Neoadjuvant Systemic Therapy Research Articles

Histologic comparison of the area of tumor bed after vacuum-assisted biopsy (VAB) or standard breast surgery in patients with early breast cancer after neoadjuvant systemic therapy (NST).

e12573 Background: The main goal of surgical intervention after achieving complete clinical response is to confirm it pathmorphologically. VAB of the tumor bed in the breast has demonstrated encouraging results as a minimally invasive method to determine pCR. It is not yet known whether the tumor bed can be accurately measured in the fragmented VAB material and therefore RCB index cannot be determined. From the point of view of pathologic examination, it is crucial to confirm that specimen volume after VAB is sufficient for precise assessment of the tumor bed. Methods: A single-center retrospective study included 36 patients with unifocal breast cancer (cT1-2N0-1M0). First group of patients underwent VAB instead of standard surgery as part of clinical trial NCT04293796. Second group includes patients after standard breast-conserving surgery (BCS) or mastectomy. All patients included in the analysis achieved pCR after NST. All microscope slides after preliminary cleaning were digitized using 3DHistech PANNORAMIC 1000 DX scanner. Tumor bed measurements were performed manually by experienced pathologist using the 3DHistech SlideViewer 2.8.0 software. Tumor bed area (mm 2 ) was selected as main tumor bed characteristic. Results: 36 patients were included in the analysis (20 women after VAB and 16 women after standard surgery). Mean tumor bed area in specimens obtained by VAB was 266.67 mm 2 (30.50–740.08), after BCS and mastectomy - 199.88 mm 2 . (48.67–740.6). There was no statistically significant difference in tumor bed area depending on type of intervention performed (U-test=126.0, p=0.286). No differences were observed between groups after standardization of tumor bed area measurements in each group (U-test after MinMax standardization: 117.5, p=0.181; U-test after Robust standardization: 166.0, p=0.861). Correlation analysis using Spearman’s method was performed to assess correlation between tumor bed area and quantitative clinical variables: maximum tumor size before NST (r=0.143, p=0.418), maximum tumor area before NST (r=0.113, p=0.523), maximum tumor size after NST (r=-0.161, p=0.360) and maximum tumor area after NST (r=-0.114, p=0.520). There was a significant correlation between tumor bed area and total area of VAB specimen (r=0.605, p=0.0047). Associations with categorical variables were analyzed using Kruskal-Wallis test: cT stage (0.516, p=0.473), cN stage (0.660, p=0.417), clinical stage (1.473, p=0.479). Conclusions: There is no statistically significant difference in tumor bed area measurements depending on type of surgery performed. Volume of specimen after VAB is enough for tumor bed assessment as in the specimens after standard surgery.

Setting a precedent: Development of a core outcome set for locoregional treatment outcome reporting in neoadjuvant breast cancer trials.

e12570 Background: Accurate information about locoregional (LR) treatments following neoadjuvant systemic therapy (NST) for breast cancer is essential for interpretation of oncological outcomes, but reporting is currently poor. We aimed to develop a core outcome set (COS) to improve quality and consistency of LR outcome reporting in trials. Methods: The COS was developed in three phases according to COS-STAD guidance: 1. Generation of a long list of relevant outcome domains from a systematic literature review and stakeholder interviews. 2. Prioritisation of outcome domains using two rounds of an online Delphi survey. 3. An in-person consensus meeting to agree the final COS. Results: In total, 159 unique LR outcomes were identified from phase 1 and categorised into 101 (69 surgical/32 RT) outcomes for survey inclusion. 470 international participants (206 surgeons/144 medical oncologists/98 radiation oncologists) took part in survey Round 1, of whom 336 (71.5%) (153 surgeons/90 medical oncologists/ 77 radiation oncologists) participated in Round 2. After Round 2, 31 outcomes, combined into 15 summary outcomes, were scored as ‘consensus in’, 60 as ‘consensus out’ and 10 as ‘no consensus’. 23 professionals and 5 patient advocates attended the consensus meeting, where ‘consensus in’/’consensus out’ items were ratified, and ‘no consensus’ items discussed. A final 15 item COS for LR outcome reporting was agreed and ratified (Table). Conclusions: A COS for LR treatment reporting in NST trials has been robustly developed using an internationally collaborative approach. Widespread implemention will improve the quality and value of future breast cancer NST trials. Final COS 1 Type of breast and axillary surgery planned before starting NST 2 Proportion of patients not having surgery after NST due to disease progression, treatment toxicities or other comorbidities 3 Number/proportion of patients with a complete response to NST not having surgery to the breast and/or axilla, and how response was assessed 4 How response to NST in the breast and axilla was assessed 5 Type of initial breast and axillary surgery performed after NST 6 Proportion of patients with involved margins after initial and final surgery, and number of procedures required 7 Total number of excised and involved axillary lymph nodes, with extent of involvement 8 Further axillary treatment in patients with ypN+ disease after sentinel node biopsy/targeted axillary dissection (SLNB/TAD) 9 Proportion of patients in whom breast and/or axillary surgery was downstaged 10 Proportion of patients having radiation therapy 11 Indications for radiation therapy at trial level 12 Details of breast/chest wall and nodal targets 13 Details of dose and fractionation to breast/chest wall and nodal areas 14 Receipt of boost; indications for boost (at trial level) 15 Morbidity of locoregional treatments (short/long term as defined in protocol)

