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Journal of Clinical and Experimental... Mar 2024Peritoneal lymphomatosis (PL) is a rare lymphoma-associated condition defined as the dissemination of lymphoma cells in the peritoneum. An 82-year-old man presented with...
Peritoneal lymphomatosis (PL) is a rare lymphoma-associated condition defined as the dissemination of lymphoma cells in the peritoneum. An 82-year-old man presented with abdominal pain, heartburn, and high fever. Radiological findings, including positron emission tomography-computed tomography (PET-CT), and gastrointestinal fiberscopy, showed diffuse thickening of the peritoneum, omentum, and mesentery; however, no lymphadenopathy, hepatosplenomegaly, or gastrointestinal lesions were observed. Under suspicion of peritonitis carcinomatosa of unknown origin, exploratory laparoscopy was performed that revealed multiple white nodules and masses on the surfaces of the peritoneum, mesentery, and intestinal serosa. The histopathological and cytogenetic findings of the peritoneum revealed high-grade B-cell lymphoma, not otherwise specified, and a gain of MYC by fluorescence in-situ hybridization. The patient was treated with two cycles of R-CHOP therapy, followed by six cycles of dose-adjusted EPOCH-R therapy, and a complete metabolic response was confirmed by PET-CT. Since there are no specific radiological findings to confirm the diagnosis of PL, a histopathological diagnosis is usually required. Most PL exhibit an aggressive lymphoma phenotype and can be cured by appropriate chemotherapy. Therefore, early diagnosis and treatment are desirable.
Topics: Male; Humans; Aged, 80 and over; Peritoneum; Positron Emission Tomography Computed Tomography; Peritoneal Neoplasms; Lymphoma, B-Cell; Lymphoma; Prednisone; Rituximab; Vincristine; Cyclophosphamide; Doxorubicin; Etoposide; Lymphoma, Large B-Cell, Diffuse
PubMed: 38281744
DOI: 10.3960/jslrt.23044 -
Radiation Oncology (London, England) Jan 2024It is not unusual to see some parts of tissues are excluded in the field of view of CT simulation images. A typical mitigation is to avoid beams entering the missing...
BACKGROUND
It is not unusual to see some parts of tissues are excluded in the field of view of CT simulation images. A typical mitigation is to avoid beams entering the missing body parts at the cost of sub-optimal planning.
METHODS
This study is to solve the problem by developing 3 methods, (1) deep learning (DL) mechanism for missing tissue generation, (2) using patient body outline (PBO) based on surface imaging, and (3) hybrid method combining DL and PBO. The DL model was built upon a Globally and Locally Consistent Image Completion to learn features by Convolutional Neural Networks-based inpainting, based on Generative Adversarial Network. The database used comprised 10,005 CT training slices of 322 lung cancer patients and 166 CT evaluation test slices of 15 patients. CT images were from the publicly available database of the Cancer Imaging Archive. Since existing data were used PBOs were acquired from the CT images. For evaluation, Structural Similarity Index Metric (SSIM), Root Mean Square Error (RMSE) and Peak signal-to-noise ratio (PSNR) were evaluated. For dosimetric validation, dynamic conformal arc plans were made with the ground truth images and images generated by the proposed method. Gamma analysis was conducted at relatively strict criteria of 1%/1 mm (dose difference/distance to agreement) and 2%/2 mm under three dose thresholds of 1%, 10% and 50% of the maximum dose in the plans made on the ground truth image sets.
RESULTS
The average SSIM in generation part only was 0.06 at epoch 100 but reached 0.86 at epoch 1500. Accordingly, the average SSIM in the whole image also improved from 0.86 to 0.97. At epoch 1500, the average values of RMSE and PSNR in the whole image were 7.4 and 30.9, respectively. Gamma analysis showed excellent agreement with the hybrid method (equal to or higher than 96.6% of the mean of pass rates for all scenarios).
CONCLUSIONS
It was first demonstrated that missing tissues in simulation imaging could be generated with high similarity, and dosimetric limitation could be overcome. The benefit of this study can be significantly enlarged when MR-only simulation is considered.
Topics: Humans; Tomography, X-Ray Computed; Machine Learning; Neural Networks, Computer; Radiometry; Magnetic Resonance Imaging; Image Processing, Computer-Assisted
PubMed: 38273278
DOI: 10.1186/s13014-023-02384-4 -
International Journal of Molecular... Jan 2024Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506)...
