tbuckley/cabot-search huggingface dataset:
Predictors of long-term survival in immune checkpoint inhibitor (ICI)-associated myocarditis.
Authors: Chia-Yun Wu, Nikhil Dubey, Leyre Zubiri, Sherin Juliet Rouhani, Joie Sun, Tomas G. Neilan, Kerry Lynn Reynolds, Daniel A. Zlotoff
Journal: Journal of Clinical Oncology (2024)

e24026 Background: ICI-associated myocarditis carries a high morbidity and mortality, with close to half of patients experiencing major adverse cardiac events (MACE). Risk factors previously associated with short-term MACE include troponin T (TnT), neutrophil/lymphocyte ratio (NLR), and absolute lymphocyte count (ALC). In this study, we aimed to analyze the predictors of long-term survival. Methods: This single-center retrospective study included 37 patients diagnosed with ICI-associated myocarditis at Massachusetts General Hospital between March 2016 and March 2022. We collected demographics, diagnostic results, and myocarditis treatments from the electronic medical record. Patients were grouped by survival time: short-term ( &lt; 30 day), intermediate (30 to 360 day), or long-term ( &gt; 360 days) survival. We used chi-square and Kruskal-Wallis tests for descriptive statistics. Cut-off points of continuous variables were determined by ROC curve. Predictors of survival were analyzed by logistic regression models. Results: The cohort consisted of 29 males and 8 females with a median age of 75 years (IQR 68-79), and median follow-up of 5.6 months (IQR 0.5-14.9). The median time from ICI start to myocarditis onset was 50 days (IQR 36-91). Ten, 14, and 13 patients were in the short-term, intermediate, and long-term survival groups, respectively. By univariate analysis, predictors of long-term survival included initial NT-proBNP ≤ 450, NLR ≤ 4.44, ALC ≥ 1122, normal EKG QTc interval (≤ 450 ms in male or ≤ 460 ms in female), and TnT decrement ≥ 42% by day 8 of immunosuppression (Table 1). All patients with long-term survival presented with a normal left ventricular ejection fraction (LVEF ≥ 55%), which made it uninterpretable using logistic regression models. Normal LVEF was significantly associated with long-term survival by using chi-square test (p = 0.002). While TnT elevation &gt; 75x the upper limit of normal (ULN) was strongly associated with short-term survival (p = 0.001), it was not associated with long-term survival (p = 0.23). The use of second-line immunosuppression in addition to corticosteroids did not have a significant impact on long-term survival (p = 0.69). Conclusions: NLR, ALC, NT-proBNP, QTc interval, and a substantial decrease in TnT at day 8 after immunosuppression are all associated with long-term survival in ICI myocarditis. [Table: see text]
Prevalence and predictors of coronary artery stent re-stenosis in patients with cancer with prior history of percutaneous coronary intervention: A nationwide analysis.
Authors: Badri Aryal, Alexandra Sueldo, Ekrem Turk, Andres Quevedo
Journal: Journal of Clinical Oncology (2024)

e24018 Background: Data regarding the prevalence, and predictors of development of in-stent restenosis (ISR) in cancer patients undergoing percutaneous coronary intervention (PCI) are scarce. This study aimed to identify factors associated with the development of ISR following PCI in cancer patients. Methods: This is a retrospective cohort study using the National Inpatient Sample(NIS) from 2016 to 2020. Discharges with ICD-10 CM code indicating stenosis of coronary artery stent, and secondary ICD-10 CM code indicating cancer, and prior history of PCI were included. Primary outcome was development of ISR. Multivariate logistic regression model was used to identify predictors of ISR development, and p value of less than 0.05 was considered significant. Results: There were 873,320 patients who met inclusion criteria, among which 4060 patients were admitted for coronary stent re-stenosis. Mean age of included patients was 73, and 31% were females. The prevalence rate of in-stent restenosis was 0.46%. Factors associated with increased odds of development of ISR included diabetes (OR 1.31, 95% CI 1.13-1.51, p &lt; 0.001), dyslipidemia (OR 1.92, 95% CI 1.60-2.31, p &lt; 0.001), congestive heart failure (OR 1.78, 95% CI 1.52-2.06, p &lt; 0.01), carotid disease (OR 1.99, 95% CI 1.43-2.78, p &lt; 0.001), and aortic disease (OR 1.83, 95% CI 1.12-2.98, p 0.01). Age, gender, race, median household income, hospital location and hospital teaching status didn’t exhibit statistically significant increased risk. Conclusions: The prevalence of in-stent restenosis was 0.46%. Appropriate management of risk factors such as diabetes, dyslipidaemia, congestive heart failure is prudent to prevent development of ISR in cancer patients, underscoring the importance of regular cardiology follow up, along with routine cancer care.
Feasibility of hydromorphone PCA 10-day simple mode home management of patients in severe pain: A prospective multicenter study.
Authors: Kelei Zhao, Yu Han, Chunqing Li, Guifang Zhang, Junling He, Wei Chang, Haiqing Yin, Yuelong Cui, Yanhu Dong, Yibo Yao, Guorong Chen, Pei Wang, Dongxia Tang, Hua Dong, Qiang Zhang, Bo Li, Min Zhang, Yinghua Ji, Ping Lu
Journal: Journal of Clinical Oncology (2024)