Survival for head and neck squamous cell carcinoma treated with versus without neoadjuvant systemic therapy: A national propensity score–matched analysis.

6035 Background: Neoadjuvant systemic therapies, including immunotherapy and chemotherapy, offer a promising approach for treating head and neck squamous cell carcinoma (HNSCC). These therapies aim to reduce tumor burden and enable personalized treatment. While pivotal studies like KEYNOTE 689 may redefine therapeutic paradigms, the survival outcomes associated with neoadjuvant systemic therapies in HNSCC remain underexplored. Methods: A retrospective cohort analysis using the National Cancer Database evaluated patients with HNSCC surgically treated with versus without neoadjuvant systemic therapies from 2015 to 2022. Overall survival (OS) was compared by using a Cox proportional hazards regression model. Propensity score matching was performed to adjust for stage, age, sex, race, insurance status, urban/rural, Charlson–Deyo score. Results: Among 3,569 patients (74% male, 26% female), 1,311 received neoadjuvant chemotherapy, 632 received neoadjuvant immunotherapy, 114 received a combination of neoadjuvant chemotherapy and immunotherapy, and 1,512 were matched HNSCC patients who did not receive any neoadjuvant therapy prior to surgery. Most patients had overall stage IVa/b (59%) tumors of the oral cavity (62%). On univariate analysis, neoadjuvant immunotherapy alone was associated with a 43% reduced the risk of mortality, compared to neoadjuvant chemotherapy alone (HR: 0.57; 95% CI: 0.48–0.68, P < .001 ). Combination therapy was not significantly associated with lower mortality than chemotherapy alone (HR: 0.87; 95% CI: 0.63–1.21, P = .41 ). After adjustment using a propensity matched cohort of patients with HNSCC treated without neoadjuvant therapy, neoadjuvant immunotherapy was associated with significantly improved OS (HR: 0.55; 95% CI: 0.35-0.75, P < .001 ). However, neoadjuvant chemotherapy (HR: 1.07; 95% CI: 0.96–1.18, P = .23 ) and combination therapy (HR: 0.84; 95% CI: 0.49-1.19, P = .33 ) were not significantly associated with improved OS. Conclusions: Neoadjuvant immunotherapy may potentially provide improved survival in HNSCC. Further research is needed to assess these findings through prospective trials. Overall survival for patients with head and neck squamous cell carcinoma treated with versus without neoadjuvant systemic therapy. Overall Survival HR (95% CI) P No neoadjuvant therapy Ref. Neoadjuvant chemotherapy 1.07 (0.96–1.18) 0.23 Neoadjuvant combination therapy 0.84 (0.49-1.19) 0.33 Neoadjuvant immunotherapy 0.55 (0.35-0.75) <0.001 HR, hazard ratio; CI, confidence interval.

