Recurrent Setting Research Articles

Patterns of recurrence post prostatectomy in the PSMA era: What lessons can we take to daily practice from a high-volume nuclear medicine center?

e17013 Background: PSMA has deeply modified the treatment of prostate cancer, mainly in the biochemical recurrence setting, where the therapeutic plan may be changed in up to two thirds of cases. Unfortunately, this diagnostic tool is still not fully available in many places over the world. Growing evidence from high-volume nuclear medicine centers may guide the development of adapted treatment plans based on sites of relapse according to wide available clinical information. Methods: We retrospectively reviewed 648 Ga68-PSMA-PET-CT scans in the biochemical relapse setting in patients initially treated with prostatectomy. Results were classified either as negative or positive if abnormal SUV uptake was detected in the prostate bed, pelvis, or distant organs. We then classified the patients with positive tests based on sites of relapse according to serum PSA level. Results: Among the 648 analyzed patients, there were 60, 63, and 61 recurrences in prostate bed, pelvis, or distant organs, respectively. For those with serum PSA ≤ 1.0 ng/mL, there was a higher chance of locoregional failure (prostate bed or pelvis), with less than 20% presenting distant metastasis. When assessing patients with serum PSA 1.1-2.0 ng/mL, the rate of distant metastasis increased to 22.7%, while it was found in 40.7% of patients with serum PSA between 2 and 5 ng/mL. Conclusions: PSMA-PET-CT scan is clearly modifying the therapeutic landscape of prostate cancer in different scenarios. Although it is not available in many regions due to high financial costs and logistic barriers, the emerging evidence arising from specialized cancer centers matching the clinical information with tests results may help doctors to make better treatment decisions even without PSMA-PET-CT scans. [Table: see text]

Nostalgia for utopia in the films of Theo Angelopoulos

In this article, I examine the notion of nostalgia in relation to the films of Theo Angelopoulos. I argue that the image of nostalgia that pervades his films does not call for the restoration of the past but rather lends itself to a sense of hope which I approach as an image of utopia. Drawing a line of comparison between Angelopoulos and the Greek poet George Seferis (who had a pivotal role in the shaping of a modern Greek identity and whose images of melancholy were recurrent points of reference for the director), I claim that Angelopoulos’s films are haunted by an image of utopia which is registered as a possibility in the present rather than an abstract projection into the future. Unlike Seferis’s nostalgia which is directly related to the fate of the nation, in Angelopoulos’s work the past returns to foreshadow a utopia beyond the frame of the nation state and away from the figuration of a one-way future projected by the capitalist social relations of the present.

Pathways to single fatality and serious injury incidents in coal and metalliferous mining in NSW, Australia: Can we learn from multiple fatality incidents to prevent serious injury?

IntroductionConsiderable research has been undertaken to identify key causes of major incidents and disasters. Single fatalities and incidents resulting in serious injury have received less attention. These incidents, often referred to as occupational incidents, are investigated and prevented by identifying and managing risks related to proximate causes. The plateau in rates of fatalities and serious injuries suggests this approach is not working. AimTo examine if recurrent failures identified in major incidents are also present in other serious incidents and if regulatory failure and economic pressures are contributing factors. MethodsThe Ten pathways model was used to analyse 51 serious incidents investigated by the mining regulator in New South Wales (NSW), a major mining jurisdiction in Australia. The sample included incidents at 16 underground and nine surface coal mines, and four underground metalliferous mines. The primary data source was official regulatory investigation and prosecution summary reports published on the NSW mining regulator’s website. To understand the socio-economic context, the study used other sources. ResultsThe study confirmed the Ten pathways model identified the recurrent failure points for serious incidents. Seventy five percent of incidents exhibited at least five pattern-failures and 25% exhibited eight or more. The most common pattern-failures were engineering (98%); risk assessment failures (98%); and safety management system flaws such as inadequate statutory inspection, information transfer between shifts and levels, and an overreliance on personal safety routines to control risks (96%). Economic pressures and regulatory failure were identified in 71% and 55% of incidents respectively. ConclusionsWhen investigating incidents and designing injury prevention strategies regulators and mine operators should consider economic pressures arising from the broader socio-economic environment.

Identification of incidental brain tumors in prostate cancer patients via PSMA PET/CT.

