Patient Selection Research Articles

Tyrosine kinase inhibitors with and without upfront CNS radiation for brain metastases in oncogene-driven non-small cell lung cancer (TURBO-NSCLC).

2019 Background: Newer generation tyrosine kinase inhibitors (TKI) for NSCLC with EGFR mutations and ALK rearrangements have demonstrated encouraging central nervous system (CNS) activity with CNS objective response rates, greatly improved from 1st generation TKIs. In response to these data, guideline statements have acknowledged a strategy of CNS-penetrant TKI +/- upfront stereotactic radiosurgery (SRS) for the treatment of select patients with BM. However, optimal use of upfront SRS for BM in these patients is controversial since upfront CNS radiation has been the historical standard of care, and there are limited data guiding patient management with upfront TKI alone. Additionally, results from a large multi-institutional series reported inferior overall survival (OS) with the omission of SRS in patients with EGFR-mutated NSCLC treated with first-generation TKI. Methods: Data on TKI-naïve patients with EGFR- and ALK-driven NSCLC with BM treated with CNS-penetrant TKIs +/- upfront SRS were retrospectively collected from 7 centers in the United States. Time to CNS progression (PD), local CNS PD, and OS were analyzed, with multivariable adjustment (MVA) in Fine and Gray and Cox proportional hazards models for baseline factors including age, sex, performance status, mutation, extracranial metastases, prior therapy, neurologic symptoms, and number and size of BM. Results: We identified 317 patients (200 TKI only and 117 TKI+SRS). 250 (79%) and 61 (19%) patients received osimertinib and alectinib, respectively. Patients who received TKI+SRS were more likely to have BM ≥1 cm (p<0.001) and neurologic symptoms (p<0.001) at baseline. The median follow-up from treatment of BM was 23 months and 26 months in the TKI and TKI+SRS groups, respectively. Median OS was similar between the TKI and TKI+SRS groups (median 41 months [95% CI: 35-NR] vs 40 months [95% CI: 40-NR], respectively; p=0.5). On MVA, TKI+SRS was associated with a significant improvement in time to CNS PD (HR 0.63; 95% CI: 0.42-0.96; p=0.033). Local CNS control was significantly improved with TKI+SRS (HR 0.30, 95% CI: 0.16-0.55; p<0.001), whereas no significant differences were observed in distant CNS control. Subgroup analyses demonstrated greater CNS control benefits with TKI+SRS in patients with BM ≥1 cm. Conclusions: This is the largest multi-institutional study comparing strategies of CNS-penetrant TKIs +/- upfront SRS in TKI-naïve patients with oncogene-driven NSCLC. The addition of SRS improved time to CNS PD and local CNS control but not OS. Patients with BM ≥1 cm may benefit the most from upfront integration of SRS. [Table: see text]

Major Trauma Triage Tool Study (MATTS) expert consensus-derived injury assessment tool

Introduction: Major trauma centre (MTC) care has been associated with improved outcomes for injured patients. English ambulance services and trauma networks currently use a range of triage tools to select patients for bypass to MTCs. A standardised national triage tool may improve triage accuracy, cost-effectiveness and the reproducibility of decision-making.Methods: We conducted an expert consensus process to derive and develop a major trauma triage tool for use in English trauma networks. A web-based Delphi survey was conducted to identify and confirm candidate triage tool predictors of major trauma. Facilitated roundtable consensus meetings were convened to confirm the proposed triage tool’s purpose, target diagnostic threshold, scope, intended population and structure, as well as the individual triage tool predictors and cut points. Public and patient involvement (PPI) focus groups were held to ensure triage tool acceptability to service users.Results: The Delphi survey reached consensus on nine triage variables in two domains, from 109 candidate variables after three rounds. Following a review of the relevant evidence during the consensus meetings, iterative rounds of discussion achieved consensus on the following aspects of the triage tool: reference standard, scope, target diagnostic accuracy and intended population. A three-step tool comprising physiology, anatomical injury and clinical judgement domains, with triage variables assessed in parallel, was recommended. The triage tool was received favourably by PPI focus groups.Conclusions: This paper presents a new expert consensus derived major trauma triage tool with defined purpose, scope, intended population, structure, constituent variables, variable definitions and thresholds. Prospective evaluation is required to determine clinical and cost-effectiveness, acceptability and usability.

Circulating metabolic profiling as a biomarker for immune checkpoint blockade efficacy.

