tbuckley/cabot-search huggingface dataset:
Outcomes of personalized therapy guided by Exacta encyclopedic tumor analysis for women with broadly refractory advanced breast cancer.
Authors: Tim Crook, Sewanti Limaye, Anantbhushan Ranade, Amit Dilip Bhatt, Sachin Apurwa, Darshana Patil, Rajan Datar, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2024)

e13124 Background: Following the failure of three lines of systemic treatments in breast cancers, Standard of Care guidelines typically recommend palliative care or participation in clinical trials for such patients. Breast cancer remains a global health threat, impacting lives worldwide. For refractory patients, the outlook is grim, with limited treatment options post multiple failures. Dismal outcomes underscore the urgency for innovative approaches, as traditional interventions often fall short. Methods: The Resilient trial was a Phase-II, single-arm, open-label clinical trial. Its primary objective was to assess the effectiveness of Exacta ETA-guided treatments across a spectrum of solid organ cancers in advanced refractory cancer patients. Exacta Encyclopedic Tumor Analysis (ETA) comprising the interrogation of gene alterations, gene expression, immunohistochemistry (IHC), and in vitro chemoresistance profiling (CRP) of viable tumor cells was performed on freshly obtained tumor tissue from 21 breast cancer patients with broadly refractory advanced breast cancers who had failed multiple lines of treatment. Six (29%) patients had metastasis to the brain, 11 (52%) patients had metastasis to the liver, 9 (43%) patients had metastasis to the lungs, and 15 (71%) patients had skeletal metastasis. The findings obtained through Exacta ETA were integrated to formulate patient-specific therapy recommendations. Personalized treatment plans were devised, and organ- and label-agnostic treatment regimens were administered to each patient. Patients were monitored to ascertain Overall Survival (OS). Results: Median overall survival (OS) was not reached at the time of analysis. By considering the OS values censored at the interim (most recent follow-up), the median OS in the entire cohort (n = 21) was 11.5 months (95% CI 4.5 to 16.9). The median OS was 11.4 months (95% CI 4.0 to 15.1) among patients with brain metastases, 14.5 months (95% CI 2.6 to 22.8) among patients with liver metastases, 11.9 months (95% CI 3.7 to 22.3) among patients with pulmonary metastases and 11.4 months (95% CI 3.7 to 22.3) among patients with skeletal metastases, respectively. No grade IV adverse events or treatment-related deaths were reported in the cohort. Conclusions: Exacta Encyclopedic Tumor Analysis (ETA) guided treatments provide a viable and meaningful treatment option for patients with advanced refractory breast cancers with metastatic deposits. The observed high OS in this heavily pretreated population underscores the value of multi-analyte guided of Exacta ETA as a valuable approach to managing these challenging clinical cases. Clinical trial information: CTRI/2018/02/011808.
Understanding discordance in systematic reviews for treating chemotherapy-induced peripheral neuropathy: A focused umbrella review.
