tbuckley/cabot-search huggingface dataset:
Impact of COVID-19 on referrals to outpatient palliative care for patients with advanced cancer in a safety-net health system.
Authors: Lisa DiMartino, Vincent Merrill, Timothy P. Hogan, Celette Sugg Skinner, Navid Sadeghi, Alva Roche-Green, Arthur S. Hong
Journal: Journal of Clinical Oncology (2024)

e24071 Background: Medically underserved adults with cancer experience challenges with access to care and tend to present at later disease stage. Amidst the complex needs of safety-net patients, the value of early palliative care (PC) services can go unrecognized. Few studies have examined PC referral patterns in the outpatient setting among advanced cancer patients within a safety-net system, and none has studied how or whether referrals have evolved since the most acute stages of the COVID-19 pandemic. This study examined PC referrals for cancer patients seen as outpatients in the urban safety-net primary provider of cancer care for uninsured individuals in Dallas, TX, and assessed changes from before to after the acute pandemic phase. Methods: We used tumor registry records linked to outpatient PC referral data from the safety-net health system’s electronic health record from January 1, 2018 to July 31, 2023. The primary outcome was a binary indicator for receipt of PC referral among patients diagnosed with advanced-stage solid tumor cancer. Using a multivariate logistic regression model, we evaluated whether our independent variable – a binary indicator for pre-pandemic (January 1, 2018 to February 28, 2020) and post-pandemic (March 1, 2020 to July 31, 2023) time periods – was associated with PC referrals. We included age, sex, race/ethnicity, cancer type, preferred language, and insurance as covariates. Results: Among 1,590 eligible patients (mean age 58.1, range: 21-94), 44% were female and 75% were non-White. Diagnoses included lung (20%), gastrointestinal (17%), colorectal (14%), breast (9%), prostate (9%), head/neck (9%), pancreatic (8%), gynecologic (6%), and other (8%) cancers. Across both time periods, a total of 785 (49%) of patients received a PC referral. Whereas 53% of the 754 patients in the pre-pandemic cohort received a PC referral, 46% of the 836 in the post-pandemic cohort received a referral. In the adjusted regression model, pre-pandemic patients were 1.26 times more likely to have a PC referral than post-pandemic patients (95% CI, 1.02-1.56). Referrals varied by cancer type across both time periods – compared to breast cancer patients, gynecologic cancer patients had lower odds of PC referral (aOR, 0.19; 95% CI, 0.10-0.36) and pancreatic cancer patients had higher odds of PC referral (aOR, 2.93; 95% CI, 1.71-5.00). Conclusions: Our analysis showed that referrals declined during the COVID-19 pandemic and revealed differing underlying patterns of PC referral along disease groups. Understanding pre-existing referral patterns and lasting practice changes post-pandemic can support clinicians to integrate PC and improve cancer outcomes. Findings can be used to develop interventions, such as clinical triggers, to improve PC delivery for underserved cancer patients.
Circulating tumor DNA (ctDNA) to predict response to neoadjuvant chemotherapy (NAC) and prognosis in patients (pts) with early breast cancer (BC).
Authors: Wassim McHayleh, Ashley Young, Valeria Burkovskaya, Mariem Galuia
Journal: Journal of Clinical Oncology (2024)

e12642 Background: pCR to NAC is an important predictor of clinical recurrence. Up to 16% of patients with pCR may experience disease recurrence, 45% of patients with RD do not. Longitudinal ctDNA testing offers a minimally invasive approach for monitoring treatment response EBC patients receiving NAC. We evaluated whether ctDNA status and dynamics can predict the tumor response to NAC and the risk of recurrence in patients with EBC. Methods: We conducted an observational, retrospective, single-center study to investigate whether ctDNA can predict tumor response to NAC and prognosis in BC patients. 