tbuckley/cabot-search huggingface dataset:
Patients with a history of more than one cancer diagnosis: An opportunity to expand eligibility criteria?
Authors: Luis T. Campos, Julio Antonio Peguero, Michael Zach Koontz, Chardria Trotter, Christer Svedman, Joseph Paulson, Wei-Yi Chung, Valerie Tucker, Barbara L. McAneny, Annette Campbell Fontaine
Journal: Journal of Clinical Oncology (2024)

e23019 Background: Patients with a history of more than one cancer diagnosis are increasingly common due to improved cure rates in early-stage cancers, and a demographic shift towards an increasing proportion of elderly patients with cancer due to longer life expectancy. Having a prior cancer diagnosis is a common exclusion criteria in clinical trials but represents a large untapped pool of patients that could increase enrollment in trials. We assessed if there are differences in the clinical characteristics, NGS testing rates and the rate of actionable genomic alterations in patients with NSCLC with a history of at least one other cancer diagnosis. Methods: We analyzed patients with a NSCLC diagnosis and an appointment scheduled between Oct 23, 2023 and Jan 14, 2024 at three US community oncology sites. All patients were enrolled in the Kaleido Registry and descriptive statistical analyses were performed on curated data. Results: 221 patients were identified (110 male/111 female). Median age was 72 (range 37-95). 157 (72%) patients had NSCLC as their only cancer diagnosis and 67 (28%) had a history of other malignancy with a median time interval since the last cancer diagnosis of 78 months (interquartile range 28-141 months ). 49 patients had a history of 1 other cancer diagnosis and 18 patients had a history of 2 or more. The most common diagnoses were breast (n = 16, 7%), colon (n = 7, 3.2%), prostate (n = 7, 3.2%) and bladder (n = 4, 1.8%) cancers. There were no differences in median age (73 yrs, range 57-91 vs (72 yrs, range 37-95), or sex distribution (30/34 vs 80/77) between patients with multiple diagnoses vs those with only NSCLC. There was not enough power to detect a difference in the rates of NGS testing rates or actionable genomic alterations (EGFR/ALK/ROS1/KRAS/RET/MET/NTRK/BRAF/HER2) in the cohorts (51% vs 64%, respectively). Conclusions: One in four NSCLC patients had a history of other cancer diagnosis. There were no significant differences in baseline characteristics or actionable genomic alterations. The median interval since the last cancer diagnosis was more than 6 years and less than a third had less than 3 years. These findings indicate that a significant number of patients with prior cancer diagnoses may be suitable candidates for clinical trials as their risk of recurrence of prior disease is likely low given long follow-up in this cohort.
Procollagen C-protein enhancer 1 (PCPE-1) as a potential serum biomarker for osteosarcoma.
Authors: Gal Zvi Strauss, Sharon Halperin, Sarit Appel, Avivit Sheiman, Rony Weitzen, Ofir Ben Gal, Boaz Liberman, Eyal Ramu, Eytan Aharon Ben Ami
Journal: Journal of Clinical Oncology (2024)

e23518 Background: Osteosarcoma (OS) is the most common bone malignancy in children and young adults. Treatment with perioperative systemic chemotherapy has improved patient outcome but a third of patients will eventually develop incurable metastatic disease. Currently, there are no biomarkers for monitoring patients’ response to neo-adjuvant (NA) chemotherapy or for patients under active surveillance following treatments. Procollagen C-Proteinase Enhancer-1 (PCPE-1) is an extra-cellular matrix glycoprotein which promotes the maturation of pro-collagen into collagen in various tissues. Elevated serum levels of PCPE-1 are found in bone diseases such as Paget’s disease and Osteoporosis and in patients with breast cancer with bone metastases. Serum PCPE-1 has not been described in patients with OS. We aimed to describe PCPE-1 serum levels in patients with OS compared with healthy volunteers, and across different time points in their treatment and disease course. Methods: We collected serum samples from the Israeli national biobank of 18 adult OS patients. Serum samples were also collected from 6 healthy individuals. Additionally, we obtained serial samples from 4 OS patients prior to and after initiating NA therapy. Quantification of serum PCPE-1 levels was performed using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. Results: We successfully analyzed serum PCPE-1 levels from all patients and healthy volunteers. Mean PCPE-1 levels of 553ng/ml (range 479-614ng/ml) were observed in OS patients, compared with 313ng/ml (285-339ng/ml) in healthy volunteers. Of 4 patients undergoing treatment who had serial samples, a decrease in serum levels was observed 2 responding patients, while an increase in PCPE-1 levels were observed in one patient after NA treatment who had no response to treatment at the time of surgery. Of notice, serum levels nearly doubled in a patient during active surveillance who experienced local disease recurrence (274ng/ml and 423ng/ml, respectively). Conclusions: This is the first study to show elevated PCPE-1 serum levels in patients with OS. Our study also demonstrates potential changes in PCPE-1 levels in response to treatment. We are expanding our study to include a pediatric population to investigate the role of PCPE-1 as a potential tumor biomarker for monitoring treatment and surveillance of OS.