Distinct cellular interactions in the TNBC tumor microenvironment in association with PD-L1 expression and pathologic complete response based on spatial analysis.

e12544 Background: Immune-activated tumor microenvironments (TMEs), characterized by PD-L1 positivity or an abundance of tumor-infiltrating lymphocytes, are associated with pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant systemic therapies (NAST). We performed a spatial analysis of the TME using a highly multiplexed imaging technique in treatment-naïve TNBC tumor samples treated with NAST. Methods: We collected 28 biopsied tumor samples before NAST. Of these, 6 patients underwent preoperative immunochemotherapy with pembrolizumab. Spatial analysis of the TME was performed using CO-Detection by indexing (CODEX). Physical cell-to-cell interactions were analyzed by assessing the rate of direct contact and the closest distance between different cell types. PD-L1 expression was evaluated using the Ventana SP142 PD-L1 assay. Results: The rate of PD-L1 positivity and pCR were 42.8% and 53.6%, respectively. CD8+ T cells were classified into two groups by immune checkpoint (IC) markers (PD1, LAG3, CXCL13): CD8+IC high and CD8+IC low . Direct contact between CD8+IC high and CD4+FoxP3 low T cells was enriched in tumors with PD-L1-negative or non-pCR. In PD-L1-positive tumors, podoplanin exhibited direct interactions with various immune cell types, including CD8+IC low , CD4, CD8, and myeloid cells. When analyzing cell-to-cell distances, the distances between B cells and various cells including tumor epithelial cells were significantly shorter in cases with pCR compared to those without pCR. Conclusions: Direct interaction between CD8+IC high and CD4+FoxP3 low cells may be associated with PD-L1-negative TNBC. Podoplain potentially plays a role in the PD-L1-expressing TME in TNBC. Active physical interaction between B cells and neighbor cells was observed in tumors with pCR. Our findings, based on spatial analysis of TME, may enhance our understanding of immune-cold TNBC and its lack of response to immunochemotherapy.

Inflammation-related biomarkers as predictors of pathological complete response in early-stage breast cancer.

Neoadjuvant systemic therapy (NAT) represents an attractive option for improved outcomes of early-stage breast cancer (BC) patients, as it can significantly reduce tumor burden thus permitting breast-conserving resections. Equally important, the eradication of viable cancer cells post-NAT, also known as pathological complete response (pCR), has emerged as a strong prognostic biomarker, reflecting tumor's biology and subsequent treatment responses. Yet to date, no validated markers predictive of pCR have been identified. The present retrospective study aimed to explore the value of neutrophil-tolymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as potential predictors of pCR. Despite no statistically significant associations have been reported, NLR and PLR dynamics during NAT, as longitudinal inflammatory phenotypes, merit further investigation in larger cohorts. In the future, the integration of a comprehensive inflammatory biomarker panel into clinical practice could assist in a priori treatment selection process.

Use of superparamagnetic iron oxide for sentinel lymph node detection following neoadjuvant systemic therapy. A systematic review and meta-analysis.

Use of superparamagnetic iron oxide for sentinel lymph node detection following neoadjuvant systemic therapy. A systematic review and meta-analysis.

Is switching to T-DM1 still justified in HER2-negative residual breast cancer after neoadjuvant systemic therapy?

Is switching to T-DM1 still justified in HER2-negative residual breast cancer after neoadjuvant systemic therapy?

Role of imaging based response assesment for adapting neoadjuvant systemic therapy for breast cancer: A systematic review.

Role of imaging based response assesment for adapting neoadjuvant systemic therapy for breast cancer: A systematic review.

Impact of the lymphovascular invasion on the prognosis in pT1-2N0 early breast cancer.

e12517 Background: Lymphovascular invasion (LVI) has historically been considered a poor prognostic factor in breast cancer. However, the clinical impact of LVI on breast cancer prognosis has not been fully investigated in the recent era, when the concept of tumor subtypes and the application of multigene assays in determining adjuvant therapy are well established. Methods: A total of 1340 patients with pT1-2N0M0 (pStage I-IIA) breast cancer were included, who underwent surgery without neoadjuvant systemic therapy between 2010 and 2020. The relationships between Ly and clinicopathological factors and prognosis (relapse-free survival; RFS, distant metastasis-free survival; DMFS) were analyzed. Results: Among 1340 patients, LVI was positive in 100 (7.5%) patients (Ly1) and in other 1240 (92.5%) patients, LVI was negative (Ly0). LVI was significantly associated with premenopausal women, large tumor size, higher histological grade (HG), higher Ki67 and higher rate of postoperative adjuvant chemotherapy. There were no associations between LVI and estrogen receptor (ER), hormone receptor (HR), HER2 and tumor subtypes. Among these cases, data of Oncotype Dx were available in 41 cases (Ly0 34 cases, Ly1 7cases). There was no relationship between LVI and recurrence score (RS) (Ly1; RS 15.1±2.9, Ly0; RS 18.3±1.3, p=0.3295). The prognosis of the patients with Ly1 was significantly poorer in terms of RFS and DMFS compared with that of those with Ly0. These relationships were evident in premenopausal women, tumor size of pT1c, HG II, and HR+/HER2- subtype. Adjuvant chemotherapy did not improve the prognosis of patients with LVI. Ly1 was a poor prognostic factor in univariate and multivariate analyses in terms of both RFS and DMFS. Conclusions: LVI was shown to be a poor prognostic factor for pT1-2N0 early breast cancer even in recent years. Benefits of adjuvant chemotherapy for improving prognosis not clear, however, LVI should be considered as an important factor in determining adjuvant systemic therapy, especially in premenopausal women, pT1c, HG II, HR+/HER2- cases.

