Evaluation Of Pathological Response Research Articles

Evaluation of Major Pathologic Response and Pathologic Complete Response as Surrogate End Points for Survival in Randomized Controlled Trials of Neoadjuvant Immune Checkpoint Blockade in Resectable in NSCLC

IntroductionControversy remains as to whether pathologic complete response (pCR) and major pathologic response (MPR) represent surrogate end points for event-free survival (EFS) and overall survival (OS) in neoadjuvant trials for resectable NSCLC. MethodsA search of PubMed and archives of international conference abstracts was performed from June 2017 through October 31, 2023. Studies incorporating a neoadjuvant arm with immune checkpoint blockade alone or in combination with chemotherapy were included. Those not providing information regarding pCR, MPR, EFS, or OS were excluded. For trial-level surrogacy, log ORs for pCR and MPR and log hazard ratios for EFS and OS were analyzed using a linear regression model weighted by sample size. The regression coefficient and R2 with 95% confidence interval were calculated by the bootstrapping approach. ResultsSeven randomized clinical trials were identified for a total of 2385 patients. At the patient level, the R2 of pCR and MPR with 2-year EFS were 0.82 (0.66–0.94) and 0.81 (0.63–0.93), respectively. The OR of 2-year EFS rates by response status was 0.12 (0.07–0.19) and 0.11 (0.05–0.22), respectively. For the 2-year OS, the R2 of pCR and MPR were 0.55 (0.09–0.98) and 0.52 (0.10–0.96), respectively. At the trial level, the R2 for the association of OR for response and HR for EFS was 0.58 (0.00–0.97) and 0.61 (0.00–0.97), respectively. ConclusionsOur analyses reveal a robust correlation between pCR and MPR with 2-year EFS but not OS. Trial-level surrogacy was moderate but imprecise. More mature follow-up and data to assess the impact of study crossover are needed.

Intratumoral and peritumoral radiomics predict pathological response after neoadjuvant chemotherapy against advanced gastric cancer

BackgroundTo investigate whether intratumoral and peritumoral radiomics may predict pathological responses after neoadjuvant chemotherapy against advanced gastric cancer.MethodsClinical, pathological, and CT data from 231 patients with advanced gastric cancer who underwent neoadjuvant chemotherapy at our hospital between July 2014 and February 2022 were retrospectively collected. Patients were randomly divided into a training group (n = 161) and a validation group (n = 70). The support vector machine classifier was used to establish radiomics models. A clinical model was established based on the selected clinical indicators. Finally, the radiomics and clinical models were combined to generate a radiomics–clinical model. ROC analyses were used to evaluate the prediction efficiency for each model. Calibration curves and decision curves were used to evaluate the optimal model.ResultsA total of 91 cases were recorded with good response and 140 with poor response. The radiomics model demonstrated that the AUC was higher in the combined model than in the intratumoral and peritumoral models (training group: 0.949, 0.943, and 0.846, respectively; validation group: 0.815, 0.778, and 0.701, respectively). Age, Borrmann classification, and Lauren classification were used to construct the clinical model. Among the radiomics–clinical models, the combined-clinical model showed the highest AUC (training group: 0.960; validation group: 0.843), which significantly improved prediction efficiency.ConclusionThe peritumoral model provided additional value in the evaluation of pathological response after neoadjuvant chemotherapy against advanced gastric cancer, and the combined-clinical model showed the highest predictive efficiency.Critical relevance statementIntratumoral and peritumoral radiomics can noninvasively predict the pathological response against advanced gastric cancer after neoadjuvant chemotherapy to guide early treatment decision and provide individual treatment for patients.Key points1. Radiomics can predict pathological responses after neoadjuvant chemotherapy against advanced gastric cancer.2. Peritumoral radiomics has additional predictive value.3. Radiomics–clinical models can guide early treatment decisions and improve patient prognosis.Graphical

The assessment of pathological response to neoadjuvant chemotherapy in muscle-invasive bladder cancer patients with DCE-MRI and DWI: a systematic review and meta-analysis.

