tbuckley/cabot-search huggingface dataset:
From vision to text: A comprehensive review of natural image captioning in medical diagnosis and radiology report generation
Authors: Gabriel Reale-Nosei, Elvira Amador-Domínguez, Emilio Serrano
Journal: Medical Image Analysis (2024)

Natural Image Captioning (NIC) is an interdisciplinary research area that lies within the intersection of Computer Vision (CV) and Natural Language Processing (NLP). Several works have been presented on the subject, ranging from the early template-based approaches to the more recent deep learning-based methods. This paper conducts a survey in the area of NIC, especially focusing on its applications for Medical Image Captioning (MIC) and Diagnostic Captioning (DC) in the field of radiology. A review of the state-of-the-art is conducted summarizing key research works in NIC and DC to provide a wide overview on the subject. These works include existing NIC and MIC models, datasets, evaluation metrics, and previous reviews in the specialized literature. The revised work is thoroughly analyzed and discussed, highlighting the limitations of existing approaches and their potential implications in real clinical practice. Similarly, future potential research lines are outlined on the basis of the detected limitations.
A phase I/II study of enzalutamide in combination with indomethacin in men with castration-resistant prostate cancer (CRPC).
Authors: Ryan Leibrandt, Ayman Teeham Ullah, Rashmi Verma, Allen Gao, Primo N. Lara, Chong-xian Pan, Mamta Parikh
Journal: Journal of Clinical Oncology (2024)

e17027 Background: Metastatic castration resistant prostate cancer (mCRPC) remains an incurable disease despite recent advances in therapy. In patients (pts) receiving the second-generation androgen receptor antagonist enzalutamide (enza), primary or adaptive resistance can occur due to upregulation of the steroidogenesis pathway, including aldo-keto reductase 1C3 (AKR1C3), which can also upregulate intratumoral androgen synthesis. Indomethacin, a non-steroidal anti-inflammatory drug and selective inhibitor of AKR1C3, demonstrates synergistic activity when combined with enza against enza-resistant CRPC in vitro and in vivo. We thus sought to study this combination in a clinical trial. Methods: This investigator-initiated Phase I/II trial enrolled pts with enza-naive mCRPC on androgen deprivation therapy. Prior abiraterone was allowed. Pts must have adequate organ function and ECOG performance status 0-2. In the phase I lead-in, a 3+3 dose de-escalation design was used to identify the recommended Phase II dose (RP2D) of indomethacin in combination with enza 160 mg oral (PO) once daily, after which a Phase II expansion proceeded. Pts continued treatment until disease progression or unacceptable toxicity. Co-primary endpoints were safety and PSA response, defined as 50% or more reduction from baseline. Secondary endpoints included overall response as determined by Prostate Cancer Working Group 2 criteria (PCWG2). Results: From 2017 - 2022, 26 pts were enrolled, with a median age of 71 (range 50-88), primarily white (n=16, 62%), median baseline PSA 19.45 (range 1.5-210), ECOG 1 (n=12, 46%), and most received prior abiraterone (n=24, 92%). In 6 pts enrolled to the phase I cohort, there were no grade 3 adverse events (AEs); RP2D of indomethacin was 50mg PO twice daily. All 26 pts were evaluable for safety and efficacy. Most common treatment-related AEs (n; %) were nausea (12; 46%), fatigue (11; 42%), diarrhea (8; 31%), hypertension (7; 27%), anorexia (6; 23%). Most common ≥ grade 3 treatment-related AEs were acute kidney injury (3; 12%), hypertension (3; 12%), and anemia (2; 8%). PSA response was observed in 8 pts (31%). By PCWG2, 14 pts (54%) experienced stable disease, while 10 pts (38%) had progressive disease. Conclusions: The combination of enza and indomethacin was safe, clinically feasible, and had clinical activity in pts with abiraterone-pretreated mCRPC. Further correlative studies are needed to identify pts who may benefit from AKR1C3 inhibition. Clinical trial information: NCT02935205 .
Xerostomia and ocular dryness as predictors of PSA response to Lu177-PSMA-617 in metastatic castration resistant prostate cancer.
Authors: Rebecca Hassoun, Mark Tann, Justin Sims, Ashleigh Auxier, Sandra K. Althouse, Tareq Salous, Jennifer King, Nabil Adra
Journal: Journal of Clinical Oncology (2024)