Artificial Intelligence-Assisted Detection of Breast Cancer Lymph Node Metastases in the Post-Neoadjuvant Treatment Setting.

Artificial Intelligence-Assisted Detection of Breast Cancer Lymph Node Metastases in the Post-Neoadjuvant Treatment Setting.

Outcomes of Segmentectomy With or Without Preoperative Biopsy in Non-Small Cell Lung Cancer (NSCLC).

Outcomes of Segmentectomy With or Without Preoperative Biopsy in Non-Small Cell Lung Cancer (NSCLC).

Trastuzumab-pertuzumab combined with taxanes or eribulin in HER2-positive breast cancer: A single-arm meta-analysis of RCTs.

e13019 Background: Trastuzumab-pertuzumab combined with taxanes or eribulin has emerged as a promising therapeutic regimen for HER2-positive breast cancer, a subtype known for its aggressive clinical course. This single-arm meta-analysis of randomized controlled trials aims to evaluate the efficacy and safety of these combinations, providing evidence to guide treatment strategies for this challenging malignancy. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane, and Scopus using relevant keywords from inception till January 2025. Statistical pooling was executed using OpenMeta Software (version 5.3). Occurrence rates, presented as untransformed proportions, were pooled with the corresponding 95% confidence interval using a random-effects model. Interstudy heterogeneity was evaluated using the I² and χ² statistics, with I² > 50% being considered as significant. Results: Sixteen studies yielding 3300 patients were included. An overall mortality rate of 25.7% among patients who received prior neoadjuvant or adjuvant systemic therapy was revealed (95% CI = 0.13-0.41, I = 97.6%, p < 0.001) while those who did not get prior therapy exhibited a mortality rate of 45% (95% CI: 0.34-0.57, I = 94.38%, p < 0.001). 9.6% deaths were reported for subjects less than 65 years (95% CI: 0.05-0.16, I = 81.5%, p < 0.001) and 12.4% for subjects above 65 years (95% CI: 0.06-0.21, I = 81.68%, p < 0.001). The pooled disease-free interval was 17.92 months (95% CI: 14.52–21.32, I = 99.86%, p < 0.001). The overall tumor objective response rate was estimated at 76.5% (95% CI: 0.65-0.85, I = 92.72%, p < 0.001). The pooled analysis revealed the following adverse events: Alopecia in 70% (95% CI: 0.48-0.88, I = 95.75%, p < 0.001), anemia in 29% (95% CI: 0.09-0.55, I = 96.75, p < 0.001), diarrhea in 50% (95% CI: 0.37-0.63, I = 96.18%, p < 0.001), dry skin in 40% (95% CI: 0.14-0.71, I = 97.53, p < 0.001), fatigue in 71% (95% CI: 0.36-0.96, I = 96.69, p < 0.001), febrile neutropenia in 8% (95% CI: 0.03-0.15, I = 89.57, p < 0.001), hypertension in 11% (95%CI: 0.02-0.29, I = 95.15, p < 0.001), left ventricular dysfunction in 24% (95%CI: 0.14-0.36, I = 78.91%,p < 0.009), mucositis in 24% (95% CI: 0.14-0.36, I = 78.91%,p < 0.009), nail disorders in 14% (95%CI: 0.07-0.23, I = 0%,p = 0.76), nausea in 44% (95%CI: 0.31-0.59, I = 90.18%, p < 0.001), neutropenia in 35% (95%CI: 0.24-0.48, I = 95.68%,p < 0.001), peripheral neuropathy in 33% (95%CI: 0.09-0.64, I = 98.68,p < 0.001). Conclusions: This meta-analysis highlights the differential mortality rates and a spectrum of adverse events associated with trastuzumab-pertuzumab combined with taxanes or eribulin in HER2-positive breast cancer patients, influenced by prior therapy status and age. These findings underscore the need for personalized treatment strategies to optimize efficacy and manage toxicities effectively.