The purpose of this meta-analysis was to determine the value of dynamic contrast-enhanced-MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in evaluating the pathological response of muscle invasive bladder cancer (MIBC) to neoadjuvant chemotherapy (NAC), and further indirectly compare the diagnostic performance of DCE-MRI and DWI. Literatures associated to DCE-MRI and DWI in the evaluation of pathological response of MIBC to NAC were searched from PubMed, Cochrane Library, web of science, and EMBASE databases. The quality assessment of diagnostic accuracy studies 2 tool was used to assess the quality of studies. Pooled sensitivity (SE), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the receiver operating characteristic curves (AUC) with their 95% confidence intervals (CIs) were calculated to evaluate the diagnostic performance of DCE-MRI and DWI in predicting the pathological response to NAC in patients with MIBC. There were 11 studies involved, 6 of which only underwent DCE- MRI examination, 4 of which only underwent DWI examination, and 1 of which underwent both DCE- MRI and DWI examination. The pooled SE, SP, PLR, NLR, DOR of DCE-MRI were 0.88 (95% CI: 0.78-0.93), 0.88 (95% CI: 0.67-0.96), 7.4 (95% CI: 2.3-24.2), 0.14 (95% CI: 0.07-0.27), and 53 (95% CI: 10-288), respectively. The pooled SE, SP, PLR, NLR, DOR of DWI were 0.83 (95% CI: 0.75-0.88), 0.88 (95% CI: 0.81-0.93), 7.1 (95% CI: 4.3-11.7), 0.20 (95% CI: 0.14-0.28), and 36 (95% CI:18-73), respectively. The AUCs of SROC curve for DCE-MRI and DWI were 0.93 (95% CI: 0.91-0.95) and 0.92 (95% CI: 0.89-0.94), respectively. There were no significant differences between DWI and DCE-MRI for SE, SP, and AUC. This meta-analysis demonstrated high diagnostic performance of both DCE-MRI and DWI in predicting the pathological response to NAC in MIBC. DWI might be a potential substitute for DCE-MRI, with no significant difference in diagnostic performance between the two. However, caution should be taken when applying our results, as our results were based on indirect comparison. No previous studies have comprehensively analysed the value of DCE-MRI and DWI in evaluating the pathological response to NAC in MIBC. According to the current study, both DCE-MRI and DWI yielded high diagnostic performance, with the AUCs of 0.93 and 0.92, respectively. Indirect comparison no significant difference in the diagnostic performanceof DCE-MRI and DWI.

Stereotactic MR-guided adaptive radiotherapy (SMART) for primary rectal cancer: evaluation of early toxicity and pathological response.

The purpose of this study is to measure the effects of stereotactic MR-guided adaptive radiotherapy (SMART) for rectal cancer patients in terms of early toxicity and pathological response. For this prospective pilot study, patients diagnosed with locally advanced rectal cancer (LARC) with positive lymph node clinical staging underwent SMART on rectal lesion and mesorectum using hybrid MR-Linac (MRIdian ViewRay). Dose prescription at 80% isodose for the rectal lesion and mesorectum was 40 Gy (8 Gy/fr) and 25 Gy (5 Gy/fr), respectively, delivered on 5 days (3 fr/week). Response assessment by MRI was performed 3 weeks after SMART, then patients fit for surgery underwent total mesorectal excision. Primary endpoint was evaluation of adverse effect of radiotherapy. Secondary endpoint was pathological complete response rate. Early toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). From October 2020 to January 2022, twenty patients underwent rectal SMART. No grade 3-5 toxicity was recorded. Twelve patients were eligible for total mesorectal excision (TME). Mean interval between the completion of SMART and surgery was 4 weeks. Pathological downstaging occurred in all patients; rate of pathological complete response (pCR) was 17%. pCR occurred with a prolonged time to surgery (> 7 weeks). To our knowledge, this is the first study to use stereotactic radiotherapy for primary rectal cancer. SMART for rectal cancer is well tolerated and effective in terms of tumor regression, especially if followed by delayed surgery.

Endoscopic Evaluation of Pathological Complete Response Using Deep Neural Network in Esophageal Cancer Patients Who Received Neoadjuvant Chemotherapy-Multicenter Retrospective Study from Four Japanese Esophageal Centers.

Detecting pathological complete response (pCR) before surgery would facilitate nonsurgical approach after neoadjuvant chemotherapy (NAC). We developed an artificial intelligence (AI)-guided pCR evaluation using a deep neural network to identify pCR before surgery. This study examined resectable esophageal squamous cell carcinoma (ESCC) patients who underwent esophagectomy after NAC. The same number of histological responders without pCR and non-responders were randomly selected based on the number of pCR patients. Endoscopic images were analyzed using a deep neural network. A test dataset consisting of 20 photos was used for validation. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AI and four experienced endoscopists' pCR evaluations were calculated. For pathological response evaluation, Japanese Classification of Esophageal Cancer was used. The study enrolled 123 patients, including 41 patients with pCR, the same number of histological responders without pCR, and non-responders [grade 0, 5 (4%); grade 1a, 36 (30%); grade 1b, 21 (17%); grade 2, 20 (16%); grade 3, 41 (33%)]. In 20 models, the median values of sensitivity, specificity, PPV, NPV, and accuracy for endoscopic response (ER) detection were 60%, 81%, 77%, 67%, and 70%, respectively. Similarly, the endoscopists' median of these was 43%, 90%, 85%, 65%, and 66%, respectively. This proof-of-concept study demonstrated that the AI-guided endoscopic response evaluation after NAC could identify pCR with moderate accuracy. The current AI algorithm might guide an individualized treatment strategy including nonsurgical approach in ESCC patients through prospective studies with careful external validation to demonstrate the clinical value of this diagnostic approach including primary tumor and lymph node.

Multiparametric MRI for evaluation of pathological response to the neoadjuvant chemo-immunotherapy in resectable non-small-cell lung cancer.

