bluuebunny/crossref_metadata_2025 huggingface dataset:
The real-world impact of next-generation sequencing in advanced stages of solid tumor malignancies.
Authors: Shaw Brian S. , Shaw Ryan , Truong Rachel , Ploucher Shelby , Makani Neeharika Srivastava
Published: June 2024

e23066

Background: Next-generation sequencing (NGS) is a revolutionary technology that allows for DNA and RNA genomic analysis of malignant tumors via tissue or blood sample to aid in diagnosis and treatment while providing predictive and prognostic data about cancer patients. 75.6% of US oncologists use NGS in advanced cancer patients. As there are now site-agnostic approvals of certain targeted therapies, ASCO published a provisional clinical opinion stating that there is a rationale for genomic testing of all solid tumors. This retrospective study evaluates the impact of NGS testing in advanced solid tumor patients in a community based cancer center in Florida. Methods: Patients were diagnosed with stage 3 or 4 solid malignancy between January 1st, 2019 - December 31st, 2022. 496 patients were reviewed of which 269 patients were included in the study as they underwent NGS testing with either tissue (70.6%), blood (25.3%) or both (4.1%). Results: Median age of the study population was 71% with 87% of patients being insured with Medicare. 52.4% of patients were male. Overall, 67.7% of patients had biomarkers identified, 47.2% had FDA approved targeted therapies, and 77.3% had clinical trials identified. NGS testing impacted first line therapy in only 10% of patients where a matched therapy was initiated as first line treatment. Median time from initial diagnosis to NGS result was 53 days while the median time from diagnosis to initiation of first line of therapy was 47.5 days. In the entire study population, 14.1% never received therapy and 40.9% of patients passed. Of the 110 patients who passed, median overall survival in patients who had a biomarker identified through NGS testing was 6 months compared to 7 months in patients without a biomarker. Rates of biomarker identification and availability of FDA approved therapy were similar between deceased patients (67.3% and 45.5%) and those who were alive at time of analysis (63.1% and 48.4%). Conclusions: NGS testing has become part of routine oncologic care in patients with advanced solid malignancies, however in only 10% of cases did it impact first line therapy. Though currently NGS testing has a limited role in the initial management of advanced solid tumors, it is imperative that this technology continues to be used and developed as it leads to hypothesis generating and clinically relevant questions in discovery of oncogenic drivers, targets for novel therapeutics, and mechanisms of resistance to therapies. [Table: see text]
Innovative performance-based remuneration model for oncologists: Balancing productivity with quality of care in a Brazilian healthcare setting.
Authors: Sasse Andre Deeke , do Carmo Rafael Luis Moura Lima , de Jorge Juliana Limeira
Published: June 2024

e23089

Background: Traditional fee-for-service (FFS) models in oncology often lead to biased healthcare delivery, prioritizing quantity over quality of care. Our objective was to develop and implement a comprehensive remuneration model for oncologists in Brazil that emphasizes both productivity and quality in patient care. Methods: The '4E' model forms the basis of our remuneration strategy. 'Effectiveness' measures clinical productivity through patient consultations, treatments, and participation in multidisciplinary activities. 'Structure' evaluates academic credentials and scientific contributions, 'Efficiency' examines adherence to clinical and administrative protocols, and 'Excellence' assesses quality interactions with patients and healthcare systems. These elements provide nuanced bonus adjustments to the effectiveness score, facilitating a balanced and comprehensive compensation approach. Adapted to various healthcare settings, the model accommodates different budgeting methodologies. Results: Implemented in February 2020, the model has led to significant improvements in service delivery. Between May 2020 and August 2023, consultations in private services increased by 36.8%, and patient numbers grew by 42.2%. The financial impact was notable, with more than a doubling of revenue, reflecting the model's success in enhancing both the volume and quality of healthcare provision. Conclusions: This multi-level remuneration model offers a comprehensive, ethical approach, aligning physician compensation with a broad range of professional activities and responsibilities. It demonstrates potential for enhancing healthcare delivery quality while ensuring financial sustainability. However, a limitation of our study is the lack of longitudinal quality measurement, an aspect we aim to address in future research. This suggests the model's replicability in diverse global oncology settings and underscores its relevance in the current healthcare landscape.
Immune response to SARS-CoV-2 vaccine administered to patients with solid cancers under systemic treatment: A prospective, monocentric study (Immunocovid-19).
Authors: Caputo Francesco , Rotolo Martina , Carretto Edoardo , Albertazzi Laura , Ciardiello Giamaica , Cavuto Silvio , Savoldi Luisa , Ferretti Eleonora , Lombardi Mattia , Soncini Silvia , Galimberti Cristina , Di Girolamo Stefania , Moretti Gabriella , Iachetta Francesco , Zanelli Francesca , Fanello Silvia , Gasparini Elisa , Damato Angela , Neri Antonino , Pinto Carmine
Published: June 2024

