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BACKGROUND: Cardiovascular magnetic resonance (CMR) is increasingly utilized to evaluate expanding cardiovascular conditions. The Society for Cardiovascular Magnetic Resonance (SCMR) Registry is a central repository for real-world clinical data to support cardiovascular research, including those relating to outcomes, quality improvement, and machine learning. The SCMR Registry is built on a regulatory-compliant, cloud-based infrastructure that houses searchable content and Digital Imaging and Communications in Medicine images. The goal of this study is to summarize the status of the SCMR Registry at 150,000 exams. METHODS: The processes for data security, data submission, and research access are outlined. We interrogated the Registry and presented a summary of its contents. RESULTS: Data were compiled from 154,458 CMR scans across 20 United States sites, containing 299,622,066 total images (â¼100 terabytes of storage). Across reported values, the human subjects had an average age of 58 years (range 1 month to >90 years old), were 44% (63,070/145,275) female, 72% (69,766/98,008) Caucasian, and had a mortality rate of 8% (9,962/132,979). The most common indication was cardiomyopathy (35,369/131,581, 27%), and most frequently used current procedural terminology code was 75561 (57,195/162,901, 35%). Macrocyclic gadolinium-based contrast agents represented 89% (83,089/93,884) of contrast utilization after 2015. Short-axis cines were performed in 99% (76,859/77,871) of tagged scans, short-axis late gadolinium enhancement (LGE) in 66% (51,591/77,871), and stress perfusion sequences in 30% (23,241/77,871). Mortality data demonstrated increased mortality in patients with left ventricular ejection fraction <35%, the presence of wall motion abnormalities, stress perfusion defects, and infarct LGE, compared to those without these markers. There were 456,678 patient-years of all-cause mortality follow-up, with a median follow-up time of 3.6 years. CONCLUSION: The vision of the SCMR Registry is to promote evidence-based utilization of CMR through a collaborative effort by providing a web mechanism for centers to securely upload de-identified data and images for research, education, and quality control. The Registry quantifies changing practice over time and supports large-scale real-world multicenter observational studies of prognostic utility.
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Background and purpose: Information in multiparametric Magnetic Resonance (mpMR) images is relatable to voxel-level tumor response to Radiation Treatment (RT). We have investigated a deep learning framework to predict (i) post-treatment mpMR images from pre-treatment mpMR images and the dose map ("forward models"), and, (ii) the RT dose map that will produce prescribed changes within the Gross Tumor Volume (GTV) on post-treatment mpMR images ("inverse model"), in Breast Cancer Metastases to the Brain (BCMB) treated with Stereotactic Radiosurgery (SRS). Materials and methods: Local outcomes, planning computed tomography (CT) images, dose maps, and pre-treatment and post-treatment Apparent Diffusion Coefficient of water (ADC) maps, T1-weighted unenhanced (T1w) and contrast-enhanced (T1wCE), T2-weighted (T2w) and Fluid-Attenuated Inversion Recovery (FLAIR) mpMR images were curated from 39 BCMB patients. mpMR images were co-registered to the planning CT and intensity-calibrated. A 2D pix2pix architecture was used to train 5 forward models (ADC, T2w, FLAIR, T1w, T1wCE) and 1 inverse model on 1940 slices from 18 BCMB patients, and tested on 437 slices from another 9 BCMB patients. Results: Root Mean Square Percent Error (RMSPE) within the GTV between predicted and ground-truth post-RT images for the 5 forward models, in 136 test slices containing GTV, were (mean ± SD) 0.12 ± 0.044 (ADC), 0.14 ± 0.066 (T2w), 0.08 ± 0.038 (T1w), 0.13 ± 0.058 (T1wCE), and 0.09 ± 0.056 (FLAIR). RMSPE within the GTV on the same 136 test slices, between the predicted and ground-truth dose maps, was 0.37 ± 0.20 for the inverse model. Conclusions: A deep learning-based approach for radiologic outcome-optimized dose planning in SRS of BCMB has been demonstrated.
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Radiation therapy (RT) plays a fundamental role in the treatment of malignant and benign brain tumors. Current state-of-the-art photon- and proton-based RT combines more conformal dose distribution of target volumes and accurate dose delivery while limiting the adverse radiation effects. PubMed was systematically searched from from 2000 to October 2023 to identify studies reporting outcomes related to treatment of central nervous system (CNS)/skull base tumors with PT in adults. Several studies have demonstrated that proton therapy (PT) provides a reduced dose to healthy brain parenchyma compared with photon-based (xRT) radiation techniques. However, whether dosimetric advantages translate into superior clinical outcomes for different adult brain tumors remains an open question. This review aims at critically reviewing the recent studies on PT in adult patients with brain tumors, including glioma, meningiomas, and chordomas, to explore its potential benefits compared with xRT.
