bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracranial outcomes with ipilimumab and nivolumab in melanoma brain metastases following progression on anti-PD-1 therapy.
Authors: Lochrin Sarah E. , Kalvin Hannah L , Smithy James William , Momtaz Parisa , Shoushtari Alexander Noor , Panageas Katherine , Postow Michael A. 
Published: July 2024

9555 Background: Ipilimumab + nivolumab (ipi/nivo) is effective for melanoma brain metastases (MBM), but the efficacy of ipi/nivo in MBM in patients (pts) whose melanoma has progressed on anti-PD-1 is unknown. Methods: We conducted a retrospective analysis of pts with progressive MBM who received ipi/nivo at Memorial Sloan Kettering Cancer Center following prior anti-PD-1. Cohort A included pts with ≥1 untreated MBM (≥5mm) without local interventions (such as neurosurgery, radiotherapy). Cohort B included pts who had received local interventions for all MBMs before starting ipi/nivo. The primary endpoint was intracranial (IC) progression free survival (PFS). IC response was assessed based on clinical radiological interpretation for Cohort A. Kaplan-Meier methods were used to estimate time-to-event outcomes. Results: Fifty-seven pts were identified: 28 and 29 in Cohort A and B, respectively. All pts had received prior anti-PD-1, 42% prior ipi, a median of 2 (IQR: 1, 3) prior lines, and 21% (12/57) of pts prior treatment was in the adjuvant setting only. 79% (45/57) of pts had cutaneous, 14% (8/57) acral, 5% (3/57) unknown primary and 2% (1/57) mucosal melanoma. Median age was 64 (IQR: 58, 71) and 55 (IQR: 47, 70) years in Cohort A and B, respectively. Cohort A had median lesion size (largest measurable MBM) of 1.0cm (IQR: 0.60, 2.12), and 64% (18/28) of pts had >5 lesions; Cohort B had a median lesion size 1.5cm (IQR: 1.10, 2.00) and 28% (8/29) of pts had >5 lesions. 14% (8/57) of pts received concurrent steroid (equivalent of ≥dexamethasone 4mg daily) upon starting ipi/nivo, and leptomeningeal disease was present in 14% (4/28) and 7% (2/29) of Cohort A and B, respectively. The IC response rate was 11% (3/28, 2 were complete (CR)) in Cohort A.Both patients with CR were asymptomatic with ≤ 2 lesions and no prior CTLA-4 exposure. Most (20/28, 71%) in Cohort A had best response of progressive disease (PD); all that had a best response of stable disease (SD; 5/28, 18%) sustained that response for less than 6 months. Median IC-PFS was 1.7 (95% CI: 1.3,4.4) and 7.6 (95% CI: 3.6, -) months, and median overall survival (OS) was 6.7 (95% CI: 3.6,10) and 24 (95% CI: 11, -) months in Cohort A and B. 24-month OS was 19% (95% CI: 8.1,45) and 51% (95% CI: 35,75) in Cohort A and B. 30% (8/27) and 66% (19/29) of pts had subsequent systemic therapy, and 48% (13/27) and 52% (15/29) subsequent local therapy in Cohorts A and B. Conclusions: Ipi/nivo has limited efficacy in patients with progressive MBM post-PD-1 therapy in the absence of local therapy. These results highlight the unmet clinical need for more effective therapies to address progressive MBM post-PD-1 therapy, an increasingly relevant clinical scenario particularly in light of the growing use of adjuvant and neoadjuvant anti-PD-1.
Serum multiplex analysis of checkpoint proteins in association with immune-related adverse events in patients with melanoma receiving adjuvant anti-PD-1 therapy.
Authors: Knight Andrew David , Bruno Sabrina , Layding Caroline Jane , Wang Hong , Sander Cindy , Storkus Walter J , Karapetyan Lilit , Kirkwood John M. 