2564 Background: Immune checkpoint blockade (ICB) has changed the treatment landscape of non-small cell lung cancer (NSCLC). Despite being the mainstay of treatment for advanced NSCLC, the development of resistance to ICB is common. Hence, identifying biomarkers that can be used to select patients (pts) who will benefit from ICB is crucial. Here, we interrogate the circulating metabolome to identify the metabolic parameters associated with ICB effectiveness. Methods: This single-center retrospective analysis used a mass-spectrometry (MS) targeted metabolomics approach to assess the relative abundance of 115 metabolites in baseline (pre-ICB) plasma of 55 pts with advanced NSCLC. Pts treated with ICB at the Princess Margaret Cancer Centre from 2018-2020 were included. Electronic medical records were reviewed to collect clinicopathological and treatment data. All pts had tumour next-generation sequencing (NGS) by a targeted gene panel. Descriptive statistics were used to summarize the patient characteristics, treatment modalities, and outcomes. Time-to-event outcomes were analyzed using the Kaplan-Meier method. Progression-free survival (rwPFS) and overall survival (rwOS) were defined as the time from the first treatment dose to radiographic or clinical progression or death from any cause and time from the first dose of treatment to death from any cause, respectively. The response rate was assessed using RECIST 1.1. Statistical significance was determined as a p-value <0.05. Results: Amongst the 55 pts profiled, 42 (76.3%) had adenocarcinoma. The most common molecular alterations included KRAS (n=15), BRAF non-V600 (n=5), and METex14 (n=3). The median PD-L1 score was 65% (IQR 22.5 – 59%). All pts were treated with a single-agent PD-1 inhibitor, and 67.2% of pts received ICB as the first line of treatment. Metabolomic analysis of the pre-ICB initiation plasma samples identified 8 metabolites whose relative abundance significantly differed between responding (CR/PR) and non-responding pts (SD/PD). Amongst these metabolites was the endogenous danger signal Glucosylceramide (d 18:1/24:0), whose abundance was increased in the plasma of the responding pts. When we stratified pts by circulating levels of glucosylceramide, we found a statistically significant higher rwPFS (8.5 vs. 1.6 months, p=0.0001) and rwOS (13.5 vs. 6.1 months, p=0.0001) in pts who had high baseline plasma levels of Glucosylceramide (d 18:1/24:0) (top 50%) versus those with lower levels (bottom 50%). Conclusions: Utilizing a targeted metabolomics approach, we identified the metabolite and endogenous danger signal glucosylceramide (d 18:1/24:0) as a potential metabolic biomarker of response to ICB therapy. Future work will aim to validate this finding in a larger cohort and to understand the biological mechanism underpinning this correlation.

Associations of predictive biomarkers, MHC-I and MHC-II, with clinical and molecular features in a diverse breast cancer cohort.

517 Background: The addition of immunotherapy (IO) to chemotherapy in triple negative breast cancer (TNBC) has improved survival outcomes and recent studies have also shown improvements in pCR rates in early high-risk HR+/HER2- breast cancer. However, these improvements are not without toxicities and thus there is a critical need for biomarkers to select patients that are most likely to benefit from immunotherapy. MHC-I and tumor-specific MHC-II (tsMHC-II) expression are candidate biomarkers for predicting PD-(L)1 checkpoint inhibition benefit and have previously shown potential for predicting treatment response in multiple tumor types, including breast cancer. However, the existing data were generated from clinical trials with limited racial/ethnic diversity. Here we report associations between MHC-I and MHC-II expression and clinicopathological features in a large, racially and ethnically diverse breast cancer cohort. Methods: We performed multiplexed immunofluorescent tissue-based analysis of participants in the Carolina Breast Cancer Study (CBCS). Intrinsic subtype and P53 mutant-like status were identified using RNA-based multigene assays. To evaluate MHC-I we ranked all participants based on tumoral MHC-I intensity, with the top 33% categorized as "MHC-IHigh"; MHC-II+ expression on tumor cells was defined as ≥5% of tumor cells. Association between MHC-I/II and clinicopathological features by race was tested using Chi-square test or fisher-exact test and relative frequency difference (RFD) was calculated. Results: This study included 1630 participants (48% Black and 52% non-Black) with Stage I-III breast cancer. Black participants had a higher incidence of TNBC (25% vs. 12.5%, p=<0.001) and Basal-like (29% vs. 14%, p=<0.001) tumors. Basal-like and TP53 mutant tumors were more frequently observed among Black participants with HR+/HER2- tumors (11% vs. 5.5%, p=0.006 for Basal-like; 26% vs. 17%, p=0.003 for p53 mutant-like). While there was a similar distribution of tsMHC-II+ tumors between Black and non-Black participants, the relative frequency of tsMHC-II+ tumors was significantly more common in Black participants with HR+/HER2- breast cancer compared to non-Black participants (7.9% vs. 5%, p=0.04). Moreover, Black participants also were significantly more likely to have MHC-Ihigh tumors (38.9% vs. 28.4%, p=0.01), which, after IHC subtype stratification, was only significant among participants with HR+/HER2- breast cancer (28.2% vs. 22.3%, p=0.02). Conclusions: In this diverse breast cancer cohort, MHC-I and MHC-II expression, candidate predictive biomarkers of IO benefit, were more prevalent in tumors from Black women with HR+/HER2- breast cancer. These results underscore the importance of diverse and equitable clinical trial enrollment in future IO trials, especially in HR+/HER2- breast cancer.

