tbuckley/cabot-search huggingface dataset:
A scalable 3D spatial multi-omics method for high-plex morpho-molecular imaging of millimeter-thick tissues.
Authors: Hei Ming Lai, Shuk Ling Chan
Journal: Journal of Clinical Oncology (2024)

162 Background: Tissues are three-dimensional (3D). However, current histopathology only allows 2D and single-marker tissue views. Methods: We utilized tissue clearing, supramolecular histochemistry, light-sheet microscopy, and image processing algorithms to compile an end-to-end multi-modality pipeline for 3D digital pathology and oncology diagnostics development. Results: Our end-to-end solution allow parallelized, fully automated processing of formalin-fixed or paraffin-embedded tissues of 1cm 3 size. With a tissue-to-image time of 6 days, the whole intact tissue block can be non-destructively imaged with our newly developed 3D HnE (Hematoxylin-analogue &amp; Eosin stain) and 4-plex immunohistochemistry (IHC). Deep and homogeneous penetration of staining was achieved such that all stained markers can be quantified as ground truth. The stained and cleared tissue can be recycled for subsequent FFPE 2D histology over multiple cycles for higher-plex imaging, and is also applicable to simultaneous survey of mRNA with multiplexed fluorescent in situ hybridization (FISH), post-translational modifications such as histone modifications via IHC, and glycosylation profiling with lectins. Image analysis readily allows high-dimensional clustering of cells based on their multi-modal biomolecular expression profiles, morphology, spatial locations, and neighborhoods. The method is applicable to a wide variety of human and murine tissues. Conclusions: Our 3D digital pathology platform enables maximal information extracted for precision diagnostics and advanced biomedical research.
Disparities in self-reported pain control among cancer survivors.
Authors: Marco Santos Teles, Ganesh Modugu, Isabel C. Silva, Raj Malhotra, Munir Rahbe, Mariam F. Eskander
Journal: Journal of Clinical Oncology (2024)

151 Background: Cancer survivors often suffer from chronic pain. However, not all patients have access to medication and other pain management strategies, making pain control challenging. We aim to determine the association of sociodemographic factors with self-reported pain control in cancer survivors with cancer-related chronic pain. Methods: A cross-sectional analysis was conducted using data from the 2022 Behavioral Risk Factor Surveillance System survey. Cancer survivors who self-reported physical pain from cancer or treatment were included. Non-melanoma skin cancer survivors were excluded. The outcome of interest was pain control. Univariate analysis with chi-square and multivariable logistic regression were used to determine the sociodemographic characteristics associated with pain control. Models were adjusted for age, sex, marital status, income, insurance coverage, BMI, smoking status, and cancer site. Results: 1,670 cancer survivors with self-reported cancer-related chronic pain were identified. 9.2% were aged &lt; 40, 61.5% were female, and 71.6% were non-Hispanic white. 97.2% were insured, 50.5% earned ≥ $50,000, and 27.6% were college graduates. 29.8% of survivors reported a history of breast cancer, followed by melanoma (6.3%), and lung cancer (6.1%). Young adults (age 18-39) reported significantly lower pain control compared to older survivors (52% vs. 77.7%, p &lt;0.001). Non-Hispanic Black survivors reported the highest rates of pain control, followed by non-Hispanic white, and Hispanic survivors (87.7% vs. 77.5% vs. 60.6%, respectively, p= 0.013). Employed survivors reported significantly higher pain control than those out of the workforce (83.2% vs. 73.7%, p= 0.008, respectively). College graduates reported better pain control than those without a college degree (82.9% vs. 74.7%, p=0.009, respectively). There was no significant association between pain control and insurance coverage or income. On multivariate analysis, young adults had lower pain control than older adults (OR: 0.454; 95% CI: 0.219-0.942). Compared to non-Hispanic white survivors, being Hispanic was associated with worse pain control (OR: 0.324; 95% CI: 0.142-0.737); no significant association was found for non-Hispanic Black survivors (OR: 1.964; 95% CI: 0.851-4.631). Employment was associated with better pain control (OR: 1.997; 95% CI: 1.235-3.231). College degree attainment was not significantly associated with pain control on multivariate analysis (OR: 1.414; 95% CI: 0.934-2.142). Conclusions: Age, race/ethnicity and employment were associated with pain control among cancer survivors. Young adults, Hispanic and unemployed survivors were most likely to have poor pain control. Further research should elucidate the factors driving these relationships in order to achieve more equitable pain management in this population.