Published: July 2024

9588 Background: Immune checkpoint inhibitors have significantly improved melanoma (MEL) patient (PT) outcomes. Immune-related adverse events (irAEs) may cause significant morbidity, rarely including death. Soluble immune checkpoints have been identified as biomarkers of autoimmune activity and potential off-target pathology. Understanding their relationship to pathologic outcomes may assist in the identification of PTs at highest risk of irAEs. Methods: PTs with resectable stage IIB-IV MEL who received adjuvant anti-programmed-death-1 (PD-1) therapy were identified from the University of Pittsburgh’s MEL Center biospecimen repository (N=273). MILLIPLEX Human Immuno-Oncology Checkpoint Protein Panel 2 was used to study serum levels of immunomodulatory proteins. Mean pretreatment serum levels in PTs with and without irAEs were compared using a two-sample t-test after performing Box-Cox transformation for non-normally distributed data. Results: Sera from 43 PTs were analyzed. The cohort included 28 (65.1%) male, mean age at diagnosis (62), including MEL stage IIIA = 7 (16.3%), IIIB = 16(37.2%) and IIIC = 20(46.5%). The most common irAEs (n=24, 55.8%) were thyroiditis (n=9, 20.9%), dermatitis (n=8, 18.6%), and adrenal insufficiency (n=9, 21.0%). Multiple irAEs were observed amongst 22 (51.2%) PTs with ≥3 irAEs and 6 (13.9%) with 5 irAEs. Visceral irAEs included Hepatitis (n=3, 7.0%), pneumonitis (n=2, 4.7%), and colitis (n=5, 11.6%). Seven of 8 patients with visceral irAEs required corticosteroids. Siglec-7 (mean 23.4 vs 3.51 pg/mL, p=0.018) and siglec-9 (mean 77.0 vs 33.1 pg/mL, p=0.049) were significantly elevated in the PTs who developed any irAE. After stratifying for each individual irAE, PTs with thyroiditis had elevated Nectin-4 (mean 2785.5 vs 494.7 pg/mL, p<0.001) and serum arginase (mean 2437.5 vs 1383.1 pg/mL, p= 0.046) was elevated in PTs who developed colitis. PTs with hepatitis demonstrated increased galectin-3 (mean 10103.9 vs 9915.3 pg/mL, p=0.045) and decreased levels of CD40L (mean 2869.2 vs 9496.9 pg/mL, p=0.033). In PTs with dermatitis B7-H3 (mean 2503.3 vs 732.4 pg/mL, p=0.009) and MHC class I polypeptide-related sequence B (mean 1598.0 vs 259.1 pg/mL, p=0.048) were elevated. Conclusions: We have demonstrated unique serum checkpoint protein profiles related to specific irAEs in melanoma patients receiving adjuvant anti-PD1. Further studies are warranted to confirm and validate the utility of these irAE predictors during adjuvant anti-PD-1.
HR+/HER2- early breast cancer with a high risk of recurrence: The impact of online education on clinician knowledge, competence, and confidence in utilization of clinical practice guidelines to enhance patient care.
Authors: Patel Urvi , Dorkhom Nabil , Phoenix Victoria , Zhang Cong , Bahra Sukhbir 
Published: July 2024

e12515 Background: Clinical practice guidelines drive treatment decision making in HR-positive, HER2-negative early breast cancer with a high risk of recurrence. Understanding is necessary to incorporate the guidelines into practice and improve patient care. To address this gap, two global educational activities were developed that consisted of a 1-hour live streaming virtual meeting with a 45-minute online enduring activity and a 30-minute panel discussion. The objective of this study was to assess the educational impact of the online educational activities. Methods: To assess educational impact a repeated-pairs pre-/post-assessment study design using 6 knowledge/competence questions, in which everyone served as their own control. A paired samples t-test assessed mean differences in the average number of correct responses to the matched pre-/post-assessment questions, and a McNemar’s test assessed significance of improvement across core learning topics from pre- to post-assessment. P values <.05 are statistically significant. Confidence was also assessed using a pre/post confidence question. The activities launched in March 2023 and data was collected till January 2024. Results: 385 oncologists from the US and outside of the US who answered all the pre-/post-assessment questions were included in the analysis. Each assessment question was mapped to an activity learning objective. The learning objectives were grouped into three core topics. All core topics showed a significant improvement in education. Conclusions: These online activities resulted in a significant improvement of oncologists’ knowledge and competence related to the utilization of clinical practice guidelines. Confidence in understanding the implications of the latest guidelines also showed a statistically significant improvement. However, there is still a need for education in a significant percentage of oncologists on this topic. [Table: see text]
Trends in the management of small HER2-positive breast cancers.