e23093

Background: Despite vaccination, COVID-19 could still cause severe disease in immunocompromised patients (pts). While subsequent vaccine doses increase immune response in the general population, few data concerning cancer pts under systemic treatment are reported. Methods: This study will be conducted on blood samples from 1000 pts admitted to Reggio Emilia AUSL-IRCCS Cancer Center and undergoing systemic therapies who received ≥ 2 vaccine doses. The samples will be analyzed at Clinical Microbiology and Chemistry Laboratories of Reggio Emilia AUSL-IRCCS. We will perform antibody IgM-IgG serology by means of COVID-19 VIRCLIA® Monotest and anti-spike antibodies evaluation using LIAISON® SARS CoV-2 Trimerics IgG. We will also investigate cell immune response (B and T lymphocyte counts) and analyze specific lymphocyte subsets on the first 200 pts treated with chemo- (CT) or immunotherapy (IO). Then, we will evaluate the T-cell response on the first 50 pts and those with an inadequate anti-spike serologic response through the T-SPOT.COVID test. Statistical analyses will be conducted by the Clinical Studies and Statistical Unit Staff. Results: Here, we report preliminary data on the first 240 pts enrolled and treated with CT (55.4%), IO (26.3%), or other therapies (18.3%). Most of the pts were male (58%), had metastatic cancer (82%), and no previous COVID-19 infection (60%). 84% of pts were affected by gastrointestinal, lung, urogenital and breast cancer. We stratified pts in three groups according to the time from the last vaccine dose (0-6/6-12/ > 12 months). We showed no significant decrease in cellular and humoral immune response over time from the last vaccine dose, independent of the specific treatment received, also if CT (Table 1). Furthermore, clinical characteristics as gender, treatment, and primary tumor site appear not to influence immune response, even if a trend to a higher response in pts previously affected by COVID-19 has been observed. The T-SPOT.COVID test performed on the first 27 pts showed that 19% had no T-cell activation, even with good IgG response. Conclusions: This feasible and cost-effective study has a potential impact on public health. Although these are preliminary data, the immune response to COVID-19 vaccines remains good after 12 months from the last dose administered in cancer pts. The enrollment is ongoing, and we could provide relevant information on the influence of clinical factors on the immune response and identify specific subgroups that could benefit from different vaccine approaches. [Table: see text]
Patient reported colonoscopy barriers: A cross sectional survey.
Authors: Ozogbo Stanley , Francisco Isabella , Gemmel David
Published: June 2024

e23149

Background: As a leading cause of cancer-related death in the United States, colorectal cancer (CRC) screening is an acceptable cost-effective strategy to reducing mortality indices in the country. 10-yearly colonoscopy screening is the most effective with a mortality reduction of 73%. Despite this, CRC screening rates remain low. The purpose of this study was to describe barriers associated with colonoscopy screening in primary care settings. Methods: Postage pre-paid return envelopes and surveys were sent to all established patients aged > 50 from primary care practices (n = 4) in an employed physician group; the group also serves as a residency continuity clinic for a community teaching hospital. Variables included demographics and literature-reported barriers to colonoscopy screening. Whether or not a patient had a colonoscopy (including if > 10 years since a colonoscopy) was compared to patient reported barriers and demographics. Statistical significance was set at p < 0.05; strength of association was measured by Cramer’s V. Results: Average age of patients was 62 + 6 years; 61.4% were female; 35.3% were privately insured; and 10.3% were non-white. Older patients were slightly more likely to get screened, 63 + 6 years vs. 60 + 7 years (p = 0.006). Neither race, sex, insurance guarantor, education, marital status or income were associated with screening. Rate of colonoscopy screening in this series was 76.7% (n = 276/360), which was greater than rates reported by CDC for Ohio. In those screened, the rate of colonic or rectal polyps was remarkably noted to be up to 47.5% (131/276). The most important barriers to colonoscopy screening were knowledge of insurance coverage (p < 0.001; Cramer’s V = 0.216, p < 0.001); transportation to procedure (p = 0.001; Cramer’s V = 0.172, p = 0.001); someone to accompany patient (p = 0.002; Cramer’s V = 0.164, p = 0.002); and unaware of screening or lack of perceived health threat (p = 0.019; Cramer’s V = 0.150, p = 0.019). The remaining barriers were not associated with increased likelihood of colonoscopy: fear of finding cancer, belief in screening effectiveness, embarrassment or anxiety, or fear of invasive test. While bowel prep is often cited as a barrier to colonoscopy, this factor was not statistically significant. Likewise, physician-initiated discussion and time off from employment were not associated with screening. The most important colonoscopy barrier was patient knowledge regarding insurance for the procedure; overall, 29% of patients reported that they were unsure if colonoscopy was covered. Among those not screened, the rate rose to 47%. Conclusions: The most important colonoscopy barrier identified was patient knowledge regarding insurance for the procedure. While physician counseling for colonoscopy needs to include bowel prep and procedure risks, greater awareness of insurance coverage and social factors may facilitate physician understanding of colonoscopy screening hesitancy.
Comparing ventricular tachycardia across the nation: Stratification by different malignancies.
Authors: Ali Shafaqat , Kumar Manoj , Farooq Faryal , Devarkonda Vishal , Byreddi Laxman Yashwant , Sultan Muhammad , Atluri Sundeep , Nasir Bilal , Afzal Muhammad Sohaib
Published: June 2024

