bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the understanding and utilization of integrative oncology among patients with a history of cancer.
Authors: Luo Meiqi , Siddiqui Iqra , Lopez Ana Maria
Published: June 2024

e23231

Background: Integrative oncology (IO) is an evidence-informed field of cancer care the utilizes mind-body practices, natural products, lifestyle medicine from different traditions alongside conventional therapies. Many of these components have growing evidence of benefit and are part of guideline recommendations. The Sidney Kimmel Cancer Center (SKCC) at Thomas Jefferson University has an integrative oncology program that sought to identify patients’ understanding of integrative health, assess their utilization of integrative medicine approaches, and define interest in IO consultations. Methods: Patients with a history of cancer or at high risk for cancer who presented for care at an SKCC clinical site received an electronic record invitation to complete a brief survey with binary and free-response questions regarding current knowledge, experiences, and interest in IO. At the end of the survey, patients also had the option to express interest in an IO consultations at SKCC. Results: Among 1327 responders, 900 (67.8%) were female, and 998 (75.2%) were between 45-75 years of age. Most were white (980, 73.9%), followed by Black or African American (279, 21.0%). Breast cancer (435, 32.8%) and hematologic cancers (277, 20.9%) were the most reported malignancies. Overall, 340 (26.4%) and 123 (9.27%) had previously utilized in-person IO services and virtual IO services, respectively. 887 (66.8%) patients reported that IO was never discussed during their care. 946 (71.3%) expressed interest in an IO consultation. Conclusions: Approximately a third of patients who completed the survey had previously used an IO modality. More than double that number expressed interest in and IO consultation. With the increasing evidence of benefit for IO care and the inclusion of these recommendations in clinical guidelines, expansion of IO services is indicated. IO consultations would address knowledge gaps, enhance implementation of guideline-based care, and, perhaps, improve clinical outcomes.
Lessons learned in migrating from one commercial genetics decision-support tool to another: Assessment of data integrity and utilization readiness.
Authors: Le Calvin , Tatunay Kevin , Laurino Mercy Y. , Dubard-Gault Marianne E.
Published: June 2024

e23232

Background: Rapid advancements in health information technology have greatly influenced how clinicians engage with patient health data. In the context of clinical genetics, the electronic health record (EHR) often contains a wide array of data to identify patients at elevated risk for hereditary cancer syndromes. However, these data often exist in multiple forms and disparate locations, which in the presence of numerous commercial EHR solutions, results in significant variations in how institutions codify genetic data. Furthermore, within an institution, there is often internal pressure to migrate from one support tool to another, necessitating a focus on data integrity during such a transition. Methods: Fred Hutchinson Cancer Center (Fred Hutch) is a large academic cancer care center associated with the University of Washington. Between July and December 2023, the Fred Hutch Clinical Cancer Genetics and Genetic Counseling Service migrated their family history database from commercial pedigree software, Progeny, to another commercial pedigree and decision-support tool, CancerIQ. Following completion of the data migration on more than 13,000 patient records, study team planned to review a total of 500 randomly selected patient charts in both support tools. Each chart was reviewed to determine: (1) the presence of genetic intake information, (2) the presence and results of genetic testing, if available, and (3) whether the patient met National Comprehensive Cancer Network (NCCN) criteria for testing. A chart was noted to be concordant between the two support tools if there was agreement in all three of the above. Results: So far, a total of 240 patient charts were reviewed between the two support tools. Of these, 226 (94.2%) were noted to be fully concordant. Of the 14 charts that were noted to be discordant, the distribution of the discordant data was: 5 charts differed on whether genetic testing had been ordered, 5 charts differed on the results of the testing (often omitting one or more variants), and 4 differed on whether the patient met NCCN criteria for testing. Conclusions: At our institution, there was high data integrity following migration from one commercial and pedigree-generating software solution to another. While these results can ease clinician concerns following such support tools transitions, it also highlights areas for improvement in how family and patient genetic data is recorded.
Irradiate the knowledge gap: Empowering residents for blood product selection at Albany Medical Center.
Authors: Khan Muhammad Haseeb , Malik Uzair Ahmad , Nagesh Rao Sneha , Bellomo Courtney M.
Published: June 2024

e23236

Background: Transfusion-associated graft versus host disease (ta-GvHD) poses risks for immunocompromised patients. Indications for irradiated blood products include hematological malignancies and bone marrow transplant cases. In instances of severe acute pancytopenia, the initial contact at the emergency room (ER) is typically a nurse, followed by the ER physician. Patients referred from the local private practice, New York Oncology and Hematology (NYOH) office to our local hospital, Albany Medical Center (AMC), often bring comprehensive paper charts, but those coming directly from home frequently lack necessary documents, relying on the medical teams' expertise to ensure appropriate blood product selection. We aim to improve understanding of transfusion products and their indications. Methods: An initial pre-survey questionnaire was sent to internal medicine residents. Of the 33 responses received, 87.9% were aware of the need for irradiated blood products in hematological malignancies, 66.6% knew it was not required for solid tumors, and only 57.6% knew about the need for CAR-T patients. Additionally, only 15.2% knew where to find information on selecting irradiated blood products at AMC. The analysis highlighted a significant knowledge gap in transfusing irradiated blood products for hematological and oncological malignancies. In response, a user-friendly educational resource was created and displayed in residents' conference rooms during inpatient rotations, with plans for intermittent educational sessions over the next months. A comprehensive educational initiative addressed this aspect of patient care within the inpatient service, distributing detailed materials and discussions with the internal medicine residents at AMC. The focus was on emphasizing the critical requirement for irradiated blood products in specific clinical scenarios, particularly when managing patients with hematological malignancies and other conditions where irradiated blood is medically indicated. Results: A follow-up survey, conducted four months after distributing educational material on medicine floors, included responses from 27 internal medicine residents. Notably, 100% and 88.9% were knowledgeable about the necessity of irradiated blood products in hematological malignancies and bone marrow transplant recipients, respectively. Additionally, 24 out of 27 residents were aware that irradiated products are unnecessary for solid tumor malignancies in adult patients. All residents knew where to find information on blood product selection at AMC, and 92.6% found the education material helpful. Conclusions: Improved knowledge among residents underscores our commitment to patient care. We aim to extend education on irradiated blood product necessity beyond our residency program. Our long-term vision is to broaden this critical knowledge across the healthcare community at AMC.
Paclitaxel hypersensitivity reaction (HSR) rate: Titrated versus non-titrated infusions among gynecologic oncology patients.
Authors: Goldfeld Ester , Cantrell Leigh , Huang Marilyn
Published: June 2024