This study aimed to explore the predictive value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion kurtosis imaging (DKI) quantitative parameters for the response to neoadjuvant chemo-immunotherapy (NCIT) in resectable non-small-cell lung cancer (NSCLC) patients, so as to provide a basis for clinical individualized precision treatment. Treatment naive locally advanced NSCLC patients who enrolled in 3 prospective, open-label, and single-arm clinical trials and received NCIT were retrospectively analyzed in this study. Functional MRI imaging was performed at baseline and following 3weeks of treatment as an exploratory endpoint to evaluate treatment efficacy. Univariate and multivariate logistic regressions were used to identify independent predictive parameters for NCIT response. Prediction models were built with statistically significant quantitative parameters and their combinations. In total of 32 patients, 13 were classified as complete pathological response (pCR) and 19 were non-pCR. Post-NCIT ADC, ΔADC, and ΔD values in the pCR group were significantly higher than those in the non-pCR group, while the pre-NCIT D, post-NCIT Kapp, and ΔKapp were significantly lower than those in non-pCR group. Multivariate logistic regression analysis demonstrated that pre-NCIT D and post-NCIT Kapp values were independent predictors for NCIT response. The combined predictive model, which consisted of IVIM-DWI and DKI, showed the best prediction performance with AUC of 0.889. The pre-NCIT D, post-NCIT parameters (ADC and Kapp) and Δ parameters (ΔADC, ΔD, and ΔKapp) were effective biomarkers for predicting pathologic response, and pre-NCIT D and post-NCIT Kapp values were independent predictors of NCIT response for NSCLC patients. This exploratory study indicated that IVIM-DWI and DKI MRI imaging would predict pathologic response of neoadjuvant chemo-immunotherapy in locally advanced NSCLC patients at initial state and early treatment, which could help make clinical individualized treatment strategies. • Effective NCIT treatment resulted in increased ADC and D values for NSCLC patients. • The residual tumors in non-pCR group tend to have higher microstructural complexity and heterogeneity, as measured by Kapp. • Pre-NCIT D and post-NCIT Kapp values were independent predictors of NCIT response.

SS18-SSX Antibody: A Useful Tool to Save Time and Reduce Costs in Synovial Sarcoma Diagnosis. Proposal of a Novel Diagnostic Algorithm.

Synovial sarcoma is a rare malignant mesenchymal neoplasm mostly affecting young adults, characterized by a specific translocation which results in the fusion of the SS18 gene on chromosome 18 with one of the three highly homologous SSX genes on chromosome X. Its morphological diagnosis, especially in monophasic or poorly differentiated variants, can be challenging because histological features often overlap with other malignant mesenchymal tumors. Until recently, the differential diagnosis mostly relied on the use of cytogenetic or molecular analyses to detect the specific t(X;18)(p11;q11) translocation, thus virtually restricting its correct identification to referral centers with a high histological and molecular pathology workflow. The recently commercialized highly sensitive and fusion-specific SS18-SSX antibody has significantly improved the approach to these tumors, representing a relatively cheap and easy to access tool for synovial sarcoma diagnosis. Through a retrospective analysis of 79 synovial sarcomas and histological mimickers, this study confirms the usefulness of the SS18-SSX antibody in the diagnosis of synovial sarcoma, particularly focusing on its application in the pathological response evaluation after neoadjuvant treatment as well as its time- and cost-saving advantages. Finally, we here propose a new diagnostic algorithm to apply into the routine practice.

Prospective evaluation of pathologic response with neoadjuvant chemo-immunotherapy in metaplastic breast cancer.