Authors: Alice Ye, Ahmed Butt, Yimin Geng, Salahadin Abdi
Journal: Journal of Clinical Oncology (2024)

e24111 Background: Despite the abundance of publications on chemotherapy-induced peripheral neuropathy (CIPN), we are still lacking effective management options. CIPN-focused systematic reviews (SRs) are increasingly encountered but have not aided much in clarifying treatment guidance. Additionally, there is a rising concern that SRs are now over-saturating the clinical literature, leading to redundant and misleading publications. Umbrella reviews (URs) are an attempt to appraise SRs but do not yet have firm methodologic frameworks. The aims of our UR were to appraise the discordance in recently published CIPN SRs and use content analysis as a method for identifying risks of discordance. Methods: This is a focused UR as part of a larger study to characterize the number of efficacy trials for established CIPN. Following PRISMA guidelines, we conducted a systematic literature search of databases MEDLINE, Embase, and Cochrane Library for publications in English from 1/1/2023 to 11/21/2023. Inclusion criteria were published systematic reviews attempting a comprehensive effort to synthesize any treatment outcomes for established CIPN. The AMSTAR 2 framework was used to appraise results for bias. Measures of randomized controlled trial (RCT) overlap are presented using a novel measure of time-adjusted CA, which accounts for RCT publication dates and SR search dates. Grounded theory coding was used for content analysis on efficacy. Results: We identified 18 SRs containing CIPN treatment RCTs published in less than 1 year, resulting in 32 unique CIPN RCTs. Seven SRs assessed exercise interventions, covering 6 exercise RCTs (41% time-adjusted CA). Five SRs assessed acupuncture, with 9 RCTs (50% time-adjusted CA). One SR searched for all CIPN treatments for pain but missed 4 RCTs. One SR was concerning for spurious data. Bias was variable and imperfect across SRs. Contextual analysis identified the themes of SRs combining preventative and treatment RCTs, confusing comparative vs. controlled trials, and frequent use of p-value only reporting to conclude treatment efficacy as major risks of SR discordance. Conclusions: UR was useful in identifying 32 CIPN RCTs that were not comprehensively identified by SRs. We presented a time-adjusted CA measure to indicate concordance percentage. A higher percentage indicates more re-citation of the same RCTs across SRs, with likely better chances of more concordant conclusions. This measure showed that SRs for CIPN treatment are discordant across the topics of exercise and acupuncture interventions. Content analysis revealed multiple potential causes of discordance. However, SR redundancy was helpful for identifying more unique RCTs. CIPN SR content standards should be developed to minimize discordancy and improve clinical applicability. Clinicians should be cautious when applying CIPN SR recommendations given the high discordance.
Retrospective evaluation of drug to drug interactions with paclitaxel use in military health.
Authors: Oskar Kigelman, Thu-Lan T. Luong, Karen J. Shou, Brian J. Reinhardt, Kimberly Greenfield
Journal: Journal of Clinical Oncology (2024)

e24118 Background: Paclitaxel is an antineoplastic agent used in the management of multiple metastatic and non-resectable tumor types approved for ovarian, breast, AIDS-related Kaposi sarcoma, non-small cell lung, pancreatic, cervical, endometrial, and thymoma or thymic carcinoma cancer by the US Food and Drug Administration. Cytochrome P450 (CYP) 3A4 or 2C8 inducers, inhibitors, or substrates may alter paclitaxel metabolism. Because DDIs can have an effect on clinical outcomes, we aimed to identify drugs that interact with paclitaxel and describe their clinical manifestations. Methods: A retrospective analysis was performed on the health records of patients in the US Department of Defense Cancer Registry (retrieved March 2022), Comprehensive Ambulatory/Professional Encounter Records, and Pharmacy Data Transaction Service database (both retrieved October 2022). Patients’ medical history, diagnoses, and demographics were extracted and analyzed for differences in adverse effects when these agents were used alone vs concomitantly with other prescription drugs. Patients’ diagnoses and prescription drug use were extracted to compare completed vs discontinued treatment groups, identify medications commonly co-administered with paclitaxel, and evaluate DDIs with antidepressants. Results: Of 702 patients using paclitaxel, 338 completed treatments. The P value for paclitaxel discontinuation when used alone vs concomitantly or 1 drug (alone or before or after) vs combination (2 to 4 drugs) was &lt; .001. Patients who took paclitaxel concomitantly with a greater number of prescription drugs had a higher rate of treatment discontinuation than those who received fewer medications. Patients in the completed group received 9 to 56 prescription drugs, and those in the discontinued group were prescribed 6 to 70. Those who discontinued treatment had more diagnosed medical issues than those who completed treatment. Conclusions: This review cannot conclude that concomitant use with prescription drug(s) resulted in paclitaxel discontinuation. There were no significant DDIs determined between paclitaxel and antidepressants.[Table: see text]
Hyperammonemic encephalopathy: An unaccounted side effect of 5FU and capecitabine.