Brain metastases are rare in patients with prostate cancer and portend poor outcome. Prostate-specific membrane antigen positron emission tomography (PSMA PET)/CT scans including the brain have identified incidental tumors. We sought to identify the incidental brain tumor detection rate of PSMA PET/CT performed at initial diagnosis or in the setting of biochemical recurrence. An institutional database was queried for patients who underwent 68Ga-PSMA-11 or 18F-DCFPyL (18F-piflufolastat) PET/CT imaging at an NCI-designated Comprehensive Cancer Center from 1/2018 to 12/2022. Imaging reports and clinical courses were reviewed to identify brain lesions and describe clinical and pathologic features. Two-thousand seven hundred and sixty-three patients underwent 3363 PSMA PET/CT scans in the absence of neurologic symptoms. Forty-four brain lesions were identified, including 33 PSMA-avid lesions: 10 intraparenchymal metastases (30%), 4 dural-based metastases (12%), 16 meningiomas (48%), 2 pituitary macroadenomas (6%), and 1 epidermal inclusion cyst (3%) (incidences of 0.36, 0.14, 0.58, 0.07, and 0.04%). The mean parenchymal metastasis diameter and mean SUVmax were 1.99cm (95%CI:1.25-2.73) and 4.49 (95%CI:2.41-6.57), respectively. At the time of parenchymal brain metastasis detection, 57% of patients had no concurrent extracranial disease, 14% had localized prostate disease only, and 29% had extracranial metastases. Seven of 8 patients with parenchymal brain metastases remain alive at a median 8.8 months follow-up. Prostate cancer brain metastases are rare, especially in the absence of widespread metastatic disease. Nevertheless, incidentally detected brain foci of PSMA uptake may represent previously unknown prostate cancer metastases, even in small lesions and in the absence of systemic disease.

Prognosis of patients undergoing catheter ablation of arrhythmic storm in patients with and without history of previous ICD interventions

Abstract Funding Acknowledgements Type of funding sources: None. Background Catheter ablation (CA) improves prognosis in patients with electrical storm (ES). However, its effectiveness and timing in patients with ventricular tachycardia and appropriate ICD therapies remain a matter of debate. Purpose Our aim was to investigate whether patients with history of discrete ventricular tachycardia episodes had different clinical features and outcome compared to patients with ES as first arrhythmic occurrence. Methods We enrolled 57 consecutive patients undergoing CA for ES and collected clinical, echocardiographic and electroanatomic mapping data. The primary end point was a composite of death from any cause and recurrences of sustained VT or ventricular fibrillation, appropriate ICD therapy, or ES. Results During a median follow up of 39 months, 28 patients (49%) met the primary end point of arrhythmic recurrence or death from any cause. There were no significant differences between clinical, electrocardiographic and echocardiographic parameters in the two groups. Regarding ICD therapies, patients with who met the primary end point had a higher number of ATP/shock episodes preceding the ES event: 15 (52%) vs 25 (89%), p=0.002. At Cox regression analysis, NIDCM, previous ATP and/or shock and ≥3 ATP were associated with arrhythmic recurrences and/or death. At multivariate analysis, ≥3 ATP was the only predictor that met statistical significance for the primary end point: HR was 30.41, CI 4.42 – 209.12, p=0.001. When dividing our population in patients and without ventricular arrhythmias (VAs) with appropriate device intervention before ES, thoses with VAs arrhythmias before ES had a higher percentage of presence of late potentials (80% vs 55%, p=0.041) and a greater unipolar scar (59.2±41.6 vs 30.2±21.6, p=0.001). At univariate analysis the presence of late potentials was associated with ventricular arrhythmias before ES (OR 3.33, CI 1.03-10.84, p=0.045). Conclusions CA in patients with a long arrhythmia history, recurrent ICD therapies and presence of late potentials at electroanatomic mapping, may yield worse outcomes and therefore our results support an early referral for CA of VT to improve prognosis in these subjects.

Causal inference with recurrent and competing events.

Many research questions concern treatment effects on outcomes that can recur several times in the same individual. For example, medical researchers are interested in treatment effects on hospitalizations in heart failure patients and sports injuries in athletes. Competing events, such as death, complicate causal inference in studies of recurrent events because once a competing event occurs, an individual cannot have more recurrent events. Several statistical estimands have been studied in recurrent event settings, with and without competing events. However, the causal interpretations of these estimands, and the conditions that are required to identify these estimands from observed data, have yet to be formalized. Here we use a formal framework for causal inference to formulate several causal estimands in recurrent event settings, with and without competing events. When competing events exist, we clarify when commonly used classical statistical estimands can be interpreted as causal quantities from the causal mediation literature, such as (controlled) direct effects and total effects. Furthermore, we show that recent results on interventionist mediation estimands allow us to define new causal estimands with recurrent and competing events that may be of particular clinical relevance in many subject matter settings. We use causal directed acyclic graphs and single world intervention graphs to illustrate how to reason about identification conditions for the various causal estimands based on subject matter knowledge. Furthermore, using results on counting processes, we show that our causal estimands and their identification conditions, which are articulated in discrete time, converge to classical continuous time counterparts in the limit of fine discretizations of time. We propose estimators and establish their consistency for the various identifying functionals. Finally, we use the proposed estimators to compute the effect of blood pressure lowering treatment on the recurrence of acute kidney injury using data from the Systolic Blood Pressure Intervention Trial.