74 pts received standard of care NAC;g 4 patients were treated in the adjuvant setting. Blood samples were collected at diagnosis from 44 pts (baseline) and longitudinally during treatment from 34 patients. Tumor response and progression outcomes were reported. A clinically validated, tumor-informed ctDNA assay (Signatera). ctDNA status and dynamics were correlated with pathologic and radiologic outcomes. Results: 29 TNBC pts were ctDNA+ at baseline, 6 were ctDNA- Of the 29 pts, early ctDNA clearance by week 6 of NAC was observed in 10 pts, weeks 7-16 in 9 pts, clearance post-surgery in 1, 3 pts remained ctDNA+ after surgery, serial ctDNA testing is underway for the remaining 6 pts. All TNBC patients who had radiological complete response (CR) had early clearance of ctDNA . All pts with persistent ctDNA positivity levels after completion of NAC had radiological partial response (PR). Of the 9 TNBC pts with undetectable baseline ctDNA, 33% achieved CR on MRI and 43% achieved pathologic CR. Of the 19 TNBC pts with ctDNA clearance in response to NAC, 89% (17/19) remained ctDNA- and with no evidence of disease (NED) (length of follow up). 1 pt initially cleared their ctDNA on NAC, turned ctDNA+ 4 weeks prior to radiological recurrence. 1 pt with ctDNA clearance on NAC remained ctDNA post-surgery but experienced recurrence. All (n=3) TNBC pts with persistent ctDNA-positivity levels after curative treatment (NAC and surgery) had disease recurrence. The remaining 6 pts ctDNA are ongoing NAC. Of the 6 pts with undetectable baseline ctDNA, 6/6 continued to be ctDNA- regardless of their disease status. At diagnosis, 8/9 ER+ ps were ctDNA+. 3/8 (38%) ER+ pts with positive baseline ctDNA had early clearance of ctDNA after NAC. All 3 had residual disease on pathology. 2/8 (25%) remained ctDNA+ after surgery and neither achieved radiologic CR or pCR. The remaining 3 pts are ongoing NAC. Conclusions: In early TNBC, ctDNA monitoring can be used to predict tumor response to NAC and tailor therapeutic regimens. ctDNA persistence can predict early recurrence and helps identify patients in which treatment escalation or enrollment on clinical trials is necessary. In ER positive breast cancer, and despite the small number of patients, ctDNA clearance does not predict response to NAC.
Outcome with pertuzumab, docetaxel, and trastuzumab (PTH) regimen in patients with HER2 positive metastatic breast cancer: Real-world data from a single center in India.
Authors: Ajay Gogia, Anshul Gupta, Atul Batra, S.V.S Deo, Daya Nand Sharma, Sandeep Mathur, Ashutosh Mishra, Chandra Prakash Prasad
Journal: Journal of Clinical Oncology (2024)

e13037 Background: Pertuzumab, Docetaxel and Trastuzumab (PTH) regimen constitutes one of the standard treatment regimens in human epidermal growth factor receptor-2 (HER2) positive metastatic breast cancer (MBC). The real-world outcomes of its use from the Indian sub-continent are lacking. Methods: We retrospectively reviewed the medical records of HER2-positive MBC treated with an upfront PTH regimen at the All India Institute of Medical Sciences, New Delhi, India, between Aug 2016 to July 2023. A total of six cycles of PTH [pertuzumab (840 mg loading followed by 420 mg), docetaxel (75 mg/m2), trastuzumab (8 mg/kg loading followed by 6 mg/kg) q21 days] were planned along with granulocyte-colony stimulating factor (GCSF) prophylaxis. Patients were continued on maintenance trastuzumab after 6 cycles (till disease progression) and hormonal agent if indicated. The primary outcome was progression-free survival (PFS). The secondary outcome was overall survival (OS), overall response rate (ORR) rates, and toxicity. Results: Eighty-seven were included with a median age of 48 years (range, 25-73). Overall, 38 (43.6%) patients had hormone-positive (estrogen receptor and or progesterone receptor) disease and 48 (55.17%) were premenopausal. Thirty-five (40.2%) patients had received prior adjuvant and neoadjuvant treatment. Eighty patients (91.5%) had visceral metastasis and the most common site was the liver followed by the lung. After a median follow-up of 36 months, the median PFS was 15 months and OS was 42 months. The ORR was 85.3% and complete response (CR) was observed in 14(16.09%) patients. The survival outcomes were significantly better among those with hormone-negative disease and among those who achieved CR after 6 cycles of PTH. Grade 3/4 toxicity was seen in 12% of patients which led to dose modification, interruption, and change in chemotherapy. Two patients developed reversible left asymptomatic ventricular systolic dysfunction. None of the patients developed congestive heart failure. The most common grade 3/4 toxicities were diarrhea in 8 (9.1%) patients, cutaneous rash in 2 (2.2%) patients and thrombocytopenia in 2 (2.2%) patients. There were two cases of febrile neutropenia. Conclusions: In a real-world context, PTH is an effective and well-tolerated regimen for in patients with HER2-positive MBC in India. Hormone-positive disease has poor survival compared with hormone negative disease.
The use of complementary and alternative medicine (CAM) among patients with cancer in Hawaii.