Peripheral nerve injuries (PNIs) occur frequently and can lead to devastating and permanent sensory and motor function disabilities. Systemic tacrolimus (FK506) administration has been shown to hasten recovery and improve functional outcomes after PNI repair. Unfortunately, high systemic levels of FK506 can result in adverse side effects. The localized administration of FK506 could provide the neuroregenerative benefits of FK506 while avoiding systemic, off-target side effects. This study investigates the utility of a novel FK506-impregnated polyester urethane urea (PEUU) nerve wrap to treat PNI in a previously validated rat infraorbital nerve (ION) transection and repair model. ION function was assessed by microelectrode recordings of trigeminal ganglion cells responding to controlled vibrissae deflections in ION-transected and -repaired animals, with and without the nerve wrap. Peristimulus time histograms (PSTHs) having 1 ms bins were constructed from spike times of individual single units. Responses to stimulus onsets (ON responses) were calculated during a 20 ms period beginning 1 ms after deflection onset; this epoch captures the initial, transient phase of the whisker-evoked response. Compared to no-wrap controls, rats with PEUU-FK506 wraps functionally recovered earlier, displaying larger response magnitudes. With nerve wrap treatment, FK506 blood levels up to six weeks were measured nearly at the limit of quantification (LOQ ≥ 2.0 ng/mL); whereas the drug concentrations within the ION and muscle were much higher, demonstrating the local delivery of FK506 to treat PNI. An immunohistological assessment of ION showed increased myelin expression for animals assigned to neurorrhaphy with PEUU-FK506 treatment compared to untreated or systemic-FK506-treated animals, suggesting that improved PNI outcomes using PEUU-FK506 is mediated by the modulation of Schwann cell activity.
Topics: Animals; Rats; Tacrolimus; Myelin Sheath; Neurons; Urethane; Nerve Regeneration; Amides; Carbamates; Urea; Esters
PubMed: 38255920
DOI: 10.3390/ijms25020847 -
Annals of Hematology May 2024Indolent lymphoma, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL), can undergo histological transformation into...
Venetoclax plus dose-adjusted R-EPOCH (VR-DA-EPOCH) or G-EPOCH bridging to subsequent cellular therapy for the patients with transformed lymphoma a single center clinical experience.
Indolent lymphoma, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL), can undergo histological transformation into an aggressive subtype, typically diffuse large B-cell lymphoma (DLBCL). The prognosis of transformed lymphoma is poor. In this study, we reported the efficacy and toxicity of a combination of venetoclax, dose-adjusted rituximab or obinutuzumab, etoposide, prednisone, vincristine, doxorubicin, and cyclophosphamide (VR-DA-EPOCH or VG-DA-EPOCH) in 11 patients with biopsy-proven histology transformation into DLBCL, including 8 patients with RT and 3 with transformed FL (tFL). The study was conducted between October 2019 and March 2023 at our single center. The median age of participants at enrolment was 53 years. Six patients (85.7%, 6/7) achieved complete remission (CR) at the end of treatment. The best overall response rate (ORR) and CR rate were both 72.7%, respectively. Two patients received autologous hemopoietic stem cell transplant (ASCT) while two patients received ASCT concurrently with CAR-T therapy for consolidation. With a median follow-up of 13.5 (range, 2.4-29.8) months after enrollment, the median event-free survival, progression-free survival, and overall survival were 9.4, 11.5, and 17.5 months, respectively. Hematologic toxicities of grade ≥3 consisted of neutropenia (90.9%, 10/11), thrombocytopenia (63.6%, 7/11), and febrile neutropenia (54.5%, 6/11). In conclusion, VR-DA-EPOCH or VG-DA-EPOCH was a promising strategy to achieve an early remission, bridging to cellular therapy within this population.
Topics: Humans; Middle Aged; Prednisone; Vincristine; Etoposide; Antibodies, Monoclonal, Murine-Derived; Cyclophosphamide; Rituximab; Lymphoma, Non-Hodgkin; Doxorubicin; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Combined Chemotherapy Protocols; Virtual Reality; Sulfonamides; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 38246951
DOI: 10.1007/s00277-024-05618-x -
Blood Advances Apr 2024MYC-aberrant non-Hodgkin lymphoma (NHL) is associated with poor outcomes with conventional chemotherapy. Ixazomib is an orally bioavailable proteasome inhibitor that...
