tbuckley/cabot-search huggingface dataset:
Major pathologic response and long-term clinical benefit in hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer after neoadjuvant chemotherapy.
Authors: Lei ji, Xi Chen, Xiaoyan Qian, Min Xiao, Qing Li, Qiao Li, Jiayu Wang, Ying Fan, Yang Luo, Shanshan Chen, Fei Ma, Binghe Xu, Pin Zhang
Journal: Journal of Clinical Oncology (2024)

e12608 Background: Rates of pathological complete response (pCR) are much lower in patients with hormone receptor–positive (HR+) /HER2-negative (HER2-) breast cancer than in those with HER2-positive and triple-negative breast cancer (TNBC). The majority of HR+/HER2- breast cancer patients can also achieve long-term survival despite not attaining pCR, indicating limited prognostic value of pCR in this population. This study aimed to identify novel pathologic end points for predicting long-term outcomes in HR+/HER2- breast cancer after neoadjuvant chemotherapy. Methods: We analyzed HR+/HER2- breast cancer patients with stage II-III tumors who underwent curative surgery after neoadjuvant chemotherapy from three hospitals. Major pathologic response (MPR), defined as the presence of Miller-Payne grades 3-5 and positive lymph node ratio of ≤10%, was used as a pathological evaluation indicator. MPR evaluates the extent of residual invasive carcinoma in both the breast and axillary lymph nodes following neoadjuvant therapy. We assessed the association between MPR and event-free survival (EFS) and performed Multivariable Cox regression to identify independent factors associated with EFS. Results: From January 2010 to December 2020, 386 patients were included in the final analysis. The median age was 46 years. 244 patients (63.2%) were premenopausal, with 271 (70.2%) patients diagnosed with stage III disease. The predominant neoadjuvant chemotherapy regimen was anthracycline combined taxane (79.3%). 28 patients (7.3%) achieved pCR and 118 patients (30.6%) achieved MPR. The median duration of follow-up was 54.4 months. Multivariate analysis showed that PR expression, Clinical stage, Miller–Payne grades and Positive lymph node ratio were independent prognostic factors for EFS (all P values &lt;0.05). The prognostic effect of MPR remained in multivariable models (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.26–0.76; P = 0.008), with 5-year EFS of 87% vs. 68% in the non-MPR group. In non-pCR patients, those who achieved MPR exhibited a similar EFS compared with pCR patients (HR, 2.25; 95% CI, 0.51–9.84; P = 0.28). Conclusions: MPR was a novel pathologic end point for prognostic evaluation in HR+/HER2- breast cancer after neoadjuvant chemotherapy. Compared to pCR, MPR may hold greater applicability in the prognosis evaluation.
A retrospective, single-center study comparing two neoadjuvant protocols for patients with HER2-positive breast cancer.
Authors: Amit Itay, Opher Globus, Keren Levanon, Tal Sella, Rinat Bernstein-Molho, Tal Shapira Rotenberg, Cecilie Oedegaard, Dana Fourey, Einav Nili Gal-Yam
Journal: Journal of Clinical Oncology (2024)

e12623 Background: Neoadjuvant treatment is common in Stage 2+3 HER2 positive tumors. Cytotoxic and anti-HER2 drug combinations are used. Pathological complete response (pCR) correlates with improved survival and decreased risk of relapse. Trastuzumab may cause temporarily congestive heart failure (CHF) while anthracyclines may cause irreversible CHF. Current guidelines advise non-anthracycline based regimens. Here, we compare the efficacy and toxicity of these two regimens. Methods: Retrospective data were collected on 179 patients with clinical stage II-III, who received neoadjuvant treatment with either 6 cycles of DCHP (Docetaxel, Carboplatin AUC6 [53.2% received AUC5], Trastuzumab, Pertuzumab) or ACTHP (doxorubicin, cyclophosphamide followed by weekly Paclitaxel combined with HP). According to pCR response post surgery, adjuvant HP or TDM-1 were given to go complete one year of treatment. Efficacy Indices of pCR were evaluated in both cohorts and according to HER2 IHC staining (3+ or 2+ FISH positive), hormone receptor (HR) and nodal status. Toxicity indices were reductions in left ventricular ejection fraction (LVEF), dose reductions, hospitalizations and febrile neutropenia. Results: Between 9.2017 and 6.2022, 106 