted at the Rheumatology Department of Fatima Memorial Hospital, Lahore, Pakistan, from July 2016 to June 2019, and comprised lupus nephritis patients. For induction therapy, the patients were assigned at the discretion of the treating rheumatologist to mycophenolate mofetil group MMF, and intravenous cyclophosphamide group CYC. The latter group was further divided into NIH subgroup that received the therapy as per the protocol of the National Institutes of Health, and ELNT subgroup which recived the therapy as per the Euro Lupus Nephritis Trial protocol. Maintenance therapy in all groups was mycophenolate mofetil. Tacrolimus was added in case of non-response. The outcome was the achievement of complete renal response at 6, 12 and 24 months. Data was analysed using SPSS 26. Of the 131 patients, 126(96.2%) were females. The overall mean age was 27±7.7 years. There were 58(44.2%) patients in group MMF and 73(55.7%) in group CYC, which had subgroup NIH 46(63%) and subgrpup ELNT 27(37%). The complete renal response rates at 6, 12, and 24 months were 22 (43.1%), 35 (71.4%), and 40(83.3%) for group MMF; 5(12.5%), 9(22%) and 24 (58.5%) for subgroup NIH, and 6(26.1%), 8(36.4%) and 14(63.6%) for subgroup ELNT. Group MMF outcomes were significantly better than the rest (p<0.05). Mycophenolate mofetil induction therapy was more effective than intraveenous cyclophosphamide in terms of achieving remission at 6, 12 and 24 months.

Surgical Outcomes after Radiotherapy in Rectal Cancer.

Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program.

Analysis of the efficacy and safety of bone disease treatment in patients with newly diagnosed multiple myeloma treated with denosumab or zoledronic acid

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum β-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.

A Prospective Comparison of 180 Versus 360-Degree Gonioscopy-Assisted Transluminal Trabeculotomy Outcomes in Pseudoexfoliation Glaucoma.

Analysis of surgical success and intraocular pressure (IOP), best-corrected visual acuity (BCVA), and antiglaucomatous medication (AGM) changes between segmental 180-degree and 360-degree gonioscopy-assisted transluminal trabeculectomy (GATT) in patients with pseudoexfoliation glaucoma (PEXG) showed no significant difference. To compare surgical outcomes of segmental 180-degree and 360-degree GATT in patients with PEXG. Prospective, comparative study of 65 PEXG eyes, who underwent segmental 180-degree GATT (GATT 180-degree group, 31 eyes) and 360-degree GATT (GATT 360-degree group, 34 eyes) in a tertiary academic center over a 12-month of follow-up. Primary outcome was qualified and complete surgical success rates for criterion A (IOP <18mm Hg and >30% reduction) and criterion B (IOP <15mm Hg and >30% reduction). Secondary outcome measures included IOP reduction, BCVA change, AGM use, and postoperative complications. The probabilities of qualified and complete success rates both for criteria A and B did not significantly differ between the groups ( P > 0.05). IOP and BCVA levels were similar at each time point ( P > 0.05). IOP reduction was 59.3 ± 9.5% in the GATT 180-degree group and 55.8 ± 18.1% in the GATT 360-degree group ( P = 0.33). No significant difference in the mean number of AGM was present at the 12-month visit (1.2 ± 1.1 in GATT 180-degree group vs 1.5 ± 1.2 in GATT 360-degree group, P = 0.25). Significantly higher incidences of postoperative hyphema and IOP spikes were observed in the GATT 360-degree group ( P = 0.01 and P = 0.008, respectively). Both segmental 180-degree and 360-degree GATT similarly reduced IOP and AGM with comparable surgical success rates in patients with PEXG at the end of 12 months. Postoperative hyphema and IOP spike rates were significantly higher after 360-degree GATT. Segmental 180-degree GATT may be sufficient to adequately modulate IOP with a lower incidence of postoperative complications in PEXG.