Real-world adoption of adjuvant molecularly targeted therapy and immunotherapy for resected stage Ib-III non-small cell lung cancer within the Veterans Health Administration.

e20020 Background: Emerging evidence supports the use of adjuvant systemic therapies for appropriately selected patients with early-stage, resected non-small cell lung cancer (NSCLC). The real-world adoption of these therapies is unknown, although prior studies have highlighted slow implementation of other guideline-concordant treatments for NSCLC. This study aimed to evaluate trends in the real-world adoption of adjuvant molecularly targeted therapies and immunotherapies among patients with resected NSCLC. Methods: This study utilized a longitudinal dataset from the Veterans Health Administration Corporate Data Warehouse and queried for all patients with clinical stage IB-III NSCLC who underwent surgical resection from 2017-2023. Patients who received neoadjuvant systemic therapy (n=153, 6.2%) were excluded. Adjuvant therapies, including platinum-based chemotherapy (cisplatin and/or carboplatin), molecularly targeted therapies (osimertinib or alectinib), and immunotherapies (durvalumab, atezolizumab, pembrolizumab, or nivolumab), given within 6 months after surgery were assessed. We used the Cochran–Armitage test for trend analysis. Results: A total of 2297 patients were included in the analysis. Most patients were male (n=2218, 96.6%), of White race (n=1860, 81.0%), and had adenocarcinoma (n=990, 45.9%). Lobectomy (n=1603, 69.8%) was most frequently performed. Most patients had pathologic stage Ib (n=708, 30.8%) or II (n=946, 41.2%) NSCLC. Only 1025 (44.6%) patients received adjuvant systemic therapy (chemotherapy only: n=859, 37.4%; immunotherapy with or without chemotherapy: n=160, 7.0%; molecularly targeted therapy with or without chemotherapy: n=6, n=0.3%) [Table 1]. The overall rate of adjuvant therapy use remained stable between 2017 and 2023 (40.2% vs. 44.4%, p=0.089). While the use of adjuvant chemotherapy alone declined from 39.3% in 2017 to 19.5% in 2024 (p<0.001), the usage rates of adjuvant molecularly targeted therapies (0.0% vs. 1.2%, p<0.001) and immunotherapies (0.9% vs. 23.5%, p<0.001) significantly increased over the same period. Conclusions: While the overall rate of adjuvant systemic therapies for resected stage Ib-III NSCLC has remained stable in recent years, there has been a notable increase in the adoption of molecularly targeted therapies and immunotherapies into clinical practice. Further research is needed to examine patient selection using appropriate genomic and biomarker testing and to ensure that these emerging therapies are offered to patients with resected early-stage NSCLC who meet selected guideline- or clinical pathway-based criteria in the adjuvant setting. Frequencies of adjuvant systemic therapies. Drug Frequency, n=166 (%) Pembrolizumab 76 (45.8) Durvalumab 38 (22.9) Atezolizumab 37 (22.3) Nivolumab 9 (5.4) Osimertinib 6 (3.6)

Incorporating radiomic MRI models for presurgical response assessment in patients with early breast cancer undergoing neoadjuvant systemic therapy: Collaborative insights from breast oncologists and radiologists.

Incorporating radiomic MRI models for presurgical response assessment in patients with early breast cancer undergoing neoadjuvant systemic therapy: Collaborative insights from breast oncologists and radiologists.