P-034 ROBOTIC TAPP FOR RE-RECURRENT INGUINAL HERNIA: OUR EARLY EXPERIENCE

Abstract Aim Undoubtedly, the use of meshes has dramatically reduced recurrence rates following primary inguinal hernia repair; however, recurrences still occur with an incidence ranging from 0.5 to more than 20%, depending upon various factors that include hernia and patient characteristics, applied surgical technique and mesh characteristics, and surgeon's experience. The repair of a recurrent inguinal hernia sets a challenge for the hernia surgeon to prevent not only new recurrence, but also other complications. The challenge becomes even bigger in cases of re-recurrent inguinal hernias. The aim of this study is to present our early experience with the application of robotic system in the repair of re-recurrent inguinal hernias. Material and Methods From January to December 2022, five male patients with re-recurrent inguinal hernias (two patients with two previous repairs, one with three and one with four previous repairs) were operated in our Center using the robotic system Da Vinci X. In all cases robotic TAPP was performed and an extra-large (measuring 12×17cm) heavy-weight polypropylene mesh was implanted. Results All patients were discharged from the hospital on the first post-operative day. Their postoperative course has been uneventful, without any evidence of early or late complications, including recurrence. Conclusion Robotic-assisted repair of re-recurrent inguinal hernia is safe and feasible. The advantages of the surgical robotic system and more specifically, the magnified and three-dimensional view of the surgical field, as well as the increased maneuverability of the instruments permit the efficient treatment of this demanding subtype of inguinal hernias.

PD-0963 Lung re-irradiation with SBRT: outcomes and predictive factors of response in the recurrent setting

PD-0963 Lung re-irradiation with SBRT: outcomes and predictive factors of response in the recurrent setting

Recurrent dermatofibrosarcoma protuberans of the breast: A case report and review of literature

Dermatofibrosarcoma protuberans (DFSP) is a rare and low-grade sarcoma of fibroblast origin with a tendency to invade and recur locally. The most common sites of origin of DFSP are the head, neck, and extremities. However, DFSP breast has also been reported. It infiltrates surrounding subcutaneous tissue and fascia, with an incidence of <2% for lung metastases. Surgery being the main modality of the treatment, literature has shown that radiation therapy also plays an important role to improve local control in case of recurrent tumors. In this article, we will be discussing one such rare case of DFSP in a recurrent setting and the role of radiation therapy.

Targeted locus amplification to develop robust patient-specific assays for liquid biopsies in pediatric solid tumors.

Liquid biopsies combine minimally invasive sample collection with sensitive detection of residual disease. Pediatric malignancies harbor tumor-driving copy number alterations or fusion genes, rather than recurrent point mutations. These regions contain tumor-specific DNA breakpoint sequences. We investigated the feasibility to use these breakpoints to design patient-specific markers to detect tumor-derived cell-free DNA (cfDNA) in plasma from patients with pediatric solid tumors. Regions of interest (ROI) were identified through standard clinical diagnostic pipelines, using SNP array for CNAs, and FISH or RT-qPCR for fusion genes. Using targeted locus amplification (TLA) on tumor organoids grown from tumor material or targeted locus capture (TLC) on FFPE material, ROI-specific primers and probes were designed, which were used to design droplet digital PCR (ddPCR) assays. cfDNA from patient plasma at diagnosis and during therapy was analyzed. TLA was performed on material from 2 rhabdomyosarcoma, 1 Ewing sarcoma and 3 neuroblastoma. FFPE-TLC was performed on 8 neuroblastoma tumors. For all patients, at least one patient-specific ddPCR was successfully designed and in all diagnostic plasma samples the patient-specific markers were detected. In the rhabdomyosarcoma and Ewing sarcoma patients, all samples after start of therapy were negative. In neuroblastoma patients, presence of patient-specific markers in cfDNA tracked tumor burden, decreasing during induction therapy, disappearing at complete remission and re-appearing at relapse. We demonstrate the feasibility to determine tumor-specific breakpoints using TLA/TLC in different pediatric solid tumors and use these for analysis of cfDNA from plasma. Considering the high prevalence of CNAs and fusion genes in pediatric solid tumors, this approach holds great promise and deserves further study in a larger cohort with standardized plasma sampling protocols.