Administration of oral prednisolone to prevent esophageal stricture after balloon-type radiofrequency ablation for ultralong-segment esophageal neoplasia

Background and AimsEndoscopic radiofrequency ablation (RFA) has shown good efficacy and safety in eradicating flat-type early esophageal squamous cell neoplasia (ESCN). However, post-RFA stricture is still a major concern, especially when treating ultralong-segment ESCNs. The aim of this study was to investigate the efficacy and safety of oral prednisolone to prevent post-RFA stricture. MethodsWe prospectively enrolled 48 patients treated with balloon-type RFA who had Lugol-unstained or mosaic-like flat-type ESCNs with an expected treatment area more than 10 cm. Oral prednisolone was started at a dose of 30 mg/day on the third day after RFA and continued for 4 weeks. The results were compared to a historical control group of 25 patients who received RFA without oral steroids. The primary endpoint was the frequency of post-RFA stricture. Secondary endpoints were the number of balloon dilation sessions and adverse event rate. ResultsThere were no significant differences in the worst pathology grade at baseline, length of unstained lesions between the two groups. The complete response rates after 1 session of RFA were 73% and 72%, respectively. Compared to the control group, the oral prednisolone group had a significantly lower stricture rate (4%, 2/48 patients vs. 44%, 11/25 patients; P<0.0001) and a lower number of balloon dilation sessions (median 0, range 0-4 vs. median 6, range 0-10). There were two cases of asymptomatic candida esophagitis in the study group, and no severe adverse effects. ConclusionsOral prednisolone may offer a useful and safe preventive option for post-RFA stricture in ultralong ESCNs. Clinical trial registration numberNCT05768282

Abstract LB003: Comprehensive multi-omics analysis unveils NFE2L2/KEAP1 mutations as key drivers of treatment resistance in esophageal squamous cell carcinoma during chemoradiotherapy

Abstract Esophageal squamous cell carcinoma (ESCC) stands as one of the most formidable and lethal cancers, necessitating urgent intervention. Despite extensive research efforts to identify optimal radiotherapy and chemotherapy strategies, complete response rates remain disappointingly low, and the challenge of swift relapse persists. Previous investigations primarily focused on primary tumors, utilizing single-omics approaches to illuminate cellular responses to chemotherapy and immunotherapy. However, our understanding of the mechanistic basis for chemoradiotherapy resistance in ESCC remains severely limited. In this study, we conducted multi-omics profiling of over 100 pre-treatment primary and post-treatment relapse ESCC tumors subjected to chemoradiotherapy from a clinical trial (ESO-Shanghai6; NCT04694391). Our comprehensive approach included whole-exome/genome sequencing (WES/WGS), bulk RNA-sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptome analyses. WES/WGS revealed that tumors with rapid relapse displayed high clonal diversity. Notably, 40% of ESCC relapse patients exhibited NFE2L2/KEAP1 somatic alterations in their primary tumors, correlating with a dismal prognosis. Consistent with these findings, downstream NRF2 signaling targets were upregulated in relapse tumors and radiotherapy-resistant cell lines. Further analysis of scRNA-seq and spatial transcriptome data provided profound insights into the spatial organization of mutation-driven, relapse-associated cell populations and their interactions within the tumor microenvironment (TME). Intriguingly, a subset of epithelial tumor cells characterized by NRF2 pathway activation was highly enriched in relapse tumors. Among immune cells, the infiltration proportions of SPP1+ macrophages and SPP1+TREM2+ macrophages—exhibiting higher myeloid immunosuppressive scores—tended to increase in relapse patients. Crucially, NRF2-signaling activated epithelial cells physically co-localized with SPP1+TREM2+ macrophages exclusively in relapse samples, while SPP1+ macrophages were present in both primary and relapse samples. Interaction analysis suggested that NRF2-signaling activated epithelial cells recruit SPP1+TREM2+ and SPP1+ macrophages, thereby fostering an immunosuppressive TME and promoting post-radiotherapy relapse. In summary, our study provides a comprehensive understanding of the molecular determinants influencing ESCC tumor responses under chemoradiotherapy. NFE2L2/KEAP1 mutations emerge as predictive markers for stratifying ESCC patients, and targeting NRF2 signaling presents a potential avenue to overcome resistance to chemoradiotherapy in this challenging disease. Citation Format: Kuaile Zhao, Hu Chen, Zhenzhen Xun, Jiaying Deng, Yikai Luo, Jinjun Ye, Junqiang Chen, Weiwei Chen, Jun Li, Han Liang. Comprehensive multi-omics analysis unveils NFE2L2/KEAP1 mutations as key drivers of treatment resistance in esophageal squamous cell carcinoma during chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB003.

