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Aims The primary goal of this study is to evaluate the capabilities of Large Language Models (LLMs) in understanding and processing complex medical documentation. We chose to focus on the identification of pathologic complete response (pCR) in narrative pathology reports. This approach aims to contribute to the advancement of comprehensive reporting, health research, and public health surveillance, thereby enhancing patient care and breast cancer management strategies. Methods The study utilized two analytical pipelines, developed with open-source LLMs within the healthcare system’s computing environment. First, we extracted embeddings from pathology reports using 15 different transformer-based models and then employed logistic regression on these embeddings to classify the presence or absence of pCR. Secondly, we fine-tuned the Generative Pre-trained Transformer-2 (GPT-2) model by attaching a simple feed-forward neural network (FFNN) layer to improve the detection performance of pCR from pathology reports. Results In a cohort of 351 female breast cancer patients who underwent neoadjuvant chemotherapy (NAC) and subsequent surgery between 2010 and 2017 in Calgary, the optimized method displayed a sensitivity of 95.3% (95%CI: 84.0–100.0%), a positive predictive value of 90.9% (95%CI: 76.5–100.0%), and an F1 score of 93.0% (95%CI: 83.7–100.0%). The results, achieved through diverse LLM integration, surpassed traditional machine learning models, underscoring the potential of LLMs in clinical pathology information extraction. Conclusions The study successfully demonstrates the efficacy of LLMs in interpreting and processing digital pathology data, particularly for determining pCR in breast cancer patients post-NAC. The superior performance of LLM-based pipelines over traditional models highlights their significant potential in extracting and analyzing key clinical data from narrative reports. While promising, these findings highlight the need for future external validation to confirm the reliability and broader applicability of these methods.

BackgroundFor patients with locally advanced head and neck squamous cell carcinoma (HNSCC), combined programmed death receptor-1 inhibitor and chemotherapy improved response rate to neoadjuvant therapy. However, treatment response varies among patients. There is no tool to predict pathologic complete response (pCR) with high accuracy for now. To develop a tool based on radiomics features of MRI to predict pCR to neoadjuvant chemoimmunotherapy (NACI) may provide valuable assistance in treatment regimen determination for HNSCC.MethodsFrom January 2021 to April 2024, a total of 172 patients with HNSCC from three medical center, who received NACI followed by surgery, were included and allocated into a training set (n=84), an internal validation set (n=37) and an external validation set (n=51). Radiomics features were extracted from intratumoral and different peritumoral areas, and radiomics signature (Rad-score) for each area was constructed. A radiomics-clinical nomogram was developed based on Rad-scores and clinicopathological characteristics, tested in the validation sets, and compared with clinical nomogram and combined positive score (CPS) in predicting pCR.ResultsThe radiomics-clinical nomogram, incorporating peritumoral Rad-score, intratumoral Rad-score and CPS, achieved the highest accuracy with areas under the receiver operating characteristic curve of 0.904 (95% CI, 0.835 to 0.972) in the training cohort, 0.860 (95% CI, 0.722 to 0.998) in the internal validation cohort, and 0.849 (95% CI, 0.739 to 0.959) in the external validation cohort, respectively, which outperformed the clinical nomogram and CPS in predict pCR to NACI for HNSCC.ConclusionA nomogram developed based on intratumoral and peritumoral MRI radiomics features outperformed CPS, a widely employed biomarker, in predict pCR to NACI for HNSCC, which would provide incremental value in treatment regimen determination.

Purpose This study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR). Methods Relevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR. Results In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR. Conclusions Patients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers. Highlights • Neoadjuvant therapy causes various fasting glucose, fasting triglyceride, and fasting cholesterol abnormalities. • Fasting triglycerides may predict the pathologic complete response in some patients. • Fasting blood glucose and fasting total cholesterol do not predict the pathologic complete response. • Some patients may derive both short-term (achievement of pathologic complete response) and long-term (reduction of cardiovascular disease risk) benefits in conjunction with lipid management.