606 Background: Metaplastic breast cancer (MpBC) is a rare aggressive histologic type of breast cancer that is often resistant to standard chemotherapy with pathologic complete response (pCR) rates ranging between 2-23%. PDL1 expression has been reported in up to 95% of primary MpBCs suggesting that response rates may be improved with addition of immune checkpoint blockade (ICB). Here we evaluate pCR rates (ypT0/is ypN0) in stage I-III MpBCs receiving neoadjuvant chemo-immunotherapy (NAT). Methods: The Memorial Sloan Kettering Cancer Center Rare Breast Cancer Program (CARE-4-RARE) is a new clinical and translational program dedicated to the study of rare breast cancers. Since the start of the program, 15 patients (pts) with early-stage MpBC have completed treatment with the neoadjuvant KEYNOTE-522 regimen. Wilcoxon rank-sum and Fisher’s exact tests were used to compare characteristics according to pCR status. All statistical tests used a significance level of 5%. Results: Median age at diagnosis was 50 (range, 43-60). All pts were female, 13% self-identified as Asians, 33% as Black and 53% as White. All tumors were poorly differentiated and of triple-negative phenotype, median tumor size was 3.2cm, 80% had stage II disease and 20% were clinically node positive. Metaplastic subtypes included 5 matrix-producing (33%), 3 spindle (20%), 4 squamous (27%), 3 mixed (20%). Of the 15 pts, 4 (27%) achieved a pCR, which suggest the possibility of a higher than expected pCR rate in MpBC with the addition of ICB to chemotherapy. We did not observe a significant difference in clinicopathological features between pCR vs. non-pCR groups. We observed numerical differences in pCR between MpBC subtypes though the p-value was not significant due to limited sample size. Of these 4 pts, 2 had matrix-producing and 2 had mixed subtypes. Two pts with pCR only received Cb+P+Pem. Three pts (20%) experienced PD (squamous n = 2, spindle n = 1) necessitating discontinuation of NAT and expediting surgery. Conclusions: This is the first prospective study to evaluate neoadjuvant ICB in MpBC. These data suggest the possibility of a higher than expected pCR rate in MpBC with the addition of ICB to chemotherapy (27%). This work suggests that neoadjuvant ICB should be considered in MpBC with close monitoring. Notably, 50% of reported pCR in this cohort were in pts who only received Cb+P+Pem. In spite of improved pCR rates, 20% of pts progressed during NAT highlighting the need for better treatment strategies in this treatment-refractory subset of MpBC and close monitoring to allow resection before progression to inoperability. The dichotomy in responses to ICB (super-responsive vs. super-refractory) may suggest the presence of unique biomarkers for immune response in MpBC. By the 2023 ASCO Annual Meeting a total of 26 pts will have completed NAT; we will report updated outcomes along with correlative immune biomarkers (sTIL, PDL1, TMB).

Immunotherapy for localized dMMR/MSI tumors: First interim analysis of the IMHOTEP trial.

2591 Background: Immune checkpoint inhibitors (ICI) have demonstrated their efficacy in advanced dMMR/MSI (deficient mismatch repair/microsatellite instability) tumors and increasing data are also accumulating in localized resectable stages with about 60% of pathological complete response rate. The goal of the IMHOTEP trial is to assess the safety and efficacy of peri-operative pembrolizumab in localized dMMR/MSI tumors independently of their anatomical origin. Methods: IMHOTEP is a prospective, multicenter, phase II study aimed to include 120 patients (pts) with localized resectable dMMR/MSI tumors, eligible for curative surgery. Pembrolizumab 400 mg flat dose is administered as a perioperative treatment with 1 or 2 doses every 6 weeks before surgery and thereafter every 6 weeks for one year. Primary objective is to evaluate the pathological complete response (pCR) rate defined as ypT0N0 stage. Secondary objectives are to assess major pathological response, centralized pathological review, safety, clinical response rate, recurrence-free survival and overall survival. Here, we present the interim analysis of safety and pathologic response data for the first 70 treated pts. Results: Median age was 67.5 years (26-89), 54.3% were males, and 42.0% were ECOG-PS 0. Surgery was performed in 54/70 pts including 27/35 colorectal (CRC), 16/21 oesogastric (OGC), 4/5 endometrial (EC) and 7/9 other (6 small intestine, 1 bile duct) (OC) cancers. 16 pts (22.9%) were not operated, mainly due to patient’s decision following complete clinical response (n=7). Only one patient was not submitted to surgery because of disease progression. Focusing on the 54 operated pts, 31 and 23 pts received 1 and 2 neoadjuvant pembrolizumab doses respectively. The pCR rate was 38.9% (40.7%, 25.0%, 0.0% and 85.7% in CRC, OGC, EC and OC respectively). Grade 3-4 immune-related adverse events were observed in 4 (5.7%) patients including transaminases increase (n=1), arthritis (n=1), acute kidney injury (n=1) and pneumonitis (n=1). Conclusions: In this IMHOTEP interim analysis, we observed a limited complete pathologic response rate to short-course neoadjuvant pembrolizumab. If we add patients in clinical complete response who chose not to be operated to those with pCR, our results compare with those previously reported. But we can also hypothesize that preoperative treatment duration should be prolonged to obtain more pCR. Overall, tolerance of pembrolizumab was acceptable without new safety signal. Centralized pathological review, major pathological response evaluation and clinical response rate analysis are ongoing. IMHOTEP trial has been registered (first post: March 12th, 2021). Clinical trial information: NCT04795661 .

Comparative study of pathological response evaluation systems after neoadjuvant chemotherapy for breast cancer: developing predictive models of multimodal ultrasound features including shear wave elastography combined with puncture pathology.