e23151

Background: Cardiac arrhythmias and cancer are prevalent conditions and share common predisposing factors. No studies have assessed VT rates and their outcomes stratified by cancer types. We aim to compare the occurrence of ventricular tachycardia (VT) and its outcomes in different malignancies. Methods: The national readmission database (2016-2020) was queried to identify all-cause admissions for patients with active malignancy of any origin. The study population was divided into six subgroups based on the type of cancer (colorectal, renal, lung, breast, prostate, and hematological). Multivariate regression analysis was utilized for adjusted odds of mortality. A propensity score matching (PSM) model matched malignancy of interest with other malignancies to obtain incidence rates. Results: Among 10.6 million all-cause cancer-related hospitalizations, about 0.8% developed VT. On a propensity-matched analysis & compared to other malignancies, VT had the highest incidence in hospitalizations associated with hematological malignancies (1%), followed by prostate (0.95%), lung (0.9%), renal (0.76%), colorectal (0.75%) & breast (0.50%) malignancies [p < 0.05]. Moreover, cancer hospitalizations complicated by VT were associated with higher mortality. VT was associated with the highest adjusted odds of mortality in renal malignancies (aOR:4.62), followed by breast (aOR:4.60), hematological (aOR:4.44), colorectal (aOR:3.75), prostrate (aOR:3.44), & lung (aOR:3.11) malignancies [p < 0.001]. The rates of 30-day VT-related readmission were highest in hematological malignancies (16.8%), followed by renal (15.9%), lung (15.7%), prostrate (15%), colorectal (14%) & breast (13.9%) malignancies [p < 0.05]. Conclusions: The rate of VT in nationwide hospitalizations among cancer patients was ~ 0.8 %. VT was found to have the highest incidence & readmissions in hematological malignancies, while VT-related mortality was highest in renal malignancies.
Impact of wildfires on radiotherapy adherence in patients with cancer: A multi-clinic study.
Authors: Lichter Katie , Sabol Rachel , Yom Sue S. , Mohamad Osama , Witztum Alon
Published: June 2024

e23154

Background: Recent surges in wildfire activity due to climate change pose significant threats to the delivery of consistent oncological care. Assessing the impact of such environmental disasters on the continuity of radiotherapy treatments is essential to mitigate healthcare disruptions and informing policy. Our study investigates the association between California wildfires from 2017-2021 and the adherence to scheduled radiotherapy sessions in cancer patients across multiple clinics, highlighting the interplay between environmental catastrophes and cancer care outcomes. Methods: We retrospectively analyzed 539,292 visits across eight clinics, including Providence Northern California (Petaluma), Providence at St. Joseph Hospital (Eureka), UCSF, and Stanford, extracting data on completed and missed radiotherapy sessions from their Oncology Health Information systems. In conjunction with CAL FIRE wildfire data, we performed univariable and multivariable logistic regression analyses with robust standard errors, adjusting for seasonal variations, clinic-specific effects, and temporal trends. Covariates in the multivariable model included seasonal effects modeled as sine/cosine functions, a linear date to capture time trends, and fixed effects for each clinic. All analyses were conducted using Stata 18.0 and R 4.2.3. Results: Univariable analysis indicated a slight increase in missed appointments when a wildfire occurred within 50km (OR = 1.06 [1.00, 1.11], p = 0.039). Specifically, the missed visit rate was 4.8% without a fire and 5.1% with a fire. Multivariable analysis, controlling for seasonality, temporal trends, and clinic-specific factors, revealed a stronger association (OR = 1.07 [1.02, 1.13], p = 0.007) with adjusted missed rates of 4.8% and 5.2%, respectively. The overall missed visit rate was 4.9%, with 8.8% of visits coinciding with active wildfires within 50 km of a clinic. Conclusions: This initial investigation suggests a potential trend towards higher non-adherence to radiotherapy sessions in the context of wildfire events. While our findings indicate a statistically significant association, they should be regarded as hypothesis-generating. There is a clear imperative for more comprehensive research to delineate which clinics, patient demographics, and disease sites are most susceptible to the deleterious effects of wildfires. Future studies should aim to incorporate a broader array of variables, including physical, psychological, and socioeconomic factors that may confer increased vulnerability to climate-related disruptions. This nuanced understanding is critical to inform targeted strategies that bolster the resilience of healthcare delivery systems and protect cancer patients from the escalating risks posed by climate change.
Patients’ voices matter: Translating pretreatment patient-reported outcomes into high and low health-related quality of life provides a new clinical aspect on prognosis and survival in patients with previously untreated diffuse large B‐cell lymphoma.
Authors: Yu Peiqing , Liao Will , Campinha-Bacote Avrita , Trask Peter , Balasubramanian Sandhya , Knapp Andrea , Huang Huang
Published: June 2024

e23165

Background: Patient-reported health-related quality of life (HRQoL) measures collected prior to treatment initiation have been shown to be prognostic of disease outcomes and survival in patients with previously untreated diffuse large B-cell lymphoma (DLBCL), including progression-free survival (PFS) and overall survival (OS), However, these HRQoL measures are usually expressed as numbers from a scale (e.g. from 0 to 100), which limit their ease of clinical utility compared to binary scales (i.e. high vs. low). Using HRQoL measures collected from the phase 3 study GOYA, we aim to convert these measures into binary scales by identifying optimal cutoffs and demonstrate their clinical utility in differentiating patient risks in DLBCL. Methods: HRQoL data from the physical functioning (PF2), global health status (QL2), and fatigue (FA) scales from the EORTC QLQ-C30 questionnaire and the lymphoma subscale (LYMS) from the FACT-LYM questionnaire were used in this analysis. The optimal cutoff points were identified using statistical metrics that evaluate the prognostic value and goodness-of-fit for each assessed cutoff point. The top performing binary HRQoL scale was further assessed in its clinical utility as an addition to the Internal Prognostic Index (IPI), a standard risk classification tool in DLBCL based on 5 binary measures of patient baseline characteristics, to evaluate whether adding the HRQoL scale would potentially improve the risk classification. Results: As shown in the table, while all binary scales can clearly differentiate patient overall survival (demonstrated by the hazard ratios), PF2 numerically exhibited the best performance, and was further assessed as an addition to IPI. After adding PF2 to the base OS model containing only IPI, we observed improvements in model performance metrics, including the concordance index and the goodness-of-fit. In addition, among patients classified as high risk by IPI (n = 185, 3-yr OS: 65% [95% CI 68-72%]), those with low HRQoL (n = 102, 3-yr OS: 56% [95% CI 47-67%]) had a substantially worse OS, suggesting that further refinement of patient-risk defined by IPI may be feasible with HRQoL measures. Conclusions: Our work highlights the potential of the binary HRQoL scales to provide additional prognostic value to IPI, and suggests that patient reported outcomes may be useful in further refining patient risk classification in addition to IPI in untreated DLBCL. [Table: see text]
Can a medically integrated oncology pharmacy decrease waste and avoidance?
Authors: Weinberg Tamara
Published: June 2024