ABSTRACT Objective: To evaluate response of neoadjuvant chemotherapy in Stage I-III triple-negative breast cancer and impact of pathologic complete response on survival. Study Design: Retrospective longitudinal study. Place and Duration of Study: Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore Pakistan, from Jan 2006 to Jul 2014. Methodology: All patients with triple-negative breast cancer who received neoadjuvant chemotherapy were included and data was retrieved from cancer registry of hospital. The patients received neoadjuvant chemotherapy followed by surgery. Radiotherapy was given wherever clinically indicated. Kaplan-Meier and log-rank test was used to calculate survival. Results: Out of 1113 triple negative breast cancer patients, 150 received neoadjuvant chemotherapy. Mean age was 43±7 years. Fifty-two patients (34.7%) achieved pathological complete response (complete eradication of invasive or in situ carcinoma in breast and axilla (ypT0/is/ypN0) in surgical specimen). Over a median follow up of 61 months, 52 patients (34.7%) had disease progression. Patients with pathological complete response had significantly better 5-years disease-free survival (pvalue 0.001) and 5-years overall survival (p-value 0.002) in comparison to non-pathological complete response group. The 5years disease-free survival was 90% in pathological complete response group compared to 55% in non-pathological complete response group. Similarly, 5-years overall survival was 94% in pathological complete response group compared to 70% nonpathological complete response group. Conclusions: Neoadjuvant chemotherapy is an effective treatment modality in management of triple-negative breast cancer. Achievement of pathological complete response is a potential surrogate endpoint as it is associated with significantly better disease-free survival and overall survival.

Background: Pathologic complete response (pCR) to neoadjuvant treatment (NAT) is associated with improved survival of patients with HER2+ breast cancer. We investigated the ability of interim positron emission tomography (PET) regarding early prediction of pathology outcomes. Methods: During 61 months, consecutive patients with locally advanced or large HER2+ breast cancer patients without distant metastases were included. All patients received NAT with four cycles of epirubicin+cyclophosphamide, followed by four cycles of docetaxel+trastuzumab. 18 F-fluorodeoxyglucose ( 18 F-FDG)-PET/computed tomography (CT) was performed at baseline (PET 1 ) and after two cycles of chemotherapy (PET 2 ). Maximum standardised uptake values were measured in the primary tumour as well as in the axillary lymph nodes. The correlation between pathologic response and SUV parameters (SUV max at PET 1 , PET 2 and ΔSUV max ) was examined with the t -test. The predictive performance regarding the identification of non-responders was evaluated using receiver operating characteristics (ROC) analysis. Results: Thirty women were prospectively included and 60 PET/CT examination performed. At baseline, 22 patients had PET+ axilla and in nine of them 18 F-FDG uptake was higher than in the primary tumour. At surgery, 14 patients (47%) showed residual tumour (non-pCR), whereas 16 (53%) reached pCR. Best prediction was obtained when considering the absolute residual SUV max value at PET 2 (AUC=0.91) vs 0.67 for SUV max at PET 1 and 0.86 for ΔSUV max . The risk of non-pCR was 92.3% in patients with any site of residual uptake >3 at PET 2 , no matter whether in breast or axilla, vs 11.8% in patients with uptake ⩽3 ( P =0.0001). The sensitivity, specificity, PPV, NPV and overall accuracy of this cutoff were, respectively: 85.7%, 93.8%, 92.3%, 88.2% and 90%. Conclusion: The level of residual 18 F-FDG uptake after two cycles of chemotherapy predicts residual disease at completion of NAT with chemotherapy+trastuzumab with high accuracy. Because many innovative therapeutic strategies are now available (e.g., addition of a second HER2-directed therapy or an antiangiogenic), early prediction of poor response is critical.