Authors: Jobel Matriz, April Hamachi, Jami Aya Fukui
Journal: Journal of Clinical Oncology (2024)

e24070 Background: Complementary and alternative medicine (CAM) involves medical products and practices that are not part of standard medical care. Various studies demonstrate potential benefits of CAM in alleviating certain side effects associated with cancer and cancer treatments. Our project aims to elucidate the prevalence, pattern of use, and proposed benefits of CAM among Hawaii residents with cancer. Methods: Our questionnaire based study recruited cancer patients from several outpatient oncology clinics across Oahu (n = 126). Patients were asked about CAM use and associated symptom benefit. Sociodemographic information was collected along with details about cancer type, treatment, and associated side effects. Participation was anonymous and optional. Results: At least one CAM therapy was used by 72/126 (57.1%) patients, while 54 (42.9%) did not use any CAM therapy. Among the CAM therapies, meditation and herbal supplements were most commonly used 26 (36.6%), followed by massage 25 (32.4%), and yoga 18 (25.4%). Stress reduction was the most common symptom benefit identified for various CAM therapies including meditation 13 (50%), herbal supplement 13 (50%), massage 13 (52%), and yoga 14 (77.8%). Anxiety reduction was another symptom benefit reported for meditation 13 (50%). Massage 13 (52%), CBD 14 (82.4%), and acupuncture 9 (64.3%) were also used for pain reduction. THC 12 (75%) and CBD 14 (82.4%) were used for sleep. Among the CAM users (n = 72), 52 (72.2%) did not speak to their clinician about CAM. We found that 107 (84.9%) patients experienced at least one side effect. The most common side effects experienced by patients were fatigue 81 (64.3%), hair loss 61 (48.4%), and constipation and/or diarrhea 57 (45.2%). The most commonly reported demographic information were the following: 95 (75.4%) female, 57 (45.2%) Asian, 33 (26.2%) 60-69 years old, 80 (63.5%) with breast cancer, and 33 (26.2%) with stage 4. Conclusions: We discovered that stress reduction is a symptom benefit associated with the most commonly used CAM therapies by cancer patients in Hawaii. Other symptom benefits involve anxiety, pain, and sleep. The modalities utilized were similar to nonpharmacologic therapies recommended by the NCCN guidelines for cancer survivorship, with the exception of herbal supplements. There is a lack of physician discussion regarding CAM use, which could impact the cancer burden in Hawaii. [Table: see text]
Psychoneurological symptoms, inflammatory biomarkers and gut microbiome richness and diversity in individuals receiving hematopoietic cell transplantation (HCT).
Authors: Elham Samami, Angela Starkweather, Debra Lyon, Debra Lynch Kelly, Michael T. Weaver
Journal: Journal of Clinical Oncology (2024)

e24053 Background: Hematopoietic Stem Cell Transplantation (HCT) is a potentially curative treatment for certain hematologic cancers. Although survival rates are markedly higher than in the past, there are a growing number of long-term HCT survivors who are at risk for short and long-term sequela, which can negatively affect quality of life. Psychoneurological (PN) symptoms are common occurrences associated with heightened inflammation in other cancers and chronic conditions. Emerging research links the gut microbiota to inflammatory biomarkers and suggests that gut-microbiota-brain crosstalk impacts the severity of psychoneurological symptoms among HCT recipients. Methods: This longitudinal descriptive study investigated the relationship among a cluster of PN symptoms (pain, fatigue, and depression), inflammatory biomarkers (IL-6, IL-10, C-reactive protein (CRP), and microbiota diversity measures (Shannon and Chao Beta diversity indexes) in 55 individuals receiving HCT for a hematologic malignancy. The time periods examined covered pre-transplant, 30-days, and 100-days following transplant. The PN symptoms were collected through self-reported questionnaires via computer with assistance from study staff, along with blood samples and stool specimens obtained at each study visit. Inflammatory marker values were log-transformed when used as dependent variables. Gut microbiota samples were analyzed using 16S ribosomal gene (V4 region) amplicons using Illumina MiSeq. Data analysis was performed using SAS 9.4, with PROC MIXED used for the mixed model analyses. Results: The analysis characterized mean changes in microbiota diversity over time for both Shannon and Chao indexes. IL6 levels were consistent over time, with an inverse association with Chao but not Shannon index. IL10 and CRP levels changed over time, but without associations with either Shannon or Chao. Pain severity and interference changed over time, but with no associations with inflammatory markers or gut microbiome beta diversity. Fatigue severity and interference changed over time and were positively associated with IL10. Depression did not change over time and was not associated with inflammatory markers or diversity. Conclusions: This study provides preliminary information related to associations between PN symptoms, inflammatory markers, and selected measures of gut microbiome diversity in HCT recipients. Further research is needed to explore and validate these findings to examine the implications for microbiota diversity on inflammatory factors and PN symptoms. Clinical trial information: NCT02398708 .
