tbuckley/cabot-search huggingface dataset:
Long-term efficacy of high-dose imatinib in Hispanic patients without access to second-generation tyrosine kinase inhibitors treated in LATAM centers.
Authors: Edgar Dorsey Trevino, Olga Graciela Cantu-Rodriguez, Karen Lorena Osorno-Rodriguez, Cesar Homero Gutierrez-Aguirre, Jose Carlos Jaime-Perez, Juan Pablo Gomez-Villarreal, Miguel Ricardo Rios-Rodelo, Graciela Alejandra Gonzalez-Cantu, Alan Contreras-Arce, David Gomez-Almaguer
Journal: Journal of Clinical Oncology (2024)

6512 Background: Treatment for patients with chronic myeloid leukemia (CML) had a benchmark with the introduction of imatinib, a tyrosine kinase inhibitor (TKI). Nevertheless, resistance due to genetic mutations in the BCR::ABL1 kinase receptor remains relatively common for many patients, leading to failure, lack of response, or suboptimal response. Ideally, to bypass genetic resistance, guidelines recommend switching to a second-generation TKI, but for many developing countries, socioeconomic barriers hinder the possibility of switching medication. Despite this scenario, scarce information is available to evaluate the clinical prognosis of these patients. Methods: We conducted a retrospective cohort analysis to compare the overall mortality of patients with CML who developed a suboptimal response to standard-dose imatinib and were treated with either high-dose imatinib or a second-generation TKI. We created a marginal structural model with inverse probability weighting and stabilized weights and depicted the survival curves and median using the Kaplan-Meier estimator. Our primary outcome was overall survival (OS) at 150 months, defined as the number of deaths once patients had reached treatment response based on parameters of the European Leukemia Net Guidelines for CML. Our secondary outcomes were disease-free survival (DFS) at 150 months, defined as the number of months after patients achieved either major molecular response or deep molecular response, and adverse events that included gastrointestinal, dermatologic, hematologic, and others. Results: The cohort included 148 patients, of which 32 received high-dose imatinib and 116 a second-generation TKI. While we found no difference in the 150-month risk in both OS and DFS (Table), patients receiving second-generation TKI had an increase in median survival of OS ( p-value = 0.009). No difference was found in the median survival of DFS ( p-value = 0.55). No difference was found in either hematologic, gastrointestinal, dermatologic, or other adverse events (p-values of 0.39, 0.94, 0.24, and 0.33, respectively). Conclusions: Ideally, patients who develop a suboptimal response to imatinib should be switched to a second-generation TKI. However, If impossible, our findings suggest that patients treated with high-dose imatinib have a similar OS and DFS prognosis to those receiving a second-generation TKI. [Table: see text]
Outpatient blinatumomab with digital monitoring in patients with measurable residual disease positive (MRD+) B-ALL in a phase 4 study.
Authors: Timothy S. Pardee, Juan Varela, Deepa Jeyakumar, Michael Kenneth Keng, Michal Bar-Natan, Krishna Gundabolu, Arlene Gayle, Christopher McCann, Qing Xia, Sofia Ganzha, Noemi Mergen, Faraz Zaman, Paul R. Gordon, Sharif S. Khan
Journal: Journal of Clinical Oncology (2024)

6544 Background: Blinatumomab, a CD3/CD19-directed BiTE ® (bispecific T-cell engager) molecule, is an effective therapy for patients (pts) with MRD+ B-ALL. Hospitalization is recommended for days (D) 1–3 of cycle (C) 1 and D1–2 of C2 for these pts receiving blinatumomab to monitor for serious adverse events (SAEs). This phase 4 study evaluated the safety and feasibility of outpatient (outpt) digital monitoring to replace hospitalization in pts with MRD+ B-ALL (NCT04506086). Methods: Enrolled adults with MRD+ B-ALL in complete remission received continuous intravenous (cIV) blinatumomab at 28 μg/day. Current Health Wearable Monitoring System (CHWMS) was worn by pts at home for D1–3 (C1) and D1–2 (C2), in the presence of a caregiver, and provided heart rate, respiratory rate, and oxygen saturation; a separate patch monitored temperature. Manual blood pressure measurements were