MYC-aberrant non-Hodgkin lymphoma (NHL) is associated with poor outcomes with conventional chemotherapy. Ixazomib is an orally bioavailable proteasome inhibitor that targets drivers of MYC expression and has demonstrated preclinical activity in aggressive MYC-aberrant NHL. We conducted a phase 1/2 study evaluating the safety and efficacy of DA-EPOCH-R with adjunctive ixazomib in aggressive MYC-aberrant NHL. For induction, patients received 6 cycles of DA-EPOCH-R with ixazomib administered twice per 21-day cycle; responders continued weekly ixazomib maintenance for up to 1 year. Primary objectives were to determine the maximum tolerated dose in phase 1 and efficacy of DA-EPOCH-R with ixazomib as measured by 12-month progression-free survival (PFS) rate in phase 2. Thirty-six patients were evaluable for response. Median age was 63 years (range, 31-77) and 44% had double-hit lymphoma (DHL)/triple-hit lymphoma (THL). In phase 1, 3 mg of ixazomib was established as recommended phase 2 dose. Twenty-nine (76.3%) patients completed 6 cycles of DA-EPOCH-R and 25 (65.8%) underwent dose escalations. The ORR after induction was 97% (95% confidence interval, 81-100) with a CR rate of 69%. At median follow-up of 18.8 months, the 12-month PFS and overall survival (OS) rates were 78% and 86%, respectively. For DHL/THL vs dual expressor lymphomas (DEL), 12-month PFS rates were 53% vs 95% and 12-month OS rates were 65% vs 100%, respectively. Grade ≥3 toxicities were predominantly hematologic. Twenty-seven (75%) of patients experienced neuropathy, nearly all low-grade. DA-EPOCH-R induction with adjunctive ixazomib is feasible and appears effective in patients with DEL. This trial was registered at www.clinicaltrials.gov as #NCT02481310.
Topics: Humans; Middle Aged; Treatment Outcome; Rituximab; Cyclophosphamide; Prednisone; Vincristine; Etoposide; Doxorubicin; Lymphoma, Non-Hodgkin; Boron Compounds; Glycine
PubMed: 38237077
DOI: 10.1182/bloodadvances.2023011369 -
Advances in Therapy Mar 2024EPOCH-US is an ongoing, retrospective, observational cohort study among individuals identified in the Healthcare Integrated Research Database (HIRD) with... (Observational Study)
Observational Study
Assessing the Burden and Cost of COVID-19 Across Variants in Commercially Insured Immunocompromised Populations in the United States: Updated Results and Trends from the Ongoing EPOCH-US Study.
INTRODUCTION/METHODS
EPOCH-US is an ongoing, retrospective, observational cohort study among individuals identified in the Healthcare Integrated Research Database (HIRD) with ≥ 12 months of continuous health plan enrollment. Data were collected for the HIRD population (containing immunocompetent and immunocompromised [IC] individuals), individual IC cohorts (non-mutually exclusive cohorts based on immunocompromising condition and/or immunosuppressive [IS] treatment), and the composite IC population (all unique IC individuals). This study updates previous results with addition of the general population cohort and data specifically for the year of 2022 (i.e., Omicron wave period). To provide healthcare decision-makers the most recent trends, this study reports incidence rates (IR) and severity of first SARS-CoV-2 infection; and relative risk, healthcare utilization, and costs related to first COVID-19 hospitalizations in the full year of 2022 and overall between April 2020 and December 2022.
RESULTS
These updated results showed a 2.9% prevalence of immune compromise in the population. From April 2020 through December 2022, the overall IR of COVID-19 was 115.7 per 1000 patient-years in the composite IC cohort and 77.8 per 1000 patient-years in the HIRD cohort. The composite IC cohort had a 15.4% hospitalization rate with an average cost of $42,719 for first COVID-19 hospitalization. Comparatively, the HIRD cohort had a 3.7% hospitalization rate with an average cost of $28,848 for first COVID-19 hospitalization. Compared to the general population, IC individuals had 4.3 to 23 times greater risk of hospitalization with first diagnosis of COVID-19. Between January and December 2022, hospitalizations associated with first COVID-19 diagnosis cost over $1 billion, with IC individuals (~ 3% of the population) generating $310 million (31%) of these costs.
