tbuckley/cabot-search huggingface dataset:
Fear of Cancer Recurrence in Adult Survivors of Childhood Cancer
Authors: Alex Pizzo, Wendy M. Leisenring, Kayla L. Stratton, Élisabeth Lamoureux, Jessica S. Flynn, Kevin Alschuler, Kevin R. Krull, Lindsay A. Jibb, Paul C. Nathan, Jeffrey E. Olgin, Jennifer N. Stinson, Gregory T. Armstrong, Nicole M. Alberts
Journal: JAMA Network Open (2024)

Fear of cancer recurrence is common among survivors of adult-onset cancer and associated with increased distress, functional impairment, and health care utilization. However, little is known about the prevalence and risk factors of fear of cancer recurrence among adult survivors of childhood cancer who are also at high risk for subsequent malignant neoplasms.
A new prognostic model in patients with recurrent or metastatic head and neck cancer treated with chemotherapy: An analysis of ECOG-ACRIN E1305.
Authors: Athanassios Argiris, Yael Flamand, Panayiotis Savvides, Jennifer Maria Johnson, Shuli Li, Arlene A. Forastiere, Barbara Burtness
Journal: Journal of Clinical Oncology (2022)

6026 Background: We examined a large patient dataset based on E1305, a completed phase III randomized trial of platinum-based chemotherapy with or without bevacizumab (Argiris et al. JCO 2019), to evaluate prognostic factors in the first-line treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (RM SCCHN) and expand on our previous observations in cooperative group trials (Argiris et al. Cancer 2004). Methods: All 403 patients enrolled in E1305 were analyzed. Overall survival (OS) was the outcome of interest. Clinical and tumor characteristics were examined using Cox proportional hazards models. Variables which were significant in the univariate setting at a level of ≤ 0.10 were included in a multivariable model, and backwards selection was performed (threshold of p ≤ 0.05). The final multivariable model was then applied to the two treatment arms, separately. Variables for which the hazards ratio (HR) within an arm was more than 10% different than that for the whole cohort, were removed from the final cohort model. Results: The median OS in the whole study cohort was 11.8 months. A prognostic score model for OS was built, using the 4 independent prognostic factors identified in the multivariable model: ECOG performance status (1 vs 0), prior radiation, primary region (non-oropharynx vs oropharynx), and metastatic disease bone or liver (vs other sites/no metastases). Prognostic score was dichotomized (0-2 and &gt; 2). Patients with 0-2 risk factors (n = 249) had a median OS of 15.2 months (90% CI: 13.8, 18.1), while patients with &gt; 2 risk factors (n = 154) had a median OS of 7.6 months (90% CI: 6.5, 9.3); HR of 2.14 (95% CI: 1.73, 2.66), p &lt; 0.0001. Compared to our previous 5-factor model from analysis of older trials in a similar setting, the variable “bone/liver metastasis” is new, but “tumor cell differentiation” and “weight loss” were not significant and not included in the new model for OS. Conclusions: The new proposed model includes 4 prognostic factors for OS (performance status, primary site, prior radiation, presence of bone/liver metastasis) in the first-line treatment of RM SCCHN.
Estimated impact of a tobacco-elimination strategy on lung-cancer mortality in 185 countries: a population-based birth-cohort simulation study
Authors: Julia Rey Brandariz, Harriet Rumgay, Olalekan Ayo-Yusuf, Richard Edwards, Farhad Islami, Shiwei Liu, Mónica Pérez-Ríos, Paulo César Rodrigues Pinto Corrêa, Alberto Ruano-Ravina, Isabelle Soerjomataram
Journal: The Lancet Public Health (2024)
Adverse pregnancy outcomes attributable to overweight and obesity across maternal birth regions: a Swedish population-based cohort study
Authors: Maryam Shirvanifar, Viktor H Ahlqvist, Michael Lundberg, Kyriaki Kosidou, Ángel Herraiz-Adillo, Daniel Berglind, Cecilia Magnusson, Pontus Henriksson
Journal: The Lancet Public Health (2024)
Vaccination generates functional progenitor tumor-specific CD8 T cells and long-term tumor control
Authors: Carlos R Detrés Román, Megan M Erwin, Michael W Rudloff, Frank Revetta, Kristen A Murray, Natalie R Favret, Jessica J Roetman, Joseph T Roland, Mary K Washington, Mary Philip
Journal: Journal for ImmunoTherapy of Cancer (2024)