Comparing Genomic Landscapes of Oral and Cutaneous Squamous Cell Carcinoma of the Head and Neck: Quest for Novel Diagnostic Markers

Squamous cell carcinoma is the most common head and neck malignancy arising from the oral mucosa and the skin. The histologic and immunohistochemical features of oral squamous cell carcinoma (OSCC) and head and neck cutaneous squamous cell carcinoma (HNcSCC) are similar, making it difficult to identify the primary site in cases of metastases. With the advent of immunotherapy, reliable distinction of OSCC and HNcSCC at metastatic sites has important treatment and prognostic implications. Here, we investigate and compare the genomic landscape of OSCC and HNcSCC to identify diagnostically useful biomarkers. Whole-genome sequencing data from 57 OSCC and 41 HNcSCC patients were obtained for tumor and matched normal samples. Tumor mutation burden (TMB), Catalogue of Somatic Mutations in Cancer (COSMIC) mutational signatures, frequent chromosomal alterations, somatic single nucleotide, and copy number variations were analyzed. The median TMB of 3.75 in primary OSCC was significantly lower (P < .001) than that of 147.51 mutations/Mb in primary HNcSCC. The COSMIC mutation signatures were significantly different (P < .001) between OSCC and HNcSCC. OSCC showed COSMIC single-base substitution (SBS) mutation signature 1 and AID/APOBEC activity–associated signature 2 and/or 13. All except 1 HNcSCC from hair-bearing scalp showed UV damage–associated COSMIC SBS mutation signature 7. Both OSCC and HNcSCC demonstrated a predominance of tumor suppressor gene mutations, predominantly TP53. The most frequently mutated oncogenes were PIK3CA and MUC4 in OSCC and HNcSCC, respectively. The metastases of OSCC and HNcSCC demonstrated TMB and COSMIC SBS mutation signatures similar to their primary counterparts. The combination of high TMB and UV signature in a metastatic keratinizing squamous cell carcinoma suggests HNcSCC as the primary site and may also facilitate decisions regarding immunotherapy. HNcSCC and OSCC show distinct genomic profiles despite histologic and immunohistochemical similarities. Their genomic characteristics may underlie differences in behavior and guide treatment decisions in recurrent and metastatic settings.

Abstract CT198: Immunomodulatory effects of the ATR inhibitor ceralasertib in a window of opportunity biomarker trial in patients with head and neck squamous cell carcinoma

Abstract Head and neck squamous cell carcinoma (HNSCC) is frequently locally advanced, but has a high risk of recurrence after initial treatment. Immune checkpoint blockade with PD-1/PD-L1 inhibitors has revolutionized treatment in the recurrent setting, but resistance to these therapies frequently occurs. Combination of checkpoint inhibitors with the ATR inhibitor ceralasertib could provide an exciting opportunity, with encouraging clinical activity reported in melanoma and non-small cell lung cancer (Kwon et al. 2022; Kim et al. 2022; Besse et al. OA15.05 IASLC 2022 WCLC). This phase 1b trial provided a unique opportunity to understand the immunomodulatory impact of DNA Damage Response (DDR) inhibitors in a clinical setting. NCT03022409 is an open-label, randomized window of opportunity trial where patients with HNSCC were treated with either the PARP inhibitor olaparib (300mg BID) or ceralasertib (160mg BID) for 9-21 days, prior to definitive surgery (or on-treatment biopsy). 21 patients were randomized; n=12 to ceralasertib and n=9 to olaparib, and ceralasertib data will be presented here. Translational endpoints on frozen and fixed tumor biopsies included spatial pharmacokinetics, pharmacodynamic biomarkers, multiplexed fluorescence of tumor infiltrating immune cells and gene expression panels. Blood assessments included cytokine detection, immune cell phenotyping and gene expression. Primary endpoint analysis utilized a bespoke prognostic immune-focused gene signature and secondary endpoint an IHC immunoscore, both aimed to measure if tumors would shift from a ‘cold’ to ‘hot/active’ immune state. We observed an ‘on-drug’ selective suppression of proliferating Ki67+ T-cells (but not total T-cells) in the tumor microenvironment and periphery, followed by a repopulation and median rebound of 63.8% and 187.5% above baseline levels for peripheral helper (CD4+Ki67+; n=8) and cytotoxic (CD8+Ki67+; n=7) T-cells respectively, when ceralasertib dose stopped. IL-12 plasma cytokine levels dropped on ceralasertib treatment and returned to baseline levels ‘off-drug’ in 8/10 patients. Type-I interferon (IFN1) gene expression associated signatures were also upregulated in PBMCs, suggestive of an immune priming effect. 0/2 and 2/4 patients on ceralasertib met their primary and secondary endpoints respectively, however, interpretation is limited due to small numbers of evaluable patients. 1 patient had a grade 3 serious adverse event of chest pain in the ceralasertib arm. There were no unexpected safety findings for either drug and adverse events were generally low grade. The translational data has generated new insights into the immunomodulatory effect of ceralasertib. Further evaluation of the combination of ceralasertib with immune checkpoint blockade is warranted to explore this novel immune mechanism of action. Citation Format: Gemma N. Jones, Sonia Iyer, Marta Milo, Pei-Jen Lou, Melonie A. Nance, Carlos A. Gomez-Roca, Nathan Standifer, Paola Marco-Casanova, Shaan Gill, Michael Surace, Richard Bystry, Maria Alexandrova, Sophie Willis, Jaime Rodriguez-Canales, Andreas Dannhorn, Bienvenu Loembé, Alan Lau, Natalia Lukashchuk, Elizabeth A. Harrington, Elhan Sanai, Emma Dean, Umamaheswar Duvvuri. Immunomodulatory effects of the ATR inhibitor ceralasertib in a window of opportunity biomarker trial in patients with head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT198.