MRI-guided optimisation of neoadjuvant chemotherapy duration in stage II–III HER2-positive breast cancer (TRAIN-3): a multicentre, single-arm, phase 2 study

Patients with stage II-III HER2-positive breast cancer have good outcomes with the combination of neoadjuvant chemotherapy and HER2-targeted agents. Although increasing the number of chemotherapy cycles improves pathological complete response rates, early complete responses are common. We investigated whether the duration of chemotherapy could be tailored on the basis of radiological response. TRAIN-3 is a single-arm, phase 2 study in 43 hospitals in the Netherlands. Patients with stage II-III HER2-positive breast cancer aged 18 years or older and a WHO performance status of 0 or 1 were enrolled. Patients received neoadjuvant chemotherapy consisting of paclitaxel (80 mg/m2 of body surface area on day 1 and 8 of each 21 day cycle), trastuzumab (loading dose on day 1 of cycle 1 of 8 mg/kg bodyweight, and then 6 mg/kg on day 1 on all subsequent cycles), and carboplatin (area under the concentration time curve 6 mg/mL per min on day 1 of each 3 week cycle) and pertuzumab (loading dose on day 1 of cycle 1 of 840 mg, and then 420 mg on day 1 of each subsequent cycle), all given intravenously. The response was monitored by breast MRI every three cycles and lymph node biopsy. Patients underwent surgery when a complete radiological response was observed or after a maximum of nine cycles of treatment. The primary endpoint was event-free survival at 3 years; however, follow-up for the primary endpoint is ongoing. Here, we present the radiological and pathological response rates (secondary endpoints) of all patients who underwent surgery and the toxicity data for all patients who received at least one cycle of treatment. Analyses were done in hormone receptor-positive and hormone receptor-negative patients separately. This trial is registered with ClinicalTrials.gov, number NCT03820063, recruitment is closed, and the follow-up for the primary endpoint is ongoing. Between April 1, 2019, and May 12, 2021, 235 patients with hormone receptor-negative cancer and 232 with hormone receptor-positive cancer were enrolled. Median follow-up was 26·4 months (IQR 22·9-32·9) for patients who were hormone receptor-negative and 31·6 months (25·6-35·7) for patients who were hormone receptor-positive. Overall, the median age was 51 years (IQR 43-59). In 233 patients with hormone receptor-negative tumours, radiological complete response was seen in 84 (36%; 95% CI 30-43) patients after one to three cycles, 140 (60%; 53-66) patients after one to six cycles, and 169 (73%; 66-78) patients after one to nine cycles. In 232 patients with hormone receptor-positive tumours, radiological complete response was seen in 68 (29%; 24-36) patients after one to three cycles, 118 (51%; 44-57) patients after one to six cycles, and 138 (59%; 53-66) patients after one to nine cycles. Among patients with a radiological complete response after one to nine cycles, a pathological complete response was seen in 147 (87%; 95% CI 81-92) of 169 patients with hormone receptor-negative tumours and was seen in 73 (53%; 44-61) of 138 patients with hormone receptor-positive tumours. The most common grade 3-4 adverse events were neutropenia (175 [37%] of 467), anaemia (75 [16%]), and diarrhoea (57 [12%]). No treatment-related deaths were reported. In our study, a third of patients with stage II-III hormone receptor-negative and HER2-positive breast cancer had a complete pathological response after only three cycles of neoadjuvant systemic therapy. A complete response on breast MRI could help identify early complete responders in patients who had hormone receptor negative tumours. An imaging-based strategy might limit the duration of chemotherapy in these patients, reduce side-effects, and maintain quality of life if confirmed by the analysis of the 3-year event-free survival primary endpoint. Better monitoring tools are needed for patients with hormone receptor-positive and HER2-positive breast cancer. Roche Netherlands.

Athletic Trainers' Familiarity, Comfort, Knowledge, and Recognition of Social Determinants of Health.