This study created a predictive preoperative nomogram dependent on multimodal ultrasound characteristics and primary lesion biopsy results for various pathologic response assessment systems following neoadjuvant chemotherapy (NAC). This retrospective study included 145 breast cancer patients treated at Gansu Cancer Hospital between January 2021 and June 2022 who underwent shear wave elastography (SWE) prior to completing NAC. Intra- and peritumoral SWE features, including maximum (Emax), mean (Emean), minimum (Emin), and standard deviation (Esd) elasticity, were measured individually and linked with the Miller-Payne grading system and residual cancer burden (RCB) class. Univariate analysis was used for conventional ultrasound and puncture pathology. Binary logistic regression analysis was used to screen for independent risk factors and to develop a prediction model. Intratumor Emean and peritumoral Esd differed significantly from the Miller-Payne grade [intratumor Emean: r=0.129, 95% confidence interval (CI): -0.002 to 0.260; P=0.042; peritumoral Esd: r=0.126, 95% CI: -0.010 to 0.254; P=0.047], RCB class (intratumor Emean: r=-0.184, 95% CI: -0.318 to -0.047; P=0.004; peritumoral Esd: r=-0.139, 95% CI: -0.265 to 0.000; P=0.029) and RCB score components (r=-0.277 to -0.139; P=0.001-0.041). Two prediction model nomograms-pathologic complete response (pCR)/non-pCR and good responder/nonresponder-for the RCB class were developed using binary logistic regression analysis for all significant variables in SWE, conventional ultrasound, and puncture results. The area under the receiver operating characteristic curve for the pCR/non-pCR and good responder/nonresponder models was 0.855 (95% CI: 0.787-0.922) and 0.845 (95% CI: 0.780-0.910), respectively. According to the calibration curve, the nomogram had excellent internal consistency between estimated and actual values. The preoperative nomogram can effectively guide clinicians to predict pathological response of breast cancer after NAC and has the potential to guide individualized treatment.

P113 MRI Patterns in the evaluation of pathological response after Neoadjuvant Endocrine therapy in ER+/HER2- Breast Cancer and Implications on Surgical Planning

P113 MRI Patterns in the evaluation of pathological response after Neoadjuvant Endocrine therapy in ER+/HER2- Breast Cancer and Implications on Surgical Planning

Abstract P6-01-32: Evaluation of pathologic response and residual tumor cellularity following neo-adjuvant chemotherapy predict prognosis in breast cancer patients

Abstract Introduction: Treatment of early-stage beast cancer (BC) has changed since recent evidence showed that neoadjuvant chemotherapy (NAC) can reduce residual tumor cellularity (RTC) and improve patient outcomes. Achieving a pathologic complete response (pCR) has been associated with significantly improved disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). However, among patients treated with NAC, few experience pCR, while approximately 60-80% of them achieve a pathologic partial response (pPR). In previous studies, BC patients with different grades of pPR have been usually grouped and analyzed together, with inconsistent results and unclear prognostic significance. Objectives: The primary aims of this study were to describe the clinical and treatment characteristics of BC patients treated with NAC, to identify independent predictive factors of pCR, and to compare the oncologic outcomes between patients achieving pCR or pPR. The secondary aim of this study was to measure the RTC of BC patients with pPR and to compare the outcomes of patients with different RTC in order to improve prognostic information. Methods: All the consecutive BC patients undergoing NAC at the Breast Unit of IRCCS Humanitas Research Hospital (Milan, Italy) between October 2006 and April 2020 and their corresponding post-operative pathology slides were reviewed. The following exclusion criteria were used: excisional biopsy or debulking surgery as first BC operation, patients with a previous BC diagnosis or other prior or synchronous malignancies, male patients, unknown NAC regimen, disease progression during NAC, and follow-up ≤12 months. Results: A total of 495 BC patients received NAC. Overall, 148 (29.9%) patients achieved pCR, while 347 (70.1%) had pPR, and median RTC was 40%. At multivariable analysis, 3 independent factors predicting pCR were identified. Tumor stage pre-NAC (cT1-2 84.5% versus cT3-4 15.5%, odds ratio (OR)=0.119, 95% confidence interval (95%CI)=0.048-0.189, p=0.001), BC sub-type (HER2-enriched 54.7% versus triple-negative 29.8% versus luminal-like 15.5%, OR=2.178, 95%CI=2.055-2.301, p=0.001), and vascular invasion (absence 98.0% versus presence 2.0%, OR=0.022, 95%CI=0.004-0.090, p=0.001). Patients with BC undergoing NAC and achieving pCR presented statistically significant longer DFS, DDFS, and OS (p = < 0.001). Patients with RTC < 40% presented statistically significant better DFS and DDFS (p = 0.033, p = 0.015, respectively). However, no statistically significant difference in terms of OS was observed between RTC < 40% and RTC ≥40% groups (p = 0.148). Conclusions: Tumor stage pre-NAC, BC sub-type, and vascular invasion are significantly and independently associated with pCR. Patients with pCR present a better prognosis compared to patients with pPR in terms of DFS, DDFS, and OS. Measurement of RTC in BC patients with pPR improves the prognostic information that can be obtained from the assessment of the pathologic response. Different patterns of residual disease play an important role in predicting the risk of subsequent loco-regional and distant recurrence, and patients with RTC < 40% present significantly better DFS and DDFS. Citation Format: Damiano Gentile, Andrea Sagona, Camilla De Carlo, Bethania Fernandes, Simone Di Maria Grimaldi, Erika Barbieri, Wolfgang Gatzemeier, Lorenzo Scardina, Ersilia Biondi, Flavia Jacobs, Giulia Vatteroni, Corrado Tinterri. Evaluation of pathologic response and residual tumor cellularity following neo-adjuvant chemotherapy predict prognosis in breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-32.