Authors: Mueller Carolin , Rahul Rangan , Kruse Megan Lynn , Alhilli Zahraa 
Published: July 2024

e12523 Background: Small HER2 positive breast cancers have not been well studied in randomized trials. The treatment landscape for this population aims to optimize efficacy while minimizing potential over-treatment and associated toxicities. Due to the potential for post-neoadjuvant therapy optimization, use of neoadjuvant systemic therapy (NAT) increased in recent years. However, this approach can often lead to overtreatment of patients with small tumors. This study aims to evaluate recent trends in treatment patterns of patients with T1 HER2 positive tumors. Methods: Patients diagnosed with HER2 positive, T1, any N, breast cancer treated at a single institution from January 2018 to December 2022 were included. Clinicopathological data, treatment data, and survival data were collected and analyzed. Results: 326 patients were included. Mean age was 62 (±12.2) years. T category included 3 (0.9%) cT0, 17 (5.2%) cTmi, 28 (8.6%) cT1a, 94 (28.8%) cT1b, 178 (54.6%) cT1c tumors, and 6 patients (1.8%) had clinical T1 stage without further specification. 41 patients (12.6%) had cN+ disease and 243 (74.5%) were hormone receptor positive. Systemic therapy data was available for 288 patients; 7 (2.4%) received Herceptin monotherapy, 105 (36.5%) Taxol + Herceptin, 41 (14.2%) Taxol + Carboplatin + Herceptin, and 74 (25.7%) Taxol + Carboplatin + Herceptin + Pertuzumab (TCHP), 12 (4.2%) other. 49 patients (17%) did not receive any systemic therapy. 58 patients (17.8%) were treated with NAT and a pathologic complete response rate was noted in 39 patients (67.2%) undergoing NAT. Overall, in patients who received systemic therapy, NAT increased from 2018 (17.6%) to 2021 (37.5%) and decreased in 2022 (23.5%). Similar patterns were observed in patients with T1a/b (2021: 17.4%; 2022: 0%), as well as T1c (2021: 51.4%; 2022: 36.4%). TCHP was the most commonly administered NAT regimen (86.2%). Discontinuation or dose reduction occurred in a total of 57 patients (18.8%). Conclusions: The primary treatment for T1 HER2 positive breast cancers is surgery with adjuvant HER2 targeted therapy in combination with chemotherapy. Although NAT witnessed an upward trend from 2018 to its peak in 2021, its utilization declined again in 2022. A balance between the most effective treatment and minimizing toxicities should be ensured.
Examining a genomic test in predicting extended endocrine benefit and recurrence risk in a diverse breast cancer population.