Social determinants of health (SDOH)-education, transportation, housing, employment, health systems and services, economic status, and physical and social environments-influence patient outcomes; therefore, athletic trainers (ATs) need to understand and address these factors. However, little is known about how ATs perceive SDOH or how knowledgeable they are about social factors that contribute to patient health and well-being. To evaluate ATs' familiarity and comfort with SDOH and their perceived knowledge and recognition of SDOH. Cross-sectional study. Online survey. Our survey was distributed to 17 000 ATs; 1829 accessed it (access rate = 10.8%), and 1694 completed it (completion rate = 92.6%, AT experience = 15.2 ± 10.6 years, age = 36.6 ± 10.8 years). The survey included multipart questions that evaluated ATs' perceptions of their familiarity, comfort, and knowledge about SDOH. Data were summarized using descriptive statistics. Few respondents (4.1%, 70/1691) reported being extremely familiar with SDOH. Most indicated being moderately familiar (45.0%, 761/1691), minimally familiar (34.7%, 587/1691), or not familiar at all (16.1%, 273/1691). For questions about comfort, few described being extremely comfortable (3.5%, 59/1691) with SDOH, and most reported being moderately comfortable (35.4%, 598/1691), minimally comfortable (41.1%, 695/1691), or not comfortable at all (18.6%, 314/1691). For questions about knowledge, few indicated being extremely knowledgeable (2.7%, 46/1686) about SDOH, and the majority described being moderately (36.8%, 622/1686), minimally (41.8%, 704/1686), or not knowledgeable at all (18.6%, 314/1686). Over half of ATs accurately categorized 8 of the 9 SDOH listed in the survey, and 22% endorsed more correct than incorrect items. A majority of ATs perceived their familiarity, comfort, and knowledge about SDOH to be moderate to low, which may reflect the relatively recent emphasis on SDOH in athletic health care. Because SDOH can have a major effect on patient health and well-being, strategies should be developed for educating ATs about SDOH. Developing strategies to increase comfort with SDOH in patient care is critical to ensure that those factors that can be addressed at the patient level are identified and managed.

Parent Awareness of and Attitudes Toward Gender-Affirming Pediatric Health Care: A Cross-Sectional Survey.

We aimed to characterize parent attitudes toward gender-affirming healthcare for transgender youth, from a general parent sample in a diverse urban setting. We surveyed Chicago parents through the Voices of Child Health in Chicago Parent Panel Survey via web and phone in English and Spanish from May-July 2022. We used both probability-based and nonprobability-based sampling, with calibration weights for the nonprobability sample. Parents responded about their awareness of a debate about and support for autonomy in gender-affirming healthcare for transgender youth and provided demographic information. We used descriptive analyses and logistic regression to examine predictors of awareness and support. Data were weighted to be representative of Chicago's parent population. Surveys were completed by 1,059 parents. The survey completion rate for the probability sample was 43.1% (a completion rate was not available for the nonprobability sample from online, opt-in surveys). Most parents were unaware of the debate about gender-affirming healthcare (56.0%). More than two-thirds of parents (68.9%) support decisions about gender-affirming healthcare being left to children, their parents, and their doctor. Parents who were aware of the debate were more likely to support gender-affirming healthcare (83.7%) than parents who were not aware (57.2%, p < .0001). Parents who were aware of the debate had higher odds of supporting gender-affirming care for youth (adjusted odds ratio= 3.00, 95% confidence interval: 1.93-4.66) in a multivariable logistic regression model. Broad parent support for gender-affirming healthcare for transgender youth is an important perspective to consider in policy discussions at state and federal levels.

Novel methods for the remote investigation of emerging substances: Application to kratom.

The botanical product commonly called "kratom" is still relatively novel to the United States. Like other natural products marketed as supplements, kratom is highly variable, both in terms of the alkaloids naturally occurring in kratom leaves and in terms of processing and formulation. Kratom products sold in the United States are not well-characterized, nor are daily use patterns among regular users. Surveys and case reports have comprised most of the literature on kratom use among humans. To advance our understanding of real-world kratom use, we developed a protocol for the remote study of regular kratom-using adults in the United States. Our study had three aspects implemented in one pool of participants nationwide: an in-depth online survey, 15 days of ecological momentary assessment (EMA) via smartphone app, and the collection and assay of the kratom products used by participants during EMA. Here, we describe these methods, which can be used to investigate myriad drugs or supplements. Recruiting, screening, and data collection occurred between July 20, 2022 and October 18, 2022. During this time, we demonstrated that these methods, while challenging from a logistical and staffing standpoint, are feasible and can produce high-quality data. The study achieved high rates of enrollment, compliance, and completion. Substances that are emerging or novel, but still largely legal, can be productively studied via nationwide EMA combined with assays of shipped product samples from participants. We discuss challenges and lessons learned so other investigators can adapt these methods. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Brazil-TNT: A Randomized Phase 2 Trial of Neoadjuvant Chemoradiation Followed by FOLFIRINOX Versus Chemoradiation for Stage II/III Rectal Cancer