patients received ACTHP and 73 received DCHP. Median age at diagnosis, HR status, HER2 IHC (2+FISHpos or 3+) and nodal status were balanced. PCR occurred in 63.1% of all patients, numerically higher in the ACTHP group at 67.0% vs. 57.5% in the DCPH group (p=0.129). Symptomatic LVEF decrease (&gt;10% or LVEF≤50%) was observed in 6.6% of the ACTHP group vs. 0% in the DCHP group (p&lt;0.001). Hospitalization rates were similar (14%). Dose reductions occurred more often in the DCHP regimen vs ACTHP (54.8% vs 24.5% respectively) (p&lt;0.00001) mostly due to asthenia and diarrhea. Febrile neutropenia was slightly higher in the ACTHP group but not statistically significant. Conclusions: In this study, pCR rates were numerically better in the ACTHP regimen vs. DCHP, though not statistically significant. Dose reductions were more common in the DCHP but had less cardiotoxicity. pCR rates were relatively low in both regimens where Her-2 +2, FISH pos. This study shows that the DCHP is a safe and effective alternative to anthracycline based chemotherapy though total dosage may be an important factor in the level of pCR.[Table: see text]
Remote patient monitoring for early detection of immune checkpoint inhibitor therapy-related pneumonitis in high-risk patients: A pilot-feasibility study.
Authors: Antonious Ziad Hazim, Gordon Ruan, Joshua Pritchett, Bobby Anderson, Konstantinos Leventakos, Ashley Egan
Journal: Journal of Clinical Oncology (2024)

e13806 Background: Immune checkpoint inhibitor therapy-related (ICI) pneumonitis poses a significant challenge for patients with cancer. It is associated with increased clinical morbidity and mortality, often resulting in prolonged hospital stays and delays and/or discontinuation of cancer-directed treatment. Early detection and prompt treatment of ICI pneumonitis is critical to improve patient outcomes. Therefore, our institution implemented a remote patient monitoring (RPM) program leveraging in-home, electronic health record-integrated technology and virtual centralized nursing to monitor vital signs and patient symptoms in “high-risk” patients treated with immunotherapy. Methods: Patients receiving immunotherapy deemed to be “high-risk” for ICI pneumonitis seen at Mayo Clinic Rochester, Minnesota were offered enrollment in the RPM program beginning in June 2023. High-risk patients included those with pre-existing lung disease (chronic obstructive pulmonary disease, interstitial lung disease); those with a history of resolved ICI pneumonitis being rechallenged with immunotherapy; and those with grade 1 ICI pneumonitis continuing immunotherapy. Eligible patients who agreed to participate in the program were provided a kit consisting of RPM technology and electronic symptom questionnaires. The kit included an armband for continuous vital sign monitoring, a blood pressure monitor, a scale to measure weight, and a pre-connected cellular-enabled tablet for questionnaire answering. RPM data utilized real-time electronic health system integration and predetermined parameters to alert RPM nurses. Pre-specified escalation care pathways were then used to respond and escalate care, as necessary. The primary outcome of this pilot study was to assess the feasibility of implementing an RPM program in this patient population with a secondary outcome to determine the ability to detect ICI pneumonitis before significant clinical symptoms. Results: Sixteen patients were enrolled of whom 5 declined participation (2 due to inconvenience and 3 for unclear reasons) resulting in 11 patients who underwent monitoring. Five patients graduated monitoring without detection of ICI pneumonitis within a 4-month timeframe. Six patients are currently undergoing RPM. 372 alerts occurred of which 8 (2%) were escalated to physician review. These alerts included elevated heart rate in 4, shortness of breath in 3, and elevated blood pressure in 1. One patient was triaged to an emergency department and diagnosed with grade 2 ICI pneumonitis. Conclusions: We show that RPM in patients who are at high-risk for developing ICI pneumonitis can be effectively integrated into a care model and monitor pneumonitis related symptoms. Further studies are needed to prove whether RPM is beneficial in this population including other ICI toxicities.
