tbuckley/cabot-search huggingface dataset:
CSIG-08. EXTRACELLULAR DOMAIN MUTATIONS IN EGFR RESULT IN A HYPERSENSITIVE RECEPTOR
Authors: Pim French, Maurice de Wit, Iris de Heer, Martin van Royen, Wies Vallentgoed, youri Hoogstrate, Peter Sillevis Smitt
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION The Epidermal Growth Factor Receptor (EGFR) is a driver gene that is amplified in more than half of all glioblastomas. After the initial high copy-number amplification, secondary missense mutations in the extracellular, ligand binding domain of EGFR can evolve. We here performed analysis on these mutations to better understand their function. METHODS Activation of EGFR-mutation constructs was measured by western blot and high-throughput quantitative image analysis using EGFR and phospho-EGFR specific antibodies. RESULTS Amphiregulin (AREG) is a low affinity EGFR ligand and was able to only marginally activate EGFRwt at high concentrations. In contrast however, AREG strongly activated all extracellular domain (ECD) mutation constructs (R108K, A289V and G598V). As expected, EGF-stimulation resulted in a strong activation in both EGFRwt and ECD mutation constructs. Further dose response analysis showed that in EGFRwt, all high affinity EGFR ligands (EGF, TGFa, HB-EGF and BTC) resulted in a strong activation and all low affinity ligands AREG, EREG and EPGN resulted in a markedly weaker activation. All ECD mutations however, showed strong activation towards all EGFR ligands, including the low affinity ligands (40%-80% of EGF stimulation). The constitutively active, ligand independent EGFRvIII mutation did not respond to any of the ligands and was mainly found to have an intracellular localization. Interestingly, the presence of ECD mutations and EGFRvIII are inversely correlated: in three large datasets (TCGA, Belob and Intellance 2), the majority of samples expressing EGFRvIII do not express additional ECD mutations and vice versa. ECD mutations likely affect stability of the tethered, inactive conformation thereby increasing exposure of the dimerization domain (II), resulting in increased ligand-sensitivity. CONCLUSION These experiments show that EGFR containing extracellular missense mutations render the receptor more sensitive to stimulation by low affinity ligands. Glioblastomas evolve to either become independent of ligand (EGFRvIII) or become ligand-hypersensitive (ECD mutations).
PDTM-15. EMBRYONIC STEM CELL SIGNATURE DRIVES ATYPICAL TERATOID/RHABDOID TUMOR DEVELOPMENT IN HUMAN PLURIPOTENT STEM CELL-DERIVED TUMOR MODEL
Authors: Yoshiki Arakawa, Yukinori Terada, Yohei Mineharu, Susumu Miyamoto, Yasuhiro Yamada
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Atypical teratoid/rhabdoid tumor (AT/RT), which harbors SMARCB1 mutation and exhibits a characteristic histology of rhabdoid cells, has a poor prognosis because of the lack of effective treatment. METHODS To investigate the pathogenesis of AT/RT, we establish human SMARCB1-deficient pluripotent stem cells (hPSCs). RESULTS Although neural progenitors have been suggested as being a cell-of-origin of AT/RT, SMARCB1-deficient hPSC-derived neural progenitor-like cells (NPLCs) give rise to mostly medulloblastoma-like tumors when transplanted into the mouse brain. In contrast, transplantation of SMARCB1-deficient hPSCs cause AT/RT-like tumor containing a large number of typical rhabdoid cells. hPSC-derived tumors exhibit activation of embryonic stem cell-like gene expression signature (ESC-like signature) compare with NPLC-derived tumors. Forced activation of ESC-like signature by expression of reprogramming factors confers rhabdoid histology in SMARCB1-deficient NPLC-derived tumors. Activation of ESC-like signature is associated with poor survival. Consistently, the activation of ESC-like signature is found in clinical specimens of AT/RT. Finally, we perform CRISPR/Cas9 knockout screening to inhibit activation of ESC-like signature in AT/RT. Our effort identifies candidate genes including RAD21 that encodes a key component within the cohesin complex. Notably, chemical inhibition of HDAC8 that indirectly targets the function of cohesin with simultaneous inhibition of EZH2 efficiently suppresses the activation of ESC-like signature and inhibits the growth of AT/RT cells both in vitro and in vivo. CONCLUSION SMARCB1-deficient hPSCs offer the first human model for AT/RT, which uncovers the unappreciated role of the activated ESC-like signature in worse prognosis and unique histology. We propose that ESC-like signature could be a crucial therapeutic target for AT/RT.