Extrauterine Mesonephric-like Carcinoma: A Comprehensive Single Institution Study of 33 Cases.

Extrauterine mesonephric-like carcinoma (ExUMLC) shares histologic, immunohistochemical (IHC), and molecular (MOL) features with endometrial mesonephric-like carcinoma (EnMLC). Its rarity and histologic overlap with Mullerian carcinomas contribute to underrecognition of ExUMLC. Aggressive behavior of EnMLC is well-documented; behavior of ExUMLC is yet to be characterized. This study presents the clinicopathologic, IHC, and MOL features of 33 ExUMLC identified over a 20-year time period (2002-2022) and compares the behavior of this cohort to more common upper gynecologic Mullerian carcinomas (low-grade endometrioid, LGEC; clear cell, CCC; high-grade serous, HGSC) and EnMLC diagnosed over the same time period. ExUMLC patients ranged from 37 to 74 years old (median=59y); 13 presented with advanced stage (FIGO III/IV) disease. Most ExUMLC had the characteristic mixture of architectural patterns and cytologic features, as previously described. Two ExUMLC had sarcomatous differentiation, 1 with heterologous rhabdomyosarcoma. Twenty-one ExUMLC (63%) had associated endometriosis, and 7 (21%) arose in a borderline tumor. In 14 (42%) cases, ExUMLC was part of a mixed carcinoma representing >50% of the tumor in 12. Twenty-six cases (79%) were incorrectly classified as follows: LGEC or HGEC (12); adenocarcinoma, not otherwise specified (3); HGSC (3); LGSC (2); mixed carcinoma (1); carcinosarcoma, Mullerian type (2); seromucinous carcinoma (1); transitional pattern of HGSC (1); and female adnexal tumor of probable Wolffian origin (1). Three patients had occult synchronous endometrial LGEC. IHC facilitated diagnosis in all cases with an expression of GATA-3 and/or TTF-1 in conjunction with decreased hormone receptor expression in most tumors. MOL testing (n=20) identified a variety of mutations, most frequently: KRAS (15); TP53 (4); SPOP (4); and PIK3CA (4). ExUMLC and CCC were more likely to be associated with endometriosis ( P <0.0001). ExUMLC and HGSC had more recurrences compared with CCC and LGEC ( P <0.0001). Histologic subtype was associated with longer disease-free survival for LGEC and CCC versus HGSC and ExUMLC ( P <0.001). ExUMLC trended towards a similar poor overall survival as HGSC compared with LGEC and CCC, and EnMLC trended to shorter survival compared with ExUMLC. Neither finding reached significance. No differences were seen between EnMLC and ExUMLC with respect to presenting stage or recurrence. Staging, histotype, and endometriosis were associated with disease-free survival, but on multivariate analysis, only stage remained as an independent predictor of outcome. The tendency of ExUMLC to present at an advanced stage and have distant recurrence points to more aggressive behavior compared with LGEC with which it is most frequently confused, underscoring the importance of an accurate diagnosis.

