tbuckley/cabot-search huggingface dataset:
Predicting peripheral neuropathy following neoadjuvant therapy in patients with breast cancer.
Authors: Bradley Feiger, Matthew Biancalana, Amy Shelton, Kim Blenman, Maryam B. Lustberg
Journal: Journal of Clinical Oncology (2024)

e12639 Background: Administration of neoadjuvant chemotherapy (NACT) or radiation is widely used to improve outcomes in patients with breast cancer. This strategy has demonstrated remarkable efficacy in reducing tumor burden and increasing the likelihood of breast-conserving surgery. However, neoadjuvant therapy can induce peripheral neuropathy, a condition characterized by nerve damage or dysfunction in the extremities that often manifests as pain, tingling, or weakness in the hands and feet. The exact mechanism remains unclear, although likely involves the cumulative toxic effects of therapy on peripheral nerves. Treatment-induced neuropathy poses a substantial unaddressed challenge that can significantly impact the patient’s quality of life. Therefore, predicting and ameliorating neuropathy are crucial aspects of comprehensive cancer care. Methods: We used an AI spatial biology platform to create and assess 3D depictions of a cohort of breast cancer patients based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data. Clinical, pathological, and radiological data were collected on 74 patients from Yale New Haven Hospital. Due to missing regimen data, the final dataset included 71 patients, with mean age 51.1 (14.5) years. An AI-based segmentation algorithm was successfully employed on 63 patients, of whom 13 had neuropathy following NACT. Vascular and microvascular (MV/V) kinetic parameters were computed for each, and radiomic features were extracted. Machine learning models were developed for clinical features, MV/V features, and the combined set of features. All models were tested with leave-one-out cross-validation. Results: The clinical model did not forecast neuropathy in any patient, indicating poor predictive ability. The MV/V model performed the best, with accuracy, precision, recall, and AUROC of 0.84, 1.0, 0.18, and 0.69, respectively. The combined model showed intermediate performance, with accuracy, precision, recall, and AUROC of 0.81, 0.5, 0.18, and 0.58, respectively. The patient population limits broad conclusions, but suggests features that are aligned with increased occurrence of neuropathy. In particular, vascular features that describe transfer of nutrients between tissues, as well as the density of blood vessels within and around the tumor, are prominent within both the MV/V and combined models. Conclusions: These results indicate that features associated with the degree of proximal and intratumoral vascularity may be predictive of peripheral neuropathy in breast cancer patients. Moreover, these features can be extracted from standard-of-care DCE-MRI data. Expansion of this vascular analysis could enable physicians to better plan and manage care for patients by tailoring treatment dose. [Table: see text]
Information and support needs of young Black women with early breast cancer to enable self-management and informed decisions during breast cancer treatment.
Authors: Christine B. Weldon, Sue Steele, Virginia Leach, Arliene Ravelo, Julia R. Trosman
Journal: Journal of Clinical Oncology (2024)

e12587 Background: Black women with breast cancer are more likely to experience care delays and worse outcomes than White women (Emerson, Cancer ’20). Patient self-management contributes to more timely cancer care delivery and improved outcomes. We interviewed young black women with breast cancer to explore information needs related to their self-management interests and obtain feedback on the independent use of self-management tools developed within the 4R Oncology model. 4R (Right Info/Care/Patient/Time) is an approach to facilitate patient self-management using a Care Sequence plan- a care checklist with a visual depiction of timing and sequence of care, as well as a side effect self-care tool. These tools are typically provided in the clinic, but we aimed to explore if they could be used independently by patients. Methods: The interviewee cohort (N=20) was recruited from the Tigerlily Foundation ANGEL (Advocate Now to Grow, Empower and Lead) patient program. The cohort included Black women, average age 36 (21 to 46), stage I-III breast cancer. The framework approach of qualitative research was used. Results: All women reported information needs not addressed by their providers. Mental wellness and social support information were lacking for 70% (“I never worked with a social worker or anyone to support my mental health”). Most women (65%) wanted more information about breast cancer surgery options and post-surgery drains, bras, pain, and tingling (“before I had my surgery, my doctor didn't tell me all the options I had”). 40% mentioned a lack of reconstructive option information, including how radiation affects implants, “risk of encapsulation” and the long-term impact of having implants “changing them out every 10 years.” A slight majority (55%) desired nutrition and integrative medicine information. About one-third (35%) of women mentioned considerable skin issues during radiation treatment (“I needed skin care, for people with darker skin”). When reviewing a Care Sequence and a side-effect self-care tool, 95% reported they would use them independently if their clinic did not provide them ("I just got general information about breast cancer, I would have preferred a step-by-step process like this"; “This describes what services each role provides, and links to more support”). Most (95%) would have used the side-effect tool ("My chemo education was overwhelming, just a bunch of info thrown at me all at once, having a resource to look at would have been helpful"). Conclusions: In interviews with young Black women with breast cancer we found several information needs and a preference for tools to support self-management during treatment. These indicate considerable improvements are needed in this area. Using the input from the interviews, we are enhancing the 4R Oncology tools to better support the needs of Black patients with breast cancer.