e23240

Background: Paclitaxel is a common chemotherapeutic agent used for treatment of various cancers, and is associated with hypersensitivity reactions (HSR). An HSR is mostly likely to occur during first or second infusions. Prior studies have suggested that performing Paclitaxel infusions without titration may be safe for the majority of patients, but increase in number of HSRs. At our institution, Paclitaxel infusions without titration was implemented around April 2023. Our aim was to evaluate the rate of HSR in Paclitaxel infusions without titration among gynecologic patients. Methods: This was a retrospective review of hypersensitivity reactions in patients receiving Paclitaxel at the titrated rate versus the full rate from May 2022 through November 2023. Patients had newly diagnosed gynecologic cancers (ovarian, uterine, cervical), who presented for their first or second Paclitaxel infusions. Patients previously treated with Paclitaxel for any reason were excluded. Results: 145 patients were included in this study, each with one (4%) or two (96%) infusions, for a total of 281 infusion visits. There were 176 infusions with Paclitaxel dose titration (62.6%), and 105 infusions at full rate (37.4%). HSRs occurred in 19% of the full rate Paclitaxel infusions and in 11.9% of titrated Paclitaxel infusions (OR 1.74 [95% CI 0.89 – 3.38]; p = 0.10). When stratifying by first or second infusion, the HSR rate increased significantly for full rate second infusion to 22.4%, compared to 8.3% for titrated infusions (OR 3.18 [95% CI 1.14 – 8.86]; p = 0.026). Grade 3 or greater infusion reactions occurred in 45% of full rate infusion and in 14.2% of titrated infusion reactions (OR 4.91 [95% CI 1.08 – 22.14]; p = 0.0038). There was no difference in timing of hypersensitivity reactions in relation to initiation of Paclitaxel infusion. Conclusions: Overall, the HSR rate was higher with full rate first infusions, and significantly increased during the second infusion with full rate Paclitaxel. Additionally, Grade 3 infusion reactions were more likely to be seen with full rate infusions. There is significant variability in Paclitaxel infusion; further studies to determine optimal infusion rates are warranted.
Implementation of a hepatitis B screening program in patients receiving systemic anti-cancer therapy: A Canadian single center retrospective review.
Authors: Leigh Jennifer , Mallick Ranjeeta , Brule Stephanie Yasmin , Rambout Lisa , Newton Jennifer , Bosse Dominick , Moore Sara , Gotfrit Joanna
Published: June 2024

e23242

Background: Cancer patients receiving non-endocrine anti-cancer therapies are at risk of hepatitis B virus (HBV) reactivation (HBVr). Medical society guidelines recommend HBV screening prior to treatment, but real-world uptake is slow and variable. The Ottawa Hospital Cancer Centre implemented a screening pilot program for all patients receiving FOLFOX based regimens or FOLFOXIRI between January and April 2023 which included incorporating HBV screening tests into treatment plan builds and specifying pharmacy and nursing pre-treatment checks. Methods: Charts were retrospectively reviewed, and patient and disease characteristics were collected. The primary endpoint was to identify the proportion of patients who underwent screening prior to treatment start. Univariate analyses assessed the association between baseline characteristics and failure to screen. We also reviewed quality metrics including time from consult to testing, time to result, number of duplicate screens, and treatment delays due to testing. Results: Baseline demographics of the 42 patients included can be found in Table 1. 32 patients (76.2%) completed screening and 5 (15.6%) had a positive screen. The majority of patients screened (78.1%) completed screening prior to first treatment as intended, however 38.1% were drawn on day of treatment. 9.52% of patients had duplicate screening inadvertently. All patients who tested positive were referred to Infectious Diseases. Of those, 1 received antivirals for chronic HBV, and 4 had resolved HBV and were recommended for monitoring. There were no treatment delays due to pending screening and no HBVr. Receipt of prior systemic therapy was significantly associated with failure to screen (55% vs 95%, OR 17.1 (95% CI 1.92-153), p = 0.011). Factors including age, sex, primary disease site, therapy intent, and regimen received were not significantly associated with screening completion or HBV positivity. Conclusions: The results of this pilot highlights the importance of building HBV screening into standardized treatment plans and engaging all team members to ensure high levels of screening. Prior systemic therapy receipt was associated with failure to screen, and thus programs should include education on the necessity of screening as recommended by medical guidelines. The prevalence of HBV in this population may also be higher than previously expected, which should be explored in future research. [Table: see text]
Sleep disturbance and fatigue in patients with ovarian cancer during chemotherapy and surgery compared to PARPi maintenance therapy.
Authors: Newell Abigail , Szamreta Elizabeth A. , Fortune Erica E. , Gonzalo Maria Belen , Saxton M. Claire , Andac-Jones Elif
Published: June 2024