Abstract 79: Study of tumor microenvironment of ovarian clear cell carcinoma

Abstract Background: Clear cell ovarian carcinoma (CCOC) is characterized by a distinct histologic and molecular profile, and associated with very poor responses to standard treatment consisting of surgery and carboplatin:taxol chemotherapy. CCOC is chemo-resistant at the time of diagnosis and response to chemotherapy in the recurrent setting is less than 10%. Literature suggests a potential role for immune checkpoint inhibitors (ICI). However, only a subgroup of patients (20%) responds to ICI and little is known about the mechanisms of response and resistance to therapy. We postulate that a better understanding of CCOC tumor microenvironment (TME) could help predict patients’ response to ICI. Objective: The aim of this study is to investigate the relationship between TME immune infiltrate and clinical/outcome in 22 CCOC cases and identify subsets of CCOC who may benefit from immunotherapy. Material &amp; Methods: We characterized the immune landscape of 11 early and 11 advanced CCOC through a multiplex IHC Discovery Platform. Spatial single-cell proteomics analyses (cyclic-IF) and spatially-resolved RNAseq in 10 CCOC cases using an OC tissue microarray (TMA) were performed. Results were corelated with clinical and treatment outcome. Results: The percent of CD8, CD4, CD20 B cells Tregs, PD1, PDL1, monocytes and M2 monocytes and myeloid cells was significantly higher in advanced than early-stage cancers. Recurrent cancers were more immunosuppressive than cases with no recurrence. Tumor infiltrate was dense in 4 cases. Four patients with early-stage disease had a high number of CD8 naïve cells and experienced no recurrence. TME analysis of single case of advanced CCOC (before and after chemotherapy), revealed that hot tumor changed to cold tumor, suggesting the resistance to treatment. Cyclic IF analyses identified 3 tumor phenotype groups in a subset of 10 CCOC present on the OC TMA. The majority of CCOC had high expression of CCNE and high PI3K-AKT-mTor activity, low expression of hormone receptors (AR, ERa, PRg) and low cell cycle activity. Some tumors were also high for HER2. The stromal compartment was enriched in collagen VI, aSMA and PDGFR. The immune monitoring of several of those samples also revealed an immunosuppressive microenvironment, including the presence of M2 macrophages and expression of immune checkpoint proteins PD-L1 and B7-H4. Conclusion: Our study shows that various phenotypes of CCOC are defined by the cancer cell profiles and TME content. Importantly, a strong immunosuppressive microenvironment was detected in many samples, suggesting a potential response to ICI. Furthermore, we detected the expression of several therapeutic targets (MAPK, CCNE, PI3K-AKT-mTOR, HSP90, HER2), including oncogenic signaling pathways (RTK, MAPK). Different tumor phenotypes identified across our CCOC samples suggest that clear cell carcinoma could be subclassified into subtypes that should be treated differently. Citation Format: Tanja Pejovic, Sonali Joshi, Shawn Campbell, Dhanir Tailor, Joanna Pucilowska, Benjamin Tate, Pierre-Valérien Abate, Korina Mouzakitis, Marilyne Labrie, Elizabeth Munro, Jenna Emerson, Sanjay V. Malhotra. Study of tumor microenvironment of ovarian clear cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 79.

Abstract 2666: Preclinical investigations of concomitant tumor treating fields (TTFields) with cisplatin or paclitaxel for treatment of cervical cancer

Abstract Introduction: Cervical cancer is a serious health problem despite the fact it is highly preventable. Early-stage cervical cancer treatment often involves surgery; however advanced, recurrent, or metastatic cases require systemic therapy. Chemotherapy, mainly cisplatin, is the most commonly used systemic therapy for this cancer type. Combination regimens may be needed in the recurrent or metastatic settings, with first-line treatments including cisplatin with paclitaxel. TTFields are electric fields that disrupt cellular processes critical for cancer cell viability and tumor progression. Concomitant treatment with TTFields and cisplatin or paclitaxel has shown benefit in other tumor types. In the current in vitro study, we tested the effectiveness of TTFields for the treatment of cervical cancer, and the possible benefit of applying TTFields together with first-line treatments for cervical cancer. Methods: Human cervical cancer cell lines - squamous cell carcinoma Ca Ski and SiHa cells, and adenocarcinoma HeLa cells - were treated with TTFields (72 h, 1 V/cm RMS) at frequencies of 100 to 400 kHz, and tested for cell count. For examining the efficacy of TTFields concomitant with cisplatin or paclitaxel, various doses of the drugs were applied together with TTFields (200 kHz), followed by measurements of cell count, colony formation, and apoptosis. Overall effect was defined as the product of percent reductions in cell count and colony formation. Results: TTFields treatment reduced cell count in all tested cervical cancer cell lines. 200 kHz were found to be effective and were used throughout the experiments. Dose response effects were seen with cisplatin or paclitaxel, and were augmented when TTFields were co-applied to the cells. Conclusions: These preclinical data suggest that TTFields may be an effective treatment against cervical cancer, and that applying them concomitantly with first-line treatment for this malignancy may provide enhanced effectiveness. Citation Format: Roni Frechtel-Gerzi, Daria Gerasimova, Einav Zeevi, Inbar Schlachet-Drukerman, Helena Mumblat, Antonia Martinez-Conde, Eyal Dor-On, Itai Tzchori, Adi Haber, Moshe Giladi, Uri Weinberg, Yoram Palti, Greg Palmer, Angeles A. Secord. Preclinical investigations of concomitant tumor treating fields (TTFields) with cisplatin or paclitaxel for treatment of cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2666.

