Complete Rate Research Articles

On the solution of MHD Jeffery–Hamel problem involving flow between two nonparallel plates with a blood flow application

AbstractThe Jeffery–Hamel flow phenomenon appears in a variety of real‐world applications involving the flow of two nonparallel plates. BY using a similarity transformation derived from the equation of continuity, partial differential equations determining flow characteristics are translated into nonlinear ordinary differential equations. The problem involves the flow of a specific type of fluid, namely, an incompressible and electrically conducting fluid, between two nonparallel plates. The flow is assumed to be steady, two‐dimensional, and subject to certain boundary conditions. Specifically, the plates are impermeable, and the fluid adheres to a no‐slip condition, resulting in zero fluid velocity at the plates' surfaces. Moreover, the problem incorporates the effects of magnetic fields and pressure fluctuations, making it highly applicable to scenarios, such as blood flow through arteries in the human body, which can be modeled as a special case of the magnetohydrodynamic (MHD) Jeffery–Hamel problem referred to as the (MHD) blood pressure equation. This work compares two numerical approaches for solving the MHDs Jeffery–Hamel problem: B‐spline and Bernstein polynomial collocation. The given approaches are used to discretize and transform the equation into a system of algebraic equations. Matrix algebra techniques are then used to solve the resultant system. A complete error analysis and convergence rates for different grid sizes are derived for both methods and are used to compare the accuracy and efficiency of the two approaches. Both approaches produce correct solutions, according to the numerical findings, although the Bernstein polynomial collocation method is more efficient and accurate than the B‐spline collocation.

Abstract PO2-01-02: Clinicopathologic features and prognosis of breast cancer with low HER2 expression evaluated by fluorescence in situ hybridization

Abstract Background Although trastuzumab deruxtecan has been found to improve progression-free survival and overall survival of HER2-low breast cancer patients in DESTINY Breast04 trial, the characteristics and prognostic value of low HER2 expression remains to be elucidated. In this study, we retrospectively examined the clinicopathologic characteristics and prognosis of HER2-low expressing breast cancer. Methods A prospective database of 1026 clinical stage I to Ⅲ, HER2 negative breast cancer patients who underwent surgery from September 2012 to October 2022 at Teikyo University Hospital was analyzed. HER2 was evaluated by fluorescence in situ hybridization assay, and HER2-low and HER2-negative was defined as HER2/CEP17 ratio ≧1.0, and < 1.0, respectively. The chi-squared test was performed to estimate correlations between HER2-low status and clinicopathological factors. Distant-disease survival (DDFS) was calculated using the Kaplan-Meier curves and log-rank test. Multivariate logistic regression analyses were used to identify the independent prognostic factors. Results Median age, tumor size and ki67 of the entire 1026 patients was 56.0 years (range=23.0-93.0), 2.0 cm (range=0.3-15.0 cm), and 15.0 % (range=0.5-99.0 %), respectively. 155 (15.1 %) patients had lymph node metastasis. 904 (88.1 %) patients revealed hormone receptor positive (estrogen receptor [ER] positive; 904 patients, progesterone receptor [PgR] positive; 810 patients). Neoadjuvant and adjuvant chemotherapy was performed in 197 (19.2 %) and 160 (15.6 %) patients, respectively. Among all patients, 904 (88.1 %) patients had HER2-low tumors and 122 (11.9 %) patients had HER2-negative tumors. Positive rate of ER and PgR was significantly higher in HER2-low compared to HER2-negative patients (ER: 804 [88.9 %] patients vs 100 [82.0 %] patients; p=0.026 , PgR: 723 [80.0 %] patients vs 87 [71.3 %] patients; p=0.028). The median ki67 was significantly lower in HER2-low compared to HER2-negative patients (14.5 % vs 18.5 %, p=0.013). Pathologic complete response rates were not significantly different between HER2-low and HER2-negative patients (16.1 % [27/168 patients] vs 17.2 % [5/24 patients], p=0.528). With a median follow-up time of 39.7 months, DDFS was significantly better in HER2-low compared to HER2-negative patients (96.6 % vs 90.7 %, p=0.027). Multivariate logistic regression analyses showed that HER2-low expression was not independently related factors for DDFS. Conclusion These data suggested that HER2-low expression might not have significant association with prognosis despite significant correlation with ki67 and hormone receptor expression. Citation Format: Ayana Sato, Saki Naruse, Yuka Isono, Yuka Maeda, Miki Yamada, Akiko Matsumoto, Tatsuhiko Ikeda, Hiromitsu Jinno. Clinicopathologic features and prognosis of breast cancer with low HER2 expression evaluated by fluorescence in situ hybridization [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-02.

Optimal duration of oxaliplatin-based adjuvant chemotherapy in patients with different risk factors for stage II-III colon cancer: a meta-analysis.