e23248

Background: Sleep disturbance and fatigue are prevalent among advanced ovarian cancer (OC) patients and are associated with poor health outcomes. It is unclear how sleep disturbance and fatigue vary across treatment timelines. This study evaluated how patients rate their sleep disturbance and fatigue levels at different points in their treatment trajectory. Methods: 200 U.S. patients with stage III/IV OC diagnosed in 2020-2023 were enrolled. Survey items asked patients to retrospectively assess their sleep disturbance and fatigue levels prior to diagnosis, during treatment, and presently. Sleep disturbance and fatigue were measured using a custom set of Patient-Reported Outcomes Measurement Information System (PROMIS) items based on previous findings. Most were receiving maintenance therapy (44%) or other treatments (34%), and 23% completed treatment. Nearly all participants received surgery (93%) and chemotherapy (97%). 44% of patients had received PARP inhibitor (PARPi) therapy, 18% received immunotherapy, and < 10% received other therapies. Repeated sample t-tests compared symptom burdens. Results: Participants ranked sleep disturbance as most intense during chemotherapy (52%), followed by surgery (33%), hormone therapy (32%), and PARPi (15%). Most participants ranked fatigue as most intense during chemotherapy (67%), followed by hormone therapy (31%), surgery (20%), and PARPi therapy (17%). Paired t-tests show that among participants who received only surgery, chemotherapy and PARPi therapy, sleep disturbance was perceived to be significantly more intense during chemotherapy than when receiving PARPi, t(55) = -2.83, p = .006) and in the 2 weeks after surgery than PARPi therapy, (t(55) = -2.08, p = .043) ( Table). Fatigue was significantly more intense during chemotherapy than when receiving PARPi, (t(55) = -6.21, p < .001) and following surgery than PARPi (t(54) = -4.16, p < .001). Conclusions: OC patients experience intense sleep disturbance and fatigue and perceive levels differently depending on treatment. Chemotherapy was rated the worst for both sleep disturbance and fatigue compared to PARPi and other therapies. Targeted screening and psychosocial support can address these symptoms throughout treatment, especially after chemotherapy. [Table: see text]
Real-world safety and efficacy of concurrent immunotherapy and thoracic chemoradiotherapy: A multi-institutional analysis.
Authors: Li Ying , Han Guang , Lu Ying , Bi Jianping , Zhang Li , Verma Vivek
Published: June 2024

e23262

Background: Despite the success of Immune checkpoint inhibitors (ICIs) as consolidation following concurrent chemoradiotherapy (CCRT), 22% to 30% of patients still cannot be treated with durvalumab due to progression or adverse events (AEs) during or after CCRT. Concurrent ICIs with CCRT would offer the opportunity to receive ICIs and may provide treatment benefit to a greater proportion of patients. In this study, we performed a multicenter investigation to evaluate the safety and efficacy of ICIs and chemotherapy with concurrent thoracic radiotherapy. Methods: All patients from three institutions who underwent ICIs and concurrent thoracic radiotherapy were included. The rate of 12-month progression-free survival (PFS) was estimated using the Kaplan-Meier method and evaluated with 95% CIs calculated using the Greenwood formula. Therapy-related pneumonitis (TRP) and esophagitis (TRE) were defined per CTCAE v5.0. Statistics utilized logistic regression modeling and receiver operating characteristic (ROC) analysis. Results: 69 patients (median [range] age, 62 [52-76]; 61 [88.4%] male; median follow-up 30.4 months) were collected, including 18 (26.1 %) cases of non-small cell lung cancer (NSCLC), 26 (37.7 %) cases of small cell lung cancer (SCLC), and 25 (36.2 %) cases of esophageal cancer (EC). The 12-month PFS rates in NSCLC, SCLC and EC were 72.2%, 69.2% and 72.0%, respectively. The median PFS in NSCLC and SCLC was 24.3 and 13.1 months, and not reached (mean 29 months) for EC. The incidences of all-grade TRP and TRE were 60.7% and 57.7%, respectively. Grades 1-5 TRP occurred in 15.9%, 30.4%, 8.6%, 1.4%, and 0, respectively. Grades 1-5 TRE occurred in 20.2%, 28.9%, 8.6%, 0, and 0, respectively. On multivariable analysis, age and MLD significantly predicted for any-grade and grade ≥2 TRP. Only age significantly predicted for grade ≥3 TRP. ROC analysis was able to pictorially model RP risk probabilities for a variety of MLD and age thresholds. Conclusions: This real-world study can be helpful for understanding the true efficacy and toxicity of ICIs and chemotherapy with concurrent thoracic radiotherapy given the lack of robust clinical data. Close monitoring should be recommended in this patient population during RT and follow-up.
Different dosing strategies of pembrolizumab in the treatment of NSCLC: A real-world retrospective observational study.
Authors: Janzic Urska , Rus Zala , Knez Lea
Published: June 2024