Optimizing Triage of Ambulatory Patients With Advanced Heart Failure
Authors: Keith D Aaronson, Garrick C Stewart, Lynne W Stevenson, Blair Richards, Shokoufeh Khalatbari, Thomas C Cascino, Amrut V Ambardekar, Josef Stehlik, Anuradha Lala, Michelle M Kittleson, Maryse Palardy, Maria M Mountis, Francis D Pagani, Neal Jeffries, Wendy C Taddei-Peters, Douglas L Mann
Journal: JACC Heart Failure (2024)
Considerations in the Diagnosis and Management of Pulmonary Hypertension Associated With Left Heart Disease
Authors: Onyedika J. Ilonze, Imo A. Ebong, Maya Guglin, Ajith Nair, Jonathan Rich, Vallerie McLaughlin, Ryan J. Tedford, Sula Mazimba
Journal: JACC Heart Failure (2024)

Pulmonary hypertension associated with left heart disease (PH-LHD) remains the most common cause of pulmonary hypertension globally. Etiologies include heart failure with reduced and preserved ejection fraction and left-sided valvular heart diseases. Despite the increasing prevalence of PH-LHD, there remains a paucity of knowledge about the hemodynamic definition, diagnosis, treatment modalities, and prognosis among clinicians. Moreover, clinical trials have produced mixed results on the usefulness of pulmonary vasodilator therapies for PH-LHD. In this expert review, we have outlined the critical role of meticulous hemodynamic evaluation and provocative testing for cases of diagnostic uncertainty. Therapeutic strategies-pharmacologic, device-based, and surgical therapies used for managing PH-LHD-are also outlined. PH-LHD in advanced heart failure, and the role of mechanical circulatory support in PH-LHD is briefly explored. An in-depth understanding of PH-LHD by all clinicians is needed for improved recognition and outcomes among patients with PH-LHD.
Prediction of pathologic complete response to chemoimmunotherapy in triple-negative breast cancer using tumor-infiltrating lymphocytes: Exploiting cutoff values.
Authors: ROMUALDO BARROSO-SOUSA, Isadora Martins de Sousa, Ana Carolina Marin Comini, Monique Celeste Tavares, Fernanda Madasi Pinheiro, Jose Bines, Rafael Dal Ponte Ferreira, Daniela Dornelles Rosa, Candice Lima Santos, Zenaide Silva Souza, Daniele Assad Suzuki, Julio Antônio Pereira de Araujo, Debora De Melo Gagliato, Carlos Henrique Dos Anjos, Bruna M Zucchetti, Anezka Carvalho Rubin de Celis Ferrari, Mayana Lopes De Brito, Maria Marcela F. Monteiro, Laura Testa, Renata Colombo Bonadio
Journal: Journal of Clinical Oncology (2024)

e12629 Background: Triple-negative breast cancer (TNBC) prognosis is significantly influenced by tumor-infiltrating lymphocytes (TILs), but the lack of validated cutoff values has limited their clinical applicability. In the era of neoadjuvant pembrolizumab plus chemotherapy (P+CT) as a new standard of care, the role of TILs as predictors of response to chemoimmunotherapy remains uncertain. Methods: This study aimed to assess TILs as predictors of pathologic complete response (pCR) within the Neo-Real study, a multicenter, real-world data investigation on neoadjuvant P+CT in TNBC. TILs were evaluated using the standardized methodology of the International TILs Working Group. Logistic regression and receiver operating characteristic (ROC) curve analysis were performed to evaluate the predictive ability of TILs expression and multivariable models for pCR. Results: The analysis included 128 patients (pts) treated with neoadjuvant P+CT (68% stage II, 26% stage III). The proportion of pts in each TILs’ category and results of ROC curve analysis are presented in the Table. A cutoff value of 10% demonstrated the highest accuracy in predicting pCR, while a high specificity was observed at a cutoff value of 50%. Thus, the probability of residual disease if TILs ≥ 50% is considerably low. Incorporating categorized clinical and pathological variables, a multivariable logistic regression model, using TILs (≥ 10% vs &lt; 10%), Ki67 (≥ 50% vs &lt; 50%), and tumor stage (III vs II), exhibited the highest AUC (0.688) for predicting pCR. Conclusions: Our study underscores the predictive value of TILs for pCR in TNBC following neoadjuvant P+CT. The cutoff value of ≥ 50% identified patients with a very high probability of pCR. The results reinforce TILs’ use as a biomarker for treatment de-escalation, especially for pts with TILs ≥ 50%. Further enhancement of TILs' predictive potential may be achieved through multivariable models. [Table: see text]
Clinical outcomes in patients with early-stage breast cancer in a racially and ethnically diverse patient population.