Results of a quality improvement program to increase complete lung cancer biomarker testing rates by focusing on system, physician, and other factors associated with adverse health outcomes.
Authors: Dwight Earl Heron, Jean Blair, Jawad Elias Francis, Kristina Stoeppler-Biege, Lijo Simpson, Jeremy Stapp, Joseph Kim
Journal: Journal of Clinical Oncology (2024)

e23249 Background: Complete biomarker testing (CBT) is an underutilized standard of care for patients with advanced lung adenocarcinoma, but limited tissue samples may lead to incomplete testing. Especially if quantity is not sufficient (QNS) requiring additional samples, a prolonged time-to-initiation of treatment (TTT) has been shown to negatively impact clinical outcomes. Bon Secours Mercy Health (BSMH) Youngstown, Ohio reviewed biomarker testing data and found: 1) only 41% of patients received CBT, and 2) in the case of QNS when liquid biopsies were utilized, the time from diagnosis to results took an average of 42 days. BSMH worked in collaboration with OncoLens and Q Synthesis to address these issues and reduce the TTT. To our knowledge, there is also no data on interventions that can increase CBT across large health systems and simultaneously tackle both physician and other factors associated with known health disparities. Methods: A multidisciplinary team developed a new workflow for patients diagnosed with advanced NSCLC. The pilot involved collecting both tissue and blood at the time of needle biopsy and working with a single reference lab for testing. Physicians and nurses in radiology and pulmonology were in-serviced on the new workflow. As patients were being prepared for a biopsy procedure, nurses collected two tubes of blood for liquid biopsy. After the procedure, both the tissue and blood were sent to pathology and if pathology confirmed an advanced NSCLC diagnosis, both samples were sent to the reference lab for testing. The lab developed a new process to hold blood and test it only when the tissue was QNS. If QNS, tissue testing for PD- L1 was prioritized, and additional biomarker tests were completed with the blood sample. If tissue quantity was sufficient, unused blood was discarded. The lab charged for a single test regardless of whether the test was performed on tissue and/or blood. Results: The QI project ran from Sept 2021 - Dec 2022 and achieved four improvements: 1) a 39.6% increase in CBT in patients with advanced NSCLC (80.6% post-intervention), 2) a decrease of 15.7 days from diagnosis to complete liquid biopsy test results (27.2 days post-intervention, 3) increased CBT rates across all but one physician by an average of 55% (-5% to 220%), and 4) increased CBT by 8% in females and patients with Medicare, Medicaid or other noncommercial/underinsured/uninsured payors. Conclusions: This QI project demonstrated that CBT of advanced NSCLC can be improved by programs that are tailored to large health systems and individual physicians. Gains are also seen in patient populations at risk of adverse outcomes.
Clinical profile and response to adjuvant treatments in patients with follicular dendritic cell sarcoma in the United States: Insights from SEER analysis.