e23264

Background: Immune checkpoint inhibitors lack a dose-response relationship, allowing optimisation of dosing strategies that may reduce drug use. Pembrolizumab received its initial regulatory approval for the treatment of non-small cell lung cancer (NSCLC) at weight-based dosing (2 mg/kg every 3 weeks (Q3W)), as employed in pivotal clinical trials demonstrating its efficacy and safety. This dosing regimen was later replaced by the currently approved flat-dosing (200 mg Q3W or 400 mg Q6W) in all indications, potentially increasing drug use. This retrospective observational study evaluates differences in pembrolizumab use for different dosing strategies in a real-world patient cohort. Methods: Overall, 124 advanced NSCLC patients, treated with first-line pembrolizumab monotherapy at a single institution, were included. During the observation period, pembrolizumab flat-dosing was employed, with possible extensions of treatment administrations. Patient and treatment data were obtained from medical records. Duration of treatment was calculated from day 1 of first cycle to last day of last cycle, excluding treatment delays due to adverse events. Pembrolizumab use was calculated for 3 dosing strategies: i) as actually received, ii) as flat-dosing, iii) as body-weight dosing, capped at 200 mg Q3W. It is presented as median dose Q3W and cummulative dose in the whole cohort. Results: Included patients had a median weight of 73 kg (IQR: 65-84) and received a total of 1600 mg of pembrolizumab (IQR: 800-3600) over 24 weeks (IQR: 12-60). The median pembrolizumab dose was i) 190 mg Q3W (IQR: 172-200) as actually received by patients, and would be ii) 200 mg Q3W (IQR: 200-200) in case of flat dosing, and iii) 146 mg Q3W (IQR: 130-168) in case of body-weight dosing. Overall, total pembrolizumab dose in the whole cohort was i) 283,600 mg actually used, and would be ii) 327,800 mg in flat-dosing, and iii) 251,200 mg body-weight dosing, resulting in a 23.4% reduction of drug use in weight-adjusted vs flat-based dosing. Conclusions: Pembrolizumab dosing adjusted to body weight, as initially approved, would reduce drug use vs the currently approved flat-dosing, reaching nearly a 25% reduction in our cohort of patients.
Infections as a “cause of death” in patients with cancer: Need improved focus to improve outcomes?
Authors: Pendharkar Dinesh , Ather Mohammad Imam , Raj Abhishek , Hari Vishnu
Published: June 2024

e23281

Background: Infectious diseases are a significant contributor to both morbidity and mortality in cancer patients. Cancer's impact on the immune system and the immunosuppressive effect of its treatment make patients more susceptible to infection. Furthermore, cancer's involvement of multiple organs increases the risk of infection. It is crucial to consider causes of death beyond cancer when evaluating overall survival, as effective treatment alone is not sufficient. We conducted a study to investigate infection as a cause of in-hospital death among cancer patients in a tertiary hospital. Methods: We collected data on the causes of death for all patients with cancer who passed away in our hospital in 2022 and 2023. This included detailed medical histories, investigation charts, and test results related to infections. Infections were defined as those listed as the cause of death in the hospital records. We had access to data on age, sex, primary tumor site, and laboratory test results related to infections. Infections were identified through microbiological cultures and PCR panels for bacteria, fungi, and viruses. Percentages were used to analyze standard statistical variables. Results: The death toll for the year period amounted to 113 individuals, which included 77 males and 36 females, with ages ranging from 16 to 88 and a mean of 63.2 years, with a median of 64 years. Among the 91 patients with classifiable stages, 86% had metastatic disease. Many of the patients, amounting to 75%, were suspected or confirmed to have contracted an infection at the time of death. In 69/113 (61%) cases, the infections were confirmed through laboratory and radiological tests. Out of 90 patients in whom cultures and infection PCR tests were sent, 53/90 (59%) showed positive microbiology reports, and 37/90 (41%) had negative microbiological culture reports. Among the 41 patients with positive microbiology culture reports, 41% had blood culture positivity but no localizing signs, 34% had lung infections, 15% had both lung and blood culture positivity, and around 8% had urological origins of infection. Around 60% of the patients had bacterial infections, while approximately 4% had documented fungal infections. No cases of viral infections were recorded. Half of the patients, or 50%, were directly admitted to the Intensive Care Unit (ICU) during their last admission, while the remaining 50% were transferred from the ward to the ICU. Infection as a cause of death was attributed to 81/113 (71.6%) of the patients. Conclusions: Infectious diseases appear to be a major cause of death. Its control may play a significant role in reducing the overall survival and improving quality of life. Increased focus on detection and intervention to manage infections could substantially add to desirable endpoints in oncology. Therefore, there is an urgent need to focus on the management of infections.
Bevacizumab combination therapy versus standard chemotherapy for ovarian cancer in shorter and longer followup duration: A systematic review and meta-analysis of randomized controlled trials.
Authors: Farooq Muhammad Zain , Ur Rehman Obaid , Fatima Eeshal , Imran Hiba , Akram Umar , Ahmad Amna Badar , Nadeem Zain Ali , Fatima Laveeza , Hussain Ahmad , Mabrouk Manar Ala , Jaglal Michael Vishal
Published: June 2024