e23207

Background: Oral oncolytic medications cost thousands of dollars each month to the cancer patient. The median cost of waste from dose reduction, discontinuation due to progressive disease, and medication being held due to side effects is estimated to be an average waste of $4290 per patient (Lam et al., 2023). Additionally, The National Institutes of Health reported in 2012 that $418 billion is wasted due to suboptimal use of medications in the US (Alhomoud, 2020). On average, the monthly cost of one oral oncolytic prescription is $10,000-$25,000. This financial distress can be devastating to cancer patients emotionally and physically, significantly affecting their quality of life. Financial toxicity may cause cancer patients not to fill necessary oncolytic prescriptions, skip medication doses, or take less medication than the prescribed amount. AON Pharmacy sought to measure the value of oncology-trained nurses in a medically integrated pharmacy to continue the cancer care continuum, maximize cost avoidance, and reduce the waste of oral oncolytic medication. Methods: This study evaluated whether having oncology-trained nurses review electronic medical records before a refill of an oral oncolytic medication would decrease waste and increase cost avoidance to patients and payors. During a chart review done by an oncology nurse, if a discrepancy were found with the patient’s EMR, such as laboratory abnormalities, scans showing progressive disease, or unmanaged side effects, the nurse would triage the doctor's office via the EMR before medication was dispensed. If the doctor ordered the medication to be placed on hold or discontinued, waste and cost avoidance were tracked using the National Community Oncology Dispensing Association waste tracker. Results: Data was collected from February 2023 to December 2023. Data points included 157 nursing interventions. These interventions included six interventions for progressive disease, eight interventions for therapy change, 134 interventions for treatment held, three for dose change, five for deceased patients, and one for others. Commercial insurance payors had 17 interventions, Medicaid had eight interventions, Medicare had 129, and Patient Assistance Programs had three interventions. This resulted in $1,994,629.88 saved in waste and cost avoidance to patients receiving oral oncolytic medications for 2023. Conclusions: Using oncology-trained nurses to help patients through the cancer care continuum, improve clinical outcomes, and promote cost avoidance and waste reduction of oral oncology medications proved to be highly effective in avoiding waste and decreasing the daily financial toxicity cancer patients feel. AON Pharmacy is committed to using oncology nurses to review EMRs in 2024 to decrease waste and avoidance. 2024’s goal is to reduce waste and avoidance by over 2 million.
Trainee-led quality improvement (QI) project examining PCP prophylaxis in patients on chronic, high-dose corticosteroids.
Authors: Schonman Ian , Sterling Cole Harris , Baran Kayla Garzio , Schenk Kara M. , Wilbur H. Catherine , Campbell Yanka , Chen Allen Ray Sing , Marrone Kristen A. , Hussaini S. M. Qasim , Warrier Govind
Published: June 2024

e23211

Background: Patients with cancer who develop Pneumocystis pneumonia (PCP) have 30-day mortality rates estimated to be > 50%. Despite consensus guidelines from the American Society of Clinical Oncology (ASCO) and Infectious Diseases Society of America (IDSA), appropriate PCP prophylaxis is reported as low as 3.9% for patients with solid malignancies on chronic, high-dose corticosteroids. In this trainee-led QI initiative, we investigated rates of appropriate PCP prophylaxis at a tertiary care cancer center and surveyed clinicians regarding barriers to prescribing prophylaxis. Methods: An interprofessional, multidisciplinary team consisting of hematology-oncology fellows and cancer-center level QI staff was established. This analysis combined a retrospective chart review and survey at a tertiary care center. Retrospective chart review examined PCP prophylaxis rates among patients with solid malignancies prescribed high dose/duration corticosteroids per ASCO/IDSA guidelines (≥20mg prednisone equivalents daily for ≥1 month) between May 1, 2022 and May 31, 2023. The survey, conducted between December 2022 and May 2023, assessed prescriber knowledge of, and attitudes towards, appropriate PCP prophylaxis prescription. The survey was open to clinicians across oncology specialties. Results: Over the study period, 297 patients met inclusion criteria for PCP prophylaxis (median age 62, 178 (60%) were male, 212 (71%) were White, and 55 (18%) were Black). Fewer than half of eligible patients were prescribed prophylactic antibiotics (n = 140, 47%). There were no sociodemographic differences between patients prescribed prophylaxis and those not prescribed prophylaxis. Survey responses (n = 71) included 33 (46%) attending physicians, 21 (30%) advanced practice providers, 8 (11%) residents/fellows, and 9 (13%) unknown. Thirty participants (42%) had cared for a patient who developed PCP while on corticosteroids. While 62 participants (87%) had experience prescribing PCP prophylaxis, only 18 (25%) accurately identified the dose and duration of corticosteroids at which prophylaxis is needed. Lack of guideline knowledge/education was the most commonly cited barrier to prophylaxis (Table). Conclusions: Our study shows strikingly fewer than half of eligible patients on chronic, high-dose steroids were prescribed PCP prophylaxis. Lack of provider knowledge and systems-related obstacles were noted as primary barriers. Based on these findings, an urgent QI intervention is underway to address each barrier, increase rates of PCP prophylaxis, and reduce rates of PCP incidence towards the broader goal of improving outcomes in this at-risk patient population. [Table: see text]
Real world outcomes of 2,339 patients with early-stage triple-negative breast cancer (TNBC) treated in British Columbia.
Authors: Lucas Mairi , Chia Stephen K. L. , Speers Caroline , Lohrisch Caroline A. , Nichol Alan , Mitri Zahi Ibrahim
Published: June 2024