LBA02-12 IS LEARNING CURVE IMPORTANT WHILE PERFORMING PSMA-PET? ANALYSIS OF DETECTION RATE ACCORDING TO GLEASON SCORE AND PSA LEVEL IN TWO TIMEFRAMES AT A BRAZILIAN HIGH-VOLUME CENTER

You have accessJournal of UrologyCME1 Apr 2023LBA02-12 IS LEARNING CURVE IMPORTANT WHILE PERFORMING PSMA-PET? ANALYSIS OF DETECTION RATE ACCORDING TO GLEASON SCORE AND PSA LEVEL IN TWO TIMEFRAMES AT A BRAZILIAN HIGH-VOLUME CENTER Paulo Lages, Michelle Barbosa, Paulo Bergerot, Luciana Lages, Luciano Prado, Leonardo Prado, Pamela Muniz, Mariane Fontes, Marcella Prado, and Daniel Almeida Paulo LagesPaulo Lages More articles by this author , Michelle BarbosaMichelle Barbosa More articles by this author , Paulo BergerotPaulo Bergerot More articles by this author , Luciana LagesLuciana Lages More articles by this author , Luciano PradoLuciano Prado More articles by this author , Leonardo PradoLeonardo Prado More articles by this author , Pamela MunizPamela Muniz More articles by this author , Mariane FontesMariane Fontes More articles by this author , Marcella PradoMarcella Prado More articles by this author , and Daniel AlmeidaDaniel Almeida More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003361.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: PSMA PET/CT scan (68Ga-PSMA PET/CT) has emerged as a highly accurate method for assessing disease staging in patients with newly diagnosed localized high-risk prostate cancer and for recurrent disease. This has resulted in treatment plan modification in up to two-thirds of patients. PSMA PET/CT is commercially available in Brazil for a decade and growing experience with this test has led to more precise results over the years. METHODS: We retrospectively reviewed the results of PSMA PET/CT scans performed on patients at all disease stages in a single institution in Brasilia from 2015-2018 and 2021-2022. The results were correlated with available clinicopathological information in patients with recurrent disease in two separated timeframes. RESULTS: From 2015-2019, 351 exams were performed, with 303 in the setting of recurrent disease. From 2021-2022, 297 tests were executed with 283 in the recurrent disease setting. Clinicopathological information was available for 648 patients, with 586 patients in the setting of recurrent disease after first line treatment. CONCLUSIONS: There was a clinically relevant increase in the detection rate for patients with PSA ≤ 0.5 ng/mL and Gleason score ≤3+4, possibly as a result of the learning curve for this challenging scenario. However, we found a similar detection rate among other clinicopathological characteristics. Our data supports the need for ongoing training for the analysis of PSMA PET/CT results. Source of Funding: The authors © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1191 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paulo Lages More articles by this author Michelle Barbosa More articles by this author Paulo Bergerot More articles by this author Luciana Lages More articles by this author Luciano Prado More articles by this author Leonardo Prado More articles by this author Pamela Muniz More articles by this author Mariane Fontes More articles by this author Marcella Prado More articles by this author Daniel Almeida More articles by this author Expand All Advertisement PDF downloadLoading ...

Topological-numerical analysis of a two-dimensional discrete neuron model.

We conduct computer-assisted analysis of a two-dimensional model of a neuron introduced by Chialvo in 1995 [Chaos, Solitons Fractals 5, 461-479]. We apply the method of rigorous analysis of global dynamics based on a set-oriented topological approach, introduced by Arai et al. in 2009 [SIAM J. Appl. Dyn. Syst. 8, 757-789] and improved and expanded afterward. Additionally, we introduce a new algorithm to analyze the return times inside a chain recurrent set. Based on this analysis, together with the information on the size of the chain recurrent set, we develop a new method that allows one to determine subsets of parameters for which chaotic dynamics may appear. This approach can be applied to a variety of dynamical systems, and we discuss some of its practical aspects.