Pancreatic-enzyme replacement therapy with pancrelipase plus chemotherapy for patients with pancreatic adenocarcinoma with cachexia and exocrine pancreatic insufficiency (PANCAX-3).
Authors: Matthew Ebia, Shaowli Kabir, Brian Minton, Anser Ali Abbas, Arsen Osipov, Jun Gong, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2024)

e24059 Background: Pancreatic-enzyme replacement therapy (PERT) is the standard of care to prevent maldigestion, malnutrition, and excessive weight loss in patients with exocrine pancreatic insufficiency (EPI). The utility of this therapy for patients with EPI in the setting of pancreatic ductal adenocarcinoma (PDAC) is unclear. We report results of a single site phase 2 trial for PERT with Pancreaze® plus standard of care (SOC) chemotherapy in PDAC patients with cachexia and EPI. The primary outcome measure was to assess feasibility of completing PERT during the first 8 weeks of treatment. Secondary outcome measures included weight stability, mean change in stool frequency, stool consistency from Cycle 1 (C1) to Cycle 3 (C3) (after 8 weeks of PERT), mean change in serum levels of fat soluble vitamins (A, D, E, K) from baseline to end of study, functional activity, and safety. Methods: Feasibility was defined as adherence to therapy of ≥50% of the needed total lipase units in the first 8 weeks of treatment (84,000 IU lipase units per meal, 42,000 IU lipase units per snack). Data are presented as frequencies (%) for categorical variables and means ± standard deviation for continuous variables. Weight stability, stool frequency, fat soluble vitamin levels, walk speed, and hand grip strength compared using two-sample paired t-tests. Stool consistency (Bristol stool type) compared using Fisher’s exact test. Results: Of 36 patients enrolled, 30 were evaluable for primary endpoint. Median age was 70. 73.3% (22/30) were female. 33.3% (10/30) were borderline resectable, 33.3% (10/30) locally advanced, and 33.3% (10/30) advanced/metastatic. 30 patients completed 8 weeks of PERT and 96.7% (29/30) were compliant. Efficacy results include PR (6.7%, 2/30), SD (66.7%, 20/30) and PD (23.3%, 7/30). Imaging not available for 1 patient. 6 patients experienced grade 1/2 GI toxicities (nausea, bloating, diarrhea, abdominal pain) deemed possibly/probably related to PERT. Grade 3/4 AEs included fatigue, infection, and hematologic toxicities deemed unrelated to PERT. Among evaluable patients, weight remained stable (-0.01±0.07 kg/BMI, p = 0.511) and there was a trend toward reduced stool frequency (p = 0.052) from C1 to C3. Stool consistency from C1 to C3 showed significant association (p = 0.035). Serum fat soluble vitamins, functional activity by walk speed and hand grip strength were also explored and no statistically significant differences were observed from C1 to C3 among the evaluable patients. Conclusions: PERT plus SOC chemotherapy for PDAC patients with cachexia and EPI is feasible and well-tolerated. Patients taking PERT experienced weight stability. PERT may aid in reducing stool frequency and further analysis is warranted into how PERT affects stool consistency. Clinical trial information: NCT04098237 .
Evaluating the efficacy of neoadjuvant endocrine therapy in HER2 low vs. HER2 negative breast cancer: An NCBD analysis.