Authors: Taha Sheikh, Dean Watkins, Danae M. Hamouda
Journal: Journal of Clinical Oncology (2024)

e24108 Background: Metabolic encephalopathy is a serious but reversible condition that is characterized by a diffuse impairment of cognitive function due to the overabundance of various metabolites or toxins. Hyperammonemia ( &gt; 80 μg/dL or &gt; 47 μmol/L) is a well-known cause of metabolic encephalopathy and also a rare side effect of 5-Fluorouracil (5-FU) chemotherapy. Constipation and renal failure are two known risk factors for developing hyperammonemic encephalopathy with 5-FU use. Capecitabine is a 5-FU prodrug that is commonly used as a more tolerated and more convenient alternative chemotherapy agent. Despite being less common than with 5-FU, cases of hyperammonemic encephalopathy related to capecitabine use may be missed clinically due to under-testing. Additionally, diarrhea may be misinterpreted as a side effect of chemotherapy instead of an effective tool for identifying early disease and accelerating disease resolution. Methods: A search using Pubmed was conducted on January 4 th , 2024 to identify cases of hyperammonemia and metabolic encephalopathy related to 5-Fluorouracil and capecitabine. The search strategy was ("metabolic encephalopathy 5-fluorouracil" OR “hyperammonemia 5-fluorouracil”) AND (“metabolic encephalopathy capecitabine” OR “hyperammonemia capecitabine”). Cases were then organized into a table where factors of the cases were stratified. Results: A total of 59 total cases were identified. Every case where 5-FU was used reported a serum ammonia level, while only 5 of the 9 cases (55.55%) where capecitabine was used reported a serum ammonia level. Additionally, only 9 cases (15.25%) reported bowel movement status with 1 patient presenting with diarrhea, and 5 with constipation. The most common methods for managing metabolic encephalopathy in these patients included: branched chain amino acids (66.10%), discontinuing/changing the chemotherapeutic agent (62.71%), lactulose (37.29%), intravenous hydration (32.20%), and hemodialysis/hemofiltration (13.56%). For the 52 cases that reported it, the average duration of symptoms post-treatment was 2.15 days. Conclusions: A goal in managing patients receiving 5-FU or capecitabine with hyperammonemic encephalopathy is the excretion of ammonia without causing dehydration. This management is seen with the use of lactulose to increase bowel movements in patients with decompensated liver cirrhosis. Of note, 5FU and capecitabine have been shown to cause diarrhea as a grade 3 and 4 adverse effect in 12.7% and 16.6% of patients, respectively. Thus it can be theorized that the diarrhea from 5FU/capecitabine may offset the development of hyperammonemia. This principle could potentially be expanded to benefit patients with a history of chronic constipation. The oversight of hyperammonemia from 5-FU and capecitabine use is both dangerous and diminishes the quality of life from patients who are not proactively treated to prevent encephalopathy.
Identifying objective risk factors of financial toxicity in patients with cancer.
Authors: Aleksei Bazhenov, Luiza Doro, David M. O'Sullivan, Alvaro G. Menendez
Journal: Journal of Clinical Oncology (2024)

e24116 Background: Current financial toxicity (FT) screening tools rely on patient-reported risk factors (RF) 1 . Underrepresented populations may not be forthcoming about FT fears due to cultural concerns of treatment withholding or migratory repercussions, if applicable 1–4. Identifying objective RF, such as social determinants of health (SDH) and disease-specific factors (DSF), could reduce FT in cancer patients and healthcare systems. Methods: This was a multi-center retrospective study evaluating SDH and DSF associated with FT (defined as ≥$15,000 owed) related to cancer treatment. Inferential statistics were used to evaluate differences between the FT cohort and those who owed &lt; $15,000. Continuous data were compared with a Student’s t or Mann-Whitney U test, depending on distribution. Categorical outcomes were compared with a chi square test. A logistic regression model was used to evaluate multivariate associations with FT, using p &lt; 0.05 to define significant results. Results: The sample comprised 162 records, 81 in each group. Univariate analyses demonstrated differences in age, lack of PCP, non-US country of origin, lack of insurance, lower education levels, need for an English interpreter, stage 4 at diagnosis, recurrent or metastatic disease, use of immune checkpoint inhibitors (ICI), and use of targeted molecular therapy (TMT) (Table 1). Employment status and marital status were not statistically different. The logistic regression model showed that lack of insurance and stage 4 at diagnosis were significantly associated with FT (p = 0.001 and p = 0.0495, resp.). Conclusions: Objective FT screening can minimize response bias and incidence in those at increased risk. Non-US country of origin and lack of English proficiency suggests that first-generation Hispanics may not be appropriately navigated for FT. These findings identify specific subpopulations at risk for FT and will guide prospective interventions looking to minimize FT. Healthcare systems should analyze objective measures of FT while considering loco-regional and subcultural SDH/DSF in order to overcome response bias. Ref. Witte J et al. Methods for measuring financial toxicity after cancer diagnosis and treatment. Annals of Oncology. 2019;30(7) Strasser-Weippl K et al. Progress and remaining challenges for cancer control in Latin America and the Caribbean. Lancet Oncol. 2015;16(14) Zhu Z et al. Cancer survivors’ experiences with financial toxicity. Psychooncology. 2020;29(6) Chebli P et al. Multilevel determinants of financial toxicity in breast cancer care. Supportive Care in Cancer. 2020;28(7). [Table: see text]
Randomized, placebo-controlled trial of atorvastatin to prevent hearing loss in patients with head and neck squamous cell carcinoma receiving cisplatin based chemoradiation (CRT).