e24072 Background: Pain is a common symptom affecting patients with cancer. In clinical practice patients with advanced refractory cancer pain often face multiple anti-tumor treatments and prefer treatment at home or in community clinics versus hospitalization; thus, pain relief and drug management are challenging. Patient-controlled analgesia (PCA) is an essential component of analgesic treatment. However, difficulties associated with PCA configuration, unified pump configuration mode, and tube blockage may limit its use by both doctors and patients, negatively affecting large-scale promotion of PCA technology in hospitals and at home. In this study we optimized PCA parameters to resolve problems around cumbersome operation and tube blockage, thereby increasing pump utility and feasibility. We refer to this mode as the "10-day simple mode." The study objective is to evaluate the analgesic effect of the "10-day simple mode" of hydromorphone PCA and to explore its home-based convenience and use. Methods: A total of 100 patients with refractory cancer pain were included in this study. The pump configuration mode was divided into two stages. The first (titration) stage was: hydromorphone + normal saline with a total volume of 24 ml and pump speed of 1.0 ml/h. The second (maintenance) stage was: hydromorphone + normal saline with a total volume of 288 ml and pump speed of 1.2 ml/h with PCA of 2.4 ml. During the maintenance stage, if pain control was unsatisfactory the background dose was increased based on the number of PCA presses in the previous 24 hours. Patients' numeric rating scale (NRS) scores, quality of life scores, and adverse reactions were recorded before and after treatment. Results: Patients' average NRS score before treatment was 7.4 (7-10). Average time to successful titration was 49.6 minutes (35.6-56.9) and 40.7% of patients achieved successful titration within 30 minutes. After titration, the average NRS score was 3.2 (0-6). There was a statistically significant difference in NRS scores before and after titration (p &lt; 0.05). During maintenance, 56.0% of patients experienced breakthrough pain on day 1, when the average NRS score was 5.2. As background dosing continued breakthrough pain and average NRS score gradually decreased (p &lt; 0.05). Quality of life scores and patient satisfaction measured before and after 10 days of PCA pump use showed significant improvement (p &lt; 0.001). Conclusions: For patients with refractory cancer pain, the hydromorphone PCA "10-day simple mode" produces good analgesic effect, is easy to manage, and suitable for patients seeking home-based pain relief. These results warrant further clinical study. Clinical trial information: NCT05744089 .
Pathological complete response to predict long term outcomes in the I-SPY2 TRIAL.
Authors: Douglas Yee, Laura Esserman, Christina Yau
Journal: Journal of Clinical Oncology (2024)