Authors: Esther G Chong, Mengni Guo, Dani Ran Castillo, Jose G. Bazan, Kelly Khai Li Yap, Katharine Schultz-Costello, S.Peter Wu
Journal: Journal of Clinical Oncology (2024)

599 Background: Neoadjuvant endocrine therapy (NET) is an important treatment option for hormone receptor (HR)-positive breast cancer (BC). Innovative ADCs targeting HER2 low tumors has sparked debate regarding the distinct nature of HER2 low tumors and whether it merits a unique treatment approach. With favorable outcomes in metastatic disease, there is interest in adopting similar strategies for early-stage treatment approaches. Methods: We examined the National Cancer Database for stage I-III ER-positive BC in women who underwent neoadjuvant endocrine therapy (NET) from 2010 to 2017, for at least 90 days to a maximum of 270 days. Patients with prior neoadjuvant chemotherapy, other malignancies, HER2-positive disease by either IHC or FISH, metastatic disease, or unknown stage were excluded. HER2 status was grouped as negative or low per 2023 ASCO-CAP guidelines. Patients’ response to therapy included pathologic complete response (CR), partial pathologic response (PR), stable pathologic response, or progression in primary tumor at time of resection. We employed multivariable binomial logistic regression to examine how clinicopathologic factors influence the probability of any response (combining CR and PR) to neoadjuvant hormonal therapy. Results: 3,808 patients met the inclusion criteria. 1,055 (27.8%) patients had HER2 negative disease, and 2,753 (72.2%) patients were HER2-low. 48 (1.2%) patients had primary tumor CR, and 1,484 (39%) had PR. Among HER2-low patients, 37 (1.3%) had pathologic CR, and 1,134 (41.1%) had PR. Among HER2-negative patients, 11 (1.0%) had pathologic CR, and 350 (33.1%) had PR. Multivariable logistic models revealed that age, duration of NET, and HER2 status were significant predictors of any response to NET. HER2-low tumors were more likely to have any response compared to HER2-negative (aOR=1.16, 95% CI 1.01 - 1.34, p=0.04). Patients who received &gt;150 days of hormonal therapy were more likely to respond (aOR=1.33, 95% CI 1.16 - 1.52, p=&lt;0.001); patients &gt;50 years old were more likely to have any response (aOR=1.41, 95% CI 1.07 - 1.90, p=0.02). Clinical node positivity and tumor grade did not have significant effect on response to NET at time of resection. Conclusions: Our study offers a real-world estimate of outcomes associated with NET in localized BC. HER2 low tumors had greater significant clinical responses to NET when compared to HER2 negative, suggesting that HER2 low tumors may benefit from tailored treatment in the neoadjuvant setting. [Table: see text]
Pilot evaluation of portable scalp cooling for chemotherapy-associated alopecia in early-stage breast cancer.
Authors: David B. Page, Erin Hong, Lakhvir Kaur, Sarah Gauntt, Holley Gedney, Evthokia Hobbs, Kelly Shea Perlewitz, Amanda Seino, Zheng Zhu Topp, Alison Katherine Conlin
Journal: Journal of Clinical Oncology (2024)

12141 Background: Chemotherapy-induced alopecia significantly impacts quality of life (QOL). First-generation scalp cooling systems PAXMAN and Dignicap, while effective in reducing alopecia, are not universally adopted due to their lack of portability. Amma is a second-generation, portable and battery-powered scalp cooling system that offers the opportunity for widespread clinical usage by allowing self-administration and mobility. Here, we report first-in-human outcomes of Amma in a preliminary cohort receiving curative-intent taxane-based chemotherapy for early-stage breast cancer. Methods: We conducted a pilot clinical trial (NCT05508984) of the Amma system at Providence Cancer Institute in Oregon. Key inclusion criteria included: no baseline alopecia [Dean’s scale 0], intent to receive 4-6 cycles of taxane-based, anthracycline-sparing therapy, willingness to participate in quality-of-life questionnaires, and serial scalp photography. The primary outcome was the feasibility of Amma devices for adoption within the clinic ascertained by patient reported outcomes (PRO) and provider feedback. The secondary outcome was efficacy defined as the proportion of subjects achieving &lt; 50% hair loss [Dean’s scale 0-2] at 30 days post-treatment, and tolerability assessed by common terminology criteria for adverse events (CTCAE). Results: 14 participants were enrolled and evaluable from 9/2022-1/2024. Participants received docetaxel/cyclophosphamide (TC x 4, n=10) or weekly paclitaxel/trastuzumab+/- pertuzumab (TH(P), n=4). 93% of participants (n=13/14) successfully completed treatment. One participant discontinued scalp cooling prematurely. Primary efficacy endpoint of &lt;50% hair loss was achieved in 64% participants (n=9/14, [95% CI: 0.39, 0.89]) (TC: n=5/10; TH(P): n=4/4). On the validated “Was it Worth It?” questionnaire, 92% reported the treatment “worthwhile”, 85% would repeat participation, and 100% would recommend it to others. After treatment, 93% reported a similar or increased QOL with participation and 71% deemed the experience “better than expected”, paralleling PRO outcomes from previously published trials using first-generation cooling devices. Provider feedback was favorable regarding feasibility of treatment. Conclusions: Scalp cooling with the portable Amma system was both feasible and effective in this pilot study. Point estimates of efficacy were like those reported for PAXMAN (Dean’s 0-2: 50%) and DigniCap (66%). A follow-up clinical trial is planned with a primary outcome of efficacy in patients receiving taxane-based chemotherapy (NCT06215469, PI: Rugo). Clinical trial information: NCT05508984 .