e23274

Background: TNBC represents 15-20% of all breast cancers, and tends to exhibit more aggressive features, more frequent distant metastasis and overall worse prognosis than other breast cancer subtypes. The treatment landscape for early-stage TNBC has changed considerably in the last decade, with new additions to neoadjuvant therapy (NAT) aimed at improving pathologic responses and outcomes. In this study, we assess real world data regarding treatment and outcomes in those with early-stage TNBC. Methods: The BC Cancer Breast Cancer Outcomes Unit database contains prospectively collected data on patients residing in British Columbia and diagnosed with breast cancer since 1989. This retrospective study evaluated patients diagnosed with stage I-III TNBC from 2010 to 2019. During this era, regimens containing anthracyclines and taxanes were routinely used. TNBC was defined as per ASCO-CAP guidelines as ER≤1%, PR≤1% and negative HER 2 (0, 1+ by immunohistochemistry, or 2+ ISH negative). Outcomes of interest included event free survival (EFS), overall survival (OS), and pathologic complete response (pCR). Results: 2,339 patients withstage I-III TNBC were identified with a mean follow up of 6.5 years. OS was 87% (95% CI 85-88%) at 3-years and 79% (95% CI 77-80%) at 5-years. The presenting stage was a significant prognostic factor, with 5-year EFS of 89%, 81% and 51%- and 5-year OS of 90%, 80%, and 53% for stages I, II, and III, respectively. There was an increase in NAT use in 2019 (n = 82/230,35.7%) when compared to 2010 (n = 20/227, 8.8%). The most common neoadjuvant regimens used included anthracycline and taxane chemotherapies (n = 343,81.4%), with only a small number receiving neoadjuvant platinum chemotherapy (n = 52, 12.4%). Pathological complete response (pCR) was achieved in 24.5% (103/421) of patients who received NAT. Patients with pCR had improved 5- year EFS (91% vs. 57%, HR 0.26 [95% CI 0.15-0.45]) and 5-year OS (90% vs. 59%, HR 0.26 [95% CI 0.15-0.45]) compared to those with residual disease. The subgroup that received salvage capecitabine had a poor 3-year EFS at 22% but was enriched for patients with residual nodal disease after NAT (n = 77/130, 59.2%). Conclusions: This real-world study of TNBC in the era prior to routine immunotherapy (IO), highlights the poor prognosis of TNBC, particularly patients with locally advanced disease and those who did not achieve pCR, despite adjuvant capecitabine. This stresses the need for advances in NAT and salvage therapies for TNBC with residual disease at high risk of recurrence. [Table: see text]
Long-term survival of patients with lung cancer with kinase fusions (KF) treated at a tertiary community-based cancer program.
Authors: Doctor Vicki , Tan Bradford A. , Schink Julian C. , Prabhakar Dhivya , Khan Ajaz M. , Pisick Evan P. , Szymulanska-Ramamurthy Karina , Markman Maurie
Published: June 2024

e23279

Background: Comprehensive Genomic Profiling (CGP) has been routinely obtained on patients with advanced cancers without standard-of-care therapeutic options managed in our community-based cancer program for more than a decade. Methods: In 2018, we reported that 1% (77 of 7,260 pts) who underwent CGP (Foundation Medicine Inc. hybrid capture based CGP platform) were found to have a KF abnormality (median age 53), including 55 patients (pts) (71%) with non-small cell lung cancer (NSCLC) and 22 (29%) with other malignancies. The incidence of KF in the NSCLC population tested was approximately 5%. Of the 55 patients with NSCLC, 36 pts (65%) had ALK fusions, 12 pts (22%) has RET fusions, 7 pts (13%) had ROS1 fusions. Results: This report describes long-term survival of NSCLC pts with metastatic disease within this population treated with KF targeted therapy for > 5 years. Five pts (9% of NSCLC with a KF; all females; median age 63 [range 57-72]) remain on active therapy a median of 10 years (range 6.5-12 years) from the initiation of therapy. 2 pts have EML4-ALK fusions, 1 pt has EZR-ROS1 fusion, 1 pt has CD74-ROS1 fusion, and 1 pt has ALK PRKAR1A fusion. 2 of 5 pts have continued their initial KF agent while 2 switched >1 times to an alternative KF targeted drug and 1 is currently receiving chemotherapy. Only two pts had the identical KF abnormality. Conclusions: In this series approximately 10% of NSCLC pts with a KF experienced extended survival (greater than five years) despite the presence of metastatic disease, including three patients with brain mets. It is critical to conduct molecular testing on all NSCLC pts for the presence of a kinase fusion abnormality. Treatment directed at this molecular target can result in long-term survival.
Retroperitoneal leiomyosarcoma; Demographics, clinicopathological, survival analysis, role of adjuvant radiation and genomic analysis.
Authors: Ullah Hafeez , Khan Yasinzai Abdul Qahar , Tareen Bisma , Daino Naema , Ullah Asad , Heneidi Saleh , Rasool Basil , Karki Nabin R.
Published: June 2024