CONCLUSION
While only 2.9% of the population, IC individuals had a higher risk of COVID-19 hospitalization and incurred higher healthcare costs across variants. They also disproportionately accounted for over 30% of total costs for first COVID-19 hospitalization in 2022, amounting to ~ $310 million. These data highlight the need for additional preventive measures to decrease the risk of developing severe COVID-19 outcomes in vulnerable IC populations.
Topics: Humans; United States; Retrospective Studies; COVID-19 Testing; COVID-19; SARS-CoV-2; Health Care Costs; Hospitalization
PubMed: 38216825
DOI: 10.1007/s12325-023-02754-0 -
Blood Advances Feb 2024Large B-cell lymphoma (LBCL) carrying MYC rearrangement, alone or together with BCL2 and/or BCL6 translocations, have shown a poor prognosis when treated with rituximab...
Large B-cell lymphoma (LBCL) carrying MYC rearrangement, alone or together with BCL2 and/or BCL6 translocations, have shown a poor prognosis when treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in the HIV population. Scanty data are available on the prevalence and prognostic impact of MYC rearrangements in HIV-associated LBCL. We conducted a retrospective study to evaluate the clinical effect of MYC rearrangement in HIV-associated LBCL. We evaluated clinical characteristics, treatment received, and outcome of LBCL in patients with HIV with MYC rearrangement (MYC+) and without MYC rearrangement (MYC-). A total of 155 patients with HIV who had received fluorescence in situ hybridization analysis for MYC were enrolled in 11 European centers: 43 with MYC+ and 112 MYC-. Among patients with MYC, 10 had double-/triple-hit lymphomas, and 33 had isolated MYC rearrangement (single-hit lymphoma). Patients with MYC+ had more frequently advanced stage, >2 extranodal site at presentation, and higher proliferative index. There were no significant differences in overall survival and progression-free survival (PFS) between the 2 groups. However, patients with MYC+ received more frequently intensive chemotherapy (iCT) (44%) than (R)CHOP alone (35%) or infusional treatment (DA-EPOCH-R and R-CDE) (19%). Among patients with MYC+, those who received iCT achieved a better outcome than patients who received nonintensive treatment (complete remission, 84% vs 52%; P = .028; 5-year PFS, 66% vs 36%; P = .021). Our retrospective results suggest that HIV-associated LBCL with MYC+ could be considered for an intensive therapeutic approach whenever possible, whereas (R)CHOP seems to give inferior results in this subset of patients in terms of complete remission and PFS.
Topics: Humans; Cyclophosphamide; HIV Infections; In Situ Hybridization, Fluorescence; Lymphoma, Large B-Cell, Diffuse; Proto-Oncogene Proteins c-myc; Retrospective Studies; Rituximab; Vincristine
PubMed: 38207206
DOI: 10.1182/bloodadvances.2023010704 -
Radiation Oncology (London, England) Jan 2024The study aims to enhance the efficiency and accuracy of literature reviews on normal tissue complication probability (NTCP) in head and neck cancer patients using... (Meta-Analysis)
Meta-Analysis
PURPOSE
The study aims to enhance the efficiency and accuracy of literature reviews on normal tissue complication probability (NTCP) in head and neck cancer patients using radiation therapy. It employs meta-analysis (MA) and natural language processing (NLP).
MATERIAL AND METHODS
The study consists of two parts. First, it employs MA to assess NTCP models for xerostomia, dysphagia, and mucositis after radiation therapy, using Python 3.10.5 for statistical analysis. Second, it integrates NLP with convolutional neural networks (CNN) to optimize literature search, reducing 3256 articles to 12. CNN settings include a batch size of 50, 50-200 epoch range and a 0.001 learning rate.
RESULTS
The study's CNN-NLP model achieved a notable accuracy of 0.94 after 200 epochs with Adamax optimization. MA showed an AUC of 0.67 for early-effect xerostomia and 0.74 for late-effect, indicating moderate to high predictive accuracy but with high variability across studies. Initial CNN accuracy of 66.70% improved to 94.87% post-tuning by optimizer and hyperparameters.
CONCLUSION
The study successfully merges MA and NLP, confirming high predictive accuracy for specific model-feature combinations. It introduces a time-based metric, words per minute (WPM), for efficiency and highlights the utility of MA and NLP in clinical research.