The correlation between Ki 67 and Oncotype Dx on HR+, HER2- early breast cancer management: Insights of molecular testing.
Authors: Leticia Campoverde, Felipe Camacho, Adriana Sanchez, Paulina Lugo
Journal: Journal of Clinical Oncology (2024)

e12546 Background: Elevated Ki-67 expression serves as an indicator of tumoral proliferation in breast cancer (BC) and is used in Ecuador for survival estimation, recurrence risk assessment, and guiding chemotherapy decisions. The Oncotype DX Breast Recurrence Score (ODX RS) is a validated 21-gene assay for hormone receptor-positive, HER2-negative invasive BC. It predicts chemotherapy benefits and the risk of distant recurrence over 10 years and is a mortality indicator. ODX RS has the potential to reduce the need for chemotherapy, alleviate financial burdens, and enhance clinical outcomes. Despite conflicting evidence on the significance of Ki-67 in the ODX RS, there is a lack of exploration within Latin populations. This study aims to compare the correlation of immunohistochemical (IHC) measured Ki-67 to the ODX RS in the Ecuadorian population. Methods: A retrospective analysis included women with early BC who underwent ODX RS testing in Ecuador from May 2020 to January 2023. Inclusion criteria: early BC (T1-T3/N0-N1a); IHC estrogen receptor (ER) positive; HER2 negative; and availability of tumor size, grade, lymph node status, and Ki67 proliferation index data. Exclusion criteria: patients with recurrent BC, incomplete pathology, or lacking IHC data. Patients were categorized into low (≤5%), intermediate (6%–29%), and high Ki67 expression groups (≥30%). Using the statistical software SPSS, the correlation between ODX scores and Ki-67 expression was analyzed using Pearson’s correlation coefficient. For risk stratification groups, Spearman's correlation was employed. Results: Among 77 patients undergoing Oncotype DX testing, 64 (with a mean age of 55) met the inclusion criteria. Eighty-six percent of cases were invasive ductal carcinomas (IDC). Seventeen percent exhibited low Ki-67 expression, 61% intermediate, and 20% high. No statistically significant correlation was found between IHC Ki-67 expression and ODX RS (r=0.051; p=0.69), neither when stratified by categories (r=0.086; p=0.50). A subanalysis based on risk categories showed 82% correspondence in the low Ki-67 group, 18% in the intermediate group, and 31% in the high Ki-67 group. No significant correlation was observed when stratified by histological types (invasive ductal carcinoma and invasive lobular carcinoma), nor by sample origin (core biopsy, excisional biopsy). Conclusions: There was no correlation between IHC Ki-67 expression and ODX risk scores in this study involving Ecuadorian patients. Our findings emphasize that IHC Ki-67 expression should not be the sole determinant for guiding therapeutic decisions and predicting recurrence in early breast cancer.[Table: see text]
Prediction of pathological response to neo-adjuvant chemotherapy using texture parameters of initial 18-FDG PET/CT in estrogen receptor positive/Her2 negative (ER+/HER2-) early breast cancer (eBC).