The duration of oxaliplatin-based chemotherapy in high-risk stage II, low-risk stage III, and high-risk stage III colon cancer (CC) patients is controversial. To reduce the risk of adverse events (AEs) without compromising efficacy while improving chemotherapy compliance is crucial. The authors searched Cochrane, Embase, Pubmed, and Web of Science databases for articles from inception to August 8, 2023, the main outcomes were disease-free survival, overall survival, chemotherapy completion rates, and AE frequency. Six randomized controlled trials (RCTs) involving 10332 patients were included. Disease-free survival analysis revealed that only the high-risk stage III CC patients experienced better results with the 6-month FOLFOX regimen when compared with the 3-month regimen [Hazard ratio (HR): 1.32, 95% CI: 1.15-1.51, P <0.0001). Overall survival (OS) analysis revealed that extending the use of FOLFOX and CAPEOX regimens did not provide survival benefits for stage III CC patients (HR: 1.16, 95% CI: 0.9-1.49, and HR: 0.89, 95% CI: 0.67-1.18, P =0.40). The completion rate of the 3-month oxaliplatin-based adjuvant chemotherapy regimen was significantly higher than that of the 6-month regimen [Relative risk (RR): 1.16, 95% CI: 1.06-1.27, P =0.002]. Moreover, the 3-month regimen had significantly lower AE rates than the 6-month regimen (RR: 0.62, 95% CI: 0.57-0.68, P <0.00001), with differences mainly concentrated in grade 3/4 neutropenia (RR: 0.70, 95% CI: 0.59-0.85, P =0.0002), peripheral sensory neuropathy at ≥grade 2 (RR: 0.45, 95% CI: 0.38-0.53, P <0.00001), and hand-foot syndrome at ≥grade 2 (RR: 0.36, 95% CI: 0.17-0.77, P =0.009). The 6-month FOLFOX regimen should only be recommended for high-risk stage III CC, while the 3-month regimen can be recommended for other stages. A 3-month CAPEOX regimen can be recommended for stage II-III CC.

Comparison between Woven EndoBridge and coiling with and without stent assistance for intracranial bifurcation and wide-neck aneurysms: a comprehensive systematic review and meta-analysis.

The recent introduction of the Woven EndoBridge (WEB) has presented an alternative treatment modality for intracranial bifurcation and wide-neck aneurysms with a growing body of literature evaluating its efficacy. However, no previous systematic review has focused on comparing WEB with previously using endovascular approaches, specifically primary coiling (PC) and stent-assisted coiling (SAC). Herein, the authors present the first systematic review summarizing available literature to reach a consensus regarding the safety and effectiveness of WEB. A systematic review of articles identified through a search of PubMed, Embase, Scopus, and Web of Science was conducted. Studies were included if they compared WEB with PC or SAC from any aspect for intracranial aneurysms. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions tool. Meta-analyses of the outcomes based on stent use and rupture status were performed. A total of 16 studies were included. The three endovascular approaches were comparable in terms of baseline characteristics except for older age and smaller aneurysm neck in the PC group (p < 0.05). Moreover, the follow-up duration was shorter in the WEB group (p < 0.05). Although the WEB group demonstrated lower complete and adequate immediate occlusion rates (p < 0.01), the rates at follow-up evaluations were comparable with SAC and PC (p = 0.61 and p = 0.27, respectively). The WEB group experienced significantly fewer unfavorable neurological outcomes than the SAC group (p = 0.04), while comparable to the PC group (p = 0.36). Retreatment rates were comparable between WEB and coiling (p = 0.92). The WEB group had fewer hemorrhagic and thromboembolic complications (p < 0.01 and p = 0.01, respectively), with similar neurological and procedure-related complications compared with combined PC and SAC groups. Lastly, mortality was comparable among the different endovascular approaches. This study provides evidence on the noninferiority of WEB compared with PC and SAC in terms of angiographic outcomes. Meanwhile, our findings on lower complication rates, cost, and improved operative aspects associated with WEB establish this novel endovascular treatment as a safe and effective alternative for the treatment of bifurcation and wide-neck aneurysms.

Invasive lobular carcinoma of the breast; clinicopathologic profile and response to neoadjuvant chemotherapy over a 15-year period