597 Background: The I-SPY2 platform trial uses pathologic complete response (pCR) to identify active agents in patients with stage 2/3 breast cancer. Only patients with HR+ HER2- tumors, and low risk 70-gene assay results are excluded. 2118 patients were enrolled from March 2010 through June 2022 with follow-up data from 2005 patients as of January 2024. We have reported the improved event-free (EFS) and distant-recurrence free (DRFS) survival for 950 patients (1) who achieved a pathological complete response (pCR). Here we report the outcomes for the additional 1055 patients not included in our initial report. Methods: Patients have been randomized to one of 25 arms. Residual Cancer Burden (RCB) assessment was performed by site pathologists who were trained to ensure uniform response classification; RCB 0 = pCR. EFS is defined as time to local or distant recurrence or death. DRFS is defined as time to distant recurrence or death. Patients without events were censored at time to last follow-up. Association between pCR and EFS/DRFS was assessed using Cox proportional hazard modeling with significance assessment using the log rank test. EFS and DRFS at 3 years are estimated using the Kaplan Meier method. Results: Median follow up was 3.3 years (0.05-10.2 y). There were 144 EFS and 123 DRFS events. pCR rates varied by subtype, but achieving pCR was associated with an EFS of 96% and DRFS of 96%. For patients without pCR the EFS was 82% and DRFS was 84% at 3 years. The relationship between pCR and EFS was significant and clinically impactful within each subtype. Conclusions: pCR continues to have a strong positive association with EFS and DRFS as in our initial report. It is notable that EFS for non-pCR patients improved to 82% from our initial report of 78%. Initially few patients received additional adjuvant therapy except for standard of care endocrine and HER2-targeted therapy. Increased adoption of post neoadjuvant therapy with the approval of several agents for patients with non-pCR likely contributed to this improvement. I-SPY also reported a shift in residual cancer burden for patients receiving investigational therapies, which also may improve outcome for non-pCR patients. Taken together, these data demonstrate the value of pCR as an early endpoint regardless of tumor type or drugs delivered. These findings emphasize the need for new agents that will allow all patients to achieve pCR and potentially avoid the need for additional therapy after surgery. 1. Yee, et al. JAMA Oncol 2020. 2. Symmans, et al. JAMA Oncol 2021. Clinical trial information: NCT01042379 . [Table: see text]
Predictive biomarkers for pathological complete response in early-stage triple negative breast cancer following neoadjuvant chemotherapy.
Authors: Gabriel Berlingieri Polho, Laura Testa, ROMUALDO BARROSO-SOUSA, Renata Colombo Bonadio
Journal: Journal of Clinical Oncology (2024)

598 Background: Identifying predictive biomarkers for early-stage triple negative breast cancer (TNBC) is essential for tailoring neoadjuvant chemotherapy (NACT) strategies effectively. Methods: We investigated potential clinical and pathological biomarkers in early-stage TNBC patients who underwent NACT regimens with anthracyclines and taxanes at a single cancer center. Medical records were scrutinized for clinical and laboratory data, with categorical variables analyzed using Fisher’s exact test. Logistic regression assessed factors associated with pathological complete response (pCR). Sensitivity and specificity of the biomarkers were explored using receiver operating characteristics (ROC) curve analyses. Results: Among 110 TNBC patients receiving anthracycline- and taxane-based NACT with complete pathology data, the median age was 48 years, 60% had stage III tumors, and 30.9% achieved pCR. Stromal tumor infiltrating lymphocytes (TILs) &gt; 10% were observed in 54.5%, 32.7% had TILs ≥30%, and 90.9% had Ki67 ≥ 50%. Univariate analysis showed no association between pCR and TILs &gt;10% (p=0.5), Ki67 ≥ 50% (p=0.4), anatomic stage (p=0.06), eosinophil-to-lymphocyte ratio (p=0.3), platelet-to-lymphocyte ratio (p=0.08), age (p=0.5), grade (p=0.6), or HER2 status (p=0.6). Neutrophil-to-lymphocyte ratio (NLR) was significantly associated with pCR in both univariate (OR 3.92; 95% CI 1.67 - 9.57; p=0.002) and multivariable analyses (Table). No association was observed between NLR ≤ 1.76 and TILs, anatomic stage, or Ki67. The optimal NLR cutoff using ROC curve was 1.76, yielding 60.6% sensitivity and 71.8% specificity for pCR. NLR cutoffs of ≤ 1.43 had specificities higher than 85%. Although TILs value was not associated with pCR in the regression model, high TILs value (≥50%) yielded a specificity of 89.4% for pCR. Conclusions: NLR emerged as a significant and independent predictor of pCR in early-stage TNBC. Prospective studies should explore this readily available biomarker in assessing neoadjuvant strategy responses. Moreover, high specificities for pCR were observed with NLR ≤ 1.43 and TILs ≥ 50%, representing cutoff values that could be explored for treatment de-escalation. [Table: see text]
Outcomes among hospitalized patients with colorectal cancer and comorbid congestive heart failure: A United States population-based cohort study.
Authors: Arshi Syal, Yajur Arya, Carlo Casipit, Phuuwadith Wattanachayakul, Bruce Adrian Casipit, Sarah Eidbo, John Charles Leighton, Claudia M. Dourado
Journal: Journal of Clinical Oncology (2024)