The MP0250-CP201 Mirror Study: A Phase 2 Study Update of MP0250 Plus Bortezomib and Dexamethasone in Relapse/Refractory Multiple Myeloma (RRMM) Patients Previously Exposed to Proteasome Inhibitors and Immunomodulatory Drugs
Authors: Norbert Grząśko, Stefan Knop, Hartmut Goldschmidt, Marc S Raab, Jan Dürig, Sara Bringhen, Mattia D'Agostino, Barbara Gamberi, Elena Rivolti, Angelo Vacca, Roberto Ria, Artur Jurczyszyn, Jorge Castellano Acosta, Doris Lang, Guy Lemaillet, Bansod Sudhir, Monika Szarejko
Journal: Blood (2019)
HOUT-29. THE INFLUENCE OF PSYCHIATRIC ILLNESS ON OUTCOME AND CANCER CARE RECEIVED IN PATIENTS WITH GLIOMAS
Authors: Palak Patel, Terry Li, Janice Chou, Amie Patel, Sylvia Crispino, Minerva Utate, Sylvia Kurz
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Data related to the prevalence of different psychiatric disorders and their impact on survival and compliance in patients with glioma is scarce and mostly anecdotal. We aimed to study the prevalence of psychiatric disorders in glioma patients and the possible influence on compliance with cancer care and outcome. METHODS We performed a retrospective, observational study and compared compliance with medical care and outcome in patients who had or did not have a psychiatric illness at time of diagnosis. Kaplan-Meier method was used to compare survival between groups. RESULTS We identified 22 subjects (M=13, F=9) with intracranial glioma with psychiatric diagnosis and 22 matched control subjects (M=13, F=9) without psychiatric illness. Psychiatric diagnoses included depression (12%), anxiety disorder (6%), Adjustment disorder &amp; substance use problems (2% each), bipolar disorder (1%) and panic attacks (1%). Psychiatric diagnoses were predating tumor diagnosis in 9/22 (41%) subjects and occurred around tumor diagnosis in 11/22 (50%) patients. The time of diagnosis with psychiatric illness was unknown in 2/22 (9%) of cases. Tumor diagnoses were glioblastoma in 50%, anaplastic astrocytoma in 9%, anaplastic oligodendroglioma in 13%, oligodendroglioma in 4%, and astrocytoma in 9% of cases. MedianOS was not reached for cases with psychiatric illness (not reached due to censoring) but was 4.2 years (95% CI 1.1 – 7.4) in controls (p=0.263). Subjects with psychiatric illness had an increased risk (OR 7.5, 95% CI 0.81 -68.8) of poor compliance with cancer care (medication, clinic and MRI follow-up compliance) compared to controls (p=0.046). CONCLUSION A variety of psychiatric conditions were observed in patients with glioma and presence of psychiatric illness may influence compliance with treatment and follow-up. Studies with larger population and longer follow-up are warranted to clarify true association between psychiatric conditions and compliance and survival.