The challenge of colorectal cancer (CRC) screening in low and middle-income countries (LMIC): Acceptance, knowledge, and preferences in Brazil.
Authors: Victor Filogonio, Yara Rafaela Maia, Matheus Alexandre Rebelo, Joao Secol Rodrigues, Lucas Henrique Maia
Journal: Journal of Clinical Oncology (2024)

153 Background: Presenting an increasing incidence and high mortality rates, CRC is a challenge that many LMIC face and struggle to establish an effective screening strategy. Brazil is one of the few Latin American countries and LMIC that have a population-based CRC screening program, targeting ages 50-74 and performing a fecal occult blood test (FT) every 2 years and colonoscopy/sigmoidoscopy as a confirmatory test. Methods: We conducted a survey in patients visiting the primary care unit in the months of January and March 2024 in three distinct settings (Rural, Suburban, and Urban) aiming to estimate acceptance, knowledge, and preferences regarding FT and colonoscopy. Patients aged 50-74 were invited to join this study, excluding those with a history of CRC, and we used the integrated digital charting platform to set demographic variables. At the end of the survey, participants were invited to undergo CRC screening. Those who refuse to screen would select the main reason. Results: A total of 1,031 individuals responded the survey, which 52% were females and the median age was 62 years. A total of 763 (74%) accepted to undergo CRC screening with an overall preference for FT (72%) compared to colonoscopy (53,5%). FT acceptance remained somewhat constant in both gender subgroups (70-75%), and a lower colonoscopy acceptance in the male subgroup (46%). In the subdivided geographic setting groups, the rural population (12%) had the lowest knowledge score and the lowest overall acceptance rate (65%), ranking “No symptoms” as the main reason for not screening. The suburban and urban subgroups showed an equivalent overall acceptance rate (74-75%), ranking “Busy schedule” and “Healthy lifestyle” as the main reasons for not screening. Conclusions: Data suggests that an effective CRC screening depends on multiple factors. While literature sustains the weight of cost and long waiting times, this study contributes adding a new, more granular perspective. Efforts in patient education, and clarification of misconceptions and anxieties could prove to be an important step in the right direction. A closer contact between patient and healthcare provider could make the difference between screening or not. A leave of absence or mailed FT might be of great benefit for those with a busy schedule, while interaction with CRC survivors seems to drastically increase colonoscopy acceptance, an important intervention that should be encouraged and widespread. Although this study has its limitations due to sample size and geographic characteristics, it lays down a new layer in understanding the individuals and planning actions to prevent the advance of CRC in LMIC.
Validating process mining in pediatric oncology: Demonstrating protocol adherence and variability in neuroblastoma treatment.