Authors: Nicole C. Schmitt, Katharine Fernandez, Shawn Newlands, Paul Allen, Adam Kaufman, Garnett P. McMillan, Jeffrey M. Switchenko, William A. Stokes, Ranee Mehra, Anant Mandawat, Robert Shamburek, Nabil F. Saba, Lisa L. Cunningham
Journal: Journal of Clinical Oncology (2024)

TPS12153 Background: Cisplatin chemotherapy is associated with several adverse effects, including a permanent, high-frequency, sensorineural hearing loss in about 50% of patients. Preclinical studies suggest that statin drugs can mitigate cisplatin ototoxicity (Fernandez et al., Hearing Research 2020). In our prior combined retrospective/prospective dataset of patients with head and neck squamous cell carcinoma (HNSCC) treated with cisplatin-based CRT, the incidence of CTCAE grade ≥ 2 hearing loss was 29.4% in statin non-users, versus 9.7% in atorvastatin users (Fernandez et al., J Clin Invest 2021). An adjusted odds ratio analysis indicated that atorvastatin users are significantly less likely to develop hearing loss versus statin non-users (odds ratio 0.47), providing the rationale for a randomized, controlled, prospective study. Methods: This multi-center, randomized, placebo-controlled study is enrolling patients with previously-untreated, locally advanced head and neck squamous cell carcinoma (HNSCC) for which cisplatin-based chemoradiation is indicated, either in the definitive or adjuvant setting. Patients who will be treated with cisplatin (at 75-100 mg/m2 bolus every three weeks or 40 mg/m2 weekly) are eligible. Patients currently taking a statin or those without measurable hearing in at least one ear are excluded. A baseline audiogram is performed, and patients are randomized to atorvastatin (40 mg/day) or placebo, which is started 2-7 days before CRT and taken daily until 3 months after completion of CRT. Post-treatment audiometry is repeated at 3 months and 2 years after CRT, along with collection of patient-reported outcomes on hearing, tinnitus, and peripheral neuropathy. Patients are monitored for liver and muscle toxicity, with dose de-escalation or cessation of atorvastatin as needed. The primary endpoint is the incidence of CTCAE grade ≥2 hearing loss at 3 months after CRT. Secondary endpoints include other treatment related grade 3-4 adverse events, overall survival, and disease-free survival. Up to 214 subjects will be enrolled at 4 U.S. sites (NIH Clinical Center, Emory University, University of Maryland, University of Rochester). Funding: NIH/NIDCD, U01 DC020452 and intramural project ZIA DC000079. Clinical trial information: NCT04915183 .
Enhancing prostate cancer diagnosis communication: A multicenter study evaluating the impact of animated videos, CartDiag Prostate study.