taken every 3-6 hrs. Vital signs (VS) were streamed to a provider smartphone/laptop; changes outside a predetermined threshold generated audible alarms. The primary endpoint was incidence of grade (G) ≥3 cytokine release syndrome (CRS), neurotoxicity, or any adverse event (AE) requiring hospitalization during the monitoring period. Results: As of 12/15/2023, 9 pts (median age 43 [20-73] years) received outpt blinatumomab for (completed C1, n=7; C2, n=6). During outpt monitoring, dose interruption was reported in 5 of 9 pts (1 pt had 2 dose interruptions: AE, n=2; dose administration error, n=2; other, n=2). CRS was reported in 2 pts (SAE, n=1; G≥3, n=0; led to interruption, n=1) and neurologic events in 4 pts (SAE, n=0; G≥3, n=0; led to interruption, n=0). Two pts experienced AEs requiring hospitalization (CRS, n=1; fever, n=1). Most VS changes were physiological or from routine pt activity. Median (range) number of alarms triggered/pt was 79 (12-135); among 3 pts, 1.2%, 5.1% and 8.9% of alarms led to therapeutic intervention (Table). Conclusions: To date, outpt administration of cIV blinatumomab in pts with MRD+ B-ALL was feasible and safe with appropriate outpt digital monitoring. Study enrollment is ongoing. Clinical trial information: NCT04506086 . [Table: see text]
Phase I study of CN201, a novel CD3xCD19 IgG4 bispecific antibody, in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Authors: Ying Wang, Qingsong Yin, Jinhai Ren, Hongsheng Zhou, Tiejun Gong, Feng Zhu, Xi Zhang, Qin Wen, Heng Mei, Wei Huang, Haiying Li, Jianxiang Wang
Journal: Journal of Clinical Oncology (2024)

6505 Background: Patients with relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL) still need more and better treatment options. CN201 is a novel CD19-targeting T-cell-engaging IgG4 bispecific antibody. This phase I study is to investigate the safety, tolerability and preliminary efficacy of CN201 in B-ALL (ClinicalTrials.gov identifier: NCT05579132). The data from the dose escalation and expansion of the ongoing study is presented. Methods: The study is enrolling patients with B-ALL who are refractory to primary induction therapy or to salvage therapy, or relapse. Patients with Philadelphia chromosome-positive after two or more tyrosine kinase inhibitors (TKIs) were eligible. Single-agent CN201 was administered intravenously once per week with a step-up dose approach during cycle 1, a priming dose on Day 1 followed by an intermediate dose on Day 8 and the target dose administered on Day 15 and thereafter. The patients will receive 2 cycles of CN201 for induction. Responders will continue to receive a further 3 cycles for consolidation, and up to an additional 7 cycles for maintenance treatment or until PD or unacceptable toxicity. Results: As of January 31, 2024, 42 adult patients received CN201 with full dose from 600 μg to 40mg. 37 patients were evaluable for efficacy (Table1). Maximum tolerated dose has not reached. The most common adverse events (≥20%) of grade 3 or higher were leukopenia (47.6%), lymphopenia (42.9%), neutropenia (38%), thrombopenia (33.3%) , anaemia (26.2%). 6 patients (14.3%) had infections of grade 3 or higher. Cytokine release syndrome occurred in 13 (30.9%) patients, mainly occurred following the first dose, most were low-grade, except for one patient with grade 3. No immune effector cell-associated neurotoxicity syndrome was observed. Overall, 11 (30%) of 37 patients had complete remission (CR), 1 (2.7%) patient had complete remission with incomplete haematological recovery (CRi), 75% of responders had MRD negativity. The CR rate significantly increased with dose descalation, reached 50% (4 of 8 patients) with 10mg target dose, two of those occurred within the first two weeks following CN201 treatment. Among those responders, 100% were MRD negative. The CR rate in patients with higher dose levels are under investigation. Conclusions: Preliminary data show CN201 has a well tolerable safety profile and promising activity in adult patients with relapsed or refractory ALL. Clinical trial information: NCT05579132 . [Table: see text]
Impact of pneumocystis pneumonia on clinical outcomes in patients with lung malignancy compared to other malignancies.