Comprehensive clinicopathologic analysis and management approaches for metaplastic breast cancer: A retrospective, single institution study.

e13176 Background: Metaplastic breast cancer (MpBC) is a rare and aggressive subtype of breast cancer characterized by its heterogeneous histology and poor prognosis. Effective systemic therapies for both definitive and salvage treatment remain poorly defined. Due to the rarity of MpBC, the relationship between its clinicopathologic features, optimal therapeutic strategies, and patient outcomes are largely understudied. Methods: This study is a single-center, retrospective analysis of patients with MpBC treated at Cedars-Sinai Medical Center between 2004-2023. Patients were identified using the Cancer Registry database. The primary outcomes are overall survival (OS) and disease-free survival (DFS). All endpoints were evaluated utilizing the Kaplan-Meier method. Hazard ratios (HR) were estimated using a stratified Cox proportional-hazards model. All reported 95% confidence intervals (CI) are two-sided. Results: Of 81 patients with MpBC identified, the median age at diagnosis was 63 years (range 27-98). 65.4% were White, 27.2% were Black, 6.2% were Asian, and 4.9% were Hispanic. 76.5% (n = 62) had triple negative BC (TNBC) (ER < 1% and HER2 negative by ASCO CAP guidelines), 17.2% (n = 14) had hormone receptor positive (HR+), HER2 negative (HER2-) disease, 2.4% (n = 2) had HR-HER2+ disease, 3 were unknown. At diagnosis, 67.6% (n = 48) had Stage I/II disease, 25.3% (n = 18) had Stage III disease, 7.0% (n = 5) had de novo stage IV MpBC, 10 were unknown. 13 patients had squamous morphology, 8 had mesenchymal, 4 had mixed, 2 had spindle cell, and 54 had NOS (not otherwise specified) subtype. Of the 17 patients who underwent genetic testing, 6 patients tested positive for a BRCA mutation. Of the 66 early-stage patients with available treatment records, 30.3% (n = 20) received neoadjuvant systemic therapy, all underwent surgical resection, 75.7% (n = 50) received adjuvant radiation therapy, and 60.6% (n = 40) received adjuvant chemotherapy. In the entire cohort, the 5-year OS was 68% and 5-year DFS was 62%. 5-year OS by stage is as follows: Stage I: 100%, II: 82.0%, and III: 46.6%. 5-year DFS is as follows: Stage I: 100%, II: 79.6%, and III: 42.3%. Multivariate Cox proportional analysis showed an OS benefit in patients who received adjuvant chemotherapy (HR 0.30, CI 0.10-0.85, p = 0.024) and in patients who received adjuvant radiation therapy (HR 0.31, CI 0.10-0.98, p = 0.046). Of the patients who received adjuvant chemotherapy, the most commonly used regimen was AC-T (Adriamycin, Cytoxan, and Taxol) at 47.5% (n = 19). Conclusions: Our dataset demonstrates that adjuvant chemotherapy and radiation therapy confer a significant overall survival benefit in patients with MpBC. Additional prospective data and randomized control studies are warranted to determine the most effective treatment strategies for this rare subtype of breast cancer.

ENABLE-App-Based Digital Capture and Intervention of Patient-Reported Quality of Life, Adverse Events, and Treatment Satisfaction in Breast Cancer: Protocol for a Randomized Controlled Trial.

In recent years, breast cancer treatment has taken the path toward personalized medicine. Based on individual tumor biology, therapy tailored to the particular subtype of cancer is increasingly being used. The aim here is to find the most suitable therapy for the disease. However, the success of therapy depends to a large extent on the patient's adherence to treatment. This, in turn, depends on how the therapy is tolerated and how the treatment team cares for the patient. Patient-centered care seeks to identify and address the individual needs of each patient and to find the best form of care for that person. In order to improve comprehensive oncological care of patients with breast cancer, the ENABLE trial digitally recorded the health-related quality of life (HRQoL), adverse events (AEs), and patient satisfaction using a mobile smartphone app. The trial provided individualized responses to reported AEs and offered assistance. Additionally, it assessed the impact of a patient-reported outcome-based intervention across various therapy settings. Patients with breast cancer were eligible to participate in the study before neoadjuvant, adjuvant, postneoadjuvant, or palliative systemic therapy against breast cancer was initiated at the Heidelberg, Mannheim, and Tuebingen, Germany, university hospitals. After 1:1 randomization into an intervention and a control group, HRQoL assessments were performed at six fixed time points during the therapy using validated questionnaires. In the intervention group, HRQoL was also assessed briefly every week using a visual analog scale (EQ-VAS). In cases of significant deterioration, therapy-associated side effects were assessed in a graduated manner, recommendations were sent to the patient, and the treatment team was informed. Additionally, the app served as an "eHealth companion" for education, training, and organizational support during therapy. Recruitment started in March 2021; follow-up was completed in February 2024. In total, 606 patients were enrolled, and 592 patients participated in the study. Enrollment was completed in September 2023, and the last visit was in February 2024. The first results are expected to be published in Q2 2025. Participation in the intervention group is expected to improve treatment satisfaction, adherence, detection, and timely treatment of critical AEs. The close-meshed, weekly, brief HRQoL assessment will also be tested as a screening tool to detect relevant side effects during therapy. The study offers a more objective HRQoL assessment across treatment strategies. Deutsches Register Klinischer Studien DRKS00025611; https://drks.de/search/en/trial/DRKS00025611. DERR1-10.2196/69855.