Immune checkpoint blockade (ICB) therapies are an important treatment for patients with advanced cancers; however, only a subset of patients with certain types of cancer achieve durable remission. Cancer vaccines are an attractive strategy to boost patient immune responses, but less is known about whether and how immunization can induce long-term tumor immune reprogramming and arrest cancer progression. We developed a clinically relevant genetic cancer mouse model in which hepatocytes sporadically undergo oncogenic transformation. We compared how tumor-specific CD8 T cells (TST) differentiated in mice with early sporadic lesions as compared with late lesions and tested how immunotherapeutic strategies, including vaccination and ICB, impact TST function and liver cancer progression.
Effects of oral sepiapterin on blood Phe concentration in a broad range of patients with phenylketonuria (APHENITY): results of an international, phase 3, randomised, double-blind, placebo-controlled trial
Authors: Ania C Muntau, Nicola Longo, Fatih Ezgu, Ida Vanessa D Schwartz, Melissa Lah, Drago Bratkovic, Lali Margvelashvili, Ertugrul Kiykim, Roberto Zori, Jaume Campistol Plana, Amaya Bélanger-Quintana, Allan Lund, Laura Guilder, Anupam Chakrapani, Halise Neslihan Mungan, Arlindo Guimas, Ixiu Del Carmen Cabrales Guerra, Anita MacDonald, Kimberly Ingalls, Neil Smith
Journal: The Lancet (2024)
Xpert Breast Cancer STRAT4 Assay using fine-needle aspiration biopsy samples in a resource-constrained setting: a prospective diagnostic accuracy study
Authors: Dianna L Ng, Edda Vuhahula, Asteria H Kimambo, Marie Claire Ndayisaba, Godfrey S Philipo, Beatrice P Mushi, Kenneth E Ho, Alan Paciorek, Zainab Illonga, Li Zhang, Poonam Vohra, Jodi Weidler, Michael Bates, Elia J Mmbaga, Katherine Van Loon
Journal: The Lancet Oncology (2024)
Sepsis survivors call for the development of a European sepsis plan
Authors: Krista Bracke, Elena Moya, James Corcoran, Ilse Malfait, Idelette Nutma, Jamila Hedjal, Mariah McKimbrough, Shahrzad Kiavash, Angels Garcia, Marianne Haverkamp, Oliver Jones, Simone Mancini, Mariam Jashi, Djillali Annane
Journal: The Lancet (2024)
Biomarkers of neurodegeneration across the Global South
Authors: Eimear McGlinchey, Claudia Duran-Aniotz, Rufus Akinyemi, Faheem Arshad, Eduardo R Zimmer, Hanna Cho, Boluwatife Adeleye Adewale, Agustin Ibanez
Journal: The Lancet Healthy Longevity (2024)
Safety and preliminary efficacy of GQ1001, a next generation HER2-targeting ADC, combined with pyrotinib in pretreated patients with HER2-positive metastatic breast cancer: A phase 1b clinical trial.
Authors: Biyun Wang, Chengcheng Gong, Leiping Wang, Xichun Hu, Ting Li, Zhonghua Tao, Mingchuan Zhao, Yannan Zhao
Journal: Journal of Clinical Oncology (2024)