PIK3CA testing and treatment patterns among patients with metastatic breast cancer in US community clinical practice.

e13059 Background: PIK3CA mutations are present in ~35-40% of HR+/HER2- breast cancer patients. Targeted treatments are approved and in development for patients with advanced disease, and clinical guidelines recommend biomarker testing. This retrospective cohort study characterized PIK3CA mutation testing and treatment patterns among HR+/HER2- metastatic breast cancer (mBC) patients in United States (US) community clinical practices. Methods: We used the nationwide Flatiron Health electronic health record-derived de-identified database to select patients diagnosed with HR+/HER2- mBC from January 2011 to May 2023. We described baseline characteristics of patients tested and not tested for PIK3CA mutation. We captured rates of PIK3CA mutation testing (anytime and ≤1 year) prior to starting first-line (1L), second-line (2L), and third-line (3L) treatment; test and sample types; secular trends over time; and test turnaround time (TAT). Treatment patterns for patients with a PIK3CA-mutated tumor were also described from 2019 onwards. Results: Among 14,246 HR+/HER2- mBC patients treated at community sites, 4,537 had a PIK3CA mutation test result during the study period. 25% of patients had more than one PIK3CA mutation test. Test rates increased from 2011 to 2023 for all patients starting 1L, 2L, or 3L during the study period (Table). In 2023, the percentage of patients tested anytime prior to 1L, 2L, and 3L start dates were 11% (37 of 324 patients), 52% (140 of 271 patients), and 65% (133 of 204 patients), respectively. Among tested patients, those who were tested between 1L and 2L increased from 32% in 2018 to 45% in 2023. Median time from mBC diagnosis date to first test was variable across years: 8, 10, and 3 months in 2018, 2020, and 2022, respectively. During the study period, most PIK3CA mutation tests were next-generation sequencing (NGS) (88%) and used tumor tissue (72%). Median TAT decreased from 12 days in 2018 to 7 days in 2023. Among patients with a PIK3CA-mutated tumor in 2019 and onwards who received treatment, 36% of patients received alpelisib-containing regimens. Conclusions: PIK3CA mutation testing in HR+/HER2- mBC patients has increased over time in community clinical practice, and timing has shifted to earlier lines of therapy among tested patients. However, overall testing and subsequent treatment with pathway-directed therapy are still low despite clinical guidelines, which may reflect potential gaps in access to PIK3CA mutation testing and the continued unmet need regarding available targeted agents within the current treatment landscape. [Table: see text]

Therapeutic potential of immune-cold solid tumors through homologous recombination deficiency.