Abstract OT2-18-01: Nab-paclitaxel followed by dose-dense epirubicin/cyclophosphamide in neoadjuvant chemotherapy for triple-negative breast cancer: an open-label, single-arm phase II study

Abstract Purpose: The anti-tumor activity of nab-paclitaxel followed by epirubicin/cyclophosphamide (EC) as neoadjuvant chemotherapy (NAC) in Asian patients remains unclear, particularly in the aggressive subtype triple-negative breast cancer (TNBC). This study aimed to evaluate the efficacy and safety of this NAC regimen in TNBC. Methods: In this Simon’s two-stage, phase II study, treatment-naïve patients with resectable unilateral primary invasive TNBC were enrolled. Eligible patients received nab-paclitaxel 125 mg/m2 weekly on day 1 for 12 weeks, followed by dose-dense EC (epirubicin 90 mg/m2; cyclophosphamide 600 mg/m2) on day 1 for four 2-week cycles. The primary endpoint was the total pathological complete response (tpCR, ypT0/is ypN0) rate. Secondary endpoints included breast pathological complete response (bpCR, ypT0/is) rate, objective response rate (ORR), the proportion of patients requiring breast-conserving surgery, and safety. Results: 55 eligible patients were enrolled and treated. After neoadjuvant therapy, tpCR and bpCR were respectively observed in 43.1% (95% CI, 29.3%-57.8%) and 49.0% (95% CI, 3)4.8%-63.4%) of 51 evaluable patients for pathological response evaluation. 44 had an ORR as their best response (80.0%; 95% CI, 67.0%-89.6%). No correlations between clinicopathological variables and pathological/clinical response were observed. Grade 3 or more AEs occurred in 63.6% of 55 patients. The most frequent AEs were alopecia. No treatment-related surgical delay or death occurred. Conclusions: Nab-paclitaxel followed by dose-dense EC as NAC demonstrates promising anti-tumor activity and acceptable tolerability for patients with TNBC. Citation Format: Yin Liu, Lei Fan, Zhi-Ming Shao, Zhong-Hua Wang. Nab-paclitaxel followed by dose-dense epirubicin/cyclophosphamide in neoadjuvant chemotherapy for triple-negative breast cancer: an open-label, single-arm phase II study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-18-01.

Safety and feasibility of robotic-assisted thoracic surgery after neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

This study aimed to evaluate the safety and feasibility of robotic-assisted thoracic surgery (RATS) after neoadjuvant chemoimmunotherapy in NSCLC. We retrospectively collected data for NSCLC patients who received thoracic surgery after neoadjuvant chemoimmunotherapy from May 2020 to August 2022. Surgery details, pathological response, and perioperative outcome were compared between video-assisted thoracic surgery (VATS) group and RATS group. Inverse probability of treatment weighting (IPTW) was used to equal the baseline characteristics. A total of 220 patients were divided into 78 VATS patients and 142 RATS patients. There was no 90-day mortality in either group. RATS patients demonstrated better results in conversion rate to thoracotomy (VATS vs. RATS: 28.2% vs. 7.5%, P < 0.001), number of lymph node stations harvested (5.63 ± 1.75 vs. 8.09 ± 5.73, P < 0.001), number of lymph nodes harvested (13.49 ± 9.325 vs. 20.35 ± 10.322, P < 0.001), yield pathologic-N (yp-N) assessment (yp-N0, 88.5% vs. 67.6%; yp-N1, 7.6% vs. 12.6%; yp-N2, 3.8% vs. 19.7%; P < 0.001), and visual analog scale pain score after surgery (4.41 ± 0.93 vs. 3.77 ± 1.21, P=0.002). However, there were no significant differences in pathological response evaluation for neoadjuvant chemoimmunotherapy (P = 0.493) and complication rate (P = 0.803). After IPTW-adjustment, these results remained constant. RATS reduced the risk of conversion to thoracotomy, provided a better yp-N stage evaluation, and improved pain score; this suggests that RATS is safe and feasible for NSCLC patients after neoadjuvant chemoimmunotherapy.