Authors: Carole Helissey, Marie Pautas, Laurent Brureau, Anatole Cessot, Hugo Picchi, Audrey Le Roy, Marie-Anne Audisio, Aline Barhli, Hélène Vanquaethem, Antoine Schernberg
Journal: Journal of Clinical Oncology (2024)

TPS12148 Background: Prostate cancer is the leading cancer among men. Advances in therapeutic techniques, personalized medicine, and the integration of targeted therapies have significantly improved patient outcomes, resulting in a 5-year overall survival of 93%. However, effective patient care requires a shared decision-making framework and clear communication between healthcare professionals and patients. The initial step in patient care involves disclosing the cancer diagnosis during a dedicated consultation, laying the foundation for the patient-physician trust relationship. Nowadays, less than 50% of patients declared that they understood the information provided during the announcement consultation. The main objective of our study is to assess the effect of the announcement system, reinforced by animated videos, on patients' overall understanding of their diagnosis and treatment. Methods: To enhance the disclosure process, animated videos were developed to outline the patient care journey. This multicenter, controlled before-and-after study aimed to evaluate the impact of the usual disclosure process enhanced by animated videos on patients' understanding of advanced or metastatic prostate cancer. Patients were sequentially assigned to two arms: the standard arm (first 45 patients) received usual written and oral information, while the intervention arm (next 45 patients) received written and oral information supplemented by animated videos. To evaluate the effect of the enhanced disclosure process on patients' overall understanding of their diagnosis and treatment using the EORTC QLQ-INFO25 questionnaire at baseline (Day 0) and after 1 month (Day 30), compared to the standard group without enhanced disclosure. This prospective study is the first to assess the impact of supplementing the standard disclosure process with animated videos positively impacts patients' comprehension of advanced or metastatic prostate cancer. The findings will support the potential value of integrating visual aids into the diagnostic disclosure consultation to enhance patient understanding and promote informed decision-making. Clinical trial information: NCT06117696 .
Cardiotoxicity in patients with breast cancer after modern therapy.
Authors: Xiaocao Xu, Nataniel Hernan Lester-Coll, Mikaela-joy Mari, Kim Dittus, Puyao Li
Journal: Journal of Clinical Oncology (2024)

e24117 Background: Breast cancer survivors are at increased risk of adverse cardiac events (ACE). Many patient and treatment characteristics, including the use of radiation, anthracyclines, and anti-HER2 therapy, have been reported to affect the rate of ACE. Most prior studies evaluated patients treated with older techniques and therapies, and examined only ischemic events as an endpoint. We report the incidence and risk factors associated with a range of ACE in patients receiving modern systemic and radiation treatments. Methods: Retrospective review identified 235 women with breast cancer who received definitive treatment including radiation between 2017-2023. Coronary artery calcifications (CAC) were defined as density in the heart with ≥130 HU on simulation CT. Event free survival estimates were calculated by Kaplan-Meier method. Uni- and multivariate analyses (MVA) were performed by Cox proportional hazards model. Median follow-up was 3.9 years (range, 0.8-6.9). Results: Patient characteristics are listed in table 1. At 4 years, ACE-free survival was 91.6%. Sixty-six patients had ACE, including arrhythmias (n = 21), valvular disease (17), acute coronary syndrome (9), ventricular dysfunction (20), and pericarditis (1). On MVA, radiation mean heart dose (MHD) &gt; 4 Gy [HR 2.8, 95%CI 1.05-7.5, p = 0.04] and presence of CAC [HR 2.5, 1.2-5.2, p = 0.017] were independently associated with increased ACE. Endocrine therapy was associated with decreased risk (HR 0.4, 0.2-0.8, p = 0.012). Smoking (p = 0.88), hypertension (p = 0.97), diabetes (p = 0.52), treatment with chemotherapy (p = 0.89) including anthracyclines (p = 0.43), treatment with anti-HER2 therapy (p = 0.53), and radiation field (p = 0.65) were not significantly related to ACE in this limited cohort. A subset of patients participated in oncology rehab (n = 43) and there was no clear association with decreased ACE (p = 0.96) in in an exploratory analysis. Conclusions: The rate of ACE is low with modern therapy, even when accounting for a full spectrum of ACE. Consistent with prior studies, we found that higher MHD and CAC are independently associated with ACE, including previously under-reported ACE. Treatment with endocrine therapy was associated with fewer ACE. In this limited cohort with shorter-term follow up, hypertension, diabetes, smoking, and treatment with anthracyclines and anti-HER2 therapy were not associated with ACE, suggesting that these may be less important risk factors. [Table: see text]