Authors: Hugo Corda, Hamza Lasla, Camille Guillerminet, Marie Lacombe, Sylvie Girault, Mario Campone, Jean-Sebastien Frenel, Pascal Jézéquel, Anne Patsouris
Journal: Journal of Clinical Oncology (2024)

e12567 Background: ER+/HER2- phenotype represents 70% of eBC and is itself a heterogenic entity in which neoadjuvant chemotherapy (NAC) can be indicated. Early change in 18F-FDG uptake on PET/CT, using standardized uptake value (SUV) parameter, has been shown as a predictive biomarker of response to NAC. However, this parameter can be defaulted in ER+/HER2- BC. The objective of this work was to evaluate the correlation of textural parameters of initial 18-FDG PET/CT with histologic response in ER+/HER2- eBC. Methods: All patients receiving NAC for ER+/HER2- eBC, with 18F-FDG PET/CT prior NAC at the Integrated Center for Oncology Pays de Loire were included between 2012 and 2023. Twenty-nine metabolic and volumetric parameters and 42 textural features (DOSISOFT software, Planet Onco v2.0) were collected. Pathological response was assessed for each breast tumoral lesion in case of multifocal disease. Results: A total of 161 patients with 179 lesions were included. Medium age was 51 years old. 89% and 10% of patients presented a cT1 or cT2 tumoral lesion, 78% with lymph node involvement, 44% with a grade 3 and 46% with a HER2 low status. 21% of patients achieved a pathological complete response in breast (ypT0) and 11% a complete histologic response (ypT0N0). Examinations were performed using three types of PET/CT systems (GE Healthcare and Philips Healthcare). In order to harmonize radiomics data Combat method was used. Thirteen semi-quantitative (MTV and SUV max , SUV mean , SUV mean(EVPc) , SUV peak , TLG for weight-normalized and lean-body-mass-normalized, respectively) and 6 textural parameters (entropy, homogeneity, SRE, LRE, LGZE, and HGZE) were retained. For all radiomics features used in this study, no statistical difference was found between ypT0 and non-ypT0 patients (p ≥ 0.05). Conclusions: Selected textural parameters were not associated with histologic response in our cohort of ER+/HER2- eBC. However, many other textural features, not retained in this study because influenced by acquisition parameters and segmentation methods, could be taken into account. An ongoing preliminary work (as resampling, normalization) is needed to improve their robustness before evaluating their interest in predicting histologic response to NAC.
Arterial stiffness and aortic hemodynamics as predictors for new or worsening cardiovascular events in childhood cancer survivors: A report from the St. Jude lifetime cohort.
Authors: Arun Maharaj, Rikeenkumar Dhaduk, Daniel A. Mulrooney, Gregory T. Armstrong, Matthew Wogksch, Melissa M. Hudson, Matthew J. Ehrhardt, Daniel Duprez, Stephanie B. Dixon, Kevin R. Krull, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2024)

e24006 Background: Survival following childhood cancer has improved due to advances in treatment and supportive care. However, survivors are at high risk of cardiovascular diseases (CVDs) later in life. Aortic artery stiffening, captured by measuring the speed and magnitude of forward and reflected pulse waves, is an independent predictor of CVD and mortality in the general population. Methods: We evaluated associations between vascular function and new or worsening CVDs [coronary artery disease (CAD), cardiomyopathy, and hypertension (HTN)] among a subset (n = 249) of St. Jude Lifetime Cohort (SJLIFE) participants who had baseline vascular function assessment and returned for a standard follow up study visit (mean age at baseline (years) ± standard deviation: 34 ± 9 years, follow-up: 39 ± 9 years). CVD conditions were graded (dichotomized as grades 0-1 and 2-4) using the Common Terminology Criteria for Adverse Events (CTCAE). Aortic stiffness, brachial and aortic blood pressure (BP), and aortic wave reflection (augmented pressure, augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (AIx 75 ), time and magnitude of the forward and reflected waves) were assessed using wave separation analyses. T-tests were used to test mean values between the groups with higher (2-5) and lower (0-1) grades. These tests informed the selection of identified variables for multivariate logistic models, which were adjusted for age, sex, race, body mass index, physical activity, smoking status, drinking behavior and vasoactive medications. Results: Most participants had a history of Hodgkin lymphoma (53.8%) or leukemia (20.5%) and 25.7% other diagnoses. There were 169 (67.9%) participants who had cranial/neck radiation, 167 (67.9%) received anthracyclines, and 150 (60.2%) alkylating agents. At baseline 38.2% had ≥grade 2 HTN, 9.2% cardiomyopathy, and 4% CAD. Having ≥ grade 2 CVDs was significantly associated with augmented markers of brachial and aortic BP, arterial stiffness, and wave reflection. Regression analyses revealed that AIx 75 ≥ 17% was associated with an increased risk of new or worsening HTN (odds ratio (OR) 3.29, 95% confidence interval (CI) 1.03-10.48) and new or worsening cardiomyopathy (OR 4.06, 95% CI 1.02-16.16) an average of 5 years after baseline vascular testing. Conclusions: Childhood cancer survivors diagnosed with grades 2-4 CVDs at a baseline visit had elevated aortic stiffness and augmented indices of wave reflection compared to those with &lt; grade 2 CVDs. Elevated AIx 75 was associated with new or worsening HTN and cardiomyopathy five years later. Early detection and treatment of vascular dysfunction may ameliorate CVD late effects in childhood cancer survivors.