Authors: Denny Donggun Shin, Jeffrey M. Switchenko, Angelo Marra, Kevin Kalinsky
Journal: Journal of Clinical Oncology (2024)

e12532 Background: Despite the growing evidence that substantial disparities exist in breast cancer care per socioeconomic status, the racial and ethnic disparities that contribute to clinical outcomes in patients with early breast cancer are not well understood. This analysis attempts to better characterize these differences in a diverse group of patients with early breast cancer. Methods: Patients were identified from an institutional database from the Winship Cancer Institute, which included those with pathologic stage I-III breast cancer with varying hormone receptors (HR) and HER2 receptor status who received care between 1999-2023. Patients with ductal carcinoma in-situ (DCIS) and with metastatic breast cancer at diagnosis were excluded from this retrospective analysis. Using variables such as race, treatment received, pathological stage, tumor grade, and histology, we performed univariate and multivariate analysis for IDFS, defined as pts who are alive and free of any breast or other cancer. Results: 449 patients were included, which comprised of 148 non-Hispanic African American (33%) and 301 (66%) Caucasian women. Mean age at diagnosis was 60; 77.3% of patients were post-menopausal, and 79.1% received operable endocrine therapy. 76.4% of patients had invasive ductal carcinoma (IDC) and 13.1% invasive lobular carcinoma (ILC). Only 9.8% received chemotherapy. In univariate analysis, patients who were triple negative (n=30, 6.8%) had worse IDFS compared to those who were HR+/HER2- (n=351) (Hazard Ratio=2.49, p=0.036) Additional patients with larger tumors with pT2-pT4 (n=133, 30.4%) had worse IDFS compared to those with pT0-pT1 (p=297, 67.8%) tumors (HR=2.04, p=0.014). There were no significant differences in clinical outcomes by patient race or by lymph node involvement. Conclusions: In our lower-risk, racially diverse cohort, our findings demonstrate that patients with HR-/HER2- breast cancer and larger tumors have worse IDFS. More analyses should be performed on a population with higher-risk patients and larger cohort. Future studies should continue to focus on early screening, as well as novel therapeutics to treat HR-/HER2- disease.
The feasibility and preliminary efficacy of a locally developed digital health intervention in improving breast cancer survivor’s quality of life (QOL): Qualitative and quantitative analysis result.
Authors: Mohd Hanafi Bin Ramlee, Nur Fadhlina Abdul Satar
Journal: Journal of Clinical Oncology (2024)

e13803 Background: Breast cancer is the most prevalent cancer type amongst females of all ages and the highest reported cancer cases in Malaysia. Breast cancer survivors may have distinctive struggles. Inadequate recovery preparation can have a detrimental effect on the quality of life of breast cancer survivors. Digital health interventions (DHI) can enhance patient rehabilitation. Methods: This is an open-label feasibility study conducted at the University of Malaya Medical Center. The study involved 40 patients diagnosed with stage I-III breast cancer. They were randomly assigned to either the intervention group (12-week program with DHI) or the control group (follow-up at UMMC). Unfortunately, 3 patients withdrew from the intervention group during the study. This resulted in a study size of 17 in the intervention group and 20 in the control group. At the end of the 12-week period, we conducted individual interviews to explore the experiences of DHI users. The primary endpoint of this study was to evaluate the feasibility and acceptability of the smartphone application in enhancing the quality of life for breast cancer survivors. Secondary objectives included estimating the variability of body mass index, health, and physical and psychological status. Results: The study showed the engagement of breast cancer survivors with our Digital Health Intervention (DHI), indicating a 100% retention rate over a 12-week period. This emphasizes the accessibility of DHI, as shown by users logging in at least once within 12 weeks. Quantitative data analysis reveals that the DHI app's engagement rates are 53%, implying that users are logging in at least once a week and over 30% throughout the study period. Farago's study shows a 27-30% user retention rate for medical and health apps within 90 days. (5) Clinical outcome for both control and experimental shown not significant result with p&gt;0.05, however we can appreciate absolute changes in intervention arm BMI. Qualitatively, we are able to code to utility and usability of the DHI apps. Users enjoyed the exercise module, valued admin support, and found the app intuitive. Users were engaged in exercise, diet, and psychology, while disengagement was associated with other social media platforms and personal motivation levels. Conclusions: Study showed a 100% retention rate and a promising 53% engagement rate, showing success in health app engagement. The feasibility study intentionally used a small sample for specific disease and patient demographics. Users reflect on app relevance in exercise, diet, and psychology. In summary, assessing the effectiveness of DHI in providing comprehensive support to cancer survivors requires larger-scale studies.