Authors: Ayobami Gbenga Olafimihan, Inimfon Jackson, Stanley Ozogbo, Gbolahan Olatunji, Emmanuel Kokori, Nicholas Aderinto, Praise Fawehinmi, Michael Russell Mullane, Alexandra Sueldo, Alejandro Vallejo
Journal: Journal of Clinical Oncology (2024)

e20001 Background: Pneumocystis pneumonia (PCP) is an opportunistic infection that causes significant morbidity and mortality in cancer patients. Although infrequent in solid malignancies, limited studies suggest that PCP portends a worse outcome in patients with lung cancer. We examined hospitalization outcomes for PCP among patients with lung cancer relative to other malignancies. Methods: A retrospective cohort analysis using the Nationwide Inpatient Sample (NIS) database (2010-2019) was conducted. Using ICD-9 and ICD-10 codes, cancer patients admitted for PCP were identified and stratified based on their diagnosis of lung cancer versus other cancer types. Primary outcomes were inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included odds of mechanical ventilation, ICU care, bronchoscopy, and palliative care. Statistical analyses were performed using t-tests, univariate and multivariate logistic regression. Results: Among 5,408 hospitalizations for PCP in cancer patients, 10.6% had a diagnosis of lung cancer and 89.4% had other cancer types. Lung cancer patients were older (mean age: 66 vs 62 years; p = 0.001) and had a higher Charlson comorbidity burden (&gt;2) compared to those with other cancers (69.8 vs 34.2%; p&lt;0.001). 31% of lung cancer patients admitted for PCP died compared to 16% of patients with other cancer types ( p&lt;0.001). Multivariate regression analysis showed that hospitalized PCP patients with lung cancer had two-fold higher odds of hospital-associated mortality relative to those with other cancer types (adjusted odds ratio (aOR): 2.2; 95% confidence interval (CI): 1.39-3.37; p = 0.001). Both cohorts had similar LOS (aOR: 0.86; P=0.61; 95% CI: 0.5-1.5) and THC (β -15,377; p=0.113; 95% CI= -34,407-3,653). Among secondary outcomes, lung cancer patients admitted for PCP had higher odds of mechanical ventilation (25.3 vs 17.7%; aOR: 1.61; p = 0.046) and palliative care utilization (24 vs 13%; p=0.002). Conclusions: Pneumocystis pneumonia is associated with significantly higher inpatient mortality among patients with lung cancer compared to other cancers. These patients also had higher rates of mechanical ventilation and palliative care utilization. Health care providers need to maintain a high index of suspicion to facilitate early diagnosis and intervention in order to mitigate adverse outcomes.[Table: see text]
Long-term survival of single and multifocal stage 1 lung carcinoma using image-guided thermal ablation.
Authors: Noor J. Jahanshahi, Soheil Kooraki, Bianca Villegas, Grace Hyun J. Kim, Jonathan W. Goldman, Scott J. Genshaft, Robert D. Suh, Fereidoun Abtin
Journal: Journal of Clinical Oncology (2024)

e20087 Background: Image-guided thermal ablation (IGTA) is an effective treatment option for patients with non-small cell lung cancers (NSCLC), offering an excellent alternative to invasive surgery. We seek to compare long-term survival metrics between single and multifocal stage IA NSCLC patients who underwent IGTA. Methods: IRB-approved, HIPAA-compliant, retrospective study of patients who underwent IGTA for NSCLC during 2015 and 2016. Patient demographics, clinical and imaging follow-ups, tumor characteristics, and procedural technical outcomes were reviewed. We analyzed technical success, 5-year overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), and Kaplan-Meier survival analysis between single and multifocal NSCLC cohorts, as well as different tumor stages. Results: 37 patients (mean ± SD age=71.6±8.8) ablated for single (n=15 (40.5%)) or multifocal (n=22 (59.5%)) NSCLC were identified. Multifocal NSCLC were sub-classified into 2-3 (n=12 (32.4%)) and ≥4 tumors (n=10 (27%)). All ablations were completed successfully. Across 119 IGTA encounters, patients were treated using cryoablation (n=66), microwave ablation (MWA) (n=49), and radiofrequency ablation (RFA) (n=4). At the time of ablation, individual nodules were staged at T1A=46 (38.7%), T1B=54 (45.4%), T1C=16 (13.5%) and T2A=3 (2.5%). Local recurrence was observed in 4/119 (3.3%) tumors; two were reablated once with MWA and cryoablation with no further recurrence, the third was reablated twice with MWA and had no recurrence, and the fourth was reablated once with MWA and subsequently treated with radiotherapy. Multifocal NSCLC patients exhibited significantly better 5-year OS of 85.6% compared to single NSCLC patients at 35.7% (HR=0.14, p=0.003, 95% CI: 0.037, 0.51). PFS and CSS at 5 years were higher for multifocal NSCLC compared to single NSCLC, but only significant for PFS (HR=0.25, p=0.014, 95% CI: 0.084, 0.76). PFS and CSS of subjects with ≥4 tumors were both 100%, 2-3 tumors at 58.7% and 90.9%, and single tumors at 35.7% and 83.1%, respectively. There was no significant difference between tumor T stages for OS and PFS (p=0.48 and p=0.56, respectively; see Table). No patient staged at T1A at the initial IGTA encounter died as a result of cancer, meaning cancer-specific survival was greatest in T1A tumors (see Table). Conclusions: IGTA is an effective treatment for multifocal and early-stage NSCLC. Our results demonstrated consistent trends in improved survival for multifocal NSCLC. The size of tumor up to 3 cm did not have significant impact on overall survival or progression-free survival. [Table: see text]
Cardiac substructure radiation dose study of conventional radiotherapy for stage N2-3 non-small cell lung cancer.