Phase 2 Study of Preoperative SABR for Early-Stage Breast Cancer: Introduction of a Novel Form of Accelerated Partial Breast Radiation Therapy

Pre-operative delivery of partial breast irradiation (PBI) facilitates smaller target volumes and reduced dose to normal tissues. We hypothesized that pre-operative stereotactic ablative radiotherapy (SABR) delivered to intact breast tumor would achieve pathological complete response (pCR) in 25% of patients while preserving low rates of toxicity and good cosmesis. Eligible patients had hormone receptor-positive, clinically node-negative breast cancer measuring ≤2cm on magnetic resonance imaging (MRI). Patients received SABR to 28.5 Gy in three fractions of 9.5 Gy to the tumor defined on MRI and computed tomography in the prone position. Lumpectomy was performed 6-8 weeks later. Tumor pathologic response was assessed and adverse events (AEs) were rated on the Common Terminology Criteria for AEs version 4.0 scale. Physician-rated cosmesis are also reported. Twenty patients were enrolled and completed treatment; the study was terminated prior to full accrual due to pre-specified stopping rules. Median follow-up was 14 months. Median patient age was 65 years (range 54-78) and median tumor size on MRI was 10.5mm (range 5-22). All patients had negative surgical margins. Four patients (20%) required post-operative whole breast and axillary radiation due to positive sentinel lymph nodes. No pCR were observed, although the median percent residual tumor cellularity was 30% (range 10-80) and 90% had ≤50% residual cellularity. Three patients had late grade 3 AEs, including 2 of the 4 patients who received post-operative RT. Cosmesis was good in 85% of cases, fair in 10%, and poor in 5%. We observed a 0% incidence of pCR with pre-operative SABR for early-stage BrCa as evaluated 6-8 weeks following treatment. Evolution of pCR may require longer than 6-8 weeks. Patients requiring post-operative whole breast radiotherapy after pre-operative SABR may be at increased risk for high-grade soft tissue toxicity. Further studies are needed to determine optimal patient selection, treatment methodology and timing of pathologic response evaluation.

The role of MRI and 18F-FDG PET/CT with respect to evaluation of pathological response in the rectal cancer patients after neoadjuvant chemoradiotherapy.

We aimed to evaluate the role of magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) in determining the correct stage and predicting the pathological response. Seventy one patients with pathologic proven rectal adenocarcinoma, clinical stage IIA-IVA, and neoadjuvant chemoradiotherapy (CRT) were evaluated retrospectively. Radiotherapy was delivered 45-50 Gy in 25 fractions with concomitant oral capecitabine. Pelvic MRI, colonoscopy, and 18F-FDG PET-CT were performed before the neoadjuvant treatment (NAT). After NAT, MRI and PET-CT were performed for re-evaluation. The median follow-up time was 25 months (range: 3-57 months). Of the 71 patients who underwent NAT, 57 patients underwent surgery. Downstaging was recorded in 48 (84.2%) of 57 patients who underwent surgery. There was no statistically significant difference between both MRI and PET-CT with pathology results in terms of response evaluation. As a result of the comparison of MRI and PET-CT with pathological results; sensitivity and specificity were 91.6% (44/48) and 22.2% (2/9) for MRI, and 100% (47/47) and 12.5% (1/8) for PET-CT, respectively. PET-CT and MRI are effective in predicting response to NAT and predictive for the pathological response. A more accurate response can be judged when both PET-CT and MRI are executed together in restaging after NAT.

The Importance of the Pathological Perspective in the Management of the Invasive Lobular Carcinoma.

Background Invasive lobular carcinomas (ILC) account for 10–15% of all breast cancers and are the second most common histological form of breast cancer. They usually show a discohesive pattern of single cell infiltration, tend to be multifocal, and the tumor may not be accompanied by a stromal reaction. Because of these histological features, which are not common in other breast tumors, radiological detection of the tumor may be difficult, and its pathological evaluation in terms of size and spread is often problematic. The SSO-ASTRO guideline defines the negative surgical margin in breast-conserving surgeries as the absence of tumor detection on the ink. However, surgical margin assessment in invasive lobular carcinomas has not been much discussed from the pathological perspective. Methods The study included 79 cases diagnosed with invasive lobular carcinoma by a Tru-cut biopsy where operated in our center between 2014 and 2021. Clinicopathological characteristics of the cases, results of an intraoperative frozen evaluation in cases that underwent conservative surgery, the necessity of re-excision and complementary mastectomy, and consistency in radiological and pathological response evaluation in cases receiving neoadjuvant treatment were questioned. Results The tumor was multifocal in 37 (46.8%) cases and single tumor focus in 42 (53.2%) cases. When the entire patient population was evaluated, regardless of focality, mastectomy was performed in 27 patients (34.2%) and breast-conserving surgery (BCS) was performed in 52 patients (65.8%). Of the 52 patients who underwent BCS, 26 (50%) required an additional surgical procedure (cavity revision or completion mastectomy). There is a statistical relationship between tumor size and additional surgical intervention (p < 0.05). BCS was performed in 7 of 12 patients who were operated on after neoadjuvant treatment, but all of them were reoperated with the same or a second session and turned to mastectomy. Neoadjuvant treatment and the need for reoperation were statistically significant (p < 0.05). Additional surgical procedures were performed in 20 (44.4%) of 45 patients in BCS cases who did not receive neoadjuvant therapy. Conclusions Diagnostic difficulties in the intraoperative frozen evaluation of invasive lobular carcinoma are due to the different histopathological patterns of the ILC. In our study, it was determined that large tumor size and neoadjuvant therapy increased the need for additional surgical procedures. It is thought that the pathological perspective is the determining factor in order to minimize the negative effects such as unsuccessful cosmesis, an additional surgical burden on the patient, and cost increase that may occur with additional surgical procedures; for this reason, new approaches should be discussed in the treatment planning of invasive lobular carcinoma cases.