e14585 Background: Genome-wide homologous recombination deficiency (HRD) score is an important parameter to select patients for HRR pathway inhibitors. HRD scores are independent therapeutic predictors unlike tumor mutation burden (TMB), and microsatellite instability (MSI) values to stratify tumors for predicting immunogenicity. Since solid tumors often choose the hallmark of immune evasion to disseminate to distant tissues, their identification and treatment through genomic signatures for immunotherapy is essential. Low TMB and MSI values are often associated with immune evasion and immune cold tumors. For such patients HRD scores can be important determinants to inform on the therapeutic potential of HRR pathway inhibitors and immune checkpoint inhibitors (ICI). In this study, we retrospectively investigated solid tumors with metastatic phenotypes exhibiting microsatellite stable (MSS), MSI-Low and TMB low phenotypes. The presence of HRR pathway deficiency in these patients may lead to chromosomal instabilities and cell surface neo-antigens thereby offering potential therapeutic benefit to PARP inhibitors and ICI. Methods: 53 metastatic cancer patients were retrospectively analysed for genome-wide HRD, TMB and MSI scores based on OncoIndx comprehensive gene panel (CGP). OncoIndx CGP targets 1080 cancer related genes along with 47 HRR genes and 1600 MSI signature sites. HRD, TMB and MSI scores were determined by sequencing the individual sample libraries in pair end mode on Illumina Nextseq platform (depth 5500X). Cutoff scores HRD high (≥50), TMB high (≥10 Mutations/MB), MSI high (≥20). Results: A cohort of 53 solid tumor patients were evaluated retrospectively of which 71.6% (n=38) patients showed metastasis (brain, Popliteal fossa, skeletal, and nodal metastasis). Of these, 9.4% (n=5) patients were detected with MSI-high, 56.6% (n=30) were MSI-Low and 1.8% (n=1) were MSS. 13.2% (n=7) patients were TMB-High, 3.7% (n=2) were TMB intermediate and 41.0% (n=22) were TMB-Low. Most importantly, 41.0% (n=22) patients were both MSI and TMB low thus transforming the tumor suggestively immune-cold. Only 22.7% (n=5) patients showed PD-L1 expression on IHC with scores ranging from TPS: 2% to 20%. In this dominantly immune-cold patient cohort, 40.9% (n=9) patients showed high/intermediate HRD (22.7% high (n=5); 18.18% Intermediate (n=4)). Conclusions: The presence of HRD in 40.9% patients in the dominant immune-cold patients was observed with increased chromosomal instability and cell surface neo-antigens. Thus, HRD could potentially transform tumors to become immune-hot to benefit from PARP inhibitors and ICI.

A 13- to 17-year Retrospective Evaluation of the Clinical Performances of Anterior and Posterior Lithium Disilicate Restorations onto Teeth and Implants.

This retrospective study aimed at evaluating the clinical outcomes of lithium disilicate prostheses onto teeth and implants. A total of 860 restorations were delivered to 312 patients, including crowns, veneers and onlays. Patients with uncontrolled gingival inflammation and/or periodontitis were excluded, whilst subjects with occlusal parafunctions were included. The retrospective observational period ranged between 13 to 17 years. The mechanical and esthetic performances of the restorations were rated according to the modified CDA criteria. The recorded data were analyzed statistically. In total, 26 mechanical complications were noticed: 17 ceramic chippings, 5 core fractures and 4 losses of retention. Mechanical complications occurred predominantly in posterior areas; monolithic prostheses showed the lowest percentage of structural problems. The clinical scores of layered and monolithic restorations were fully satisfactory according to the modified CDA rating. The cumulative survival and success rates ranged between 95.46-100% and 93.75-100% respectively up to 17 years of follow-up. Although patient selection and the rigorous application of validated clinical protocols were considered paramount, the use of lithium disilicate prostheses onto teeth and implants was reported to be a viable and reliable treatment option in the long-term.

Australian rheumatologists' perception of autologous haemopoietic stem cell transplantation for the treatment of systemic sclerosis: a cross-sectional survey.

Autologous haemopoietic stem cell transplantation (AHSCT) is an effective treatment for systemic sclerosis (SSc); however, treatment-related toxicity remains a key issue. To investigate the perceptions of rheumatologists on the use of AHSCT for SSc. Australian rheumatologists were asked for their opinion on the role of AHSCT, the indications for treatment and the barriers to the use of AHSCT for SSc. A secondary analysis assessed what factors influenced the perception of AHSCT. A total of 77.8% rheumatologists agreed or strongly agreed with the statement that AHSCT is an accepted treatment for SSc. While 65.1% agreed or strongly agreed that treatment-associated mortality was a significant barrier to referral for AHSCT, only 15.2% agreed or strongly agreed that this risk was unacceptable. Progressive lung or skin disease, or lack of response to other therapies, were considered the main referral criteria. A total of 92.0% of respondents agreed or strongly agreed that reduction of treatment toxicity would increase their likelihood to refer patients for AHSCT. Rheumatologists who were aware of the correct evidence base were more likely to consider AHSCT an acceptable treatment for SSc (4.21 ± 0.7 vs 3.64 ± 0.9, P = 0.007). Rheumatologists desire improved patient selection criteria and access to treatment. In this national survey of rheumatologists, AHSCT is considered an accepted therapy. However, concern about toxicity remains a potential barrier to patient referral. Access, studies to refine patient selection and development of AHSCT protocols that improve safety were identified as key areas of need.

Phantom and in vivo accuracy of frameless optical navigation in stereotactic laser interstitial thermal therapy.