IntroductionInvasive lobular carcinoma (ILC) accounts for 5–15% of invasive breast cancers. Typical ILC is oestrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative. Atypical biomarker profiles (ER- and HER2+, ER+ and HER2+ or triple negative) appear to differ from typical ILCs. This study compared subtypes of ILC in terms of clinical and pathological parameters, and response to neoadjuvant chemotherapy (NACT) according to biomarker profile. MethodsAll patients with ILC treated in a single centre from January 2005 to December 2020 were identified from a prospectively maintained database. Clinicopathologic and outcome data was collected and analysed according to tumour biomarker profile. ResultsA total of 582 patients with ILC were treated. Typical ILC was observed in 89.2% (n = 519) and atypical in 10.8% (n = 63). Atypical ILCs were of a higher grade (35% grade 3 vs 9.6% grade 3, p < 0.001).A larger proportion of atypical ILC received NACT (31.7% vs 6.9% p < 0.001). Atypical ILCs showed a greater response to NACT (mean RCB (Residual Cancer Burden Score) 2.46 vs mean RCB 3.41, p = 0.0365), and higher pathological complete response rates (15% vs 0% p = 0.017). Despite this, overall 5-year disease-free survival (DFS) was higher in patients with typical ILC (91% vs 83%, p = 0.001). ConclusionsAtypical ILCs have distinct characteristics. They are more frequently of a higher grade and demonstrate a superior response to NACT. Despite the latter, atypical ILCs have a worse 5-year DFS which should be taken into consideration in terms of prognostication and may assist patient selection for NACT.

Electrical acupoint stimulation for the treatment of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis

BackgroundChemotherapy-induced nausea and vomiting (CINV) is the most common adverse effect of chemotherapy and affects the continuation of chemotherapy in cancer patients. Electrical acupoint stimulation (EAS), which includes electroacupuncture and transcutaneous electrical stimulation (TES), has been used to treat CINV. This meta-analysis aimed to evaluate the efficacy of EAS in the treatment of CINV. MethodsRandomized controlled trials (RCTs) of EAS for CINV retrieved form five key databases. Two researchers independently performed article screening, data extraction and data integration. The Cochrane Collaboration's tool for assessing risk of bias was used to assesse the methodological quality according to Cochrane Handbook for Systematic Reviews of Interventions. RevMan 5.4 was used to perform analyses. Results10 RCTs with a total of 950 participants were included. The results showed that there was no significant difference between EAS compared to sham EAS in terms of increasing the rate of complete control of CINV and decreasing the overall incidence of CINV [RR = 1.26, 95 % CI (0.96, 1.66), P = 0.95; RR = 1.16, 95 % CI (0.97, 1.40), p = 0.71]. In terms of CINV severity, EAS reduced the occurrence of moderate-to-severe CINV [RR = 0.60, 95 % CI (0.38, 0.94), P = 0.03; RR = 0.50, 95 % CI (0.33, 0.76), P = 0.001]. ConclusionEAS could improve moderate-to-severe CINV. However, EAS did not show a significant difference in reducing overall incidence and improving complete control rates compared with sham EAS. Due to limitations in the quality of the included articles, the available studies are insufficient to have sufficient evidence to confirm the efficacy of EAS for CINV. Validation with rigorously designed, large-sample, high-quality clinical trial studies may also be needed.

Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial

Antibodies targeting the immune checkpoint molecules PD-1, PD-L1 and CTLA-4, administered alone or in combination with chemotherapy, are the standard of care in most patients with metastatic non-small-cell lung cancers. When given before curative surgery, tumor responses and improved event-free survival are achieved. New antibody combinations may be more efficacious and tolerable. In an ongoing, open-label phase 2 study, 60 biomarker-unselected, treatment-naive patients with resectable non-small-cell lung cancer were randomized to receive two preoperative doses of nivolumab (anti-PD-1) with or without relatlimab (anti-LAG-3) antibody therapy. The primary study endpoint was the feasibility of surgery within 43 days, which was met by all patients. Curative resection was achieved in 95% of patients. Secondary endpoints included pathological and radiographic response rates, pathologically complete resection rates, disease-free and overall survival rates, and safety. Major pathological (≤10% viable tumor cells) and objective radiographic responses were achieved in 27% and 10% (nivolumab) and in 30% and 27% (nivolumab and relatlimab) of patients, respectively. In 100% (nivolumab) and 90% (nivolumab and relatlimab) of patients, tumors and lymph nodes were pathologically completely resected. With 12 months median duration of follow-up, disease-free survival and overall survival rates at 12 months were 89% and 93% (nivolumab), and 93% and 100% (nivolumab and relatlimab). Both treatments were safe with grade ≥3 treatment-emergent adverse events reported in 10% and 13% of patients per study arm. Exploratory analyses provided insights into biological processes triggered by preoperative immunotherapy. This study establishes the feasibility and safety of dual targeting of PD-1 and LAG-3 before lung cancer surgery.ClinicalTrials.gov Indentifier: NCT04205552.

Efficacy of Venetoclax and Azacitidine in Acute Myeloid Leukemia Compared to Azacitidine Monotherapy: Real-World Experience.