Authors: Nikhil Vojjala, Sumeet Kumar Yadav, Kim Abbegail Tan Aldecoa, Bolun Liu, Guleid Hussein, Ibrahim Azar, Sri Yadlapalli, Geetha Krishnamoorthy, Judie R. Goodman
Journal: Journal of Clinical Oncology (2024)

e23537 Background: Follicular Dendritic Cell Sarcoma (FDCS) is a rare, indolent, low-grade sarcoma known for local recurrences managed primarily by surgery. The role for adjuvant therapy has not been established for either radiation or chemotherapy. We aimed to comprehensively analyze clinical and epidemiological profiles and responses to treatment in these patients. Methods: This is a retrospective study using the National Cancer Institute (NCI) Surveillance, Epidemiology, and End Result (SEER) database. Cases of FDCS between 2001 to 2022 were identified utilizing the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9758/3. Only adults &gt; 18 years of age and diagnosed by positive histology or cytology were included. Descriptive statistics were used to describe demographic and tumor characteristics. Logistic regression was used to identify the factors influencing survival. Kaplan-Meier method was used to plot survival based on different treatment regimens and stages. Results: A total of 168 patients with FDCS were identified, with more than 50% of the patients ≥ 50 years of age. The mean age at diagnosis was 52.6 years, 56% were female, and 74.4% were white. Most of the patients had localized disease (63.7%), 17.9% had distant disease, and the remaining had unknown stages. About 90% of the patients underwent surgery, with 41% receiving local tumor excision. In Univariate analysis, older age, and distant disease were found to have poor outcomes. Surgery, irrespective of stage, was found to improve overall Survival (Table 1). While chemotherapy and distant disease had poor outcomes in univariate analysis, they were not statistically significant in multivariate analysis. The majority of the patients who received chemotherapy alone without surgical intervention had distant disease, explaining the poor outcome seen in univariate analysis. Among 107 patients with localized disease, 41 patients (41.1%) underwent only surgery and 43 patients (40.1%) received adjuvant therapy (either chemotherapy or radiation vs both) along with surgery. 5-year overall survival was significantly lower in patients who received adjuvant therapy. (88.4% vs 68.4%, p = 0.001). Conclusions: In conclusion, FDCS has a fair overall 5-year survival with surgery alone. Patients with localized disease, who received adjuvant therapies had poor survival outcomes as compared to the surgery-only group owing to disease burden. Large prospective studies are required to properly evaluate the benefit of adding chemotherapy or radiotherapy in resectable disease.
Physician justification for anti-cancer treatment decisions in the evolving oncology market.
Authors: Angelena Moseley, Margaret Brierly
Journal: Journal of Clinical Oncology (2024)

e23317 Background: Oncology is a rapidly expanding pharmaceutical space, driven by innovative research and clinical technology. Continued growth in anti-cancer therapy has generated an exceedingly competitive market. As treatment options increase, physicians must weigh a variety of factors to make individualized care decisions. Many elements are patient-specific, but physician biases may also impact selection. As the market evolves, it is unknown whether oncology providers will shift priorities to align with contemporary findings or continue to trust in historical experiences. Methods: The Ipsos Global Oncology Monitor is an online, multi-center medical chart review of oncology patients receiving drug therapy. Over 1,900 cancer-treating physicians in the United States were screened for seniority and caseload and submitted data on 253,051 cancer patients (aggregate; all tumor types) between January 2020 to December 2023. Upon record submission, physicians were prompted to select up to three responses most associated with the reason for prescribing the reported therapy. Responses were chosen from a finite list of closed-ended options. Results: Influence of “Approved Standard of Care” fell amongst sampled physicians, cited as a reason for selecting treatment in 61% of reported annual patients in 2023, declining by 2.94 percentage points since 2020. “Biomarker results” recorded increased influence on therapy selection, rising in association with 8% of reported patients in 2020 to 11% in 2023. Within tumor-specific cohorts, “Maintain/improve quality of life” was a notable reason for drug therapy decisions in both breast and colorectal cancer patient subsets in 2023 (10% and 19% respectively). Contrary to the overall patient cohort, drug therapy choice for reported prostate cancer patients has increasingly shown association with “Approved Standard of Care” (53% in 2020 to 60% in 2023). Conclusions: Results of this study highlight the evolution of factors influencing anti-cancer treatment decisions in sampled physicians. Sampled providers appear to be shifting away from universal treatments, as shown by lowered association with “Approved Standard of Care”. Sampled physicians seem to be opting for specific therapies, demonstrated by rising influence of “Biomarker results”. Discrepancies between tumors merit expansion of research in rarer indications and emphasize the importance of diagnostic testing to continue improving quality of care. Further investigation using comparator cohort is warranted.