e23327

Background: Retroperitoneal leiomyosarcoma (RPL) is an exceedingly rare malignancy and is the second most common subtype of leiomyosarcomas. Most of the information concerning this rare disease is limited to case studies and few literature studies. The study's objectives were to assess the demographics, pathological factors, survival outcomes, genomic landscape and potential for targeted therapy. Methods: Data of retroperitoneal leiomyosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database, with cases diagnosed between 2000 and 2020 used for this study and the Cancer Genome Atlas containing sequencing information for 27 cases of RPL. Results: A total of 1406 cases were extracted with mean age of diagnosis of 62.1 years. Of these, RPL had a higher incidence in women (71.5%), more cases affected Whites (58.7%). Histologically, in patients with known grading, most patients’ i.e. 62.35% were grade 3, G3 (poorly differentiated). Nearly all (99.9%) patients presented with a tumor size ≥4.1 cm. Local lymph nodes metastasis were positive in 76.0% of cases when lymph node status was reported. In known cases of distant metastases, the most common site was liver (8.9%). The main treatment modality was surgery only (26.7%, hazard ratio, HR 1.17, p-value < 0.001), followed by the standard of care (surgery and radiation) (18.4%, HR 1.03, p-value < 0.001), and radiation only (18.4%). Five-year overall survival was 40% and 5-year cause-specific survival was 64%. The highest 5-year survival was observed in patients undergoing surgery and radiation (57%), and in combination therapy (chemotherapy, surgery, and radiation) the 5-year survival was 39%. Genetic analysis found the most common mutations included TP53 (51.9%), RB1 (25.9%), and ATRX (14.8%). When accounting for deep deletions and rearrangements, total frequency of the alterations was higher such that TP53 (63.0%), RB1 (51.9%), and ATRX (18.5%). Potentially actionable alterations were rare but included activating alterations in FGFR1, PIK3CA and ESR1, as well as deep deletions of BRCA1. Conclusions: Retroperitoneal leiomyosarcoma is a very rare tumor where surgery and radiation has been the conventional therapy. Our study indicates there are genetic alterations in the majority of retroperitoneal leiomyosarcoma. To further understand the pathogenesis and survival factors, patients with RPL should be enrolled into national and international registries.
Evaluation of tumor immune microenvironment for PD-L1 score and tumor infiltrating lymphocytes in high grade osteosarcomas and their correlation with disease progression.
Authors: Khan Shah Alam , PUSHPAM DEEPAM , Mridha Asit R. , Barwad Adarsh , Sampath kumar Venkatesan , Bakhshi Sameer
Published: June 2024

e23510

Background: Tumor Immune Micro-environment is being increasingly recognised as a potential target for improving overall survival for osteosarcomas, especially in the metastatic setting. Our study purpose was to evaluate the PD- L1 (Programmed cell Death- Ligand 1) expression in neoplastic cells well as Tumor Infiltrating Lymphocyte (TIL) density of osteosarcoma specimens and correlate it with oncological outcomes. Materials & Methods: A prospective cohort study was conducted between March 2017 and March 2022 among osteosarcoma patients who underwent primary biopsy and neo-adjuvant chemotherapy followed by surgical excision at our centre. We excluded patients who had alternative diagnoses such as low grade osteosarcoma, secondary osteosarcoma, recurrent osteosarcoma as well as patients who had undergone initial treatment (chemotherapy/ surgery) outside our institute. De-paraffinized sections (4μ) incubated with primary antibody (PDL1) and a universal secondary detection kit used. Average percentage of positive cells calculated from at least 10 representative fields at 400X magnification. Positive staining was considered when ≥1% cells showed positivity. IHC scoring of PD-L1 was graded as negative, low positive and high positive. We calculated the number of TILs under 400X magnification in ten fields and then took their average. TILs staining was scored semi quantitatively using a 3 tiered scale. Results: Forty patients who fulfilled the inclusion & exclusion criteria were included in the study with most common age group being 10 to 19 years (27 patient, 68%). The male: female ratio was 1.6: 1 and the most common location of tumor was distal femur. Majority of patients had the histological subtype of conventional osteosarcoma (37 patients, 92.5%). Lung metastasis was present at time of initial diagnosis in 27 patients (67.5%). At the end of 2 years, 27 patients were alive (60%) while 13 patients had died due to disease. PD-L1 expression was negative in 17.5%, low positive in 15% and high positive in 67.5%. Among TIL category, 19 patients belonged to category 1, 10 belonged to category 2 & 11 belonged to category 3. There was significant correlation between PD-L1 expression score & TIL category. PD-L1 score did not correlate with percentage of necrosis following chemotherapy, metastasis on presentation or overall survival. Conclusions: PD-L1 score had significant correlation with density of Tumor Infiltrating lymphocytes (TIL). However, PD-L1 score did not correlate with overall survival, tumor-free survival, progression of metastasis or local recurrence.
Analysis of demographic and socioeconomic factors in mixed type rhabdomyosarcoma using NCDB.
Authors: Gill Sukhmani Kaur , Moroz Mark , Grover Jasika , Rafie Susan , Silberstein Peter T. , Heise Craig , Hsia Beau
Published: June 2024