Targeting accuracy presents a key factor in achieving maximal safe ablation in laser interstitial thermal therapy (LITT). The VarioGuide system has proven precise for brain biopsies, but data showing its accuracy in combination with LITT are limited. The aim of this study was to determine the phantom and in vivo accuracy of LITT probe placement using the VarioGuide system and to evaluate the effect of targeting error on maximum possible ablation volume. Stereotactic LITT probe placement was performed using the VarioGuide system in 3 phantom skulls. The same system was used in 10 patients treated with LITT, for which data were retrospectively analyzed. Target point error (TPE), target depth deviation (TDD), target lateral deviation (TLD), and angular deviation (AD) were derived from intraprocedural MRI scans of both the phantom and in vivo trajectories. In vivo, the effect of targeting error on the maximum reachable ablation was calculated as the difference between the planned maximal achievable tumor ablation (PTA) and the actual maximal achievable tumor ablation (ATA). In total, 24 phantom and 16 in vivo trajectories were analyzed. In the phantom setting, the median TPE was 3.3 mm and median AD was 1.9°. Targeting accuracy significantly decreased for longer trajectories and those less perpendicular to the skull. In patients, the authors observed a comparable median TPE of 4.0 mm but significantly higher AD of 3.2°. In vivo, targeting inaccuracy resulted in a median decrease in maximum achievable ablation volume of 6% as compared to the planned trajectory. The authors' study indicates that utilizing the VarioGuide system in combination with LITT yields an average targeting error as large as 4 mm, which was smaller for shorter and straighter trajectories. In patients, targeting inaccuracy resulted in a median 6% decrease of the planned tumor ablation volume. These are important factors that should be considered in optimal case planning and patient selection in LITT.

Stereotactic body radiation therapy for primary renal cell carcinoma: A review on behalf of the CC-AFU

IntroductionThe incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. Material and methodsWe conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. ResultsStudies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately −5 to −17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. ConclusionStereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited. Level of evidence5.

Low body mass index and risk of mortality after mitral transcatheter edge-to-edge repair procedure: The "obesity paradox".

Most patients undergoing the mitral transcatheter edge-to-edge repair (TEER) technique are elderly comorbid patients. Low body mass index (BMI) < 23 kg/m2 has been identified in other elderly populations as a risk factor, but has not been studied sufficiently in mitral TEER. We aimed to study the impact of low BMI (23 kg/m2) on the outcome after mitral TEER. Patients undergoing first-time TEER for mitral regurgitation at a single tertiary center were included, with the exclusion of patients with preprocedural hemodynamic instability or missing BMI. The primary endpoint was all-cause mortality. Secondary endpoints were long-term major bleeding or admission with heart failure. A total of 120 patients (mean age 76 ± 10 years, 76% men) were included in the study. Thirty-nine (31%) had low BMI. Patients with low BMI had a similar symptomatic benefit as patients with BMI ≥ 23 kg/m2 at 1 year regarding decrease in diuretics dose and decrease in New York Heart Association(NYHA)class (p > 0.05). In a multivariable Cox regression analysis, BMI as a continuous variable (hazard ratio [HR]: 0.93 [95% confidence interval, CI: 0.87-0.99],p = 0.03) and low BMI (HR: 1.99 [95% CI: 1.12-3.52], p = 0.02) were associated with the primary outcome. Low BMI was not significantly associated with major bleeding (subdistribution hazard ratio [SHR]:2.39 [95% CI: 0.96-5.97], p = 0.06) or admission with heart failure (SHR: 1.06 [95% CI: 0.61-1.88], p = 0.83) during follow-up with univariable competing risk regression analysis. Low BMI is a risk factor for mortality after mitral valve TEER, confirming the presence of an "obesity paradox" in this population and should receive attention in patient selection.

Tumor burden score as a prognostic factor in patients with intermediate and locally advanced hepatocellular carcinoma undergoing liver resection: an attempt to extend resectability criteria

BackgroundSurgery is currently recommended as a curative treatment option for hepatocellular carcinomas (HCC) belonging to Barcelona Clinic Liver Cancer (BCLC) stage A only. This study aims to classify various BCLC groups as per Tumor Burden Score (TBS) in an attempt to identify patients who could benefit from resection. Materials and methodsA retrospective analysis of a prospectively maintained database of all patients operated for HCC between January 2010 and July 2022 was performed. TBS was defined as, TBS2 = (maximum tumor diameter)2 + (number of tumors)2. ResultsTwo hundred and ninety-one patients who underwent resection were staged as per the latest BCLC (A = 219, B = 45, C = 27) staging. Patients were segregated into low (<7.3) and high (>7.3) TBS. With a median follow-up of 36.2 months, the median OS for stages, A and B in the low TBS group was 107.4 and 42.7 months respectively. Median OS was not reached for patients in the BCLC C stage. In patients with high TBS, the median OS for BCLC A, B and C was 42.3, 25.72, and 16.9 months respectively. ConclusionTBS is a significant factor influencing survival in patients of HCC. TBS can be used to stratify patients in BCLC B and C stages and help select patients who would benefit from surgical resection to achieve good long-term survival with acceptable morbidity.