A phase 2 study of regorafenib in metastatic/unresectable, refractory synovial sarcomas.
Authors: Sanal Canute Fernandes, Sameer Rastogi, Shamim Ahmed Shamim, Adarsh Barwad, Rambha Panday, Ekta Dhamija
Journal: Journal of Clinical Oncology (2024)

e23551 Background: Current therapeutic options for advanced synovial sarcomas remain limited. Adoptive T-cell therapies against NY-ESO-1 and MAGE-4 benefit a subset of patients, but is of limited value in Asian patients due to the absence of the HLA-A*02 genotype. Methods: The trial had a single arm, Simon two-stage design that included patients with advanced synovial sarcomas who had progressed on 2 lines of therapy, one of which could be an anti-VEGF therapy. Regorafenib was administered orally in a continuous regimen with 80mg and 120 mg doses on alternate days. The primary end point was 3-month progression-free rate (PFR). A 3-month PFR of greater than 40% was taken to be a marker of drug efficacy. Secondary end points included median PFS, OS and safety analysis. Quality of life assessment was carried out at baseline and at 3 months using the EORTC C-30 questionnaire. Radiological responses were assessed using RECIST 1.1 criteria after independent review by 2 radiologists. Results: A total of 22 patients were included in the study during the period from January 2022 to December 2023 with baseline characteristics as shown in Table 1. 18 patients were eligible for assessment of the primary outcome. The 3-month PFR with regorafenib was 57% with an ORR of 5%. At a median follow up of 9 months, the median PFS was 5.0 (2.9-7.0) months, and the median OS was 10.0 (7.8-11.2) months. In an exploratory analysis, the subset of patients previously exposed to pazopanib showed a 3-month PFR of 46% and a median PFS of 3 months. The grade ¾ toxicities seen included HFSR (52%), diarrhea (5%) and oral mucositis (5%). The quality-of-life analysis showed symptom burden to be highest in the fatigue, pain and financial difficulties domain at baseline. No worsening of symptom burden scores was seen over the study period. The global health status score showed a numerical improvement at 3 months. Conclusions: The study had a significant number of patients with poor PS. Regorafenib in the above-mentioned dosing regimen demonstrated meaningful clinical activity in a heavily pre-treated population of patients with synovial sarcoma, including those previously exposed to pazopanib, with a preserved quality of life. The treatment was associated with manageable toxicities and no new safety signals, albeit with higher HFSR rates. [Table: see text]
Cancer burden across South Asia in 2020: A global cancer observatory analysis.