e23538

Background: Mixed type rhabdomyosarcoma is a rare soft tissue tumor characterized by the presence of two histologically different subtypes of rhabdomyosarcoma, commonly found in the testis. Despite a majority of the patients undergoing aggressive treatment, the prognosis is poor. Analysis of its diagnostic trends could prove valuable in understanding mixed type rhabdomyosarcoma’s epidemiology. The 2004-2020 National Cancer Database (NCDB) was analyzed to determine the demographic factors of patients with mixed type rhabdomyosarcoma. Methods: A retrospective cohort analysis of the 2004–2020 NCDB, using ICD-O-3 code 8902/3, included patients diagnosed with mixed type rhabdomyosarcoma (N = 94). Descriptive statistics were used to analyze various demographic factors such as sex, age, race, Hispanic status, educational background, insurance status, facility type and location, distance from facility, and Charlson-Deyo score. Incidence trends were examined through regression analysis. Results: The NCDB identified a total of 94 patients with a confirmed diagnosis of mixed type rhabdomyosarcoma from 2004-2020, with a slight decline in incidences diagnosed per year (R² = 0.0903). Females had a slightly higher likelihood of being diagnosed (55%) compared to males (45%), with average age at diagnosis being 40.06 years (SD = 2.8, Range = 1-90). The majority of patients were White (72%) and of non-Hispanic descent (82%). The top primary site was the testis (23%), with endometrium being another major site (15%). Most (83%) patients had a Charles/Deyo comorbidity score of 0. All patients received immunotherapy as primary treatment. Most (46%) patients were privately insured. A majority (26%) of patients received treatment at an academic/research program. A greater number (53%) of patients resided in metropolitan counties with a population larger than 1 million. Most (40%) patients belonged to the highest quartile of income earners of $74,063 or greater. Conclusions: Our research on mixed type rhabdomyosarcoma, the first NCDB analysis of its kind, aims to address a notable knowledge gap on the topic. Similar to information presented in earlier studies, our analysis revealed mixed type rhabdomyosarcoma has a relatively poor prognosis and is mostly observed in White, Non-Hispanic individuals. Analysis on the demographics of this patient population revealed most patients were top quartile income earners, resided in a metropolitan location, and were more likely to be treated at an academic/research program. Further research should aim to better understand the impact of such demographic and socioeconomic features on the diagnosis, treatment plans, and overall mortality rates of patients with mixed type rhabdomyosarcoma.
Quality of life outcomes in patients with resectable dedifferentiated liposarcoma treated with neoadjuvant immunotherapy.
Authors: Malik Neha , Peterson Susan K. , Keung Emily Zhi-Yun , Hunt Kelly , Torres Keila E , Lyu Heather , Lillemoe Heather A. , Nassif Haddad Elise F , Somaiah Neeta , Roland Christina Lynn , Scally Christopher
Published: June 2024

e23552

Background: Currently there is a lack of robust data on health-related quality of life outcomes for patients with retroperitoneal sarcoma. The purpose of this study was to look at trends in health-related quality of life outcomes for patients and determine what symptoms impacted patients the most. Patients with surgically resectable dedifferentiated liposarcoma who were participating in a randomized, phase II, non-comparative trial of combination nivolumab (nivo) and ipilimumab (ipi/nivo) were selected to participate in this study. Methods: Five patients were randomized to participate in structured qualitative interviews. Three patients were randomized to the nivo/ipi arm and 2 to the nivo arm. The interviews were conducted at 6 separate time points, both during receipt of neoadjuvant therapy and after tumor resection. Questions were structured around ten themes which included treatment side effects, abdominal complications, appetite, energy levels, quality of life effects, and financial complications. Patient responses were transcribed, coded, and themes in symptoms during treatment were identified. Results: Different themes in symptoms emerged during each time-period of treatment. During the pretreatment period patients were more likely to report abdominal complaints that they attributed to their primary tumor. During neoadjuvant immunotherapy (week 3) patients reported more skin complaints, including the development of rashes and pruritis. These tended to improve by their preoperative visit. Patients reported typical postoperative symptoms at their 6-week post operative visit including increases in pain medications, muscle pain, and some abdominal soreness. By one year patients reported no significant symptoms and demonstrated resolution of all prior symptoms. Overall patients reported few energy and sleep related symptoms throughout their treatment course. Conclusions: For patients with resectable dedifferentiated liposarcoma receiving immune checkpoint blockade, health-related quality of life symptoms were present throughout their treatment course. Common themes that emerged demonstrated a lack of severe symptoms experienced by patients in either arm and resolution of symptoms by one year post treatment. Our interview results can help clinicians focus on symptoms that are impactful to patients in future clinical trials.
A Systematic Review Supporting the Endocrine Society Clinical Practice Guidelines on Vitamin D
Authors: Shah Vishal Paresh , Nayfeh Tarek , Alsawaf Yahya , Saadi Samer , Farah Magdoleen , Zhu Ye , Firwana Mohammed , Seisa Mohamed , Wang Zhen , Scragg Robert , Kiely Mairead E , Lips Paul , Mitchell Deborah M , Demay Marie B , Pittas Anastassios G , Murad Mohammad Hassan
Published: June 2024

Context

Low vitamin D status is common and is associated with various common medical conditions.