e13020 Background: GQ1001 is a novel HER2-targeted antibody-drug conjugate (ADC) that was generated by conjugating trastuzumab to DM1 via a unique open-ring containing linker and the enzymatic site-specific conjugation technology, which significantly improves homogeneity and stability of the study drug [1]. Preclinical studies showed robust anti-tumor activities in multiple HER2+ PDX and CDX models, and excellent pharmacokinetics and safety profiles in rats and cynomolgus monkeys. Phase 1a study (NCT04450732) showed superior tolerability and promising antitumor efficacy in heavily pretreated HER2-positive advanced solid tumors [2]. In vivo study also demonstrated a synergistic anti-tumor efficacy of GQ1001 combined with pyrotinib, an irreversible pan-HER2 receptor tyrosine kinase inhibitor (TKI) [1]. Thus, a phase 1b study (NCT05575804) was designed to investigate the safety and preliminary efficacy of the combination of GQ1001 and pyrotinib in pretreated patients with HER2-positive metastatic breast cancer. Methods: In the “3+3” dose-escalation phase, the dose of GQ1001 was 6.0 mg/kg, 7.2 mg/kg and 8.4 mg/kg intravenously in a 21-day cycle, and pyrotinib was taken orally in a fixed dose of 320 mg once daily in 28-day cycles. The dose escalation or de-escalation was based on the incidence of specified dose-limiting toxicities (DLTs) in the initial dose group. DLTs were observed for the first 21 days. Results: A total of 15 HER2-positive metastatic breast cancer patients received GQ1001 and pyrotinib treatment. All patients (15/15) had failed on previous trastuzumab (or its biosimilars) containing therapy and 33.3% of the patients (5/15) had been treated with pertuzumab. By Dec. 31, 2023, dose escalation has been completed with no DLT reported. Maximal tolerable dose was not reached up to 8.4 mg/kg, the highest dose tested. Most patients (13/15; 73.3%) experienced grade 3-4 treatment-related adverse event, including diarrhea (66.7%), anemia (13.3%), alanine aminotransferase increase (6.7%), thrombocytopenia (6.7%), and urticaria (6.7%). At the data cut off date (Dec. 31, 2023), nine patients were still on going, with the longest treatment duration of 348 days. The objective response rate (ORR) was 66.7% (10/15) in all patients enrolled, and 71.4% (10/14) in patients who had received tumor evaluation. At 6.0 mg/kg, 7.2 mg/kg and 8.4 mg/kg dose level, the ORR was 75% (3/4), 100% (5/5), 33.3% (2/6), respectively. Conclusions: GQ1001 in combination with pyrotinib demonstrated manageable safety profile and promising preliminary antitumor activity among pretreated patients with HER2-positive metastatic breast cancer. [1] HUANG L, et al. Cancer Research, 2023, 83(7_Supplement): 2702-. [2] LEMECH C, et al. Cancer Research, 2023, 83(8_Supplement): CT178-CT. Clinical trial information: NCT05575804 .
Enhancing HER2 evaluation: Correlation of APIS Breast Cancer Subtyping Kit and IHC/ISH with accurate HER2 quantification.
Authors: Anna Gasior, Anne-Sophie Wegscheider, Jack Paveley, Kimberly Jane Howard, Mathew Harrison, Leanne Gough, Joanna Gorniak, Sara Rollinson, Zoe Pounce, Axel Niendorf
Journal: Journal of Clinical Oncology (2024)

e13028 Background: Human epidermal growth factor receptor 2 (HER2) status is a crucial prognostic and predictive biomarker in invasive breast cancer (BC). The advent of novel-anti HER2 therapies (such as Trastuzumab deruxtecan (T-DXd)) has cast doubt upon traditional HER2 detection methods, as emerging data indicates the effectiveness of T-DXd in individuals who were previously categorized as HER2 immunohistochemistry (IHC) 1+ or 0 scores. More sensitive and precise methods capable of detecting HER2-low expression are therefore crucial to correctly identify patients who could benefit from treatment with these novel anti-HER2 therapeutics. As IHC methods were primarily developed for the identification of tumors exhibiting HER2 overexpression, rather than for distinguishing between HER2-low and complete absence of expression, the ability of these assays to precisely detect HER2-low cases remains uncertain. APIS Breast Cancer Subtyping Kit (APIS BCSK) was developed to detect expression level of four BC biomarkers – HER2, ER, PR, Ki67. Here, we report the correlation between HER2 mRNA expression levels detected by APIS BCSK, and IHC HER2 scoring. Methods: A total of n=642 formalin-fixed paraffin-embedded (FFPE) BC sections, obtained by core needle biopsy or resection, underwent histological assessment observing the ASCO/CAP guidelines for IHC. The HER2 status of specimens with a HER2 2+ IHC score was resolved via in situ hybridization (ISH) amplification. All specimens underwent testing with APIS BCSK. To evaluate the diagnostic accuracy of the kit, the concordance between IHC/ISH and APIS BCSK mRNA expression level was reported in terms of Overall Percent Agreement (OPA), Negative Percent Agreement (NPA), and Positive Percent Agreement (PPA). Results: Strong correlation between IHC/ISH results and HER2 expression detected by APIC BCSK was observed (OPA of 94.2%, PPA of 89.2% and NPA of 94.9%). ERBB2 mRNA expression was detected by APIS BCSK in a subset of patients with 0 and 1+ IHC HER2 score, highlighting the continuous nature of ERBB2 expression and higher sensitivity of RT-qPCR-based detection approaches. Conclusions: APIS BCSK accurately detects HER2 expression. The results confirm that IHC stratification may not be an adequate method for predicting the response to novel anti-HER2 therapies, such as T-DXd. Implementation of additional cut offs could allow further stratification of ERBB2 mRNA expression, however, additional studies correlating the expression level to anti-HER2 treatment response are required to validate this approach.
Efficacy and toxicity of trastuzumab emtansine among patients with HER-2-positive metastatic breast cancer in Saudi Arabia.
Authors: Ahmed Ali Badran, Waleed Fallatah, Abdullaah Khaleel Hinkston, Tarek Arabi, Ghada Algwaiz, Mahmoud Abdelsatar Elshenawy, Ayman Elshentenawy, Emaan Ul Haque, Taher Twegieri, Saad Akhtar, Adher Alsayed, Dahish Saed Ajarim, Meshari Alzahrani, Sabah Alaklabi, Tusneem Elhassan, Kausar Suleman
Journal: Journal of Clinical Oncology (2024)