Overcoming chemoresistance in triple-negative breast cancer (TNBC): Targeting PD-L1 stability and ferroptosis through integrated lipid metabolism and immune modulation.
Authors: Sujin Yang, Jinhai Tang, Jian Zhang
Journal: Journal of Clinical Oncology (2024)

e15149 Background: Triple-negative breast cancer (TNBC) is notorious for its aggressive nature and high recurrence rates, exacerbated by the lack of specific molecular targets, leading to poor prognosis and emergent chemoresistance. Our study explores ferroptosis mechanisms in TNBC, focusing on the interaction between lipid metabolism and immune system modulation to identify targets that enhance chemosensitivity, potentially improving chemotherapy efficacy. Methods: We employed RNA transcriptomics, proteomics, metabolomics, and lipidomics to compare gene transcription, protein expression, and metabolic profiles between TNBC cell lines MDA-MB-231/ADR (doxorubicin-resistant) and MDA-MB-231/S (sensitive). The impact of the ferroptosis inducer Erastin on MDA-MB-231/ADR was assessed through lipidomics. We also performed gene expression profiling on 152 TNBC patients unresponsive to Anthracycline-based chemotherapy, correlating with data from TCGA and METABRIC. Functional loss and gain experiments were undertaken to explicate the role of the SCD1-TRIM28-PD-L1 axis in mediating ADR resistance. Immunohistochemistry and RT-qPCR analyses were performed on tumor tissues and serum EVs from TNBC patients to identify chemosensitivity-enhancing targets. Results: Our investigation revealed marked transcriptional and proteomic variances between MDA-MB-231/ADR and MDA-MB-231/S cell lines, with SCD1 showing significant upregulation at both mRNA and protein levels. Metabolomic analyses revealed distinct lipid metabolic profiles between these two cell lines. Further studies found that Erastin treatment increased PD-L1 expression, along with changes in SCD1, p53, and TNFAIP3 expression levels. These molecules are closely associated with poor prognosis and resistance to therapy. Our findings also elucidated that TRIM28 modulates PD-L1 stability via SUMOylation and facilitates p53 ubiquitination and degradation through a TRIM28-MDM2 dependent pathway, thereby impacting immune surveillance and therapeutic response. Additionally, in TNBC patients treated with anthracycline-based chemotherapy, higher SCD1 and TNFAIP3 but lower TRIM28 expressions were observed in the PD/SD group compared to PR/CR. Similar expression patterns were observed in serum EVs. Conclusions: Our study highlights the potential of targeting the SCD1-TRIM28-PD-L1 axis in TNBC to overcome chemoresistance. We propose combining SCD1 inhibition with ferroptosis inducers to enhance PD-L1 blockade efficacy, offering a promising approach for TNBC patients with limited response to Anthracycline-based chemotherapy. This investigation represents a pivotal step towards advancing targeted therapeutics in TNBC, potentially transforming the clinical management of this aggressive and refractory breast cancer subtype.
Novel prognostic staging system for patients with de novo metastatic breast cancer: A real-world experience.