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AIM: To compare the cost-effectiveness of termination-of-resuscitation (TOR) rules for patients transported in cardiac arrest. METHODS: The economic analyses evaluated cost-effectiveness of alternative TOR rules for OHCA from a National Health Service (NHS) and personal social services (PSS) perspective over a lifetime horizon. A systematic review was used to identify the different TOR rules included in the analyses. Data from the OHCAO outcomes registry, trial data and published literature were used to compare outcomes for the different rules identified. The economic analyses estimated discounted NHS and PSS costs and quality-adjusted life-years (QALYs) for each TOR rule, based on which incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: The systematic review identified 33 TOR rules and the economic analyses assessed the performance of 29 of these TOR rules plus current practice. The most cost-effective strategies were the European Resuscitation Council (ERC) termination of resuscitation rule (ICER of £8,111), the Korean Cardiac Arrest Research Consortium 2 (KOC 2) termination of resuscitation rule (ICER of £17,548), and the universal Basic Life Support (BLS) termination of resuscitation rule (ICER of £19,498,216). The KOC 2 TOR rule was cost-effective at the established cost-effectiveness threshold of £20,000-£30,000 per QALY. CONCLUSION: The KOC 2 rule is the most cost-effective at established cost-effectiveness thresholds used to inform health care decision-making in the UK. Further research on economic implications of TOR rules is warranted to support constructive discussion on implementing TOR rules.
Subject(s)
Cost-Benefit Analysis , Out-of-Hospital Cardiac Arrest , Humans , Out-of-Hospital Cardiac Arrest/therapy , Out-of-Hospital Cardiac Arrest/economics , Quality-Adjusted Life Years , Cardiopulmonary Resuscitation/economics , Cardiopulmonary Resuscitation/methods , United Kingdom , Resuscitation Orders , State Medicine/economicsABSTRACT
BACKGROUND: EGFR-targeted therapy (ETT) and immune-checkpoint blockade (ICB) have shown promising results in treating NSCLC brain metastases (BM). However, little is known of their effect in treating leptomeningeal disease (LMD). PATIENTS AND METHODS: This is a retrospective review of 80 patients diagnosed with NSCLC LMD from January 2014 to March 2021. Patients were grouped based on initial LMD treatment: radiotherapy (RT) alone, ETT, ICB, and intrathecal chemotherapy (ITC). RESULTS: EGFR mutation was present in 22 patients (28%). Twenty patients had positive cytology in cerebrospinal fluid, while 60 patients were diagnosed based on MRI with clinical correlation. The RT alone group consisted primarily of whole brain radiation (n = 20; 77%), stereotactic radiation (n = 3; 12%), and palliative spine radiation (n = 2; 7%). There were no significant differences amongst the treatment groups in age, performance status, or neurologic symptoms. Overall, the 6-month overall survival (OS) and craniospinal progression free survival (CS-PFS) were 35% and 24%, respectively. The 6-month OS for the ETT, ICB, ITC, and RT alone groups was 64%, 33%, 57%, and 29% respectively (log-rank P = .026). The 6-month CS-PFS for the ETT, ICB, ITC, and RT alone groups was 43%, 33%, 29%, and 19% respectively (log-rank P = .049). Upon univariate analysis, receipt of ETT compared to RT alone reached significance for OS (HR 0.35, P = .006) and CS-PFS (HR 0.39, P = .013). CONCLUSIONS: The prognosis for patients with NSCLC LMD remains poor overall. However, the receipt of ETT for patients with EGFR-positive disease was associated with improved outcomes.
Subject(s)
Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Immune Checkpoint Inhibitors , Lung Neoplasms , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Male , Female , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Retrospective Studies , Middle Aged , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Aged , Immune Checkpoint Inhibitors/therapeutic use , Immune Checkpoint Inhibitors/administration & dosage , Injections, Spinal , Meningeal Neoplasms/therapy , Meningeal Neoplasms/pathology , Adult , Meningeal Carcinomatosis/secondary , Meningeal Carcinomatosis/drug therapy , Molecular Targeted Therapy , Aged, 80 and over , Survival Rate , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , Prognosis , Treatment Outcome , Follow-Up Studies , MutationABSTRACT
This nonrandomized controlled trial examines the safety of radiation therapy (RT) followed by intrathecal trastuzumab and pertuzumab for patients with ERBB2-positive breast leptomeningeal disease (LMD).