Bacillus Calmette–Guérin strains with defined resistance mutations: a new tool for tuberculosis laboratory quality control
Authors: S.N. Danchuk, F. McIntosh, F.B. Jamieson, K. May, M.A. Behr
Journal: Clinical Microbiology and Infection (2019)

Laboratory quality control (QC) is essential to assess the reliability of tuberculosis diagnostic testing. To provide safe QC reagents for the detection of drug-resistant Mycobacterium tuberculosis, we generated antibiotic-resistant mycobacterial strains of attenuated virulence (M. bovis bacillus Calmette-Guérin (BCG)).Seven mono-resistant BCG strains were developed by introducing resistance-conferring mutations into wild-type BCG strains. Mutations were confirmed by dideoxynucleotide sequencing. Phenotypic resistance was quantified by microbroth dilution to determine the MIC90. The capacity of two commercial tests (GeneXpert TB/RIF and Genotype MTBDRplus) to detect resistance-conferring mutations was evaluated independently.Our panel included BCG strains with mutations in rpoB (S450L, I491F), katG (deletion at AA428), gyrA (D94G), rpsL (K43R) and Rv0678c (S63R). These mutations translated respectively into phenotypic resistance to rifampin (MIC ≥8 mg/L), isoniazid (MIC ≥8 mg/L), moxifloxacin (MIC 4 mg/L) and streptomycin (MIC ≥8 mg/L); the Rv0678c mutant showed decreased susceptibility to both clofazimine (MIC 4 mg/L) and bedaqualine (MIC 1 mg/L). GeneXpert (Cepheid) and Genotype MTBDRplus (Hain Lifesciences) both called the rpoB S450L strain rifampin-resistant and the I491F mutant rifampin-susceptible, as expected based on single nucleotide polymorphism positions. Likewise, MTBDRplus called the novel katG deletion mutant isoniazid susceptible despite phenotypic resistance.BCG strains engineered to be mono-resistant to anti-tuberculosis drugs can be used as safe QC reagents for tuberculosis diagnostics and drug susceptibility testing.
Impact of natural neuromedin‐B receptor variants on iron metabolism
Authors: Raffaela Rametta, Paola Dongiovanni, Guido A. Baselli, Serena Pelusi, Marica Meroni, Anna L. Fracanzani, Fabiana Busti, Annalisa Castagna, Stefania Scarlini, Elena Corradini, Antonello Pietrangelo, Domenico Girelli, Silvia Fargion, Luca Valenti
Journal: American Journal of Hematology (2019)

Abstract Iron overload heritability remains partly unexplained. By performing whole exome sequencing in three patients with a clinical phenotype of hemochromatosis not accounted by known genetic risk factors, we identified in all patients rare variants predicted to alter activity of Neuromedin‐B receptor (NMBR). Coding NMBR mutations were enriched in 129 patients with hereditary hemochromatosis or iron overload phenotype, as compared to ethnically matched controls, including 100 local healthy blood donors and 1000Genomes project participants (15.5% vs 5%, P = .0038 at burden test), and were associated with higher transferrin saturation in regular blood donors ( P = .04). Consistently, in 191 patients with nonalcoholic fatty liver, the most common low‐frequency p.L390 M variant was independently associated with higher ferritin ( P = .03). In 58 individuals, who underwent oral iron challenge, carriage of the p.L390 M variant was associated with higher transferrin saturation and lower hepcidin release. Furthermore, the circulating concentration of the natural NMBR ligand, Neuromedin‐B, was reduced in response to iron challenge. It was also decreased in individuals carrying the p.L390 M variant and with hemochromatosis in parallel with increased transferrin saturation. In mice, Nmbr was induced by chronic dietary iron overload in the liver, gut, pancreas, spleen, and skeletal muscle, while Nmb was downregulated in gut, pancreas and spleen. Finally, Nmb amplified holo‐transferrin dependent induction of hepcidin in primary mouse hepatocytes, which was associated with Jak2 induction and abolished by the NMBR antagonist PD168368. In conclusion, NMBR natural variants were enriched in patients with iron overload, and associated with facilitated iron absorption, possibly related to a defect of iron‐induced hepcidin release.