Neoadjuvant immunotherapy plus chemotherapy improves event-free survival (EFS) and pathologic complete response (0% residual viable tumor (RVT) in primary tumor (PT) and lymph nodes (LNs)), and is approved for treatment of resectable lung cancer. Pathologic response assessment after neoadjuvant therapy is the potential analog to radiographic response for advanced disease. However, %RVT thresholds beyond pathologic complete response and major pathologic response (≤10% RVT) have not been explored. Pathologic response was prospectively assessed in the randomized, phase 3 CheckMate 816 trial (NCT02998528), which evaluated neoadjuvant nivolumab (anti-programmed death protein 1) plus chemotherapy in patients with resectable lung cancer. RVT, regression and necrosis were quantified (0–100%) in PT and LNs using a pan-tumor scoring system and tested for association with EFS in a prespecified exploratory analysis. Regardless of LN involvement, EFS improved with 0% versus >0% RVT-PT (hazard ratio = 0.18). RVT-PT predicted EFS for nivolumab plus chemotherapy (area under the curve = 0.74); 2-year EFS rates were 90%, 60%, 57% and 39% for patients with 0–5%, >5–30%, >30–80% and >80% RVT, respectively. Each 1% RVT associated with a 0.017 hazard ratio increase for EFS. Combining pathologic response from PT and LNs helped differentiate outcomes. When compared with radiographic response and circulating tumor DNA clearance, %RVT best approximated EFS. These findings support pathologic response as an emerging survival surrogate. Further assessment of the full spectrum of %RVT in lung cancer and other tumor types is warranted. ClinicalTrials.gov registration: NCT02998528 . Analysis of the phase 3 CheckMate 816 trial shows that the depth of pathologic response as assessed by percent residual viable tumor is correlated with event-free survival following neoadjuvant immunotherapy plus chemotherapy, supporting pathologic response as a biomarker of survival.

BackgroundIn breast cancer, immune checkpoint inhibitor (ICI)-based neoadjuvant therapy has been approved for clinical practice since 2021. Nonetheless, the predictive values of routinely collected clinicopathological and molecular characteristics in neoadjuvant immunotherapy remain unknown.MethodsWe searched EMBASE and MEDLINE databases for randomized controlled trials (RCTs) comparing ICI-based neoadjuvant therapy with conventional treatment. The primary outcome was pathological complete response (pCR). The odds ratio (OR) and its 95% confidence intervals (CIs) were calculated. This meta-analysis was registered in PROSPERO (CRD420261307112).ResultsHere, with 5674 patients enrolled in 12 RCTs, our study revealed ICI-based neoadjuvant therapy was associated with significantly increased pCRs (OR, 1.59; 95% CI, 1.32-1.90; P < 0.001). Notably, neoadjuvant immunotherapy did not demonstrate a statistically significant improvement of pCRs in patients with HER2+ tumors (OR, 1.17; 95% CI, 0.92-1.49; P = 0.23). Moreover, the interactions between ICI-based neoadjuvant therapy and nodal status (PInteraction < 0.001) or stromal tumor-infiltrating lymphocyte (sTIL, PInteraction = 0.05) were statistically meaningful. More pCRs were observed in patients with nodal-positive (OR, 1.89; 95% CI, 1.56-2.28; P < 0.001) or high-density sTIL tumors (OR, 2.89; 95% CI, 1.49-5.61; P < 0.001), but not in women with nodal-negative (OR, 1.05; 95% CI, 0.80-1.39; P = 0.71) or low-density sTIL tumors (OR, 1.26; 95% CI, 0.73-2.17; P = 0.41). There was insufficient evidence to support other characteristics, including race, age, PD-L1 expression, clinical stage, hormone receptor (HR) status, menopausal status, Eastern Cooperative Oncology Group (ECOG) performance status, and T stage, as predictive biomarkers to guide patient selection for neoadjuvant immunotherapy in breast cancer.ConclusionNeoadjuvant immunotherapy was associated with favorable outcomes in breast cancer. However, for patients with HER2+, nodal-negative, or low-density sTIL tumors, clinicians need to carefully balance efficacy, safety, and patient preferences to deliver individualized treatment. Further randomized trials with long-term outcomes are needed to confirm the predictive values of these biomarkers.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261307112, identifier PROSPERO CRD420261307112.