EP05.02-019 Transitioning to Neoadjuvant Therapy for Resectable Non-Small Cell Lung Cancer: Surgical Outcomes in a Regionalized Pulmonary Oncology Network

Neoadjuvant therapy (NAT) allows pre-operative tumor downstaging and evaluation of pathological response. Clinical trials have demonstrated benefit of using NAT in the context of locally advanced non-small cell cancer (NSCLC). However, NAT is not commonly employed around the world and data are lacking as to how to establish a NAT program for locally advanced resectable NSCLC. The aim of this study is to evaluate the evolution in care patterns for patients with resectable locally advanced NSCLC within a regionalized pulmonary oncology academic network and to assess the impact of transition towards a large-scale NAT program.

Pathological Response and Immune Biomarker Assessment in Non-Small-Cell Lung Carcinoma Receiving Neoadjuvant Immune Checkpoint Inhibitors.

Simple SummaryRecently, the U.S. Food and Drug Administration (FDA) approved neoadjuvant immunotherapy plus chemotherapy for the treatment of resectable non-small-cell lung carcinoma (NSCLC) due to the clinical benefits reported in several clinical trials. In these settings, the pathological assessment of the tumor bed to quantify a pathological response has been used as a surrogate method of clinical benefit to neoadjuvant therapy. In addition, several clinical trials are including the assessment of tissue-, blood-, or host-based biomarkers to predict therapy response and to monitor the response to neoadjuvant treatment. In this manuscript, we provide an overview of current recommendations for the evaluation of pathological response and describe potential biomarkers used in clinical trials of neoadjuvant immunotherapy in resectable NSCLC.Lung cancer is the leading cause of cancer incidence and mortality worldwide. Adjuvant and neoadjuvant chemotherapy have been used in the perioperative setting of non-small-cell carcinoma (NSCLC); however, the five-year survival rate only improves by about 5%. Neoadjuvant treatment with immune checkpoint inhibitors (ICIs) has become significant due to improved survival in advanced NSCLC patients treated with immunotherapy agents. The assessment of pathology response has been proposed as a surrogate indicator of the benefits of neaodjuvant therapy. An outline of recommendations has been published by the International Association for the Study of Lung Cancer (IASLC) for the evaluation of pathologic response (PR). However, recent studies indicate that evaluations of immune-related changes are distinct in surgical resected samples from patients treated with immunotherapy. Several clinical trials of neoadjuvant immunotherapy in resectable NSCLC have included the study of biomarkers that can predict the response of therapy and monitor the response to treatment. In this review, we provide relevant information on the current recommendations of the assessment of pathological responses in surgical resected NSCLC tumors treated with neoadjuvant immunotherapy, and we describe current and potential biomarkers to predict the benefits of neoadjuvant immunotherapy in patients with resectable NSCLC.

Evaluation of pathological complete response after neoadjuvant systemic treatment of invasive breast cancer using diffusion-weighted imaging compared with dynamic contrast-enhanced based kinetic analysis

PurposeThis study compared the performance of diffusion-weighted imaging (DWI) to dynamic contrast-enhanced (DCE)-MRI for diagnosing pathological complete response (pCR) before surgery. MethodOverall, 133 lesions from 133 patients who underwent pre-surgical MRI evaluation after neoadjuvant systemic treatment were included. Two readers blinded to the pathological diagnosis evaluated the images. MR images were obtained using a routine protocol sequence that included DWI and DCE-MRI. DWI of the target lesion was scored using a three-point scale. Kinetic patterns of lesions on DCE-MRI were scored using a four-point scale. The capacities of DWI and kinetic parameters for discriminating pCR and non-pCR were assessed via receiver operating characteristic (ROC) analysis. ResultsFor DWI scores, ROC analysis showed areas under the ROC curve (AUCs) of 0.84 (95% confidence interval: 0.77–0.90) and 0.85 (0.77–0.90) for readers 1 and 2, respectively; corresponding AUCs of kinetic scores were 0.89 (0.82–0.94) and 0.88 (0.81–0.93). Among the triple-negative subtype, the AUCs of DWI scores were 0.84 (0.70–0.93) and 0.88 (0.75–0.96) for readers 1 and 2, respectively; corresponding AUCs of kinetic scores were 0.94 (0.83–0.99) and 0.93 (0.82–0.99). Among the luminal subtype, the AUCs of DWI scores were 0.85 (0.71–0.94) and 0.82 (0.68–0.92) for readers 1 and 2, respectively; corresponding AUCs of kinetic scores were 0.82 (0.68–0.92) and 0.72 (0.56–0.85). ConclusionsOur DWI-based visual score and kinetic score showed similar diagnostic performances. Both DWI and kinetic scores tended to perform better in predicting pCR for the triple-negative subtype.