Association of High Body Mass Index with Response Outcomes in Patients with CML-CP Treated with Dasatinib Versus Imatinib in the First Line: Exploratory Post Hoc Analysis of the Phase 3 DASISION Trial
Authors: Massimo Breccia, Jorge E. Cortes, Neil P Shah, Giuseppe Saglio, Antonio Jiménez-Velasco, Philipp Le Coutre, Alexander Brun, Irene DeGutis, Sai Bathena, Oumar Sy, Elias Jabbour
Journal: Blood (2019)
Chitinase 3-like 1 Produced By Fibrocytes Promotes Myelofibrosis
Authors: Shoichiro Kato, Takaaki Maekawa, Hiraku Ogata, Yukiko Osawa, Kawasaki Kota, Kohei Takada, Takehiro Sone, Keita Saito, Takuya Izumi, Shigeki Nagao, Takano Kosuke, Yosuke Okada, Masahiro Teramoto, Noriaki Tachi, Toshikuni Kawamura, Toshikatsu Horiuchi, Ayako Kobayashi, Shinichi Kobayashi, Ken Sato, Kaori Endo-Umeda, Shigeyuki Uno, Soji Morishita, Marito Araki, Makoto Makishima, Norio Komatsu, Fumihiko Kimura
Journal: Blood (2019)
Adjunctive Antithrombotic Therapy for Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Replacement
Authors: Yuichi Saito, Tamim Nazif, Andreas Baumbach, Didier Tchétché, Azeem Latib, Ryan Kaple, John Forrest, Bernard Prendergast, Alexandra Lansky
Journal: JAMA Cardiology (2019)

Transcatheter aortic valve replacement (TAVR) is an established alternative to surgery for patients with severe symptomatic aortic stenosis. Adjunctive antithrombotic therapy used to mitigate thrombotic risks in patients undergoing TAVR must be balanced against bleeding complications, since both are associated with increased mortality.Stroke risk associated with TAVR is lower than that associated with surgical aortic valve replacement in recent trials including patients at intermediate or low risk, but it is constant beginning at the time of implant and accrues over time based on patient risk factors. Patients with aortic stenosis undergoing TAVR also have a sizable risk of life-threatening or major bleeding. Although dual antiplatelet therapy for 3 to 6 months after TAVR is the guideline-recommended regimen, this practice is not well supported by current evidence. In patients with no indication for oral anticoagulation, current registry-based evidence suggests that single antiplatelet therapy may be safer than dual antiplatelet therapy. Similarly, oral anticoagulation monotherapy appears superior to anticoagulation plus antiplatelet therapy in those where oral anticoagulant use is indicated. To date, no risk prediction models have been established to guide antithrombotic therapy.Despite the growing volume of TAVR procedures to treat patients with severe aortic stenosis, evidence for adjunctive antithrombotic therapy remains rather scarce. Ongoing clinical trials will provide better understanding to guide antithrombotic therapy.
Combined Retro- and Prospective Analysis of Adherence to Guidelines and Patient-Tailored Therapeutic Recommendations in Patients with Myelodysplastic Syndromes (MDS) at a Tertiary Care Centre
Authors: Annika Kasprzak, Kathrin Nachtkamp, Mustafa Kondakci, Thomas Schroeder, Guido Kobbe, Andrea Kündgen, Jennifer Kaivers, Christina Rautenberg, Rainer Haas, Norbert Gattermann, Nicolas Bonadies, Ulrich Germing
Journal: Blood (2019)
Prevention of cardiac allograft arteriosclerosis by protein tyrosine kinase inhibitor selective for platelet-derived growth factor receptor
Authors: R Sihvola, Petri Koskinen, M Myllarniemi, M Loubtchenkov, P Hayry, E Buchdunger, K Lemstrom
Journal: Circulation Research (1999)

Background—Increased immunoreactivity of platelet-derived growth factor (PDGF)-AA, -Rα, and -Rβ in intimal cells correlates with the development of cardiac allograft arteriosclerosis, a condition for which there is little or no current therapy. Therefore, we hypothesized that PDGF may have a rate-limiting role in the development of this disease. Methods and Results—The hypothesis was tested in a rat model of heterotopic cardiac and aortic allografts using dark agouti (AG-B4, RT1a) donors and Wistar-Furth (AG-B2, RT1u) recipients. The recipients received CGP 53716, a selective PDGF-R protein tyrosine kinase inhibitor, 50 mg · kg−1 · d−1, or vehicle for 60 days. Cardiac allograft recipients also received background cyclosporin A immunosuppression. Our results demonstrate that CGP 53716 significantly reduced the incidence and intensity of arteriosclerotic lesions in rat cardiac and aortic allograft recipients. When rat coronary smooth muscle cells were stimulated in vitro with PDGF-AA or -BB in the presence ...