e24019 Background: Colorectal cancer is one of the leading causes of cancer related deaths in the United States. Advances in chemotherapeutics have improved survival in these patients, although with the potential for more adverse effects. Congestive heart failure continues to be an important comorbidity in patients with colorectal cancer. However, its impact on outcomes in this subgroup needs further exploration. Methods: We utilized the 2020 National Inpatient Sample (NIS) Database in conducting this retrospective cohort study. We identified patients with colorectal cancer and congestive heart failure using appropriate ICD-10 diagnostic codes. We stratified patients with colorectal cancer based on the presence or absence of congestive heart failure. A survey multivariable logistic and linear regression analysis was used to calculate adjusted odds ratios (ORs) for the primary and secondary outcomes. A p value of &lt; 0.05 was considered statistically significant. The aim of this study was to investigate the impact of congestive heart failure on in-hospital mortality, hospital length of stay (LOS), and total hospitalization charge among hospitalized patients with colorectal cancer. Results: We identified a total of 77130 hospitalized patients with colorectal cancer, of which 10.08% (7755/77130) had comorbid congestive heart failure. The overall in-hospital mortality among patients with colorectal cancer was 2.74% (2115/77130). Among those with comorbid congestive heart failure, the mortality rate was significantly higher at 6.5% (504/7755, p &lt; 0.001). Utilizing a stepwise survey multivariable logistic regression model that adjusted for patient and hospital level confounders, congestive heart failure was found to be an independent predictor of increased in-hospital mortality (adjusted OR 1.79; 95% (confidence interval [CI], 1.33-2.41; p &lt; 0.001), longer LOS (coefficient 2.42; CI 1.91-2.92; p &lt; 0.001), and higher total hospitalization charge (coefficient $22464; CI $15132- $29795; p &lt; 0.001). Conclusions: Our analysis demonstrated that congestive heart failure is widely prevalent in patients with colorectal cancer, and significantly worsens outcomes including increased in-hospital mortality, LOS, and cost of healthcare utilization. Early diagnosis and management of heart failure using guideline directed medical therapy along with close follow up may improve outcomes. Further prospective multicentric studies are warranted to better describe these associations.
Soluble guanylate cyclase activator vericiguat prevents anthracycline-mediated cardiotoxicity and sarcopenia through cGMP-NLRP3-cytokine pathway: Potential application in patients with cancer.
Authors: Martina Iovine, Vincenzo Quagliariello, Ilaria Giacobbe, Matteo Barbato, Vienna Giordano, Raffaele Arianna, Francesca Izzo, Massimiliano Berretta, Alessandro Inno, Michelino De Laurentiis, Nicola Maurea
Journal: Journal of Clinical Oncology (2024)

e24015 Background: Anthracycline-induced cardiomyopathies and sarcopenia are frequently seen in cancer patients, affecting their overall survival and quality of life; therefore, new cardioprotective strategies are needed in cardioncology. Vericiguat is a new oral guanylate cyclase activator that reduces heart failure hospitalizations or cardiovascular death through improvement of smooth muscle cell relaxation and reduction of myocardial fibrosis and inflammation. In this study, we highlight on the potential cardioprotective properties of vericiguat against anthracycline.mediated cardiotoxicity and sarcopenia. Methods: Human cardiomyocytes (AC-16 cells) and Primary Skeletal Muscle Cells (HSkMC cells) were exposed for 24h h to doxorubicin (DOXO) at 0,3 and 1 µM with or withour a pre-treatment with Vericiguat at 0.1 or 1 or 10 µM for 1h. Mithocondrial cell viability, LDH and Citocrome C release were performed to study cytoprotective properties. TUNEL assay, cGMP and NLRP-3, Myd-88 intracellular levels were quantified through colorimetric and selective ELISA methods. IL-1β, IL-6, IL-8, CXCL-2, TGF-β and IL-18 were also analyzed in cardiac and muscle cell lysates after treatments. Results: Vericiguat exerts a significant cytoprotective and anti-apoptotic effect in cardiac and muscle cell lines during exposure to DOXO. A drastic increase in cGMP expression and reduction in NLRP-3, Myd-88 levels were also seen in Vericiguat-DOXO groups vs DOXO groups ( p &lt; 0.001). Pro-inflammatory and cytotoxic cytokines were also downregulated after Vericiguat treatment during DOXO exposure. Conclusions: Vericiguat significantly reduced cardiotoxic effects and sarcopenia induced by DOXO therapy though enhancement of cGMP levels and reduction of NLRP-3/Myd-88/cytokines pathways. These findings provide a framework for future studies aiming to assess vericiguat for the primary prevention of anthracycline-mediated cardiotoxicity and sarcopenia.
Time to surgery after neoadjuvant chemotherapy in breast cancer and its impact on survival in a middle-income country.
Authors: Katherine Garcia, Lorena Sandoya, Walter Morquecho, Guillermo Paulson, Mayra Santacruz, Norma Castro, Ruth Engracia
Journal: Journal of Clinical Oncology (2024)