Authors: Astrid van Barneveld, Matthijs Berkhout, Max Van Noesel, Patrick Kemmeren, Lieve Tytgat
Journal: Journal of Clinical Oncology (2024)

166 Background: Neuroblastoma is the most common extracranial tumor in children. The mortality rate for patients with metastatic disease is over 50%. In the Netherlands, 30 new patients are diagnosed annually. Current clinical treatment guidelines are complex and include multiple treatment arms consisting of chemotherapy, surgery, radiotherapy, and immunotherapy (IT). Although poor patient health and complications are known to cause adaptations to the otherwise standardized treatment regimen, the extent to which these variations occur is unknown. This study aimed to validate the use of process mining, a data-driven technique, to retrospectively examine protocol adherence and variability within current clinical guidelines based upon the GPOH-DCOG NBL2009 neuroblastoma treatment protocol. Methods: Data was extracted from electronic health records, as well as laboratory, pathology, and pharmaceutical databases, to create individual event logs for each patient. Process mining was performed using a fuzzy mining algorithm. The treatment courses for all neuroblastoma patients were mapped. Commonalities and variations were highlighted, and the throughput time for key treatment phases was calculated. Subsequently, conformance with protocol was determined. Results: Analysis of 70 patients treated between 2018-2022 showed 62 distinct treatment processes, revealing significant variations in patient care. Patients with high-risk disease showed the least variation (n=47, 42 variants). Notably, 17 variants were identified among 18 patients who died, indicating a highly personalized approach in the advanced stages of the disease. Subgroup analysis of 17 high-risk patients who received IT consisting of alternating cycles of anti-GD2 antibody and retinoic acid showed 6 variants. 12/17 patients (70.6%) completed the full IT regimen. Other treatment adjustments included shortened anti-GD2 infusions for two patients (5 and 8 days versus the prescribed 10 days, respectively), potentially indicating treatment toxicity. One patient received a 15-day infusion, exceeding the prescribed limit of 11 days. The recorded interval between the administration of anti-GD2 and retinoic acid was a median 5.5 hours (range: 60 seconds – 6.4 days), deviating from the prescribed interval of 24 hours and warranting further investigation. Conclusions: Process mining is a valuable tool for analyzing protocol performance and adherence in neuroblastoma treatment. Despite standardized treatment protocols, significant heterogeneity was observed in the treatment of neuroblastoma patients, especially those with poor prognosis. Throughput time analysis revealed variabilities in the IT regimen that warrant further investigation. This study underscores the potential of data-driven approaches to optimize treatment protocols and support evidence-based practices in clinical oncology.
CORRECT-MRD I: A clinical validation study to predict recurrence in stage II-III colorectal cancer (CRC) using a bespoke circulating tumor DNA (ctDNA) assay to detect molecular residual disease (MRD).
Authors: Yuichiro Tsukada, Tamotsu Sagawa, Gopalakrishnan Srinivasan, Ayala Hubert, Ofer Purim, Valeriya Semenisty, Nangi Lo, Giuseppe Mondello, Antonio Cubillo Gracian, Tara Marti, Somasundaram Subramaniam, Melanie R. Palomares, Frederick Baehner, Floris A de Jong, David James Kerr, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2024)

TPS98 Background: Despite standard of care management with surgery ± adjuvant chemotherapy treatment (ACT), &gt;30% of patients (pts) with resectable CRC recur. The presence of ctDNA in plasma after resection and after ACT, has been shown to be a strong prognostic factor for the risk of recurrence, suggesting that the presence of ctDNA in blood is molecular evidence of residual disease. As such, ctDNA analysis may enable post-surgical risk stratification for ACT decision-making, as well as detection of molecular recurrence during surveillance and subsequent early intervention. The CORRECT-I study aims to validate the association of post-definitive therapy and pre-recurrence follow-up ctDNA positivity with recurrence-free interval (RFI) in pts who have undergone complete surgical resection for stage II or III CRC. Methods: This study is a prospective, observational, multicenter study, which is open in Israel, Italy, Japan, Spain, and the UK. Pts must have pathologically confirmed stage II or III CRC, have undergone complete surgical resection, and have tissue available from the primary resection. Pts may not have started ACT prior to baseline blood draw post-surgery. Pts are asked to provide serial whole blood specimens for ctDNA analysis at a) post-surgical baseline, b) pre-recurrence follow-up visits (max 15 blood draws over max 5 years), and c) clinical recurrence. ctDNA will be analyzed with an NGS-based tumor-informed MRD assay that identifies somatic genomic alterations from DNA derived from the patient’s tumor tissue and detects a selected subset of tumor-specific (bespoke) ctDNA in their blood. The primary objective of this study is to validate the association of post-definitive therapy and serial pre-recurrence follow-up ctDNA positivity with RFI, using a Cox proportional hazards regression analysis. Further objectives include the assessment of sensitivity and specificity of the ctDNA assay, the association between ctDNA at individual timepoints and RFI, ctDNA dynamics and RFI, and the time from ctDNA positivity to clinical recurrence. A multivariable model, including ctDNA, clinicopathological risk features, serial serum CEA assessments, and recurrence risk as determined by the Oncotype Colon Recurrence Score will be fit with RFI as endpoint. The primary analysis will be conducted when ≥30 histologic and/or radiographic confirmed cases of clinical recurrence have been observed. As of April 2, 2024, 158 pts of 400 have been enrolled.