Inhibition of the MiR-185-PAK6-Mediated Survival and Metabolic Pathways Selectively Targets Drug-Resistant CML Stem/Progenitor Cells
Authors: Andrew Wu, Katharina Rothe, Min Chen, Hanyang Lin, Artem Babaian, Ryan Yen, Donna L. Forrest, Xiaoyan Jiang
Journal: Blood (2019)
Disruption of the Akt-FoxO Axis As a Safeguard Mechanism for the Hematopoietic Stem Cell Compartment during Chronic Metabolic Stress
Authors: Vinothini Govindarajah, Jung-Mi Lee, Michael Solomon, Bryan Goddard, Ramesh C. Nayak, Jose A Cancelas, Damien Reynaud
Journal: Blood (2019)
Incidence of Invasive Fungal Infections in Acute Leukemia Patients Utilizing Micafungin Prophylaxis Compared to Second-Generation Azole Prophylaxis
Authors: Heather Morris, Meredith T. Moorman, Melissa C. Mackey, Harry P. Erba, Thomas W. LeBlanc, David A. Rizzieri, Ian Barak, Zhiguo Li, Tanya Zapolskaya
Journal: Blood (2019)
ACTR-37. ASSOCIATION BETWEEN MGMT PROMOTER METHYLATION SCORE AND SURVIVAL IN PATIENTS WITH GLIOBLASTOMA
Authors: Carlos Romo, Pavan Shah, Yuqing Sun, Xiaobu Ye, Stuart Grossman
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND MGMT promoter methylation is associated with longer survival in patients with high-grade gliomas who receive alkylating therapy. Methylation status is commonly determined by methylation-specific PCR and results are reported in two forms: a dichotomization of “present” or “not present,” and as a methylation score (MGMT/beta-actinx1000). The primary objective of this study is to determine the association between the degree of methylation and overall survival (OS) in newly diagnosed patients with glioblastoma. METHODS A retrospective IRB-approved study was conducted of 684 patients treated at Johns Hopkins from 2007–2015. Adults with a histologically confirmed glioblastoma treated with standard therapy were included in the analysis. OS was estimated from the date of diagnosis to time of death or last follow up using the Kaplan–Meier method. Cox regression model was used to assess possible positive association between MGMT score and OS. For purposes of this analysis IDH1-mutated patients were excluded. RESULTS In 100 evaluable patients, median age at diagnosis was 56 years [45–77]. Fifty-two patients were MGMT promoter methylated (score ≥2.00) and 48 were unmethylated. The median OS was 31 months in the methylated patients and 15 months in the unmethylated (p=0.0001). Methylated patients had MGMT scores ranging from 2.53-1278. The methylated scores were classified into 3 groups; #1: 0-25th percentile, #2: 25-75th percentiles, and #3: &gt;75th percentile. mOS was: 30.8 months for group 1 (n=13); 34.8 months for group 2 (n=27); and 20.9 months for group 3 (n=12) (p=0.19). Difference in mOS between groups 1 and 3 was not statistically significant (HR 0.819 [95% CI, 0.3–2.2], p=0.69). DISCUSSION The prognostic value of MGMT promoter methylation in patients with glioblastoma was replicated in our study sample. The degree of methylation reported as a score on routine testing does not appear to be directly related to OS in this patient population.