Topics: Humans; Natural Language Processing; Head and Neck Neoplasms; Neural Networks, Computer; Probability; Xerostomia
PubMed: 38195582
DOI: 10.1186/s13014-023-02381-7 -
Frontiers in Neurology 2023Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated...
BACKGROUND
Treatment switching is a common challenge and opportunity in real-world clinical practice. Increasing diversity in disease-modifying treatments (DMTs) has generated interest in the identification of reliable and robust predictors of treatment switching across different countries, DMTs, and time periods.
OBJECTIVE
The objective of this retrospective, observational study was to identify independent predictors of treatment switching in a population of relapsing-remitting MS (RRMS) patients in the Big Multiple Sclerosis Data Network of national clinical registries, including the Italian MS registry, the OFSEP of France, the Danish MS registry, the Swedish national MS registry, and the international MSBase Registry.
METHODS
In this cohort study, we merged information on 269,822 treatment episodes in 110,326 patients from 1997 to 2018 from five clinical registries. Patients were included in the final pooled analysis set if they had initiated at least one DMT during the relapsing-remitting MS (RRMS) stage. Patients not diagnosed with RRMS or RRMS patients not initiating DMT therapy during the RRMS phase were excluded from the analysis. The primary study outcome was treatment switching. A multilevel mixed-effects shared frailty time-to-event model was used to identify independent predictors of treatment switching. The contributing MS registry was included in the pooled analysis as a random effect.
RESULTS
Every one-point increase in the Expanded Disability Status Scale (EDSS) score at treatment start was associated with 1.08 times the rate of subsequent switching, adjusting for age, sex, and calendar year (adjusted hazard ratio [aHR] 1.08; 95% CI 1.07-1.08). Women were associated with 1.11 times the rate of switching relative to men (95% CI 1.08-1.14), whilst older age was also associated with an increased rate of treatment switching. DMTs started between 2007 and 2012 were associated with 2.48 times the rate of switching relative to DMTs that began between 1996 and 2006 (aHR 2.48; 95% CI 2.48-2.56). DMTs started from 2013 onwards were more likely to switch relative to the earlier treatment epoch (aHR 8.09; 95% CI 7.79-8.41; reference = 1996-2006).
CONCLUSION
Switching between DMTs is associated with female sex, age, and disability at baseline and has increased in frequency considerably in recent years as more treatment options have become available. Consideration of a patient's individual risk and tolerance profile needs to be taken into account when selecting the most appropriate switch therapy from an expanding array of treatment choices.
PubMed: 38187157
DOI: 10.3389/fneur.2023.1274194 -
European Journal of Medical Research Jan 2024This review article explores the dynamic field of radiopharmaceuticals, where innovative developments arise from combining radioisotopes and pharmaceuticals, opening up... (Review)
Review
This review article explores the dynamic field of radiopharmaceuticals, where innovative developments arise from combining radioisotopes and pharmaceuticals, opening up exciting therapeutic possibilities. The in-depth exploration covers targeted drug delivery, delving into passive targeting through enhanced permeability and retention, as well as active targeting using ligand-receptor strategies. The article also discusses stimulus-responsive release systems, which orchestrate controlled release, enhancing precision and therapeutic effectiveness. A significant focus is placed on the crucial role of radiopharmaceuticals in medical imaging and theranostics, highlighting their contribution to diagnostic accuracy and image-guided curative interventions. The review emphasizes safety considerations and strategies for mitigating side effects, providing valuable insights into addressing challenges and achieving precise drug delivery. Looking ahead, the article discusses nanoparticle formulations as cutting-edge innovations in next-generation radiopharmaceuticals, showcasing their potential applications. Real-world examples are presented through case studies, including the use of radiolabelled antibodies for solid tumors, peptide receptor radionuclide therapy for neuroendocrine tumors, and the intricate management of bone metastases. The concluding perspective envisions the future trajectory of radiopharmaceuticals, anticipating a harmonious integration of precision medicine and artificial intelligence. This vision foresees an era where therapeutic precision aligns seamlessly with scientific advancements, ushering in a new epoch marked by the fusion of therapeutic resonance and visionary progress.
Topics: Humans; Precision Medicine; Radiopharmaceuticals; Artificial Intelligence
PubMed: 38183131
DOI: 10.1186/s40001-023-01627-0