Authors: Yiying Zhu, Weiwei Ouyang, Shengfa Su, Zhu Ma, Qingsong Li, Wengang Yang, Bing Lu
Journal: Journal of Clinical Oncology (2024)

e20071 Background: There has been widespread reporting on predictive dose parameters for cardiac substructures in radiotherapy for non-small cell lung cancer (NSCLC). However, most advanced NSCLC patients are staged as N2-3, and there is a lack of research on the dose distribution, dose contribution and prognosis of the heart in conventional radiotherapy for N2-3 stage NSCLC. Methods: Retrospective analysis of 274 patients of stage N2-3 NSCLC treated with radiotherapy (RT) of prescription dose from 60Gy to 70Gy. Experienced radiation oncologists delineated the cardiac substructures. All patients were categorized according to different lymph node irradiation and tumor spatial locations. Spearman and linear regression were used for variation of dose-volume parameters, as well as the impact of different primary tumor locations and irradiated lymph nodes on the parameters of the entire heart and substructures. Receiver operating characteristic (ROC) curves, Kaplan-Meier, and Cox regression were performed on the influencing factors of adverse cardiac events after radiotherapy and prognosis analysis. Results: There are significant differences in the dose-volume parameters of the whole heart and its substructures. Mean heart doses (MHD),and the mean doses (Dmean) for the left atrium, right atrium, right ventricle, left ventricle and the left anterior descending coronary artery (LAD) were 15.7Gy (range 0.2-30.0Gy), 19.7Gy (range 0.3-55.0Gy), 9.7Gy (range 0.3-59.8Gy), 7.9Gy (range 0.1-48.2Gy), 6.4Gy (range 0.1-52.6Gy) and 5.2Gy (range 0.1-45.0Gy), respectively. The left atrium Dmean has the most significant impact on MHD compared to other substructures (B = 0.418, P &lt; 0.05). Dose-volume parameters of the whole heart and the left atrium were positively correlated with the irradiation of the 7th lymph node region (P &lt; 0.05). MHD and left atrium Dmean for tumors located in the lower region were significantly higher than those in the upper region (P &lt; 0.001). Patients with LAD V30 ≥ 26.9% had a significantly higher risk of mortality compared to those with LAD V30 &lt; 26.9% (P = 0.003, HR = 2.883, 95% CI = 1.436-5.788). Conclusions: With the dose distribution differences among the whole heart and its substructures. We observed the base of the heart received the highest dose, the dose to the left atrium is particularly required attention. The irradiation of different lymph nodes and different primary lesions has an impact on the dose variations of different cardiac structures. LAD V30 is an independent influencing factor of overall survival (OS) for N2-3 stage NSCLC. This study provides considerable information for the dose optimization of cardiac substructure in radiotherapy planning for N2-3 stage NSCLC.
Incidence trends and factors affecting survival in mucinous adenocarcinoma of the lung: Insights from SEER data.