e23296

Background: Bevacizumab is an anti-angiogenesis drug commonly added to standard chemotherapy regimens in the treatment of ovarian cancer. However, its comparative efficacy and safety in shorter and longer followup duration leaves a research gap that needs to be addressed. This systematic review and meta-analysis aims to evaluate the efficacy and safety of bevacizumab in patients with ovarian cancer in shorter and longer follow up duration. Methods: We searched Medline, Cochrane CENTRAL, Scopus, and Google Scholar for all phase 3 randomized controlled trials (RCTs) that administered bevacizumab to women with ovarian cancer. Review Manager 5.4 was used to calculate risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (95% CIs). We assessed the quality of included studies using version 2 of the Cochrane Risk of Bias tool (RoB 2). Results: After screening the titles, abstracts, and full texts, we included nine RCTs in our systematic review and meta-analysis. Four RCTs had low risk of bias while five had some concerns. Bevacizumab was associated with a progression free survival benefit for < 36 months (HR 0.59, 95% CI 0.45 to 0.76, p < 0.0001, I2= 90%) and > 36 months (HR 0.66, 95% CI 0.55 to 0.80, p < 0.0001, I2= 80%), and an overall survival benefit for < 36 months (HR 0.87, 95% CI 0.78 to 0.98, p = 0.02, I2= 0%) but not for > 36 months (HR 0.98, 95% CI 0.89 to 1.09, p = 0.77, I2= 30%). There was no difference in deaths between intervention and control groups < 36 months (RR = 0.95, 95% CI 0.86 to 1.04, p = 0.26, I2= 10%) or > 36 months (RR 1.02, 95% CI 0.97 to 1.06, p = 0.50, I2= 0%). Bevacizumab reduced disease progression < 36 months (RR 0.82, 95% CI 0.72 to 0.92, p = 0.0008, I2= 82%) but not at > 36 months (RR 0.83, 95% CI 0.58 to 1.19, p = 0.30, I2= 94%). The adverse events reported with Bevacizumab use included thrombocytopenia, neutropenia, leukocytopenia, anemia, hypertension, bleeding or hemorrhage, and gastrointestinal, cardiac, and dermatological adverse events. Conclusions: Bevacizumab may improve progression free survival within and after 36 months, overall survival within 36 months, and reduce disease progression within 36 months. Future studies should explore the long-term effectiveness of bevacizumab in diverse patient populations and focus on individual patient-tailored treatment approaches to optimize outcomes.
In-hospital outcomes of patients with lung cancer with and without superior vena cava thrombosis: A nationwide analysis.
Authors: Sanghvi Ankushi , Nanavaty Dhairya , Patel Sagar , Vachhani Bhavyakumar , Gaddam Mrunanjali , Ginjupalli Manasa , Jayakumar Jayalekshmi , Adhikari Nawaraj , Sinha Rishav , Kumar Vikash , Hotwani Priya , Nadeem Ahmed
Published: June 2024

e23322

Background: Malignant superior vena cava syndrome (SVCS) is a clinical problem that results from the obstruction of blood flow in the superior vena cava by an underlying malignancy. It may be caused by external compression or internal obstruction due to a thrombus or direct invasion by tumor cells. Though lung malignancy is the most common cause of SVCS, there is a lack of data on in-hospital outcomes in these patients. Methods: We queried the National Inpatient Sample 2018-2020 to identify hospitalizations with lung cancer including both small cell and non small cell lung cancer. Hospitalizations with diagnosis of acute SVC thrombosis were determined by using ICD-10 codes.Demographics and mortality rates were compared between two groups using chi square for categorical variables and t test for continuous variables. Multivariate regression analysis was further performed to study the impact of SVC thrombosis on mortality, LOS and total hospitalization cost. Results: A total of 2011620 hospitalizations with lung cancer were identified. Of these, 2855 (0.0014%) had acute SVC thrombosis. These patients were younger with a mean age of 63 years. African-Americans and Hispanics were in a higher proportion in the cohort of hospitalizations with SVC thrombus as compared to those without. (Table 1). Multivariate regression analysis revealed higher odds of mortality (OR-1.94; C.I: 1.53-2.47; P < 0.001), LOS (OR 1.66; C.I:1.20- 2.31; P < 0.005) and total hospitalization cost (26211.15; C.I:22183.56- 30238.74; P < 0.001) in lung cancer hospitalizations. Conclusions: Our study shows that SVCT, has higher odds of mortality, length of stay and total hospital cost. Though the general recommendation is to continue anticoagulation, sometimes patients may require endovascular stent placement with/without thrombectomy. Though rare, SCVT can be life threatening and requires prompt attention.[Table: see text]
Survival trends of soft tissue sarcomas and gastrointestinal stromal tumors from 1995 to 2019: A SEER database analysis.
Authors: Hardy Nicole Janell , Deshpande Hari Anant , Olino Kelly , Costa Philippos Apolinario
Published: June 2024