Evaluation of early response in association with pathological response in patients with breast cancer receiving neoadjuvant chemotherapy.
Authors: Yongjiu Wang, Zequn Feng, Xinyu Liu, Lixiang Yu, Liang Li, Qiang Zhang, Qinye Fu, Chao Zheng, Yujuan Xiang, Fei Zhou, Wenzhong Zhou, Mingming Guo, Fei Wang, Zhigang Yu
Journal: Journal of Clinical Oncology (2024)

e12628 Background: Neoadjuvant therapy (NAT) has now been widely used for patients with operable breast cancer (BC) to test drug sensitivity. Studies have indicated that early assessment of clinical response to NAT can help identify patients who are resistant to initial regimens, providing an additional opportunity to change treatment plan. However, there is a lack of evidence regarding the optimal timing for conducting early evaluations of clinical response. This prospective study was conducted to evaluate the association between early evaluation of clinical response at different timing (post 2 cycles versus post 4 cycles) and pCR post NAT, in order to determine the most appropriate timing for NAT response evaluation. Clinical evaluations using ultrasound and MRI (magnetic resonance imaging) were also compared. Methods: A prospective cohort study including BC patients who received NAT was conducted between January 2018 and December 2023. Multivariable logistic regression analysis was used to estimate the Odds Ratios (OR) and 95% confidence intervals (CI) for the clinical response evaluated at different timings in association with pCR. The heterogeneity of the associations for the post-cycle 2 and post-cycle 4 assessments was assessed. Linear regression analyses were used to assess the associations between extent of tumor reduction post 2 cycles and that post 4 cycles of NAT. Agreement of tumor measurements using ultrasound and MRI was also assessed. Results: A total of 186 BC patients were consecutively enrolled and included in this analysis. 55 (29.6%) of them achieved pCR. Partial response (PR) post 2 cycles and 4 cycles of NAT were both significantly associated with pCR post NAT, though the point estimate of association for PR post 2 cycles of NAT (OR=5.06, 95%CI:2.29-12.09) was more evident than that post 4 cycles (OR=2.79, 95%CI:1.20-7.21). Extent of tumor reduction post two cycles of NAT was highly correlated with that post four cycles (r=0.89, 95%CI=0.79-0.98, P&lt; 0.01). Poor concordance was observed between ultrasound and MRI measurements of tumor size, whether at initial diagnosis (r=0.66, adjusted r 2 =0.43) or after two cycles of NAT (r=0.59, adjusted r 2 =0.35). Among those patients who had PR post 2 cycles of NAT, tumor reduction by greater than 50% was not associated with higher probability of reaching pCR in comparison to those lower than 50% (OR=1.86, 95%CI=0.82-4.37, P=0.143). Conclusions: Tumor response assessed using MRI after two cycles of NAT was highly correlated with pCR, and may be adopted as an optimal strategy for early evaluation of the efficacy of NAT regimen. Further studies are warranted to evaluate changes in treatment plan at early phase of NAT for those resistant to initial regimens.