No Skin Paddle, No Problem: Burying Deep Inferior Epigastric Artery Flaps in the Immediate Setting is Safe in Select Patient Populations.

In appropriately selected patients, it may be possible to fully bury breast free flaps deep to the mastectomy skin flaps. Because this practice forgoes the incorporation of a monitoring skin paddle for the flap, and thus limits the ability for physical exam, it may be associated with an increased risk of flap loss or other perfusion-related complications, such as fat necrosis. We hypothesized that fully de-epithelialized breast free flaps were not associated with an increased complication rate and reduced the need for future revision surgery. A single-institution retrospective review of 206 deep inferior epigastric artery (DIEP) flaps in 142 patients was performed between June 2016 and September 2021. Flaps were grouped into buried or nonburied categories based on the absence or presence of a monitoring paddle. Patient-reported outcomes were assessed postoperatively using the BREAST-Q breast reconstruction module. Electronic medical record data included demographics, comorbidities, flap characteristics, complications, and revision surgery. The buried flap patients (N = 46) had a lower median body mass index (26.9 vs 30.3, p = 0.04) and a lower rate of hypertension (19.5 vs. 37.5%, p = 0.04) compared with nonburied flap patients (N = 160). Burying flaps was more likely to be adopted in skin-sparing mastectomy or nipple-sparing mastectomy (p = 0.001) and in an immediate or a delayed-immediate fashion (p = 0.009). There was one flap loss in the nonburied group; complication rates were similar. There was a significantly greater revision rate in the nonburied flap patients (92 vs. 70%; p = 0.002). Buried flap patients exhibited a greater satisfaction with breasts (84.5 ± 13.4 vs. 73.9 ± 21.4; p = 0.04) and sexual satisfaction (73.1 ± 22.4 vs. 53.7 ± 29.7; p = 0.01) compared with nonburied flap patients. Burying breast free flaps in appropriately selected patients does not appear to have a higher complication rate when compared with flaps with an externalized monitoring paddle. Furthermore, this modification may be associated with a better immediate aesthetic outcome and improved patient satisfaction, as evidenced by a lower rate of revision surgery and superior BREAST-Q scores among buried DIEP flaps.

Comparison of allo-SCT, auto-SCT and chemotherapy for the treatment of patients with low- or intermediate-risk acute myeloid leukemia: a network meta-analysis

BackgroundThe therapeutic status of allogeneic stem cell transplantation (allo-SCT) as a post-remission treatment for patients with high-risk acute myeloid leukemia (AML) was well-accepted. However, the optimal treatment for patients with low/favorable- or intermediate-risk AML who achieve complete remission has remained controversial. Therefore, we conducted a network meta-analysis to discuss this disputed problem.MethodsWe compared the effects of treatment strategies including allo-SCT, autologous stem cell transplantation (auto-SCT) and consolidation chemotherapy (CT) for patients with low/favorable- or intermediate-risk AML. The pooled HRs and 95% CIs for overall survival and disease-free survival were estimated with Stata12 and R software. Thirty clinical studies with 6682 patients were included in the meta-analysis.ResultsThe results indicated that the treatment outcome of allo-SCT was the best, followed by auto-SCT, and CT was likely the worst in the total AML patients. In patients with low/favorable-risk AML, the treatment outcome of auto-SCT was likely ranked first, followed by allo-SCT, and CT was the worst. In patients with intermediate-risk AML, the treatment outcome of haploidentical stem cell transplantation (haplo-SCT) was the best, followed by allo-SCT (excluding haplo-SCT), and auto-SCT and CT were the worst. However, the median age of the haplo-SCT group was much younger than that of the control group, which may be one of the reasons for the better prognosis of the haplo-SCT group.ConclusionsPatients with low/favorable- and intermediate-risk (non-high-risk) AML should prioritize allo-SCT if they are eligible for transplantation, and auto-SCT is optional. However, in the subgroup analysis, auto-SCT was the optimal treatment choice for patients with low/favorable-risk AML, and allo-SCT was the priority selection for patients with intermediate-risk AML, especially young patients. These findings could provide references for clinical practice.