e23528

Background: In the last 25 years, new therapies have been developed for gastrointestinal stromal tumors (GISTs), while treatments for many soft tissue sarcomas (STSs) have remained relatively stagnant with 90% of phase I/II trials focusing on repurposing existing drugs. This study compares survival changes over time in patients with STSs and GISTs. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER)-9 registry were analyzed for patients aged 20+ diagnosed with GISTs and STSs from 1995 to 2019. Patients were categorized into time periods: 1995-2004, 2005-2014, 2015-2019. The primary outcomes were the 5-year overall survival (OS) difference between GISTs and STSs and survival variations across the periods. Survival was calculated using the Kaplan–Meier method, and differences were assessed with log-rank tests. Results: 26,633 STS and 3,818 GIST patients were identified. The 5-year OS rate was 53.0% (95% CI: 52.4-53.7) for STSs and 68.7% (95% CI: 67.1-70.3) for GISTs (p < 0.001), with a respective median OS of 72 (95% CI: 69-75) and 121 (95% CI: 113-128) months. For STS, the 5-year OS rate was 53.3% (95% CI: 52.3-54.4), 52.8% (95% CI: 51.9-53.8), and 54.2% (95% CI: 52.2-56.3) (p = 0.66) for groups 1995-2004, 2005-2014, and 2015-2019, respectively. For GIST, the 5-year OS rate was 60.7% (95% CI: 57.3-64.2), 70.6% (95% CI: 68.5-72.7), and 71.0% (64.5-78.3) (p < 0.001). In the locoregional setting (L), the GIST median 5-year OS was 70.5% (95% CI: 66.9-74.3), 78.1% (95% CI: 75.9-80.3), and 79.0% (95% CI: 71.4-87.4) (p < 0.001). In the metastatic setting (M) for GIST, the 5-year OS rate was 30.7% (95% CI: 24.8-37.9), 45.7% (95% CI: 41.1-50.7), and 46.3% (95% CI: 35.8-59.8) (p < 0.001). However, no significant difference was seen for STSs in either setting (L1995-2004 61.6% 95% CI: 60.5–62.8, M1995-2004 11.2, 95% CI: 9.7–12.9, L2005-2014 61.5%, 95% CI: 60.5–62.5, M2005-2014 10.2, 95% CI: 8.9–11.7, L2015-2019 63.4%, 95% CI: 61.2–65.7, M2015-2019 12.1, 95% CI: 9.4–15.6, p(L) = 0.71 and p(M) = 0.74). Conclusions: While GIST survival rates significantly improved, those for other STSs remain unchanged, highlighting an urgent need for novel STS therapies. [Table: see text]
Adult genitourinary sarcomas: A single-centre experience over 25 years.
Authors: Arham Abdul Baseet , O'Donnell Michael A. , Mott Sarah L.
Published: June 2024

e23532

Background: Genitourinary sarcomas are a rare entity. This study is a retrospective review of the patient characteristics, types of adult GU sarcomas, treatments and outcomes in a single institution over the past 25 years. Methods: Survival probabilities were estimated and plotted using the Kaplan-Meier method. Estimates along with 95% pointwise confidence intervals were reported. Recurrence-free survival (RFS) is defined as time from when the patient was disease-free to recurrence. Otherwise, patients were censored at last disease evaluation. OS was defined as time from when the patient was disease-free to death due to any cause. Patients still alive were censored at last known alive. Results: 29 patients presented with various types of GU sarcomas, with the majority being paratesticular tumors (n = 22, 75.9%). Others included bladder leiomyosarcomas (n = 5), prostatic leiomyosarcoma (n = 1), renal leiomyosarcoma (n = 1). Median age for diagnosis was 51 years (range: 21-79) for leiomyosarcoma vs 61 (range: 36-89) for liposarcoma. Among the paratesticular tumors majority were (n = 16) were liposarcoma, remaining 5 being leiomyosarcoma and 1 being rhabdomyosarcoma. Majority tumors were stage III and above (n = 16, 55.17%), high and intermediate grade (65.51%). All tumors were resected ± adjuvant therapy (n = 4). Leiomyosarcomas had a higher stage (66%) and grade (83%) at diagnosis, recurrence rate was also higher at 37.5% (vs 6.6% for liposarcoma) along with a higher mortality (41.6%). Commonest site of recurrence for leiomyosarcoma was the lungs (n = 3, 100%). Treatment for recurrence commonly involved radiotherapy, pembrolizumab etc. Paratesticular liposarcomas were found to be associated with a lipomatosis syndrome with n = 5 (31.25%) having lipomas elsewhere in the body and n = 2 (12.5%) patients having had previously resected spermatic cord lipoma. Paratesticular sarcomas often required (n = 15, 68%) revision surgery due to being initially diagnosed as a hernia, cord lipoma or hydrocele and requiring high ligation of the cord with hemiscrotectomy and radical orchiectomy ± LND on revision surgery, which often demonstrated a focus of residual tumor in liposarcomas (n = 5, 31%). N = 4 patients (25%) had positive margins in spite of revision surgery. Majority of these were MDM2+ positive on FISH (n = 9, 56%). Overall, GU sarcomas had an RFS of 63% (53-94%) and OS of 82% (53-94%) at 36 months since NED was achieved. The median length of follow-up was 19.9 months for leiomyosarcoma, 33.8 months for liposarcoma. Conclusions: Leiomyosarcomas in adults have worse outcomes compared to other GU sarcomas especially if it originates in the bladder. [Table: see text]
Factors predicting surgical receipt in extracranial rhabdoid tumors.
Authors: Nooney Marlaena Nicole , Chaddha Jasleen Kaur , Silberstein Peter T.
Published: June 2024