e13001 Background: Trastuzumab emtansine (T-DM1) significantly prolongs progression-free survival (PFS) with a safe drug profile in advanced HER-2-positive (HER+) breast cancer (BC) patients. However, there are currently no reports regarding its efficacy and safety in the Middle East. Methods: We retrospectively reviewed the data of 55 metastatic HER+ BC patients who received T-DM1 at our center. Results: The median age at diagnosis was 44 years (25-69). 65.45% patients presented as a de novo metastatic presentation and 56.46% were hormone receptor-positive (Table). 80%, 65.45%, 43.63% suffered visceral, CNS, and skeletal metastasis, respectively. The median duration of follow up was 31.5 months (3-61). 54.45% of patients were alive with disease at the date of last follow up, and 35.45% passed away. The median number of cycles given was 12 cycles (1-60). The best response, according to RECIST criteria v1.1, was complete remission in 5.45%, partial response in 40%, and stable disease in 23.64%. The mean overall survival (OS) was 117.3 months (95% CI: 97.35-137.24), and the median OS was not reached. The median PFS was 10.91 months (95% CI: 5.61-16.21) and the 3-year PFS was 17.6%. Four patients are still receiving T-DM1 treatment at the time of analysis. 85.45% stopped their treatment due to disease progression, and two (3.63%) patients stopped due to severe drug toxicity. Drop in ejection fraction and allergic reactions were the most common side effects, which were both seen in 18.18% of patients. Conclusions: The efficacy and safety profile of T-DM1 in our patient is comparable to that of other international populations. Larger, multicenter studies are needed to confirm our findings. ECOG performance status at presentation 0 6 (10.7%) 1 45 (80.4%) 2 4 (7.1%) Metastectomy Brain 10 (18.18%) Bone 1 (1.81%) Lungs 1 (1.81%) Total number of drug lines 2-4 31 (56.36%) 5-7 23 (41.81%) 8 1 (1.81%)
Four-year result of diffusion-weighted, MRI-guided, dose-painting radiotherapy following induction chemotherapy in patients with locally advanced recurrent nasopharyngeal carcinoma: A randomized controlled trial.
Authors: Feng Liu, Cuihong Jiang, Xiangwei Wu, Wen Liu, Changgen Fan, Lili He, Shuai Xiao, Yanxian Li, Xu Ye, Wenqiong Wu, Qi Zhao, Hui Wang
Journal: Journal of Clinical Oncology (2022)

6033 Background: We hypothesized that diffusion-weighted MR imaging (DWI) guided dose-painting radiotherapy (DP-RT) following induction chemotherapy (IC)was associated with improved local tumor control and progression-free survival compared with conventional MRI-based radiotherapy (RT) in locally advanced recurrentnasopharyngeal carcinoma (rNPC). The purpose of this randomized phase II trial was to compare the efficacy and toxicity of DWI guided DP-RT following IC versus standard conventional MRI-based radiotherapy following IC in locally advanced rNPC. Methods: Tow hundred and four patients with locally recurrent T3 to T4 NPC were randomly assigned to receive DWI-guided dose-painting radiotherapy (DP-RT) or conventional MRI-based radiotherapy. Patients in both groups received reirradiation using intensity modulated radiation therapy (IMRT) following cisplatin-based induction chemotherapy. In DP-RT group (group A, n = 102), subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC &lt; mean). The dose to GTVnx-DWI was escalated to DT 65.4 Gy/30 Fx in 2.18 Gy per fraction. In conventional MRI-based RT group (group B), PGTVnx was irradiated at DT 60.0 Gy/30 Fx in 2.0 Gy per fraction. This trial is registered with chictr.org.cn, number ChiCTR2100052340. Results: Compared with conventional MRI-based radiotherapy, DWI-guided DP-RT significantly improved 4-year progression-free survival (PFS, 48.0% vs. 33.3%; P = 0.033), local control rate (LC, 85.3% vs. 69.6%; P = 0.007), and overall survival (OS, 52.0% vs. 37.3%; P = 0.035). No statistically significant differences in acute and late toxic effects (mucosal necrosis, trismus, temporal lobe necrosis, and cranial nerve palsy) were observed between the two groups. Dose painting (DWI-guided DP-RT vs conventional MRI-based RT) was a significant independent prognostic factor for PFS and LC (P = 0.035 and P = 0.020, respectively). Conclusions: Diffusion-weighted MRI guided dose-painting radiotherapy following induction chemotherapy is associated with a considerable progression-free survival and local control benefit, without increasing toxicity, as compared with standard conventional MRI-based RT following IC, among patients with locally recurrent T3 to T4 nasopharyngeal carcinoma. Clinical trial information: ChiCTR2100052340.
Benefit of Whole-Pelvis Radiation for Patients With Muscle-Invasive Bladder Cancer: An Inverse Probability Treatment Weighted Analysis
Authors: Gautier Marcq, Ronald Kool, Alice Dragomir, Girish S. Kulkarni, Rodney H. Breau, Michael Kim, Ionut Busca, Hamidreza Abdi, Mark Dawidek, Michael Uy, Gagan Fervaha, Nimira Alimohamed, Jonathan Izawa, Claudio Jeldres, Ricardo Rendon, Bobby Shayegan, Robert Siemens, Peter C. Black, Fabio L. Cury, Wassim Kassouf
Journal: Journal of Clinical Oncology (2024)