Efficacy of pembrolizumab and biomarker analysis in patients with WGS-based intermediate to high tumor mutational load: results from the Drug Rediscovery Protocol.

To evaluate efficacy of pembrolizumab across multiple cancer types harboring different levels of Whole-Genome Sequencing (WGS)-based tumor mutational load (TML; total of non-synonymous mutations across the genome) in patients included in the Drug Rediscovery Protocol (NCT02925234). Patients with solid, treatment-refractory, microsatellite-stable tumors were enrolled in cohort A: breast cancer TML 140-290, cohort B: tumor-agnostic cohort TML 140-290, and cohort C: tumor-agnostic cohort TML >290. Patients received pembrolizumab 200 mg every three weeks. Primary endpoint was clinical benefit (CB: objective response or stable disease (SD) ≥16 weeks). Pre-treatment tumor biopsies were obtained for WGS and RNA-sequencing. Seventy-two evaluable patients with 26 different histotypes were enrolled. CB rate was 13% in cohort A (3/24 with partial response (PR)), 21% in cohort B (3/24 with SD, 2/24 with PR), and 42% in cohort C (4/24 with SD, 6/24 with PR). In cohort C, neoantigen burden estimates and expression of inflammation and innate immune biomarkers were significantly associated with CB. Similar associations were not identified in cohort A and B. In cohort A, CB was significantly associated with mutations in the chromatin remodeling gene PBRM1, while in cohort B, CB was significantly associated with expression of MICA/MICB and butyrophilins. CB and clonal TML were not significantly associated. While in cohort A pembrolizumab lacked activity, cohort B and cohort C met the study's primary endpoint. Further research is warranted to refine selection of patients with tumors harboring lower TMLs and may benefit from a focus on innate immunity.

Prevalence and Impact of Psychiatric Co-Morbidity in Patients with Spinal Pathology in Basrah, Iraq

Background and objective: to minimize complications by proper selection of patients for surgery and to evaluate what is the impact of psychiatric co-morbidity in patients admitted to a spinal surgical unit in Basrah, Iraq. Patients and Methods: A multi-center cross-sectional prospective cohort study was conducted on 247 patients. In Basrah province. During admission complete history was taken in form of identity, complaint, past medical and surgical history, drug history, type of previous and the coming surgery and lastly special emphasis on the questioner to assess patient psychological status using the Patient Health Questioner. Somatic Anxiety Depressive Symptoms (PHQ.SADS) After one week and one-month the same questions were addressed to the patient to check the general condition,and any complications or readmission. Results: Out of the 247 patients: Eight patients refuse to be part of this study, thirty-one patients lost follow up, three patients excluded from the study due to exclusion criteria, five patients their surgery postponded because they were psychologically unstable and advised for psychiatrist consultation. 111 patients (55.5%) of the sample size were male patients. A 90 (45%) patients were at age of 38-57 years, 111 (55.5%) of the sample were male 82 patients (41%) were of moderate degree using the PHQ.SADS. 62 patients (31%) were within the severe scale PHQ.SADS.132 patients (66%) complained from radiculopathy with or without backache,192 (96%) patients discharged safely postoperatively. 41(39.4%) patients were diagnosed with lumber canal stenosis belongs to the severe group. Psychological break down occurs in 10 (5%) patients, 9 (90%) of those patients belong to severe grade category of PHQ.SADS. Conclusion: There was a strong association between pre-operative psychological conditions and post-operative complications in form of repeated visit after surgery and persistence of pain and disability.

Robotic thoracic surgery for neurogenic tumors.