e23541

Background: Extracranial rhabdoid tumors (ERTs) are a very rare and aggressive carcinoma that grow in a wide range of tissues, including but not limited to the lungs, kidneys, muscles, skin, and other soft tissues. These tumors most commonly present in infants between 11-18 months old, with an estimated annual incidence of less than 1 per million in the United States. Metastasis is common, and average survival time after diagnosis is approximately 5 years. Though most patients appear to undergo tumor resection at the primary site, a standardized treatment protocol for ERTs has not yet been developed. This study aimed to analyze the factors predicting receipt of this surgery. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with SEF from 2004 to 2020 using histology code 8963 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Logistic Regression tests were performed, and data were analyzed using SPSS version 29. Statistical significance was set at α = 0.05. Results: 208 patients with extracranial rhabdoid tumors formed the initial sample. Of these patients, 128 patients (61.5%) received surgery at the primary site. 80 patients (38.5%) did not have tumor resection. Median overall survival of surgical patients was significantly higher than nonsurgical patients ( 91.6 months vs. 32.1 months, p < 0.001). Head, neck, and face, were the most common primary tumor sites (25.4%). Wider surgical margins were associated with improved outcomes ( p < 0.05). On nominal regression, stage I, II, and III disease, grade 1 and 2, and younger age were associated with increased likelihood of receiving surgery ( p < 0.05). Metastasis to distant sites was associated with decreased likelihood of receiving surgery ( p < 0.05). Treatment at an academic facility, income status, tumor size, insurance status, and race were not significant predictors of receiving surgery. 77 patients (37%) received adjuvant chemotherapy, 1 patient received adjuvant radiation, and 4 patients received adjuvant chemoradiation. 121 patients (58.2%) did not receive adjuvant therapy. Conclusions: Resection of the primary tumor in ERT is associated with improved overall survival. Younger age, stage I, II, or III disease, and grade 1 or 2 disease are factors predicting a higher likelihood of receiving surgery. Improved outcomes of tumor resection are associated with wider surgical margins. The presence of metastasis decreased likelihood of undergoing surgery. Treatment location, insurance, status, race, income, and tumor size did not affect surgery receipt. Interestingly, the majority of patients sampled did not receive any adjuvant therapies, such as chemotherapy or radiation. Future research should continue delineating what factors predict both receipt of surgery and improved surgical outcomes, as well as better understand what the role of adjuvant therapies is in managing ERT.
An update on SOC-1882: A phase 2 study using talimogene laherparepvec, nivolumab, and trabectedin for advanced leiomyosarcoma.
Authors: Chawla Sant P. , Chawla Neal Shiv , Omelchenko Nadezhda , Jeffrey Samantha , Agarwal Anmol Dia , Chua Victoria , Moradkhani Ania , Quon Doris V. , Gordon Erlinda Maria
Published: June 2024

e23570

Background: Intratumoral injection of Talimogene Laherparepvec (TVEC) has a local oncolytic effect and evokes a cytotoxic immune response. The combination of Trabectedin (T) and Nivolumab (N) is a safe and effective therapy in soft tissue sarcoma (STS). Here, we report an update on an ongoing Phase 2 study that aims to determine the efficacy and safety of adding TVEC to the combination of T and N in advanced leiomyosarcoma (LMS). Objectives: Primary: To assess progression-free survival (PFS). Secondary: (1) To evaluate the best overall response, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 9, and 12 months, (4) Incidence of conversion from unresectable to the resectable tumor, and (5) Incidence of treatment-related adverse events (TRAEs). Patients and Methods: Eligible patients included patients ≥ 18 years of age with locally advanced unresectable or metastatic LMS, measurable disease by RECIST v1.1, and at least one accessible tumor for TVEC intratumoral injection. N (3 mg/kg q2 weeks), T (1.2 mg/m2 q3 weeks), and TVEC (1x108 PFU/ml q 2 weeks depending on tumor size) were administered. A starting dose of TVEC (1x106 PFU/ml) was initially given, followed by a total dose of 1x108 PFU/ml q 2 weeks depending on tumor size) three weeks later. Results: Efficacy: Per protocol, there were 17 evaluable subjects (Modified Intention to Treat [mITT] patients who had completed at least one treatment cycle and had a follow-up CT scan). The median number of prior lines of therapy was 4 (range 1-9). The disease control rate (PR+SD) was 94% with 1 PR, and 15 SD. The median PFS was 8.0 months (95% CI:4.8-11.28) with a 6-month PFS rate of 71%; median OS 19.2 months (95% CI:12.7- 25.7); 6-month OS rate, 82%. Safety: 22 patients (Intention to treat [ITT] who had received at least one-time drug administration) were evaluated for safety analysis. The > Grade 3 TRAEs include anemia (n = 3), thrombocytopenia (n = 3), neutropenia (n = 1), increased ALT (n = 1), increased GGT (n = 1), decreased LVEF (n = 1), dehydration (n = 1), hyponatremia (n = 1). There were no new safety signals noted in this study. Conclusions: Taken together, the data confirms our previous report that (1) the combination regimen using Talimogene laherparepvec, Nivolumab & Trabectedin may be more effective and treatment for previously treated patients with advanced leiomyosarcoma with manageable toxicity, and (2) The best responders are patients with HR+ uterine LMS. Clinical trial information: NCT03886311 .
Vitamin D Insufficiency and Epistemic Humility: An Endocrine Society Guideline Communication
Authors: McCartney Christopher R , McDonnell Marie E , Corrigan Maureen D , Lash Robert W
Published: June 2024