e17028 Background: Prostate specific membrane antigen (PSMA) is highly expressed in salivary and lacrimal glands. Dry eyes and/or mouth can occur with Lu177-PSMA-617 (PSMA Lu177) therapy in metastatic castration resistant prostate cancer (mCRPC) pts. We evaluated the difference between the presence of dry mouth/eyes with PSA responses in pts with mCRPC treated with PSMA Lu177. Methods: The Indiana University Prostate Cancer database was queried for pts with mCRPC who were treated with PSMA Lu177. Toxicities were documented throughout the course of treatment. Association of xerostomia and ocular dryness with PSA30 and PSA50 response was compared using the Chi Square test, or Fisher’s Exact test, if more appropriate. Results: Between 6/21/22-11/14/23, 107 pts with mCRPC were treated with PSMA Lu177 with at least 2 doses. Median age was 73 (56, 90). 86 pts had metastatic disease in bone, 65 lymph nodes, 11 lungs, 6 liver, and 2 brain. 39 pts had 1 prior ARPI, 68 pts had ≥2 prior ARPI. 17 pts had no prior taxane regimen, 45 had 1 prior taxane, 33 had 2 prior taxanes and 12 had ≥3 taxane regimens. 19 pts had prior PARP inhibitor. Median follow-up from start of PSMA Lu177 treatment was 8.3 months (1.4-18.7). 40 (37%) pts experienced dry mouth, 7 (7%) pts experienced dry eyes, and 6 (6%) pts experienced both. 65 (61%) pts achieved PSA30 response. 57 (53%) pts achieved PSA 50 response. Conclusions: The presence of dry eyes and/or dry mouth in pts with mCRPC treated with PSMA Lu177 was associated with improved PSA response. [Table: see text]
Real-world treatment landscape in advanced metastatic castration resistant prostate cancer.
Authors: Elizabeth Sacchi, Hari Singhal, Jose Zamalloa, Beatriz Lopez Sanchez, Ke Zhang, Harish Parihar, Joel Greshock, Steven I Max
Journal: Journal of Clinical Oncology (2024)

e17032 Background: Despite a rapidly evolving treatment landscape in advanced prostate cancer (aPC) marked by recent emergence of therapies such as radioconjugates and PARP inhibitors, outcomes remain poor for many patients. Future care improvements will require innovative treatments and simplifying treatment planning. The goal of this study is to understand how the evolving treatment landscape has impacted care and outcomes in patients with aPC using real world (rw) data. This study evaluates outcomes of mCRPC patients who have advanced to a 3rd line of therapy (L3) with prior exposure to both an androgen receptor signaling inhibitor (ARSI) therapy and a taxane or platinum-based chemotherapy, in any aPC disease setting. Methods: mCRPC patients in the Flatiron Database who progressed to L3 with pre-L3 exposure to both an ARSI (abiraterone, enzalutamide, apalutamide, and darolutamide) and chemotherapy (cabazitaxel and docetaxel) were eligible for inclusion. Patients whose mCRPC diagnosis occurred between Dec 2010 and Nov 2023 were included. As the objective was to study the aPC treatment landscape, patients with prior exposure to therapies approved in the mCRPC disease setting such as radioconjugates, PARP inhibitors, radiation, investigational and palliative drugs were excluded. Outcomes were reported as median real-world overall survival (rwOS) indexed to start of L3 treatment, and median rw time to next treatment (rwTTNT) from the start of L3 to the beginning of L4 treatment. Results: 660 patients met all inclusion criteria and had at least one year of treatment history in the aPC disease setting. Median follow up time (indexed to L3 start) for all patients was 7.55 months. Median rwOS for all patients was 10.8 months (95% CI 9.9 - 12.2), while median rwTTNT was 5 months (95% CI 4.6 - 5.4). The most common L3 therapy class was chemotherapy, followed by ARSIs (Table). To aid in treatment planning strategies, drug sequence patterns were also analyzed. Frontline ARSIs were followed by second line chemotherapy for most of the patients (n = 349; 53%). Conclusions: Relatively short survival times and short durations on L3 therapies for aPC demonstrate a high unmet need, with therapeutic options dominated by ARSIs and chemotherapy. Recently approved radioconjugate therapies, like Pluvicto â, have reported median OS 15.3 months (Fallah, 2023) in prostate-specific membrane antigen (PSMA)-positive patients, which is greater than the 10.8 months observed in general mCRPC population analyzed in this study. These findings underscore the need to develop effective therapies and treatment strategies that are tailored for advanced prostate cancer. [Table: see text]
Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with advanced germ cell tumors.
Authors: Cherry Au, Mukti Patel, Alan Tan
Journal: Journal of Clinical Oncology (2024)