e12640 Background: The time to surgery after neoadjuvant chemotherapy (NACT) in breast cancer and its impact on survival has not been sufficiently evaluated in low- or middle-income countries. The objective of this study was to analyze the impact on overall survival in a cancer hospital in Guayaquil, Ecuador. Methods: This is a retrospective study carried out at the SOLCA Guayaquil Hospital in Ecuador from January 2009 to December 2011. The inclusion criteria were women ≥18 years old, diagnosed with invasive breast cancer in stages II and III, who were treated with NACT followed by surgery. The data were collected from clinical records; those with incomplete data were excluded, and the variables age, stage, lymphovascular invasion (LVI), and pathological response were included. Survival was grouped into &lt;8 and ≥8 weeks for the comparative analysis. Survival time was calculated from diagnosis by biopsy until death; A p-value of ˂0.05 was taken as significant; The Kaplan-Meier estimate was used for overall survival, then the groups were compared by Log Rank, and the influence of the covariates was estimated in the Cox regression model. The data were analyzed in an SPSS v29 statistical program. Results: 200 patients were identified, 195 of whom had all the information for the analysis. The median time between the end of NACT and surgery was 7.57 weeks (range, 2.43-29.14 weeks). In the &lt; 8 and ≥ 8 weeks group, there were 111 and 84 patients, respectively. The clinical characteristics are described in the Table. The median overall survival in the entire cohort was 8.32 years (CI: 6.68-9.96), and for the &lt; 8 and ≥ 8 weeks groups, it was 10.0 and 6.56 years, respectively, with a Log-Rank of 0.031. The follow-up (median) of the entire cohort was 7.54 years (range 0.63 – 10.99 years). The multivariate Cox regression showed that LVI, HR: 2.35 p&lt;0.001; clinical stage III (II vs III), HR: 2.47 p&lt;0.001; residual disease (pathological complete response vs residual disease), HR: 2.70 p=0.012; age ≤ 50 years (≤ 50 years vs &gt; 50 years), HR: 1.69 p=0.011; were factors that statistically contributed to worse survival, however, the time between the end of NACT and surgery &lt; 8 and ≥ 8 weeks (p = 0.07) had no statistical impact on survival. Nonetheless, a numerical trend towards better survival was noted in the &lt; 8 week group. Conclusions: The delay in time to surgery after NACT had a negative trend in survival, although it was not statistically significant, which may be due to the small sample size. [Table: see text]
The efficacy of ketamine for pain management in patients with cancer: A systematic review.
Authors: Leila Azari, Kimia Saleh Anaraki, Homa Hemati, Ronia Tavasolian, Sareh Shahdab, Stephanie M. Tomlinson, Margarita Bobonis Babilonia, Jeffrey Huang, Danielle Tometich, Kea Turner, Heather S.L. Jim, Amir Alishahi Tabriz
Journal: Journal of Clinical Oncology (2024)

e24069 Background: Managing cancer-related pain poses significant challenges, prompting research into alternative approaches such as the study of ketamine. This systematic review aims to analyze and summarize the impact of ketamine as an adjuvant to opioid therapy for cancer-related pain. Methods: We conducted a literature review in MEDLINE, EMBASE, and Scopus, spanning from January 1, 1982, to October 20, 2022. Abstracts were screened against inclusion criteria, and eligible studies underwent a thorough full-text review. Data were extracted from the included studies, and a framework analysis approach was employed to summarize the evidence regarding ketamine's use in patients with cancer. The quality of included studies was assessed using the NIH Quality Assessment Tool for controlled intervention studies. Results: A total of 22 studies conducted between 2001 and 2019 were included, all assessed as having good quality. Three studies focusing on intrathecal administration of ketamine following oncological surgery demonstrated a substantial improvement in pain scores and a reduction in postoperative morphine requirements. Two studies exploring intramuscular use concluded that it led to improved pain scores. In contrast, three studies on subcutaneous administration and two studies on topical ketamine did not exhibit a significant impact on reducing pain scores or alleviating chemotherapy-induced peripheral neuropathy. Findings from two studies on oral administration and eight studies on intravenous administration indicated that intravenous ketamine reduced postoperative morphine requirements, while oral ketamine had no discernible effect on lowering pain scores. Conclusions: The use of intrathecal ketamine demonstrates significant improvement in post-op oncological pain and refractory cancer pain, resulting in lowered pain scores and decreased morphine requirements. Further research is essential to ascertain the extent to which incorporating ketamine with opioids in cancer pain treatment can enhance pain outcomes, especially in morphine-tolerant patients.