A long-held precept is that vitamin D supplementation primarily, if not exclusively, benefits individuals with low circulating 25-hydroxyvitamin D (25[OH]D) concentrations at baseline. However, the most appropriate 25(OH)D threshold to distinguish unacceptably low vs reliably adequate concentrations remains controversial. Such threshold proposals have largely been based on observational studies, which provide less robust evidence compared to randomized clinical trials (RCTs). Since the Endocrine Society's first vitamin D–related guideline was published in 2011, several large vitamin D–related RCTs have been published, and a newly commissioned guideline development panel (GDP) prioritized 4 clinical questions related to the benefits and harms of vitamin D supplementation in generally healthy individuals with 25(OH)D levels below a threshold. The GDP determined that available clinical trial evidence does not permit the establishment of 25(OH)D thresholds that specifically predict meaningful benefit with vitamin D supplementation. The panel noted important limitations in the available evidence, and the panel's overall certainty in the available evidence was very low. Nonetheless, based on the GDP's analyses and judgments, the Endocrine Society no longer endorses its previously proposed definition of vitamin D “sufficiency” (ie, at least 30 ng/mL [75 nmol/L]) or its previously proposed definition of vitamin D “insufficiency” (ie, greater than 20 ng/mL [50 nmol/L] but lower than 30 ng/mL [75 nmol/L]). The Endocrine Society's rationale for such is the subject of this Guideline Communication.
Diabetes Insipidus Complicating Diabetes Mellitus Type 1: A Pituitary Abscess Diagnosis
Authors: Lionetti Barbara , Minuto Nicola , Bassi Marta , Napoli Flavia
Published: June 2024

In this report we present a case of a 14-year-old girl with type 1 diabetes mellitus (T1DM) who experienced glycemic instability and multiple hormonal deficits, including diabetes insipidus, central hypothyroidism, and central adrenal insufficiency. Brain and sellar magnetic resonance imaging revealed a mass in the suprasellar region, which was confirmed to be a pituitary abscess through transsphenoidal biopsy.

T1DM is a chronic systemic disease that can lead to suboptimal glycemic control and increased susceptibility to infections. Pituitary abscess is a rare and serious infection that can manifest with nonspecific signs and symptoms, as well as pituitary hormonal deficiencies.

Currently, after a 6-year follow-up the pituitary hormone deficiencies have resolved apart from persistent partial diabetes insipidus. Through a review of the current literature, we discuss the clinical characteristics of pituitary abscess, the challenges in diagnosing it, and speculate on the potential clinical and pathophysiological relationship between this uncommon infection and T1DM in our patient.
Teleneurology and Artificial Intelligence in Clinical Practice
Authors: Jones Elaine C. , Kummer Benjamin R. , Wilkinson Jayne R.
Published: June 2024

As teleheath becomes integrated into the practice of medicine, it is important to understand the benefits, limitations, and variety of applications. Telestroke was an early example of teleneurology that arose from a need for urgent access to neurologists for time-sensitive treatments for stroke. It made a scarce resource widely available via video conferencing technologies. Additionally, applications such as outpatient video visits, electronic consultation (e-consult), and wearable devices developed in neurology, as well. Telehealth dramatically increased during the COVID-19 pandemic when offices were closed and hospitals were overwhelmed; a multitude of both outpatient and inpatient programs developed and matured during this time. It is helpful to explore what has been learned regarding the quality of telehealth, disparities in care, and how artificial intelligence can interact with medical practices in the teleneurology context.
Insights into digit evolution from a fate map study of the forearm using Chameleon, a new transgenic chicken line
Authors: Oh Julia Dong Hwa , Freem Lu , Saunders Dillan D. Z. , McTeir Lynn , Gilhooley Hazel , Jackson Melany , Glover James D. , Smith Jonathan , Schoenebeck Jeffrey J. , Lettice Laura A. , Sang Helen M. , Davey Megan G.
Published: June 2024

The cellular and genetic networks that contribute to the development of the zeugopod (radius and ulna of the forearm, tibia and fibula of the leg) are not well understood, although these bones are susceptible to loss in congenital human syndromes and to the action of teratogens such as thalidomide. Using a new fate-mapping approach with the Chameleon transgenic chicken line, we show that there is a small contribution of SHH-expressing cells to the posterior ulna, posterior carpals and digit 3. We establish that although the majority of the ulna develops in response to paracrine SHH signalling in both the chicken and mouse, there are differences in the contribution of SHH-expressing cells between mouse and chicken as well as between the chicken ulna and fibula. This is evidence that, although zeugopod bones are clearly homologous according to the fossil record, the gene regulatory networks that contribute to their development and evolution are not fixed.
miR-137 confers robustness to the territorial restriction of the neural plate border
Authors: Scatturice Luciana A. , Vázquez Nicolás , Strobl-Mazzulla Pablo H.
Published: June 2024

The neural plate border (NPB) of vertebrate embryos is segregated from the neural plate (NP) and epidermal regions, and comprises an intermingled group of progenitors with multiple fate potential. Recent studies have shown that, during the gastrula stage, TFAP2A acts as a pioneer factor in remodeling the epigenetic landscape required to activate components of the NPB induction program. Here, we show that chick Tfap2a has two highly conserved binding sites for miR-137, and both display a reciprocal expression pattern at the NPB and NP, respectively. In addition, ectopic miR-137 expression reduced TFAP2A, whereas its functional inhibition expanded their territorial distribution overlapping with PAX7. Furthermore, we demonstrate that loss of the de novo DNA methyltransferase DNMT3A expanded miR-137 expression to the NPB. Bisulfite sequencing revealed a markedly elevated presence of non-canonical CpH methylation within the miR-137 promoter region when comparing NPB and NP samples. Our findings show that miR-137 contributes to the robustness of NPB territorial restriction in vertebrate development.