The combination of venetoclax (VEN) and azacitidine (AZA) (VEN+AZA) leads to higher complete remission rates and longer overall survival (OS) in patients with untreated acute myeloid leukemia (AML) who are ineligible for intensive combination chemotherapy. In practice, the doses of VEN and AZA are reduced at the attending physician's discretion to avoid adverse events; however, the impact of dose and duration reductions has not been fully clarified. We analyzed whether the efficacy was maintained with reduced VEN+AZA compared to AZA monotherapy in the real world. A total of 33 patients were included; 17 (10 newly diagnosed, 7 primary refractory or relapsed) received VEN+AZA, and 16 (7 newly diagnosed, 9 primary refractory or relapsed) received AZA. We analyzed complete remission (CR) and CR with incomplete hematologic recovery (CRi) rates, OS, and the incidence of adverse events. CR/CRi were achieved in 7/17 (41.2%) and 11/17 (64.7%) patients in the VEN+AZA group and 0/15 (0%) and 2/15 (6.7%) patients in the AZA group, respectively. The CR/CRi rate was higher in the VEN+AZA group than in the AZA group (p=0.001). OS was longer in the VEN+AZA group than in the AZA group (p=0.03), with a median of 506 days [95% confidence interval (CI)=234-585 days] and 208 days (95% CI=52-343 days), respectively. The doses of the VEN+AZA combination were reduced at the attending physician's discretion, resulting in a higher CR/CRi rate and longer OS than AZA monotherapy and is considered useful for AML in the real world.

The addition of bortezomib to rituximab, high-dose cytarabine and dexamethasone in relapsed or refractory mantle cell lymphoma—a randomized, open-label phase III trial of the European mantle cell lymphoma network

The therapy of relapsed or refractory (r/r) mantle cell lymphoma (MCL) patients remains a major clinical challenge to date. We conducted a randomized, open-label, parallel-group phase-III trial hypothesizing superior efficacy of rituximab, high-dose cytarabine and dexamethasone with bortezomib (R-HAD + B) versus without (R-HAD) in r/r MCL ineligible for or relapsed after autologous stem cell transplant (ASCT). Primary endpoint was time to treatment failure (TTF), secondary endpoints included response rates, progression free survival, overall survival, and safety. In total, 128 of 175 planned patients were randomized to R-HAD + B (n = 64) or R-HAD (n = 64). Median TTF was 12 vs. 2.6 months (p = 0.045, MIPI-adjusted HR 0.69; 95%CI 0.47–1.02). Overall and complete response rates were 63 vs. 45% (p = 0.049) and 42 vs. 19% (p = 0.0062). A significant treatment effect was seen in the subgroup of patients >65 years (aHR 0.48, 0.29–0.79) and without previous ASCT (aHR 0.52, 0.28–0.96). Toxicity was mostly hematological and attributable to the chemotherapeutic backbone. Grade ≥3 leukocytopenia and lymphocytopenia were more common in R-HAD + B without differences in severe infections between both arms. Bortezomib in combination with chemotherapy can be effective in r/r MCL and should be evaluated further as a therapeutic option, especially if therapy with BTK inhibitors is not an option. Trial registration: NCT01449344.

Comparison of response and toxicity of induction chemotherapy with cisplatin and 5-fluorouracil versus cisplatin and paclitaxel followed by concurrent chemoradiotherapy in advanced head and neck cancer

Background: Head and neck cancer poses a prevalent oncological challenge in Bangladesh, often diagnosed in advanced stages. Standard treatment for inoperable cases involves concurrent chemo-radiotherapy, but induction chemotherapy has shown significant benefits. This study aimed to compare the response and toxicity of induction chemotherapy with cisplatin and 5-fluorouracil versus cisplatin and paclitaxel followed by concurrent chemo-radiotherapy in advanced head and neck cancer. Methods: From January 2019 to June 2020, a multicenter study enrolled 150 cases with inoperable squamous cell carcinomas in the head and neck. Ethical approval was obtained from Bangabandhu Sheikh Mujib Medical University. Divided into two arms, Arm A had 75 patients receiving cisplatin and 5-fluorouracil, while Arm B had 75 patients receiving cisplatin and paclitaxel for three cycles. Results: After 24 weeks of treatment, complete response rates were 53.33% in Arm A and 56.0% in Arm B, with partial response rates of 29.33% and 32.0% respectively. Overall response was 82.66% in Arm A and 88.0% in Arm B, showing no statistically significant difference (p&gt;0.05). Arm A exhibited more anemia, oral mucositis, skin toxicity, and hand- foot syndrome, while Arm B had higher neuropathy. Hematological and non-hematologic toxicities during concurrent chemo-radiotherapy were similar in both arms. Conclusions: Induction chemotherapy with cisplatin and paclitaxel, followed by concurrent chemo-radiotherapy, is equally effective as induction chemotherapy with cisplatin and 5-fluorouracil, followed by concurrent chemo-radiotherapy, in treating advanced head and neck squamous cell carcinoma. However, the former regimen demonstrates significantly fewer toxicities, indicating a safer treatment option.

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 (&gt;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.

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.

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...

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.