Authors: Nikhila Aimalla, Meghana Kesireddy, Lekha Yadukumar
Journal: Journal of Clinical Oncology (2024)

e20090 Background: Lung cancer is the second most common cancer in terms of incidence and the leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) accounts for 80 to 85% of cases. Adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma are the main subtypes of NSCLC. Mucinous adenocarcinoma is the least common subtype of lung adenocarcinoma with poor prognosis. Our study aims to identify demographics, incidence trends, and factors impacting overall survival (OS) in mucinous adenocarcinoma of the lung. Methods: We conducted a retrospective cohort analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database to investigate patients diagnosed with mucinous adenocarcinoma of the lung between the years 2000 and 2020. Demographics, treatment data were characterized using descriptive statistics. The Cox proportional regression analysis was used to identify the factors that impact the OS. Results: Between 2000-2020, a total of 7,953 patients were diagnosed with mucinous adenocarcinoma of the lung. The highest incidence of mucinous adenocarcinoma was in older adults, accounting for 67% of all cases. Females had a higher incidence rate at 53.6%. Caucasians comprised the majority of patients at 83.1%, followed by blacks at 8.8%. The majority of patients, 89.3% resided in urban areas, and 43.6% had annual incomes exceeding $75k. Most of the patients were married at 58.2%. The incidence trends revealed a significant increase from 2000 to 2020. The incidence rates were: 15.76% (2000 -2004), 16.37% (2005 -2009), 31.08% (2010 - 2014), and 36.79% (2015-2020). However, the survival rates improved over time (See table). Among the demographic factors: adults, females, Asian/ Natives/ &amp; other races combined, urban residence, higher annual income (&gt; $75k), and married status had better OS outcomes than their counterparts. Among disease stages, localized disease had the best, while regional disease had a better OS than distant disease. In terms of treatment, surgery was associated with better OS; interestingly, receipt of radiation or chemotherapy was not associated with better OS. The HRs of all these factors are shown in Table. Conclusions: Our study, the largest to date on mucinous adenocarcinoma of the lung, demonstrated a rising incidence yet with improved OS rates from 2000-2020. Our findings shed light on the demographics and other factors influencing OS in this rare subtype of NSCLC. [Table: see text]
CASTOR1 phosphorylation as a predictor of survival in male patients with <i>KRAS</i>-mutated lung adenocarcinoma.
Authors: Suet Kee Loo, Gabriel Sica, Xian Wang, Tingting Li, Luping Chen, Autumn Gaither-Davis, Yufei Huang, Timothy F. Burns, Laura P. Stabile, Shou-Jiang Gao
Journal: Journal of Clinical Oncology (2024)

e20015 Background: Lung cancer, a leading global cause of cancer-related mortality, necessitates enhanced prognostic markers for improved treatment outcomes. This study focuses on the predictive value of phosphorylated cytosolic arginine sensor for mTORC1 subunit 1 at S14 (pCASTOR1) in lung adenocarcinoma (LUAD) patients, specifically in males with KRAS mutations. Methods: This retrospective study, approved by University of Pittsburgh IRB, utilized formaline-fixed paraffin embedded primary tissues from two independent cohorts of patients who underwent thoracic surgical procedures at the University of Pittsburgh Medical Center (UPMC) from 2002 to 2011. Comprehensive clinical, demographical and pathological information was obtained from UPMC Cancer Registry, with cases lacking incomplete information excluded from analysis. Study endpoints included overall survival (OS) and relapse-free survival (RFS). An antibody targeting pCASTOR1 was employed to analyze LUAD tumor and adjacent non-tumor lung tissues from both cohorts. A pathologist, blinded to patient information and survival outcomes, conducted scoring in 5% increments. Scores were categorized as low or high pCASTOR1 based on second or third quartile. Correlations between pCASTOR1 scores and OS/RFS were examined, stratifying by clinical, pathological, demographic, or genotype data. Univariate OS and RFS analyses were conducted using the Kaplan-Meier method and log-rank test, while multivariate survival significance was assessed via Cox regression analysis. Additionally, unpaired T-tests were utilized to compare pCASTOR1 levels between non-tumor and tumor cells. A significance threshold of p &lt; 0.05 was applied for all analyses. Results: Tumor cells exhibited significantly elevated pCASTOR1 scores compared to non-tumor cells in both cohorts (P &lt; 0.05). High pCASTOR1 scores predicted poor OS (HR = 3.3, P = 0.0008) and RFS (HR = 3.0, P = 0.0035) in male patients with KRAS mutations in Cohort 1. pCASTOR1 remained an independent predictor for OS (HR = 4.1, P = 0.0047) and RFS (HR = 3.5, P = 0.0342) after controlling for other factors. Cohort 2, comprised solely of smokers with incomplete genotype information, validated these findings, with high pCASTOR1 scores correlating with worse OS (HR = 4.8, P = 0.0363). Notably, in early-stage LUAD, elevated pCASTOR1 scores were associated with significantly worse OS (HR = 3.3, P = 0.0176) and RFS (HR = 3.1, P = 0.0277) in male patients with KRAS mutations in Cohort 1, and worse OS (HR = 5.0, P = 0.0069) and RFS (HR = 5.0, P = 0.0069) in Cohort 2, akin to late-stage patients. Conclusions: Elevated pCASTOR1 score serves as a robust biomarker predicting poor OS and RFS in male LUAD patients with KRAS mutations, offering potential clinical utility in optimizing treatment strategies for this subgroup.