Surgical treatment outcomes in patients with non-small cell lung cancer treated with neoadjuvant systemic therapy. A pilot single-center retrospective study

Objective: to evaluate the effectiveness of surgical treatment in patients with stage II–III non-small cell lung cancer, who received neoadjuvant systemic chemotherapy or chemoimmunotherapy, as well as to assess radiological and pathological tumor responses to drug therapy. Material and Methods. The study included 22 patients with stage IIB, IIIA and IIIB non-small cell lung cancer, who received neoadjuvant systemic therapy in the period from May 2022 to June 2024. Of these patients, 12 received platinum-containing chemotherapy (neoChT group) and 10 received chemoimmunotherapy including pembrolizumab (neoChIT group). The median number of therapy courses was 4 in each group. Radical surgery was performed in 7 patients from the neoChIT group and in 12 patients from the neoChT group. Results. Radiological complete response was observed in 1 patient from the neoChIT group, and partial response in 6 patients from the neoChIT group and in 7 patients from the neoChT group. Pathological complete response was observed in 3 patients from the neoChIT group and in 2 patients from the neoChT group. Lobectomy was the most common type of lung resection in both groups: in 5 patients from the neoChIT group and in 10 from the neoChT group. The majority of patients (60 %, 9/15) underwent sleeve lobectomies. Postoperative complications were recorded in 2 patients from the neoChIT group and in 4 from the neoChT group. Postoperative mortality in the group of radical surgeries was 5.3 % (1 out of 19). The follow-up period was 25.2 months. All patients who underwent surgery, excluding postoperative mortality, are alive. The 2-year recurrence-free survival rate was 77.4 ± 15.2 %. Disease progression 5 and 16 months after surgery was observed in 2 patients from the neoChT, respectively. Conclusion. Neoadjuvant systemic therapy is a safe and promising approach in the treatment of patients with locally advanced non-small cell lung cancer. The surgical component is characterized by a high frequency of organ-preserving interventions, a non-increased frequency of complications and satisfactory long-term results. The preliminary data obtained are comparable with the available data in the world literature. Unambiguous conclusions require further accumulation of experience and more extensive research.

PULS (Pulmonary Artery Sarcoma) – An International Collaboration for the Assessment of Pulmonary Artery Sarcoma Patients’ Outcome

Abstract Background Pulmonary artery sarcomas (PAS) are rare with a poor prognosis and limited curative therapeutic options. This scarcity of evidence poses significant challenges. Aims This study aims to enhance the understanding of clinical characteristics and current management of PAS. Methods An international working group (PULS) was launched. Patients with PAS treated at participating institutions between 1994-2024 were included. Six centers collected data from patients diagnosed with PAS retrospectively. Results Among 49 patients with PAS, the median age was 54.0 years (range: 27.0–82.0), including 24 females (49.0%). Chest pain, dyspnea, and cough were present in 24.5% (n=12), 42.9% (n=21), and 24.5% (n=12), respectively. Initial diagnosis included PAS in 26.5% (n=13) and embolism in 24.5% (n=12). PAS was confirmed by surgery in 40.8% (n=20), imaging in 16.3% (n=8), and biopsy in 12.2% (n=6) and this information is missing in 30.6% (n=15). 33 (67.3%) patients underwent surgery. Tumor endarterectomy was most common, (n=20, 40%), including 1 (2%) patient undergoing additional lobectomy, and two (4.1%) patients additional pneumonectomy. 9 (18.3%) patients underwent pneumonectomy only and 4 (8.2%) debulking surgery only. 10 (20.4%) patients underwent multimodal treatment. One (2%) patient received neoadjuvant systemic therapy. Postoperative adjuvant systemic therapy (Doxorubicin/Ifosfamide) was given to 7 patients (14.3%) and 6 patients (12.2%) underwent radiotherapy. The 1-,2- and 5-year survival was n=20 (40%), n=14 (28.5%), and n=1 (2%) respectively. The subgroup of patients undergoing multimodal treatment had a better overall survival (p=0.05). Relapse of PAS occurred in 32.7% (n=16). Conclusion To date this is one of the largest reported multi-center cohort of patients with PAS. Our findings highlight the clinical variability in PAS presentation, challenges in achieving a timely diagnosis, and poor prognosis. Outcomes are most promising if patients undergo surgery embedded in multimodality treatment compared to patients undergoing surgery alone.