e17022 Background: Germ cell malignancies, commonly manifesting as testicular cancer, is one of the most common malignancies in men 15 to 45 years of age, with the incidence doubling over the past 40 years. When identified promptly and treated with a multidisciplinary approach, germ cell tumors have an excellent prognosis with cure rate &gt;90% and 5-year survival rate &gt;95%. Treatment involves radical orchiectomy for diagnostic and therapeutic purposes. Further management includes active surveillance, adjuvant chemotherapy, retroperitoneal lymph node dissection (RLND), and radiation therapy. While AFP, B-HCG, and LDH are good biomarkers, they are not sensitive or specific for detecting molecular residual disease (MRD). B-HCG is detected in &lt;30% of individuals with seminoma and B-HCG and AFP are detected in 50–60% of patients with non-seminomatous tumors. We describe the use of circulating tumor DNA (ctDNA) for detection of MRD in advanced germ cell malignancy, especially when baseline biomarkers are negative. Methods: This is a retrospective analysis of 20 patients with testicular cancer treated at Rush University Medical Center who monitored closely for MRD. Signatera (Natera Inc.), a personalized tumor-informed ctDNA assay, was utilized for detection and quantification of ctDNA in patients’ plasma samples, measured at MRD (1-12 weeks post-orchiectomy) and regular intervals thereafter, regardless of treatment modality. Event free survival (EFS) was determined, defined as the period from radical orchiectomy to date of radiographic progression of disease. Results: There was a total of 20 patients (35% seminoma, 65% non-seminoma) with 2 of the patients having extragonadal disease. The mean age was 32.2 years old with IQR (28-36). Post operatively, 20% underwent RLND, 10% were on surveillance, 53% received post-orchiectomy chemotherapy, 6.7% of patients underwent autologous stem cell transplant. The median follow up time is 1.14 years. Two patients had positive ctDNA despite negative baseline traditional biomarkers. There were 23.3% (7/30) of patients that had evidence of radiographic progression. Of the patients with progression, serial ctDNA monitoring had high rates of concordance (85%, 6/7) of ctDNA positivity with biomarker positivity and radiographic progression. Conclusions: Overall, ctDNA correlated with, and sometimes even preceded, traditional biomarkers and radiographic findings of disease progression. The ctDNA positivity of 2 patients in this cohort despite negative baseline AFP, B-HCG, and LDH, highlights the sensitivity and specificity of ctDNA for MRD compared to more traditional biomarkers. Serial monitoring of ctDNA offers valuable insights into germ cell tumor disease status, including presence of MRD, and there is a need for prospective studies to guide treatment escalation and de-escalation in germ cell tumors.
Association of baseline characteristics with adverse events (AEs) in the PROpel trial of olaparib (ola) plus abiraterone (abi) as first-line (1L) treatment for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Andrew J. Armstrong, Fred Saad, Mototsugu Oya, Neal D. Shore, Giuseppe Procopio, Karina Vianna, Niven Mehra, Mustafa Özgüroğlu, Craig Gedye, Emma Brown, Friederike Schlürmann, Ji Youl Lee, Jae Young Joung, Mikio Sugimoto, Urban Emmenegger, Emma Oscroft, Bob Shaw, Maria Winter, Christian Hosius, Noel Clarke
Journal: Journal of Clinical Oncology (2024)