Functional rs4693608 SNP is Located into Strong Hpse Gene Intron Enhancer and Thereby Influences to the Ability of Nuclear Proteins Binding and Activity of This Enhancer in Broad Number of Hematological Cell Lines and ALL/AML Primary Samples
Authors: Olga Ostrovsky, Ania Hava Grushchenko Polaq, Katia Beider, Rita Mayorov, Avichai Shimoni, Israel Vlodavsky, Arnon Nagler
Journal: Blood (2016)
Spontaneous Post-Transplant Air-Leak Syndrome in Adult Patients Receiving Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Sheng-Hsuan Chien, Yao-Chung Liu, Nai-Wen Fan, Chia-Jen Liu, Tzeon-Jye Chiou, Cheng-Hwai Tzeng, Jyh-Pyng Gau, Jin-Hwang Liu
Journal: Blood (2016)
Mantle CELL Lymphoma (MCL) in Elderly Patients (PTs): The Experience in Real-Life of Rete Ematologica Laziale Linfomi (RELLI)
Authors: Alessandro Alessandro Andriani, Gabriella Tomei, Cristiano Tesei, Ombretta Annibali, Cristina Andrizzi, Fiammetta Natalino, Paola Anticoli Borza, Elisabetta Abruzzese, Elena Maiolo, Alice Di Rocco, Luigi Petrucci, Maria Cantonetti, Fioretta Palombi, Natalia Cenfra, Luigi Rigacci, Stefan Hohaus, Maurizio Martelli, N. Christina Cox
Journal: Blood (2019)
EPID-22. NEWLY-DIAGNOSED BRAIN TUMORS IN PEDIATRIC PATIENTS: EPIDEMIOLOGY IN THE UNITED STATES
Authors: Matthew Torre, Mustafa Ascha, Maya Harary, Timothy Smith, Ayal Aizer, Keith Ligon, David Reardon, Jill Barnholtz-Sloan, Bryan Iorgulescu
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION Herein we examine the epidemiology across all pediatric intracranial tumors in the U.S. METHODS Pediatric patients (&lt; 20yo) presenting between 2010–2015 with an intracranial tumor as the first evidence of cancer were queried from the National Cancer Database, which comprises &gt;70% of cancers newly-diagnosed in the U.S. Tumor types were classified by WHO2016 ICD-O3. RESULTS 14,952 pediatric patients without a history of cancer presented with intracranial tumors between 2010–2015. Across all ages, these were comprised of 1) 22% diffuse astrocytic and oligodendroglial (n=3,328), 2) 17% sellar region (n=2,530), 3) 16% other astrocytic (n=2,378, 2,131 were pilocytic and pilomyxoid), 4) 13% embryonal (n=1,896; 1,092 were classic histology medulloblastomas), 5) 7% neuronal and mixed neuronal-glial (n=981), 6) 5% ependymal (n=752), 7) 4% GCTs (n=615), 8) 3% mesenchymal non-meningothelial (n=492), 9) 3% nerve sheath (n=428), and 10) ≤2% each of meningioma, choroid plexus, brain metastatic (44% from neuroblastoma), pineal region, hematologic, and other glioma tumors. Embryonal tumors predominated in neonates and infants (0-2yo), diffuse gliomas in childhood (3-11yo), and sellar tumors in adolescents (12-19yo). Females represented 49% of the cases, but sellar tumors predominated (23%, vs. only 11% in males); whereas in males diffuse gliomas predominated (23%; vs. 22% in females) overall and in pediatric patients older than 2yo. CONCLUSIONS In U.S. pediatric patients that present with a new intracranial tumor, embryonal tumors and diffuse gliomas predominate in infants ≤2yo, and continue to predominate in male children 3-11yo, whereas female children 3-11yo shifted towards a predominance by diffuse gliomas and other astrocytic tumors (e.g. pilocytic and pilomyxoid). In female adolescents 12-19yo, sellar tumors predominated, followed by diffuse gliomas; whereas in male adolescents diffuse gliomas predominated, followed by other astrocytic tumors and sellar tumors. Our findings demonstrate that newly-diagnosed intracranial masses in pediatric patients significantly vary by both age and sex.
NCCN Guidelines Insights: Ovarian Cancer, Version 1.2019
Authors: Deborah K. Armstrong, Ronald D. Alvarez, Jamie N. Bakkum-Gamez, Lisa Barroilhet, Kian Behbakht, Andrew Berchuck, Jonathan S. Berek, Lee-may Chen, Mihaela Cristea, Marie DeRosa, Adam C. ElNaggar, David M. Gershenson, Heidi J. Gray, Ardeshir Hakam, Angela Jain, Carolyn Johnston, Charles A. Leath III, Joyce Liu, Haider Mahdi, Daniela Matei, Michael McHale, Karen McLean, David M. O’Malley, Richard T. Penson, Sanja Percac-Lima, Elena Ratner, Steven W. Remmenga, Paul Sabbatini, Theresa L. Werner, Emese Zsiros, Jennifer L. Burns, Anita M. Engh
Journal: Journal of the National Comprehensive Cancer Network (2019)

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living &gt;5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.