Authors: Lee Ho Hyun , Siu-Li Nicholas , Pagano Ian , Fukui Jami Aya 
Published: July 2024

e12526 Background: Extending adjuvant endocrine therapy (EET) beyond five years for early-stage hormone receptor-positive (HR+) breast cancer reduces late distant recurrence risk. The genomic test, Breast Cancer Index (BCI), has prognostic value and predicts the benefits of prolonged therapy, yet no studies have explored this testing in a diverse population. This study assesses late distant recurrence risk and predictive benefits of EET to better understand its relevance in a diverse early-stage HR+ breast cancer population. Methods: We analyzed patient demographics, clinical and pathologic characteristics, and BCI scores of 150 women in Hawaii with early-stage HR+ breast cancer, self-identifying as White, Filipino, Japanese, Native Hawaiian, or other. Tumor characteristics examined include size, grade, histology, lymph node, and ER/PR/HER2 receptor status. Logistic regression analyses used race, distant recurrence risk, and tumor features as predictor variables. BCI prediction of benefit and distant recurrence risk served as outcome variables. Results: Japanese patients had significantly lower odds of having a high risk for distant recurrence (OR = 0.02, p < 0.0001) compared to White. Other Asian PIs also showed reduced odds of high distant recurrence risk (OR = 0.07, p = 0.02), albeit to a lesser extent than Japanese. Patients with high distant recurrence risk had significantly greater odds of a score predicting benefit than those with low risk (OR = 5.03, p = 0.009). Racial or ethnic differences in predicting benefit with EET were not statistically significant. Conclusions: Results show no racial or ethnic differences in predicting the benefit of EET, strengthening BCI’s universal applicability in diverse women with early-stage HR+ breast cancer. Patients with higher distant recurrence risk were predicted to benefit from EET. This suggests potential variations in tumor features or other factors affecting distant recurrence risk among racial groups. Limitations include a relatively small sample size and lack of data from patients representing other racial groups. Future studies should expand the sample size and adjust for known breast cancer risk factors to better understand the racial and ethnic implications of BCI.
De-escalation of breast cancer surgery using vacuum-assisted biopsy (VAB): Interim results.
Authors: Krivorotko Petr , Amirov Nikolay , Mortada Viktoriia , Emelyanov Alexander , Yereshchenko Sergey , Pesotskiy Roman , Tabagua Tengiz , Artemyeva Anna , Zhiltsova Elena , Gigolaeva Larisa , Bondarchuk Yana , Enaldieva Diana , Ulrikh Daria , Levchenko Valerii , Krzhivitskiy Pavel , Busko Ekaterina , Semiglazova Tatiana , Novikov Sergey , Semiglazov Vladimir 
Published: July 2024

e12590 Background: Currently, there is a point of view according to which, in patients diagnosed with breast cancer (BC), surgical intervention when achieving a complete pathological response (pCR) after neoadjuvant systemic therapy (NST) is diagnostic, not therapeutic, and does not affect long-term treatment outcomes. Vacuum-assisted biopsy (VAB) of the tumor bed in breast cancer has shown promising results as a minimally invasive method for diagnosing pCR. This work presents a prospective analysis of treatment of patients with triple-negative and HER2-positive breast cancer who achieved pCR after NST and who underwent VAB alone without subsequent breast surgery. Methods: Women aged 18 years old and older with unicentric (cT1-2N0-1M0) triple-negative or HER2-positive breast cancer were included. Primary lesions were marked with a single clip before NST. In cases with nodal involvement (cN1) the affected lymph nodes were also clipped. Patients with TNBC received 4 cycles of AC q21d followed by 12 cycles of weekly paclitaxel and carboplatin AUC 2.0. HER2+ patients received dual anti-HER2 blockade with chemotherapy (TCHP or AC-DHP regimen). Breast US, mammography and mammolymphoscintigraphy were used at baseline and at response evaluation. Patients with complete clinical response after NST underwent VAB with 7G needle and US-guidance simultaneously with the sentinel lymph node biopsy and/or targeted axillary dissection. In case if no invasive or in situ residual tumor cells were detected (ypT0N0), no further breast surgery was performed and patients underwent subsequent radiation therapy. Primary endpoint was 2-year ipsilateral breast tumour recurrence-free survival [IBTR-FS]. Secondary endpoints included 2-year disease-free survival (DFS) and complication rates. The study is registered on сlinicaltrials.gov, NCT04293796. Results: 35 patients with a mean age of 48.3 (31–67) years were included in the trial. Examination of VAB samples showed that 11 (31.4%) patients had a residual tumor, and in 24 (68.6%) patients no tumor cells were detected (ypT0N0). This 24 patients were included in the analysis. Median follow-up was 26 months. Median survival was not reached for any endpoint. 2-year IBTR-FS was 91.7% in the VAB group. 2-year DFS was 83.3% in the VAB group. We registered 4 events: in 2 patients biopsy-proven de novo breast cancer occurred in contralateral breast, in 1 patient recurrence occurred in the postoperative zone and in 1 patient recurrence occurred in another quadrant of the ipsilateral breast. Conclusions: Additional observation and large randomized prospective studies are needed to determine the safety of VAB use. Clinical trial information: NCT04293796 .