BackgroundNeoadjuvant radiation and oxaliplatin-based systemic therapy (total neoadjuvant therapy—TNT) have been shown to increase response and organ-preservation rates in localized rectal cancer. However, trials have been heterogeneous regarding treatment protocols and few have used a watch-and-wait (WW) approach for complete responders. This trial evaluates if conventional long-term chemoradiation followed by consolidation of FOLFIRINOX increases complete response rates and the number of patients managed by WW. MethodsThis was a pragmatic randomized phase II trial conducted in 2 Cancer Centers in Brazil that included patients with T3+ or N+ rectal adenocarcinoma. After completing a long-course 54 Gy chemoradiation with capecitabine patients were randomized 1:1 to 4 cycles of mFOLFIRINOX (Oxaliplatin 85, irinotecan 150, 5-FU 2400)—TNT-arm—or to the control arm, that did not include further neoadjuvant treatment. All patients were re-staged with dedicated pelvic magnetic resonance imaging and sigmoidoscopy 12 weeks after the end of radiation. Patients with a clinical complete response were followed using a WW protocol. The primary endpoint was complete response: clinical complete response (cCR) or pathological response (pCR). ResultsBetween April 2021 and June 2023, 55 patients were randomized to TNT and 53 to the control arm. Tumors were 74% stage 3, median distance from the anal verge was 6 cm, 63% had an at-risk circumferential margin, and 33% an involved sphincter. The rates of cCR + pCR were (31%) for TNT versus (17%) for controls (odds ratio 2.19, CI 95% 0.8-6.22 P = .091) and rates of WW were 16% and 9% (P = ns). Median follow-up was 8.1 months and recurrence rates were 16% versus 21% for TNT and controls (P = ns). ConclusionsTNT with consolidation FOLFIRINOX is feasible and has high response rates, consistent with the current literature for TNT. This trial was supported by a grant from the Brazilian Government (PROADI-SUS - NUP 25000.164382/2020-81).

Real world evaluation of pathological complete response rates following the use of pembrolizumab alongside neo-adjuvant chemotherapy in early triple negative breast cancer

Real world evaluation of pathological complete response rates following the use of pembrolizumab alongside neo-adjuvant chemotherapy in early triple negative breast cancer

Combinational therapy of CAR T-cell and HDT/ASCT demonstrates impressive clinical efficacy and improved CAR T-cell behavior in relapsed/refractory large B-cell lymphoma

BackgroundApproximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to...

Safety and efficacy of chimeric antigen receptor T-cell therapy for acute myeloid leukemia: A subgroup based meta-analysis

IntroductionAcute myeloid leukemia (AML) is a significant hematological malignancy in the United States, with a high mortality rate and limited treatment options. CAR T-cell therapy, a new and promising treatment, is being investigated for its efficacy and safety in AML. This meta-analysis aims to assess the safety and efficacy of CAR T-cell therapy in AML, considering various subgroups such as study location, study design, prior transplantation status, conditioning regimen, and CAR T-cell source. MethodsWe conducted a comprehensive literature review across multiple databases, adhering to PRISMA guidelines and focusing on studies concerning CAR T-cell therapy in AML. We included original articles in English and excluded non-original reviews, abstracts, and non-English studies. The risk of bias was assessed using the Cochrane ROBINS-I tool. Statistical analysis involved meta-analysis with Cochrane’s Q-test and I² statistic, using both fixed-effect and random-effects models, and assessed for publication bias. ResultsOur search yielded studies encompassing 57 AML patients treated with CAR T-cell therapy. The meta-analysis revealed a 48% incidence of complete remission with CAR T-cell therapy, varying significantly across subgroups based on study design, location, prior transplantation, conditioning regimen, and CAR T-cell source. The highest complete remission rates were observed in patients from China, those who had undergone prior hematopoietic cell transplantation, and those treated with fludarabine and cyclophosphamide conditioning regimen. Adverse events included graft-versus-host disease (7%) and cytokine release syndrome (53%). ConclusionsThis meta-analysis highlights the potential of CAR T-cell therapy in AML treatment, especially when integrated with certain prior treatments and conditioning regimens. The findings suggest a higher efficacy in patients with previous hematopoietic cell transplantation and specific conditioning regimens. Further large-scale, randomized trials are essential to confirm these findings and establish CAR T-cell therapy as a standard treatment for AML.