Neoadjuvant nivolumab plus chemotherapy significantly improved pathological complete response and event-free survival in patients with resectable non-small-cell lung cancer (NSCLC) in a phase 3 trial. Data are needed on overall survival. In this open-label, phase 3 trial, patients with stage IB to IIIA resectable NSCLC were randomly assigned to receive nivolumab plus chemotherapy or chemotherapy alone for three cycles, followed by surgery. The primary end points were event-free survival and pathological complete response. Here, we report the results of the planned analysis of overall survival. A total of 358 patients were concurrently assigned to receive nivolumab plus chemotherapy (179 patients) or chemotherapy alone (179 patients). The final analysis of overall survival significantly favored neoadjuvant nivolumab plus chemotherapy over chemotherapy (hazard ratio for death, 0.72; 95% confidence interval [CI], 0.523 to 0.998; P = 0.048). At a median follow-up of 68.4 months, the 5-year overall survival was 65.4% with nivolumab plus chemotherapy and 55.0% with chemotherapy alone, with consistency across most subgroups. In exploratory analyses, the 5-year overall survival in the nivolumab-plus-chemotherapy group was 95.3% (95% CI, 82.7 to 98.8) among the patients with a pathological complete response and 55.7% (95% CI, 46.9 to 63.7) among those without such a response; survival was 75.0% among the patients with presurgery clearance of circulating tumor DNA (ctDNA) and 52.6% among those without such clearance. No new safety signals were observed. Three cycles of neoadjuvant nivolumab plus chemotherapy significantly improved overall survival among patients with resectable NSCLC as compared with chemotherapy alone. (Funded by Bristol Myers Squibb; CheckMate 816 ClinicalTrials.gov number, NCT02998528.).

Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2–54·1), 49·2 months (47·2–53·2) in the BCRi-naive group, and 49·7 months (47·4–54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8−41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8–39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. AbbVie.

The pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is a surrogate endpoint for predicting long-term clinical benefit in breast cancer. Recently, the use of radiomic features extracted from [sup.18]F-FDG PET/CT has emerged as a promising tool for predicting treatment outcomes in various cancers. We developed and externally validated a predictive model using [sup.18]F-FDG PET-based radiomics with the least absolute shrinkage and selection operator (LASSO) logistic method for pCR following NAC in breast cancer. Our radiomic-score model demonstrated satisfactory discriminative performances in training, internal validation, and external validation cohorts. Furthermore, the integrated radiomic model incorporating human epidermal growth factor receptor 2 (HER2) status showed improved performance compared to the radiomic-score model alone in all cohorts. The newly developed radiomic-score model might enable a more accurate and personalized assessment of the tumor response to neoadjuvant chemotherapy in breast cancer. The aim of our retrospective study is to develop and externally validate an [sup.18]F-FDG PET-derived radiomics model for predicting pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer patients. A total of 87 breast cancer patients underwent curative surgery after NAC at Soonchunhyang University Seoul Hospital and were randomly assigned to a training cohort and an internal validation cohort. Radiomic features were extracted from pretreatment PET images. A radiomic-score model was generated using the LASSO method. A combination model incorporating significant clinical variables was constructed. These models were externally validated in a separate cohort of 28 patients from Soonchunhyang University Buscheon Hospital. The model performances were assessed using area under the receiver operating characteristic (AUC). Seven radiomic features were selected to calculate the radiomic-score. Among clinical variables, human epidermal growth factor receptor 2 status was an independent predictor of pCR. The radiomic-score model achieved good discriminability, with AUCs of 0.963, 0.731, and 0.729 for the training, internal validation, and external validation cohorts, respectively. The combination model showed improved predictive performance compared to the radiomic-score model alone, with AUCs of 0.993, 0.772, and 0.906 in three cohorts, respectively. The [sup.18]F-FDG PET-derived radiomic-based model is useful for predicting pCR after NAC in breast cancer.