Subject(s)
Antibodies, Monoclonal, Humanized , Breast Neoplasms , Injections, Spinal , Receptor, ErbB-2 , Trastuzumab , Humans , Trastuzumab/administration & dosage , Trastuzumab/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Breast Neoplasms/pathology , Female , Receptor, ErbB-2/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Middle Aged , Meningeal Neoplasms/secondary , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult , AgedABSTRACT
A methodology for the mapping of residual stresses in metal alloys has been developed by analyzing an isotropic and homogeneous Al2024 alloy with scanning transmission electron microscopy (STEM), combined with diffraction (4DSTEM) and electron energy loss spectroscopy (STEM-EELS) techniques of TEM. The investigations on the alloy's microstructure and elemental distributions were also carried out with conventional dark-field STEM (DFSTEM) and X-ray energy dispersive (EDS) techniques, respectively. Using the STEM-EELS technique, the Young's modulus (YM) is mapped in the (001) plane of the Al alloy in the same regions where the residual strain maps are generated in [1â¾ 00] and [010] directions by using 4DSTEM technique. The YM vs. residual strain plot for the Al 2024 alloy revealed that the value of YM decreased by about â¼ 7 % after the tensile residual strain reached 0.02 %. Whereas such a decrease in YM happens after the compressively residual strain reaches -0.015 %. The residual stress maps were also obtained in accordance with the Hooke's law i.e., by multiplying YM map with the corresponding residual strain maps.
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PURPOSE: Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS. METHODS: 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan-Meier method. RESULTS: 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24 months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01). CONCLUSION: In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.
Subject(s)
Antineoplastic Agents, Immunological , Brain Neoplasms , Melanoma , Radiosurgery , Humans , Ipilimumab/therapeutic use , Melanoma/pathology , Nivolumab/therapeutic use , Radiosurgery/methods , Prospective Studies , Antineoplastic Agents, Immunological/therapeutic use , Brain Neoplasms/drug therapy , Brain Neoplasms/secondary , Retrospective StudiesABSTRACT
Galleria mellonella larvae have emerged as an invertebrate model for investigating bacterial pathogenesis and potential therapies, addressing ethical concerns related to mammalian models. This model has the advantage of having a simple gut microbiome, which is suitable for gut colonization studies. Intestinal colonization by Enterobacteriaceae significantly contributes to the spread of antibiotic resistance. This study aimed to establish a novel Enterobacteriaceae gut colonization larval model and assess its suitability for evaluating distinct antimicrobial efficacies. Larvae were force-fed sequentially with bacterial doses of K. pneumoniae and E. coli at 0, 24, and 48 h, with survival monitoring at 24 h intervals. Bacterial counts were assessed after 48 h and 120 h of force-feeding. Successfully colonized larvae were subjected to one-time force feeding of a bacteriophage cocktail (107 PFU/larvae) or MIC-based meropenem and ciprofloxacin. The colonized bacterial load was quantified by CFU count. Three doses of 106 CFU/larvae resulted in stable gut colonization, independent of the K. pneumoniae or E. coli strain. Compared with the control, force-feeding of the bacteriophage reduced the colonization of the strain Kp 419614 by 5 log10 CFU/larvae, while antibiotic treatment led to a 3 log10 CFU/larval reduction. This novel G. mellonella model provides a valuable alternative for gut colonization studies, facilitating proof-of-concept investigations and potentially reducing or replacing follow-up experiments in vertebrate models.
Subject(s)
Bacteriophages , Moths , Animals , Anti-Bacterial Agents/pharmacology , Bacteria , Enterobacteriaceae , Escherichia coli , Klebsiella pneumoniae , Larva/microbiology , Mammals , Moths/microbiologyABSTRACT
Leptomeningeal disease (LMD) remains a major challenge in the clinical management of metastatic melanoma patients. Outcomes for patient remain poor, and patients with LMD continue to be excluded from almost all clinical trials. However, recent trials have demonstrated the feasibility of conducting prospective clinical trials in these patients. Further, new insights into the pathophysiology of LMD are identifying rational new therapeutic strategies. Here we present recent advances in the understanding of, and treatment options for, LMD from metastatic melanoma. We also annotate key areas of future focus to accelerate progress for this challenging but emerging field.