Trends in the Management of Small HER2-Positive Breast Cancers.

The treatment approach for small HER2-positive (+) breast cancers seeks to optimizeefficacy while minimizing potential overtreatment and associated toxicities. This study aims to evaluate recent trends in treatment patterns for small HER2+ tumors. Patients diagnosed with HER2+, cT1, cN0/pN0 breast cancer treated at a single institution from January 2018 to December 2022 were included. Clinicopathological, treatment, and follow-up data were collected and analyzed. A total of 207 patients were included. Mean age was 63 (± 12.0) years. T category included cT1a in 12.1% (n = 25), cT1b in 28.0% (n = 58), and cT1c in 57.5% (n = 119), while 2.4% (n = 5) had clinical T1 category without further specification. Moreover, 74.4% (n = 154) were hormone receptor positive. Also, 66.7% (n = 138) received adjuvant therapy, 12.6% (n = 26) received neoadjuvant systemic therapy (NAT), and 12.1% (n = 25) received no systemic therapy. Administered regimens included: trastuzumab monotherapy in 6.1% (n = 10), taxane/trastuzumab in 55.5% (n = 91), taxane/carboplatin/trastuzumab in 18.9% (n = 31), and taxane/carboplatin/trastuzumab/pertuzumab in 15.2% (n = 25). In the 26 patients who received NAT, pathological complete response (pCR) was noted in 69.2% (n = 18). Overall, use of NAT increased from 2018 (7.1%) to 2021 (30.2%) and then decreased in 2022 (9.1%). The overall mastectomy rate was 35.3% (n = 73). Young age and multiple tumors were associated with a higher rate of mastectomy (age p < 0.001; multiple tumors p = 0.006). Upstaging of clinically node-negative patients occurred in 14.1% of patients at surgery. The treatment for cT1N0 HER2+ breast cancers includes primary surgery with adjuvant HER2-targeted therapy in combination with chemotherapy. Primary surgery may allow for an opportunity to deescalate adjuvant therapy with no impact on surgical plan.

Predictive factors for pCR and relapse following neoadjuvant dual HER2-blockade in HER2+ breast cancer: an international cohort study.

Neoadjuvant systemic therapy with dual HER2-blockade, trastuzumab and pertuzumab, combined with chemotherapy has become a standard approach in patients with HER2-positive (HER2+) breast cancer (BC). However, the variability in treatment outcomes, such as pathological complete response (pCR) or relapse rates, underscores the need to identify predictive factors to optimize therapeutic strategies. This study aims to explore the relationship between clinicopathological factors and both pCR and disease-free survival (DFS) in an international cohort of patients with HER2+ BC, contributing to defining personalized treatment strategies. An international, multicenter, retrospective cohort study was conducted, including 517 patients with HER2+ BC who received neoadjuvant therapy comprising trastuzumab, pertuzumab, and chemotherapy. Data were collected between January 2016 and December 2023. The relationship between clinicopathological factors and treatment outcomes was analyzed using univariate tests, logistic regression for pCR, and Cox proportional hazards regression for DFS. Kaplan-Meier survival curves with log-rank tests and hazard ratios were used to compare DFS across subgroups. Multivariable analysis revealed that hormonal receptor (HR) expression and nodal status significantly predicted the achievement of pCR in this cohort. Factors such as age, HR status, tumor grade, Ki-67 index, nodal status, and pathological response were associated with relapse risk. Our real-world data demonstrates that a comprehensive approach considering pCR, age, HR status, and nodal involvement is essential for personalized treatment strategies. These factors should be taken into account when deciding whether to escalate or de-escalate treatment, contributing to improved HER2+ BC patient outcomes.