A single-arm, exploratory study of disitamab vedotin (DV) combined with camrelizumab and platinum-based chemotherapy as first-line treatment in patients with HER2 expressing locally advanced or metastatic esophageal squamous cell carcinoma (ESCC).
Authors: Meihong Wu, Yingyi Zhang, Dan Feng, Bin Wang, Wei Wang, Tianran Chen, Anjing Zhao, Meng Xu, Linli Zhang, Xianbao Zhan
Journal: Journal of Clinical Oncology (2024)

TPS217 Background: Esophageal cancer (EC) is one of the most common cancers worldwide with esophageal squamous cell carcinoma (ESCC) being the predominant histological subtype. PD-1 blockades combined with chemotherapy are now standard-of-care in first-line setting for patients with ESCC. HER2 expression, prevalent in an estimated 7.6% to 28.5% of ESCC cases, correlates with diminished overall survival, suggesting HER2-targeted therapy as a potential novel approach. To our knowledge, there is currently no clinical trial regarding anti-HER2 therapy in ESCC. Clinical evidence has suggested the potential synergistic anti-tumor effect of Disitamab Vedotin (DV) with PD-1 inhibitors in HER2-expressing gastric or gastroesophageal junction (G/GEJ) cancers. This single-arm, exploratory study aimed to evaluate the safety and preliminary anti-tumor activity of DV combined with camrelizumab and platinum-based chemotherapy in ESCC. Methods: This is a single-arm, exploratory study (NCT06055153). Approximately 20 patients will be enrolled in this study, phase 1 will initiate with a 3+3 dose-escalation scheme (2.5mg/kg to 2.0mg/kg) to identify dose-limiting toxicities (DLTs) and establish a safe dosage of DV. The expansion cohort will subsequently evaluate this dose for both efficacy and safety. The study population will included both male and female patients over the age of 18 with histologically confirmed ESCC, and locally advanced unresectable, recurrent unresectable or metastatic EC verified by imaging examination. This group also includes those patients who have experienced relapse or progression more than six months post the conclusion of last therapeutic regimen. Required HER2 expression levels in tumor specimens range from IHC 1+ to 3+. According to RECIST v1.1, participants must have at least one measurable lesion, an ECOG performance status of 0 or 1, and a minimum expected survival of 12 weeks with suitable organ function. Treatment protocol includes intravenous administration of DV (either 2.5 mg/kg or 2.0 mg/kg on day 1), Camrelizumab (200 mg on day 1), and Cisplatin (75mg/m2) or Nedaplatin (75mg/m2) on a 21-day cycle, continued until disease progression or the advent of unacceptable toxicity. The primary outcomes for evaluation are DLT for safety and the objective response rate (ORR) for efficacy. Adverse events will be monitored in accordance with the CTCAE 5.0 criteria. Secondary endpoints encompass progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR), and time to response (TTR). Clinical trial information: NCT06055153 .
Identifying risk factors associated with self-reported lower quality of life (QoL) in individuals with PTEN hamartoma tumor syndrome.