Subject(s)
Melanoma , Radiosurgery , Humans , Melanoma/secondary , Prospective Studies , Radiosurgery/adverse effectsABSTRACT
Combination therapies have improved outcomes for patients with acute myeloid leukemia (AML). However, these patients still have poor overall survival. Although many combination therapies are identified with high-throughput screening (HTS), these approaches are constrained to disease models that can be grown in large volumes (e.g., immortalized cell lines), which have limited translational utility. To identify more effective and personalized treatments, we need better strategies for screening and exploring potential combination therapies. Our objective was to develop an HTS platform for identifying effective combination therapies with highly translatable ex vivo disease models that use size-limited, primary samples from patients with leukemia (AML and myelodysplastic syndrome). We developed a system, ComboFlow, that comprises three main components: MiniFlow, ComboPooler, and AutoGater. MiniFlow conducts ex vivo drug screening with a miniaturized flow-cytometry assay that uses minimal amounts of patient sample to maximize throughput. ComboPooler incorporates computational methods to design efficient screens of pooled drug combinations. AutoGater is an automated gating classifier for flow cytometry that uses machine learning to rapidly analyze the large datasets generated by the assay. We used ComboFlow to efficiently screen more than 3000 drug combinations across 20 patient samples using only 6 million cells per patient sample. In this screen, ComboFlow identified the known synergistic combination of bortezomib and panobinostat. ComboFlow also identified a novel drug combination, dactinomycin and fludarabine, that synergistically killed leukemic cells in 35 % of AML samples. This combination also had limited effects in normal, hematopoietic progenitors. In conclusion, ComboFlow enables exploration of massive landscapes of drug combinations that were previously inaccessible in ex vivo models. We envision that ComboFlow can be used to discover more effective and personalized combination therapies for cancers amenable to ex vivo models.
Subject(s)
Hematologic Neoplasms , Leukemia, Myeloid, Acute , Humans , Drug Synergism , Drug Combinations , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/pathology , Panobinostat/therapeutic use , Hematologic Neoplasms/drug therapyABSTRACT
PURPOSE: Juvenile myelomonocytic leukemia (JMML) is an aggressive pediatric malignancy with myelodysplastic and myeloproliferative features. Curative treatment is restricted to hematopoietic stem-cell transplantation. Fludarabine combined with cytarabine (FLA) and 5-azacitidine (AZA) monotherapy are commonly used pre-transplant therapies. Here, we present a drug screening strategy using a flow cytometry-based precision medicine platform to identify potential additional therapeutic vulnerabilities. METHODS: We screened 120 dual- and 10 triple-drug combinations (DCs) on peripheral blood (n = 21) or bone marrow (n = 6) samples from 27 children with JMML to identify DCs more effectively reducing leukemic cells than the DCs' components on their own. If fewer leukemic cells survived a DC ex vivo treatment compared with that DC's most effective component alone, the drug effect was referred to as cooperative. The difference between the two resistant fractions is the effect size. RESULTS: We identified 26 dual- and one triple-DC more effective than their components. The differentiation agent tretinoin (TRET; all-trans retinoic acid) reduced the resistant fraction of FLA in 19/21 (90%) samples (decrease from 15% [2%-61%] to 11% [2%-50%] with a mean effect size of 3.8% [0.5%-11%]), and of AZA in 19/25 (76%) samples (decrease from 69% [34%-100+%] to 47% [17%-83%] with a mean effect size of 16% [0.3%-40%]). Among the resistant fractions, the mean proportion of CD38+ cells increased from 7% (0.03%-25%; FLA) to 17% (0.3%-38%; FLA + TRET) or from 10% (0.2%-31%; AZA) to 51% (0.8%-88%; AZA + TRET). CONCLUSION: TRET enhanced the effects of FLA and AZA in ex vivo assays with primary JMML samples.
Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myelomonocytic, Juvenile , Child , Humans , Leukemia, Myelomonocytic, Juvenile/drug therapy , Leukemia, Myelomonocytic, Juvenile/diagnosis , Leukemia, Myelomonocytic, Juvenile/pathology , Tretinoin/pharmacology , Tretinoin/therapeutic use , Azacitidine/therapeutic useABSTRACT
BACKGROUND: Immunotherapy and targeted BRAF/MEK inhibitors (i) have revolutionised the systemic management of advanced melanoma. Given the role of stereotactic radiosurgery (SRS) in the local management of brain metastases, we sought to evaluate clinical outcomes in patients with melanoma brain metastases (MBM) treated with SRS and various systemic therapies. METHODS: Patients were included if MBM were diagnosed and treated with SRS within 3 months of receiving anti-PD-1+CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, or conventional chemotherapy. Comparisons between groups were made for overall survival (OS), distant MBM control, local MBM, systemic progression-free survival (sPFS), and neurotoxicity. RESULTS: In total, 257 patients with 1048 MBM treated over 368 SRS sessions between 2011 and 2020 were identified. On MVA, treatment with anti-PD1+anti-CTLA-4, anti-PD-1, and BRAF/MEK-i improved distant intracranial control over conventional chemotherapy. No significant differences were noted in local control (LC) between groups (p = 0.78). Kaplan-Meier OS at 12 months for anti-PD-1 + CTLA-4 therapy, anti-PD-1 therapy, anti-CTLA-4 therapy, BRAF/MEK-i, BRAF-i, and conventional chemotherapy was 68%, 59%, 45%, 62%, 21%, and 15%, respectively (p = <0.0001). The sPFS rates at 12 months were 57%, 53%, 42%, 45%, 14%, and 6% (p = <0.0001). No significant differences were noted in rates of radiation necrosis (p = 0.93). CONCLUSIONS: This is among the largest series evaluating MBM treated with SRS and various systemic therapy regimens. Our analysis noted significant differences in OS, distant MBM control, and sPFS by systemic therapy. No differences in LC or radiation necrosis risk were noted.
Subject(s)
Brain Neoplasms , Melanoma , Radiation Injuries , Radiosurgery , Humans , Proto-Oncogene Proteins B-raf/genetics , Radiosurgery/adverse effects , Brain Neoplasms/therapy , Melanoma/therapy , Protein Kinase Inhibitors/adverse effects , Necrosis , Mitogen-Activated Protein Kinase KinasesABSTRACT
PURPOSE: HER2-positive breast cancer has a high risk of brain metastasis. Stereotactic radiosurgery (SRS) is standard of care for limited brain metastases. Tucatinib, a HER2-targeted tyrosine kinase inhibitor, has demonstrated intracranial efficacy in the HER2-CLIMB Trial. However, it is unknown whether tucatinib with SRS is safe or effective. METHODS: A retrospective analysis of HER2-positive breast cancer treated with SRS and tucatinib for brain metastases management was performed. All patients received tucatinib and SRS for the management of active brain metastases. The primary endpoint was local and distant brain tumor control. Secondary endpoints were intracranial progression free survival (CNS-PFS), systemic PFS, overall survival (OS), and neurotoxicity. RESULTS: A total of 135 lesions treated with SRS over 39 treatment sessions in 22 patients were identified. Median follow-up from tucatinib initiation was 20.8 months. Local brain control was 94% at 12-months and 81% at 24-months. Distant brain control was 39% at 12-months and 26% at 24-months. Median survival was 21.2 months, with 12- and 24-month OS rates of 84% and 50%, respectively. Median CNS-PFS was 11.3 months, with 12- and 24-month CNS-PFS rates of 44.9% at both time points. Median systemic PFS was not reached, with 12- and 24-month systemic PFS rates of 86% and 57%, respectively. Symptomatic radiation necrosis occurred in 6 (4%) lesions. No additional unexpected toxicities were noted. CONCLUSIONS: SRS in combination with tucatinib, capecitabine, and trastuzumab appears to be a safe and feasible treatment for HER2 + brain metastases. Further prospective evaluation of potential synergistic effects is warranted.