Authors: Ibrahim Khamees, Himil Mahadevia, Kensey Gosch, Parth Sharma, Simran Chandra, Kelly C. Gast, Timothy J. Pluard, Whitney L. Hensing
Journal: Journal of Clinical Oncology (2024)

e13167 Background: De novo metastatic breast cancer (dnMBC) is a heterogenous disease with variable survival rates. For newly diagnosed, non-MBC, the AJCC staging system incorporates non-anatomical factors, biomarkers and grade, in addition to tumor size and nodal status to define the prognostic stage group. These variables and other disease-related factors, such as sites of metastasis, have been associated with survival in MBC. Despite this, the current staging system groups all patients with dnMBC into a single prognostic group. More tools are needed to help clinicians relay important prognostic information to patients with dnMBC. Plichta et al. [1] utilized large population data sets to develop a novel staging system for dnMBC, which successfully stratified patients into four prognostic groups (IVA-D) based on disease-related variables. In this study, we sought to validate this staging system in an independent, real-world cohort of patients with dnMBC. Methods: We used a retrospective cohort of patients with MBC who received treatment in the Koontz Center for Advanced Breast Cancer (KABCC) at St. Luke’s Cancer Institute, a community-based healthcare system in the Kansas City metro area. The KABCC is a multidisciplinary clinic dedicated solely to the care of patients with MBC. Patients with dnMBC were assigned prognostic stage IVA, IVB, IVC, and IVD according to the system developed by Plichta et al. [1]. Overall survival (OS) was compared between groups using Kaplan-Meier analysis and the log-rank test. We also performed a stratified analysis based on age at diagnosis, &lt;60 years versus ≥60 years. Results: Ninety-seven patients with dnMBC were included in the analytic cohort. Mean age at diagnosis was 60 years, and most patients self-identified as non-Hispanic White (71.1%) or Black (22.7%). Nine patients were assigned stage IVA (9.3%), 39 stage IVB (40.2%), 32 stage IVC (33%) and 16 stage IVD (16.5%). Most stage IVA were HER2 positive (66.7%), while most stage IVD were triple-negative (56.3%). OS differed significantly between the four stage groups, with mortality rates increasing as stage increased. This was true in both the overall population (p&lt;0.001) and when patients were stratified by age at diagnosis (both p&lt;0.05) (Table). Conclusions: In an independent, real-world cohort of patients with dnMBC, a novel prognostic staging system that incorporates biomarkers, T-stage, grade, and sites of metastasis successfully stratified patients into four prognostic groups. Our findings help to confirm the utility of this staging system in dnMBC. [Table: see text]
Short-term and long-term survival outcomes in patients with invasive lobular carcinoma vs. invasive ductal carcinoma of the breast.
Authors: Shuwen Lin, Jesus Del Santo Anampa Mesias
Journal: Journal of Clinical Oncology (2024)

e12564 Background: Invasive lobular carcinoma (ILC) accounts for 10% of all invasive breast cancer and has distinct histological and biological features compared to the most common breast cancer histological subtype, invasive ductal carcinoma (IDC). ILC is more endocrine sensitive and chemotherapy resistant than IDC and has a different metastatic pattern. There is lack of conclusive data on the differences in survival outcomes between ILC and IDC. We aimed to assess the short-term and long-term survival outcomes in patients with ILC and IDC in a large population database. Methods: This is a retrospective, population-based study using data from the Surveillance, Epidemiology, and End Results database. We included women &gt; 18 years with stage I-III ILC or IDC diagnosed from 1992-2020. Multivariable logistic regression was used to assess factors associated with different treatment modalities in patients with IDC vs. ILC. We estimated breast cancer-specific survival (BCSS) using Kaplan-Meier methods and their survival rates were compared using the log-rank test. We analyzed BCSS at different time points using a cox regression model with time-varying coefficients. Results: 343,397 patients with IDC and 39,859 patients with ILC were included in this study. Patients with ILC were older (63.0 ± 12.5 years vs. 59.2 ± 13.5 years, p&lt;0.001). There were more non-Hispanic white patients with ILC vs. IDC (76% vs. 67%, p&lt;0.001). Patients with ILC had more advanced disease: more stage III disease (16% vs. 11%, p&lt;0.001), more T3-T4 disease (15% vs. 6%, p&lt;0.001), and more N2-N3 disease (12% vs. 9%, p&lt;0.001). Patients with ILC also had a higher frequency of hormone receptor positive disease (97% vs. 81%, p&lt;0.001). Fewer patients with ILC had grade 3-4 tumors (9% vs. 36%, p&lt;0.001). Our multivariate analysis showed that compared to patients with IDC, patients with ILC were more likely to undergo mastectomy (OR=1.85, p &lt; 0.001) and radiation (OR=1.20, p&lt;0.001), but less likely to receive chemotherapy (OR= 0.92, p&lt;0.001). After adjusting for clinicopathological features, treatment modalities, and socioeconomic variables; compared to patients with IDC, patients with ILC had better BCSS in the first five years (HR=0.71, p &lt;0.001), but worse BCSS in later years (HR=1.30, p&lt;0.001 in year 6-10; HR=1.75, p&lt;0.001 in year 11-15; HR=2.17, p&lt;0.001 in year 16-20). Annual hazard models show that IDC peaked at recurrence in the first 5 years after diagnoses, and the hazard rate declines gradually after that. ILC peaked at recurrence in the first 5 years after diagnosis with minimal decrease in hazard rates after that. Conclusions: BCSS of patients with ILC is better in early years but worse in later years compared to patients with IDC. Future studies are needed to identify predictors of late relapses in ILC, and novel therapeutic strategies are required for these patients.