e17030 Background: The PROpel trial (NCT03732820) met its primary endpoint and showed a statistically significant radiographic progression-free survival benefit (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54–0.81; P&lt;0.0001) with ola + abi vs placebo + abi in 1L mCRPC; whilst not statistically significant, overall survival (OS) was numerically prolonged (median 42.1 vs 34.7 months; HR 0.81, 95% CI 0.67–1.00; P=0.0544). To further inform clinical decision making, we provide exploratory post hoc analysis investigating the relationship between selected patient baseline characteristics and AEs for ola + abi. Methods: Anemia and venous thromboembolism events (VTEs) were identified as the only grade (Gr) ≥3 AEs or AEs of special interest reported in &gt;20 (&gt;5.0%) patients (pts) in the ola + abi arm (data cutoff 12 Oct 2022). Baseline characteristics were correlated with AEs using Cox regression by backwards elimination and analysis with AEs as dependent variables. Baseline characteristics assessed included: age (&lt;70 or ≥70 y), time since diagnosis (&lt;median or ≥median) , ECOG status (0 or 1), metastatic sites (visceral [yes or no], bone only [yes or no]), number of bone metastases (0, 1–4, 5‒9, 10‒20 or &gt;20), Gleason score (&lt;9 or 9–10), homologous recombination repair mutation status (HRRm, non-HRRm or unknown), race (white or non-white), prior docetaxel at metastatic hormone-sensitive prostate cancer (yes or no), pain (symptomatic or asymptomatic/mildly symptomatic), type of progression (prostate-specific antigen [PSA], radiographic or both), prior radiotherapy (yes or no) and albumin, creatinine, lactate dehydrogenase, alkaline phosphatase (ALP), hemoglobin (10&lt;12 or ≥12) and log PSA levels. Results: 398 pts received ola + abi. 64 (16.1%) had Gr ≥3 anemia and 34 (8.5%) a VTE. Baseline characteristics correlated significantly with increased risk of these AEs as shown (Table); characteristics not shown were not associated with AEs. Conclusions: These results provide insight into which baseline characteristics correlate with the risk of Gr ≥3 anemia. Pts with abnormal ALP, pre-existing anemia, ECOG PS 1 or age ≥70 years could be at higher risk and the development of Gr ≥3 anemia during treatment with ola + abi should be monitored. Clinical trial information: NCT03732820 . [Table: see text]
Pluvicto in the real world setting and timing to PSA50 as a predictive marker of treatment response.
Authors: Diana Vesselinovitch Maslov, Jacob New, Nikunj Patel, Michael P. Kosty, Munveer Singh Bhangoo
Journal: Journal of Clinical Oncology (2024)

e17026 Background: Prostate cancer, the leading cause of cancer mortality in men, has seen notable advances with PSMA-targeted therapies like 177Lu-PSMA-617 (Pluvicto), particularly in the metastatic castrate resistant setting. While prostate specific antigen (PSA) serves as a useful biomarker in newly diagnosed patients or those on androgen deprivation therapy, its efficacy in monitoring patients under PSMA-directed therapy remains unclear. This underscores a critical gap: the absence of established biomarkers for tracking response to these emerging treatments. Such biomarkers are vital for enhancing patient outcomes and evaluating therapeutic efficacy in early-stage trials. Methods: In this real-world, cohort study, we retrospectively followed adult patients with metastatic, castrate-resistant prostate cancer who are treated with Pluvicto at our institution beginning January 1, 2022 through November 2023. We assessed several potential biomarkers of response temporally throughout the treatment duration of Pluvicto, including serial blood counts, chemistry profiles, PSA levels, BMI, as well as their historical treatment patterns and demographics. All patients were heavily pre-treated prior to receiving Pluvicto. By using logistic regression, we identify factors associated with treatment response. Results: In our study, 21 patients qualified for enrolment. These patients received a median of 6 treatments prior to Pluvicto. Among them, 8 (38.1%) demonstrated at least PSA50 and showed response post-treatment. Of these, 6 (75%) completed all six Pluvicto treatments, while 2 (25%) are currently undergoing treatment. Remarkably, 7 of the 8 responders (87.5%) achieved a PSA50 response after two Pluvicto doses, with all 8 (100%) reaching this marker by the third dose. Furthermore, 6 of these 8 patients (75%) exhibited a PSA90 response after the fourth dose, though 2 patients (25%) did not attain PSA90. Conclusions: Our real-world study at Scripps Clinic provides valuable insights into the efficacy of Pluvicto in treating metastatic, castrate-resistant prostate cancer. Out of 21 patients treated with Pluvicto, 38.1% exhibited a significant PSA decrease during the treatment course. Notably, 87.5% of responders achieved PSA50 before their third dose, and all responders reached this benchmark prior to their fourth dose. These findings are crucial, especially as clinical trials are exploring Pluvicto's application in earlier treatment stages. Additionally, the use of PSA50 as a biomarker could guide clinicians in timely decision-making, allowing for quicker intervention and therapy adjustments, thus potentially mitigating disease progression. Updated data to be presented.
Outcome of prostate cancer with CNS metastasis: An analysis of SEER database (2010-2020).
Authors: Hyun Lee, Lin Mei, Bohdan Baralo, Andrew Stewart Poklepovic, Asit K. Paul
Journal: Journal of Clinical Oncology (2024)