The value of pelvic lymph node irradiation is debated for patients with muscle-invasive bladder cancer (MIBC) undergoing curative-intent radiation therapy (RT). We sought to compare the oncological outcomes between bladder-only (BO)-RT and whole-pelvis (WP)-RT using a large Canadian multicenter collaborative database.
Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005
Authors: Jung-Min Lee, Mark F. Brady, Austin Miller, Richard G. Moore, Helen MacKay, Leah McNally, Jayanthi Lea, Daron Street, Stephanie Lheureux, Megan E. McDonald, Linda R. Duska, Guilherme Cantuaria, Juraj Kavecansky, Charles A. Leath, Matthew Powell, Mark G. Cadungog, Peter G. Rose, Yong-Man Kim, Helen Q. Huang, Michèle Provencher, Lari B. Wenzel, Michael A. Bookman, Elise C. Kohn, Angeles Alvarez Secord
Journal: Journal of Clinical Oncology (2024)

We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC).
Phase 3 randomized study comparing docetaxel-platinum with docetaxel-platinum-5 fluorouracil as neoadjuvant chemotherapy in technically unresectable oral cancer.
Authors: Ajaykumar Singh, Vijay Maruti Patil, Vanita Noronha, Nandini Sharrel Menon, Pankaj Chaturvedi, Vijayalakshmi Mathrudev, Atanu Bhattacharjee, Sunil Ramdhan Chopade, Sujay Srinivas, Somnath Roy, Tanmoy Mondal, Hollis D'souza, Devendra A Chaukar, P. S. Pai, Sudhir Vasudevan Nair, Shivakumar Thiagarajan, Sarbani Laskar, Kavita Prakash Nawale, Sachin Babanrao Dhumal, Kumar Prabhash
Journal: Journal of Clinical Oncology (2022)

6013 Background: Neoadjuvant chemotherapy (NACT) with DCF (Docetaxel, Cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer (LAOC) and has a survival advantage over the CF (Cisplatin and 5FU) regimen. DC regimen (Docetaxel, Cisplatin) had shown promising results in small series, with a lower rate of adverse events but has never been compared with DCF. Methods: This was a phase 3 open-label superiority randomized study. Adult patients with very LAOC (technically unresectable), ECOG PS 0-2 and adequate organ function were eligible. They were randomly assigned in a 1:1 fashion to either DCF or DC regimen. After the administration of 2 cycles, these patients were evaluated in the multidisciplinary clinic. Based on the response, further treatment either surgery followed by adjuvant or radical chemoradiation or palliative therapy was planned. The primary endpoint was overall survival (OS). The key secondary endpoint was adverse events. Results: 495 patients were randomized in this study, 250 patients in arm A and 245 in arm B. At a median follow-up of 39.5 months. The 2-year OS was 29.1% in the DCF and 23.5% in the DC arm respectively (HR=0.81; 95%CI 0.66-0.99, P-value= 0.043). Grade 3 or above adverse events were higher in the DCF arm - oral mucositis (10.6% versus 1.2%), diarrhea (13.6% versus 9.6%), febrile neutropenia (23.2% versus 2.6%), hyponatremia (40.8% versus 20.8%), and hypokalemia (17.9% versus 1.6%). Conclusions: NACT with DCF has a survival benefit over DC in oral cancers but it comes at the cost of an increment in acute adverse events. Clinical trial information: CTRI/2016/04/006804.