Subject(s)
Brain Neoplasms , Breast Neoplasms , Radiosurgery , Female , Humans , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Breast Neoplasms/pathology , Radiosurgery/adverse effects , Retrospective StudiesABSTRACT
PURPOSE: Neoadjuvant radiation therapy (RT) with standard techniques (ST) offers a modest benefit in retroperitoneal sarcoma (RPS). As the high-risk region (HRR) at risk for a positive surgical margin and recurrence is posterior and away from radiosensitive organs at risk, using a simultaneous integrated boost (SIB) allows targeted dose escalation to the HRR while sparing these organs. We hypothesized that neoadjuvant SIB RT can improve disease control compared with ST, without increasing toxicity. METHODS AND MATERIALS: We retrospectively identified patients with resectable nonmetastatic RPS from 2000 to 2021 who received neoadjuvant RT of 180 to 200 cGy/fraction to standard volumes. SIB patients received 205 to 230 cGy/fraction to the appropriate HRR. Clinical endpoints included abdominopelvic control (APC), recurrence-free survival (RFS), overall survival (OS), and acute toxicity. RESULTS: With a median follow-up of 57 months (95% confidence interval [CI], 50-64), there were 103 patients with RPS who received either ST (n = 69) or SIB (n = 34) RT. Median standard volume dose was 5000 cGy (ST) and 4500 cGy (SIB), with a median HRR SIB dose of 5750 cGy. Liposarcomas (79% vs 53%; P = .004) and cT4 tumors (59% vs 19%; P < .001) were more common in the SIB cohort, without a significant difference in the rate of resection (82% vs 81%; P = .88) or R1 margin (53.5% vs 50%; P = .36); there were no R2 resections. SIB was associated with a significant improvement in 5-year APC (96% vs 70%; P = .046) and RFS (60.2% vs 36.3%; P = .036), with a nonsignificant OS difference (90.1% vs 67.5%; P = .164). On multivariable analysis, SIB remained a predictor for APC (hazard ratio, 0.07; 95% CI, 0.01-0.74; P = .027) and RFS (hazard ratio, 0.036; 95% CI, 0.13-0.98; P = .045). SIB showed no significant detriment in toxicity, albeit with a lower rate of overall grade 3 acute toxicity (3% vs 22%; P = .023) compared with ST. CONCLUSIONS: In RPS, dose escalation with neoadjuvant SIB RT may be independently associated with improved APC and RFS, without a detriment in toxicity, compared with ST. With the addition of standard RT having only a modest benefit compared with surgery alone, our study suggests that future prospective studies evaluating for the benefit of SIB RT should be considered.
Subject(s)
Liposarcoma , Retroperitoneal Neoplasms , Sarcoma , Soft Tissue Neoplasms , Humans , Neoadjuvant Therapy , Prospective Studies , Retroperitoneal Neoplasms/radiotherapy , Retroperitoneal Neoplasms/surgery , Retrospective Studies , Sarcoma/radiotherapy , Sarcoma/surgerySubject(s)
Breast Neoplasms , Lung Neoplasms , Radiosurgery , Humans , Female , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Breast , Lung Neoplasms/surgeryABSTRACT
Friction stir lap welding (FSLW) remains a pioneering technique for creating hybrid joints between AA5052 aluminium alloy and polypropylene (PP), particularly with the metal-on-top configuration. Building upon previous research, this study introduces a tapered fluted pin tool design and investigates its effectiveness in the welding process. Our results, supported by ANOVA, chemical, and microstructural analyses, reiterate that the optimal welding parameters stand at a rotational speed of 1400 RPM and a traverse speed of 20 mm/min. This combination produces a joint tensile strength of 3.8 MPa, signifying 16.54% of the weaker material's inherent strength. Microstructural evaluations revealed a unique composite of aluminium chips intermeshed with PP, strengthened further by aluminium hooks. Crucially, mechanical interlocking plays a predominant role over chemical bonding in achieving this joint strength. The study underscores the absence of significant C-O-Al bonds, hinting at the PP degradation without the thermo-oxidation process. Additionally, joint strength was found to inversely correlate with the interaction layer's thickness. The findings fortify the promise of FSLW with the novel fluted pin design for enhancing joints between AA5052 and PP, emphasising the potential of mechanical interlocking as a principal factor in achieving high-quality welds.
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Considering that the machining of composites particularly fiber-reinforced polymer composites (FRPCs) has remained a challenge associated with their heterogeneity and anisotropic nature, damage caused by drilling operations can be considerably mitigated by following optimum cutting parameters. In this work, we numerically evaluated the effects of cutting parameters, such as feed rate and spindle speed, on the thrust force and torque during the drilling of glass-fiber-reinforced polymers (GFRPs). A meso-scale, also known as unidirectional ply-level-based finite element modeling, was employed assuming an individual homogenized lamina with transversely isotropic material principal directions. To initiate the meso-scale damage in each lamina, 3D formulations of Hashin's failure theory were used for fiber damage and Puck's failure theory was implemented for matrix damage onset via user subroutine VUMAT in ABAQUS. The developed model accounted for the complex kinematics taking place at the drill-workpiece interface and accurately predicted the thrust force and torque profiles as compared with the experimental results. The thrust forces for various drilling parameters were predicted with a maximum of 10% error as compared with the experimental results. It was found that a combination of lower feed rates and higher spindle speeds reduced the thrust force, which in turn minimized the drilling-induced damage, thus providing useful guidelines for drilling operations with higher-quality products. Finally, the effect of coefficient of friction was also investigated. Accordingly, a higher coefficient of friction between the workpiece and drill-bit reduced the thrust force.