e17037 Background: Brain metastasis from prostate cancer is rare, with an estimated incidence of &lt;1%, and its characteristics and outcomes are poorly understood. We report a contemporary analysis of outcomes in patients with CNS metastasis from prostate cancer in association with clinicopathological variables by utilizing the Survival, Epidemiology, and End Result (SEER) database with data from 2010 to 2020. Methods: From the SEER database, we identified histologically confirmed primary prostate cancers with any distant metastasis. Data for survival as well as multiple clinicopathological variables including age, race, prostate-specific antigen (PSA) level, Gleason score, prior radiotherapy, histology, and specific metastatic sites were extracted. Statistical analysis included chi-square. ANOVA, and Kaplan-Meier analysis for overall survival (OS) and disease-specific survival. Results: SEER database (2010-2020) identified 27,501 patients with metastatic prostate cancer, of which 27,118 (98.6%) were adenocarcinoma and 383 (1.4%) were prostate cancer with neuroendocrine features. Brain metastasis was seen in 282 (1.04%) and 15 (5.32%) patients in these histologic groups, respectively. Brain metastases were associated with worse prognosis with median OS of 14 months compared to bone-dominant and non-regional lymph node only diseases that showed median OS of 31 months and not reached, respectively (P &lt; 0.01). Within the population with brain metastases, outcome comparison based on age (&lt;65 vs. ≥65 years), ethnicity (Caucasian vs. African American vs. Hispanic), PSA (&lt;98 vs. ≥98 ng/ml), and Gleason score (&lt;9 vs. ≥9) showed no statistically significant difference (table). Presence of metastasis to other solid organs showed numerically worse outcome without statistical significance (OS: 26 months vs. 13 months, p=0.09). Significant OS difference was observed between the adenocarcinoma and neuroendocrine tumor within the brain metastasis subgroup (OS: 14 months vs. 6 months, p=0.03). Conclusions: CNS metastasis with prostate cancer carries worse prognosis in comparison to metastases to bone or distant lymph-nodes. Neuroendocrine tumor has higher risk of CNS metastasis although most of such cases are from adenocarcinoma due to its higher prevalence. OS analysis confirms worse outcome with neuroendocrine features compared to adenocarcinoma in CNS metastatic settings. [Table: see text]
Impact of treatment approaches in patients with advance penile cancer: An analysis from a nationwide study.
Authors: Mohammad Arfat Ganiyani, Atulya Aman Khosla, Shahzaib Ahmad, Karan Jatwani, Muni Rubens, Mukesh Roy, Bruno R. Bastos, Manuel Ozambela, Ahmed Eldefrawy, Murugesan Manoharan, Rohan Garje
Journal: Journal of Clinical Oncology (2024)

e17024 Background: Advance penile cancer (APC) is a rare and aggressive malignancy, characterized by the presence of metastases to lymph nodes and/or distant organs. The rarity of patients with APC poses challenges in conducting comprehensive studies, with most existing evidence being small-scale, retrospective analyses from single institutions. Additionally, the absence of large clinical trials limits the evidence to compare the survival rates with different treatment approaches in patients with APC. Methods: Our study utilized the national cancer database (NCDB) from 2004 to 2021. Our primary analytic cohort included patients diagnosed with advance penile cancer based on the AJCC 8 th classification (T4 or N3 or M1). Treatment modalities comprised perioperative systemic therapy combined with definitive surgery (PST), concurrent chemoradiation (CCR), surgery only (S), and systemic therapy only (ST). We used Kaplan-Meier analysis and the cox proportional regression to evaluate the impact of these treatment modalities on survival outcomes. Results: We identified 1342 patients with advance penile cancer. The median overall survival (OS) was 22.24 months (CI: 15.87-27.86, P &lt;0.001) for patients who received PST, 16.99 months (CI: 13.86-27.4) for those who underwent CCR, 11.99 months (CI: 9.2-15.01) for patients managed with surgery only, and 10.94 months (CI: 9.95-14.09) for those who received only ST. Our multivariate analysis revealed combining PST with surgery was associated with 27% reduction in the risk of death (HR: 0.73, P = 0.037) compared to systemic therapy after adjusting for age, race, tumor grade, comorbidities, distant metastasis and socioeconomic factors. Conclusions: Treatment approach with systemic therapy along with definitive penile surgery is associated with improved survival in patients with advanced penile cancer compared to other treatment modalities. Whenever feasible, this treatment approach should be considered as a management strategy in patients with APC. Further prospective studies are needed to validate our observations. [Table: see text]