Particle Reirradiation of Malignant Epithelial and Neuroectodermal Sinonasal Tumors: A Case Series from CNAO

Sinonasal cancers (SNCs) are rare and heterogeneous in histology and biological behavior. The prognosis is generally unfavorable, especially in inoperable cases. In recent years, for some histologies, such as undifferentiated sinonasal carcinoma (SNUC), multimodal treatment with a combination of induction chemotherapy, surgery, and chemo/radiotherapy (RT) has improved the prognosis. Nevertheless, still about half of the patients treated incur a recurrence, in most of the cases at the local site. Surgery with and without RT is usually the treatment choice in cases of recurrence after previous RT in combination with systemic therapy or RT in a histology-driven fashion. In the case of inoperable disease or contraindications to surgery, RT is still a valid treatment option. In this context, hadron therapy with protons (PT) or carbon ions (CIRT) is often preferred due to the physical and biological characteristics of charged particles, allowing the administration of high doses to the tumor target while sparing the surrounding healthy tissues and potentially limiting the side effects due to the high cumulative dose. In the absence of a standard of care for the recurrent setting, we aimed to investigate the role of re-RT with PT or CIRT. We retrospectively analysed 15 patients with recurrent, previously irradiated, SNCs treated at our institution between 2013 and 2020. Local control (LC) and overall survival (OS) were estimated by the Kaplan-Meier method. Acute and late toxicities were scored according to the National Cancer Institute's Common Terminology Criteria for Adverse Events CTCAE version 5.0. A total of 13 patients received CIRT and 2 patients received PT. The median re-RT dose was 54 GyRBE (range 45-64 GyRBE) delivered in 3 or 4 GyRBE/fr (fraction) for the CIRT, and 2 Gy RBE/fr for the PT schedule. LC was 44% at the 1-year follow-up and 35.2% at the 3-year follow-up. OS at 1 and 3 years were 92.9% and 38.2%, respectively. Fourteen patients developed G1-G2 acute toxicity (dermatitis and mucositis), and no patients developed G3-G5. Regarding late toxicity, 10 patients encountered at maximum G1-2 events, and 4 did not experience any toxicity. Only for one patient G3 late toxicity was reported (dysphagia requiring a percutaneous endoscopic gastrostomy).

R-PCR: Recurrent Point Cloud Registration Using High-Order Markov Decision

Despite the fact that point cloud registration under noisy conditions has recently begun to be tackled by several non-correspondence algorithms, they neither struggle to fuse the global features nor abandon early state estimation during the iterative alignment. To solve the problem, we propose a novel method named R-PCR (recurrent point cloud registration). R-PCR employs a lightweight cross-concatenation module and large receptive network to improve global feature performance. More importantly, it treats the point registration procedure as a high-order Markov decision process and introduces a recurrent neural network for end-to-end optimization. The experiments on indoor and outdoor benchmarks show that R-PCR outperforms state-of-the-art counterparts. The mean average error of rotation and translation of the aligned point cloud pairs are, respectively, reduced by 75% and 66% on the indoor benchmark (ScanObjectNN), and simultaneously by 50% and 37.5% on the outdoor benchmark (AirLoc).

Effect of bevacizumab in advanced low grade serous ovarian cancer: Data from the MITO 22 trial

ObjectiveThe aim of the present analysis was to explore the efficacy of Bevacizumab (Bev) on survival outcome in advanced low grade serous ovarian cancer (LGSOC) both in first line and in recurrent setting. MethodsIn retrospective observational multicenter study, we described the outcome of LGSOC patients enrolled in the MITO 22 study and treated with chemotherapy (CT) with or without Bev. Patients receiving Bev in first-line or in recurrence were considered and compared with patients receiving CT alone (stage III and IV in first line; platinum based-CT in second line). Descriptive and survival analyses were performed for each group. ResultsOut of 128 patients included in MITO 22, 46 LGSOC patients receiving Bev in first line setting or at the time of first recurrence were identified. In first line, 30 patients received Bev + CT and 65 CT alone and the median PFS were 47.86 months (95% CI: 31.48 - NR) and 22.63 months (95% CI 15–39.24) (p-value 0.0392), respectively.In the recurrent setting, 16 patients who received Bev + CT were compared to 33 women treated with platinum-based CT alone. Median PFS were 37.1 months (95% CI: 13.42–40.56) and 11.22 months (95% CI: 8.26–15.63) (p-value 0.013), respectively. ConclusionsOur study suggests that Bev might be effective in LGSOC both at diagnosis and at the time of relapse. These data warrants further studies.