Authors: Urvish Jain, Faraan Rahim, Bhav Jain, Aditya Arkalgud, Cameron Sabat, Alessandro Hammond, Phub Tshering, Tej A. Patel, Bhawna Sirohi, Pankaj Jain, Shah Zeb Khan, Sanjeeva Gunasekera, Ramila Shilpakar, Zabihullah Stanikzai, Arman Reza Chowdhury, Nishwant Swami, Edward Christopher Christopher Dee, Bishal Gyawali
Journal: Journal of Clinical Oncology (2024)

e23292 Background: The cancer burden in South Asia is often associated with late diagnosis and poor outcomes because of barriers to accessing advanced treatment facilities and targeted therapies, financial sequelae of care, and cultural stigmas and misconceptions. We use recent estimates of the Global Cancer Observatory (GCO) to better understand the epidemiology of cancer in South Asia, which may inform national and regional cancer control. Methods: Using publicly available data from the GCO and the World Bank, we collected cancer statistics and population statistics for Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka (collectively, SAARC) from 2015-2020. Results: The crude incidence of cancer in this region was 1,733,573 cases, representing 9.0% of the incidence worldwide. The crude incidence rate (CIR, per 100,000) of cancer in SAARC was 93.4 compared to the worldwide rate of 247.5. The 5-year prevalence (in total cases) of cancer in South Asia was 3,474,184, compared to 50,550,287 globally. The crude mortality rate (CMR, per 100,000) in South Asia was 60.6, compared to 127.8 globally. However, the mortality-to-incidence ratio (MIR) (per 100,000) was 0.65, compared to 0.52 globally. Age-adjusted estimates are reported in the table. Conclusions: Our research highlights South Asia's unique cancer landscape with CIR and MIR, but elevated MIR compared to global figures. These findings underscore the need for a united, contextually relevant approach to addressing the burden of cancer in South Asia. Investment in collaborative, tailored cancer care programs will build the SAARC region's capacity to address the growing global cancer challenge. [Table: see text]
Employing machine learning (ML) and explainable artificial intelligence (XAI) to predict and explain suicidal ideation among patients with prostate cancer.
Authors: Satheesh Kumar Poolakkad Sankaran, Minu Mohan, Joel Brian Epstein, Roberto Pili
Journal: Journal of Clinical Oncology (2024)

e23086 Background: It is anticipated that implementing machine learning (ML) strategies will impact the clinical decision-making process in the future. This study aimed to compare the accuracy of various machine learning algorithms in predicting suicidal ideation in patients who were receiving treatment for prostate cancer (PC). Further, to predict suicidal ideation and explain the burden of illness (BOI) by utilizing ML algorithms and XAI-based interpretability. Methods: We analyzed the United States 2017 National Inpatient Sample database for patients hospitalized for PC using linear and non-linear ML methods. Using techniques such as forward selection (FS) and backward elimination (BE), Random Forest (RF), decision trees, Multivariate Adaptive Regression Splines, and Gradient Boosting Machine (GBM), we determined subsets and features. We used linear and non-linear MLs-- Lasso, Ridge, RF, and Neural Networks (NN). A 70% and 30% partitioning was performed on the training and test datasets. The performance of the model was tested using discrimination (C-statistics), the Receiver-Operating Characteristics (ROC) curve, and the Hosmer-Lemeshow tests on both the training data and the test data. Several XAI approaches, including permutation significance, global surrogate marker, feature interpretation, interactivity, and local interpretability, were also utilized to examine the BOI (Length of stay (LOS)) among PC cancer cohort with suicide ideation. Results: We identified 680 patients with suicidal ideation among 208,730 PC patients. The most important variable derived through FS and BE were depression, drug abuse, psychiatric disorder, alcohol dependence, race, Medicaid beneficiaries, cardiac arrhythmias, metastasis, weight loss, congestive heart failure, and un-complicated hypertension, further confirmed through the GBM and other methods. There was successful documentation of demographic, socioeconomic, and clinical characteristics through feature selection approaches. Linear models, Lasso, and Ridge demonstrated an excellent area under the ROC for all cohorts ( &gt; 0.9 in train and test datasets). On the other hand, tree-based models, such as RF, performed poorly (AUC 0.72 for train and 0.66 for test). The findings of the XAI methodologies showed that among PC suicide ideation, higher BOI was associated with patients staying in low-income neighborhoods, Whites, Medicaid beneficiaries, and those with weight loss. Conclusions: We showcase the increasing capability of predictive analytics, particularly XAI, in predicting suicidal ideation. The combination of the vast amount of data generated by the digitalization of healthcare systems with the advanced processing power of modern servers enables the development of machine learning-based care pathways, which has the potential to revolutionize clinical decision-making in cancer.