Thoracic neurogenic tumors usually present as benign nerve sheath tumors that can be resected via transthoracic or posterior approaches, depending on the anatomical location. Robot-assisted thoracic surgery (RATS) is increasingly being used for the transthoracic approach, but evidence is very limited. The authors initiated the current study to evaluate the efficacy and safety of RATS for thoracic neurogenic tumors. This retrospective study is based on a prospectively created database that includes all RATS surgeries between 2018 and 2023. All patients with histologically confirmed neurogenic tumors were included in the study. The patients' medical and surgical records as well as radiological and pathological findings were analyzed. During a 5-year period, 27 patients underwent robotic resection of neurogenic tumors at a high-volume thoracic surgery center. Two patients had previously undergone posterior laminectomy for resection of the intraspinal components. The pathologies included schwannomas (18, 64%), ganglioneuromas (8, 29%), 1 paraganglioma, and 1 neurofibroma occurring close to a schwannoma unilaterally in the same patient. The median tumor size was 4.7 cm (range 0.9-11.4 cm). The median operating time was 69 minutes (range 27-169 minutes), and the median postoperative stay was 3 days (range 1-19 days). There was one conversion due to adhesions after a previous surgery. No major bleeding occurred. There was no perioperative mortality. Morbidity included a lymphatic fistula (n = 1), pneumonia (n = 1), prolonged air leak (n = 1), and 4 cases of postoperative pain persisting for more than 4 weeks. Neurological complications were mostly observed in patients with tumors located at the thoracic apex: 2 cases of Horner's syndrome, 2 cases with compensatory hyperhidrosis, 1 patient with paresis of the recurrent laryngeal nerve, and a T1 lesion resulting in a minor motor deficit of the small hand muscles (Medical Research Council grade 4) and hypoesthesia of the respective dermatome. RATS for thoracic neurogenic tumors is feasible and safe. Tumors at the thoracic apex are at high risk of neurological deficit and should be approached with care. Close interdisciplinary collaboration between neurosurgeons and thoracic surgeons is necessary for optimal patient selection and a good postoperative outcome.

Evaluation of an automated clinical decision system with deep learning dose prediction and NTCP model for prostate cancer proton therapy

Objective. To evaluate the feasibility of using a deep learning dose prediction approach to identify patients who could benefit most from proton therapy based on the normal tissue complication probability (NTCP) model. Approach. Two 3D UNets were established to predict photon and proton doses. A dataset of 95 patients with localized prostate cancer was randomly partitioned into 55, 10, and 30 for training, validation, and testing, respectively. We selected NTCP models for late rectum bleeding and acute urinary urgency of grade 2 or higher to quantify the benefit of proton therapy. Propagated uncertainties of predicted ΔNTCPs resulting from the dose prediction errors were calculated. Patient selection accuracies for a single endpoint and a composite evaluation were assessed under different ΔNTCP thresholds. Main results. Our deep learning-based dose prediction technique can reduce the time spent on plan comparison from approximately 2 days to as little as 5 seconds. The expanded uncertainty of predicted ΔNTCPs for rectum and bladder endpoints propagated from the dose prediction error were 0.0042 and 0.0016, respectively, which is less than one-third of the acceptable tolerance. The averaged selection accuracies for rectum bleeding, urinary urgency, and composite evaluation were 90%, 93.5%, and 93.5%, respectively. Significance. Our study demonstrates that deep learning dose prediction and NTCP evaluation scheme could distinguish the NTCP differences between photon and proton treatment modalities. In addition, the dose prediction uncertainty does not significantly influence the decision accuracy of NTCP-based patient selection for proton therapy. Therefore, automated deep learning dose prediction and NTCP evaluation schemes can potentially be used to screen large patient populations and to avoid unnecessary delays in the start of prostate cancer radiotherapy in the future.

Transcatheter balloon angioplasty of internal pulmonary artery bands to improve pulmonary blood flow: a case series.

Pulmonary artery banding (PAB) is used to restrict pulmonary blood flow in select patients with large left-to-right intracardiac shunts or unrestrictive pulmonary blood flow prior to eventual surgical repair or palliation. More recently, surgical placement of an internal or intraluminal PAB (IPAB) has been used to restrict pulmonary circulation. Here we present two patients who underwent balloon angioplasty of the IPAB to treat cyanosis and improve pulmonary blood flow.

Prolonged complete response to adjuvant tepotinib in a patient with newly diagnosed disseminated glioblastoma harboring mesenchymal-epithelial transition fusion.

The prognosis of patients with glioblastoma (GBM) remains poor despite current treatments. Targeted therapy in GBM has been the subject of intense investigation but has not been successful in clinical trials. The reasons for the failure of targeted therapy in GBM are multifold and include a lack of patient selection in trials, the failure to identify driver mutations, and poor blood-brain barrier penetration of investigational drugs. Here, we describe a case of a durable complete response in a newly diagnosed patient with GBM with leptomeningeal dissemination and PTPRZ1-MET fusion who was treated with tepotinib, a brain-penetrant MET inhibitor. This case of successful targeted therapy in a patient with GBM demonstrates that early molecular testing, identification of driver molecular alterations, and treatment with brain-penetrant small molecule inhibitors have the potential to change the outcome in select patients with GBM.