A retrospective, single-center study comparing two neoadjuvant protocols for patients with HER2-positive breast cancer.
Authors: Itay Amit , Globus Opher , Levanon Keren , Sella Tal , Bernstein-Molho Rinat , Shapira Rotenberg Tal , Oedegaard Cecilie , Fourey Dana , Gal-Yam Einav Nili 
Published: July 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 (>10% or LVEF≤50%) was observed in 6.6% of the ACTHP group vs. 0% in the DCHP group (p<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<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]
Retrospective analysis of factors impacting efficacy of patients with later stage breast cancer receiving neoadjuvant therapy.
Authors: Wang Nan , Zhu Anjie , Ran Ran , Yan Ying , Shao Bin , Liang Xu , Jiang Hanfang , Song Guohong , Di Lijun , Li Huiping 
Published: July 2024

e12624 Background: Neoadjuvant treatment is the current standard of care for patients with early breast cancer (EBC), especially for patients with later stage breast cancer (LBC). We conducted this retrospective study to summarize the correlation between pathologic complete response (pCR), disease-free survival (DFS), overall survival (OS) and clinical impacting factors of patients with later stage received neoadjuvant treatment. Methods: We retrospectively analyzed the clinical data of patients receiving neoadjuvant treatment at the Department of Breast Oncology, Peking University Cancer Hospital from Jan. 2013 to Feb. 2022. Statistical analyses were carried out using IBM SPSS Statistics. We calculated pCR rate, DFS and OS. Pearson’s χ2 or Fisher’s exact tests were used for comparison of categorical variables. DFS and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression was used to identify factors impacting on survival. All p values were two sided and p<0.05 was considered to denote statistical significance. Results: Of 198 patients, most of them were in stage II (115/198, 58.1%), followed by stage III (79/198, 39.9%) and stage I (4/198, 2.0%), The pCR rates for different molecular subtypes were 31.6% TNBC, 29.7% for HR-Her2+ BC, 26.1% for HR+Her2+ BC and 1.3% for HR+Her2- BC, respectively (p=0.000). The median DFS of patients with or without pCR was 59.63 months (95%CI: NA-NA) and 29.83 months (95%CI: 21.31-38.35), respectively (p=0.012). DFS of patients who were cT1 [59.63 months (95%CI: 37.95-81.31)] or cT2 [39.56 months (95%CI: 24.19-54.93)] was significantly longer than that of patients who were cT3-4 [25.76 months (95%CI: 14.11-37.41), p=0.041]. Miller Payne (M-P) grade and ypTNM stage were also significantly associated with DFS in univariate analysis and in the multivariate cox regression model after adjusting for molecular subtypes. The 5-year OS were 87.0% for patients who reached pCR and 52.0% for patients who didn’t (p=0.009). Conclusions: The pCR was significantly associated with molecular subtypes. HR negativity and overexpression of Her2 were significantly associated with higher pCR rate. Patients reached pCR had longer DFS and OS. DFS was significantly associated with cT stage (T1 vs T2 vs T 3-4), ypTNM stage and M-P grade.