Authors: Terralyn Schmidt, Kristin Anthony, Nicholas Gorman, Amy George, Claudio Ales
Journal: Journal of Clinical Oncology (2024)

194 Background: PTEN Hamartoma Tumor Syndrome (PHTS) is a multisystem disorder that affects various organs and systems in the body, presenting with a range of clinical manifestations. Individuals with PHTS face elevated risks of cancer and neurological symptoms, along with significant physical and psychological challenges, which underscores the need for ongoing research and the development of effective management strategies. The purpose of this study is to identify risk factors that are associated with a lower self-reported quality of life in individuals with PHTS using quantitative data from the PTEN Hamartoma Tumor Syndrome Foundation's patient registry surveys. Methods: Spearman correlation analysis of survey answers from 232 registry members in the foundation revealed negative correlations between quality of life and clinical features such as autism spectrum disorder (-.20**) and cancer diagnoses (-.21**). Results: This suggests that the more severe and penetrant cases of PHTS on the spectrum of variability face challenges that negatively impact quality of life. Additionally, 72.6% of participants reported that reducing cancer risk is a top priority. Conclusions: The findings highlight the need for healthcare providers to anticipate the need for extra care and psychosocial attention for individuals with PHTS who have an autism diagnosis, and to provide education and counseling about cancer prevention strategies to those with a heightened cancer risk. [Table: see text]
Assessing the efficacy and safety of a novel, registration-free, CT-guided percutaneous transthoracic needle biopsy navigation system (RC120): A multicenter, prospective, single-arm clinical trial.
Authors: Caicun Zhou, Lei Wang, Xuhong Min, Biao Song, Zheng Zhang, Bing Bo, Anwen Xiong, Lingyun Ye, Dacheng Xie, Juanjuan Li, Shanghu Wang, Yuan Li, Qilong Song, Zhaohua Wang, Mengjie Wang, Yanan Cao, Jian Liu, Bing Niu, Chunfu Fang, Shuting Shen
Journal: Journal of Clinical Oncology (2024)

197 Background: Current optical and electromagnetic navigation systems for CT-guided percutaneous transthoracic needle biopsies (PTNB) have limitations. They require surface markers on the patient and intraoperative registration. Specific patient positioning during biopsies is required. Our team developed a new navigation system that addresses these issues. It doesn’t rely on patient surface markers or intraoperative registration, and it provides more flexibility in patient positioning during biopsies. Our research evaluates the effectiveness and safety of this system. Methods: A single-arm prospective study was conducted, including participants aged 18-80 years prepared for percutaneous lung core biopsy at two clinical centers in China. The primary endpoint was the success rate of biopsies within 2 needle adjustments. The secondary endpoint was the success rate of biopsies within a single needle adjustment. Safety endpoints were defined by the occurrence of adverse events. The number of CT scans patients underwent during the procedure was used to assess radiation dosage. Follow-up was conducted on subsequent pathological and molecular diagnoses. Results: The study included 98 patients from two sites, with a median age of 64 years. Most participants were males, accounting for 72.45% (71 out of 98). The primary endpoint was achieved with a biopsy success rate of 98.98%, requiring a maximum of two needle adjustments. The secondary endpoint was met, demonstrating a biopsy success rate of 97.96% with a maximum of one needle adjustment. The overall success rate was 98.98%, with a 95% confidence interval (CI) of 94.45% to 99.97%, significantly exceeding the target value of 85% (P &lt; 0.0001). The median number of CT scans was 3, ranging from 3 to 12. The average duration of the procedure was 18.0 minutes. Regarding safety endpoints, the two most common adverse events were hemorrhage in the lesion (14 instances, 29.17%) and pneumothorax (8 instances, 16.67%). Other adverse events included elevated blood pressure (5 instances, 10.42%), hemoptysis (4 instances, 8.33%), and other common adverse events such as cough, constipation, anemia, and bloody sputum, each occurring twice. There were 9 other less common adverse events, each occurring once. These adverse events are common in PTNB and can be attributed to the puncture operation itself, not our navigation system. Conclusions: Our new registration-free navigation system proved to be an effective, efficient, safe, and well-utilized system for assisting percutaneous lung biopsies in clinical practice. Clinical trial information: ChiCTR2300072197 .