Objective

To support the development of the Endocrine Society's Clinical Practice Guideline on Vitamin D for the Prevention of Disease.

Methods

We searched multiple databases for studies that addressed 14 clinical questions prioritized by the guideline panel. Of the 14 questions, 10 clinical questions assessed the effect of vitamin D vs no vitamin D in the general population throughout the lifespan, during pregnancy, and in adults with prediabetes; 1 question assessed dosing; and 3 questions addressed screening with serum 25-hydroxyvitamin D (25[OH]D). The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess certainty of evidence.

Results

Electronic searches yielded 37 007 citations, from which we included 151 studies. In children and adolescents, low-certainty evidence suggested reduction in respiratory tract infections with empiric vitamin D. There was no significant effect on select outcomes in healthy adults aged 19 to 74 years with variable certainty of evidence. There was a very small reduction in mortality among adults older than 75 years with high certainty of evidence. In pregnant women, low-certainty evidence suggested possible benefit on various maternal, fetal, and neonatal outcomes. In adults with prediabetes, moderate certainty of evidence suggested reduction in the rate of progression to diabetes. Administration of high-dose intermittent vitamin D may increase falls, compared to lower-dose daily dosing. We did not identify trials on the benefits and harms of screening with serum 25(OH)D.

Conclusion

The evidence summarized in this systematic review addresses the benefits and harms of vitamin D for the prevention of disease. The guideline panel considered additional information about individuals’ and providers’ values and preferences and other important decisional and contextual factors to develop clinical recommendations.
Female Reproductive Factors, Exogenous Hormone use, and Incident Chronic Kidney Disease and end-stage Renal Disease
Authors: Han Wen-Wen , Miao Meng-Yuan , Lyu Jie-Qiong , Tao Hao-Wei , Jia Yi-Ping , Liu Yu-Jie , Wang Jia-Min , Chen Jing-Si , Qin Li-Qiang , Chen Guo-Chong
Published: June 2024

Context

Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases.

Objective

To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women.

Methods

A total of 260 108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders.

Results

During a median of ∼12.5 years of follow-up, 8766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before age 50 years, menopausal before age 45 years, and menopausal hormone therapy initiated before age 50 years was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (hazard ratio [HR] = 0.89; 95% CI, 0.87-0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI, 0.79-0.95). Each 5-year delay in starting menopausal hormone therapy was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI, 0.84-0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI, 0.73-0.99).

Conclusions

Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.
Acromegaly Disease Control Maintained After Switching From Injected Somatostatin Receptor Ligands to Oral Paltusotine
Authors: Gadelha Mônica R , Casagrande Alessandra , Strasburger Christian J , Bidlingmaier Martin , Snyder Peter J , Guitelman Mirtha A , Boguszewski Cesar L , Buchfelder Michael , Shimon Ilan , Raverot Gerald , Tóth Miklós , Mezősi Emese , Doknic Mirjana , Fan Xiaolin , Clemmons David , Trainer Peter J , Struthers R Scott , Krasner Alan , Biller Beverly M K
Published: June 2024

Context

Paltusotine is a nonpeptide selective somatostatin receptor 2 agonist in development as once-daily oral treatment for acromegaly.

Objective

To evaluate the efficacy and safety of paltusotine in the treatment of patients with acromegaly previously controlled with injected somatostatin receptor ligands (SRLs).

Methods

This phase 3, randomized, double-blind, placebo-controlled trial enrolled adults with acromegaly who had IGF-I ≤1.0 times the upper limit of normal (×ULN) while receiving a stable dose of depot octreotide or lanreotide. Patients were switched from injected SRLs and randomized to receive paltusotine or placebo orally for 36 weeks. The primary endpoint was proportion of patients maintaining IGF-I ≤1.0× ULN. Secondary endpoints were change in IGF-I level, change in Acromegaly Symptom Diary score, and maintenance of mean 5-sample GH <1.0 ng/mL.

Results

The primary endpoint was met: 83.3% (25/30) of patients receiving paltusotine and 3.6% (1/28) receiving placebo maintained IGF-I ≤1.0× ULN (odds ratio, 126.53; 95% CI, 13.73->999.99; P < .0001). Paltusotine was also superior to placebo for all secondary endpoints: mean (± SE) change in IGF-I of 0.04 ± 0.09× ULN vs 0.83 ± 0.1× ULN (P < .0001); mean (± SE) change in Acromegaly Symptom Diary score of −0.6 ± 1.5 vs 4.6 ± 1.6 (P = .02); mean GH maintained at <1.0 ng/mL in 20/23 (87.0%) vs 5/18 (27.8%) patients (odds ratio, 16.61; 95% CI, 2.86-181.36; P = .0003). The most common adverse events were acromegaly symptoms and gastrointestinal effects characteristic of SRLs.

Conclusion

Replacement of injected SRLs by once-daily oral paltusotine was effective in maintaining both biochemical and symptom control in patients with acromegaly and was well tolerated.