Pathologic Complete Response Research Articles

Gadoxetic acid-enhanced magnetic resonance imaging to predict pathologic complete response of colorectal liver metastases in preoperative chemotherapy

Recent advances in chemotherapy have expanded the opportunity for curative resection of colorectal liver metastases (CRLMs). Disappearing liver metastases (DLMs) are often encountered following chemotherapy. This study aimed to determine whether the DLMs observed by contrast-enhanced computed tomography (CECT) and gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) following preoperative chemotherapy were associated with a pathologic complete response(pCR). Patients who underwent hepatectomy between April 2020 and December 2022, following preoperative chemotherapy at our institution, were selected. Before chemotherapy, all patients underwent CECT, some patients also underwent EOB-MRI, and both imaging studies were performed on all patients after chemotherapy. Pathologic responses of all resected tumors were evaluated. For the unresected DLMs, they were defined as DLMs if they did not reappear in the imaging studies conducted over the following year. A total of 29 patients were selected. After chemotherapy, 138 DLMs were found by CECT and 106 were found by EOB-MRI. Of the resected DLMs confirmed only by CECT, tumor cells remained in 90% of them. All of resected DLMs confirmed by EOB-MRI showed a pCR. Of the remaining 39 unresected DLMs, one reappeared within a year. EOB-MRI is superior to CECT for the diagnosis of DLMs.

Conversion therapy with sintilimab combined with chemotherapy and apatinib in stage IV gastric cancer.

In selected patients with stage IV gastric cancer, radical surgery after conversion therapy may increase survival benefit; however, there is currently no standard protocol for conversion therapy. We explored the feasibility and efficacy of sintilimab plus two-drug chemotherapy (S-1 plus nab-paclitaxel) and apatinib as conversion therapy in patients with stage IV gastric cancer in China. This was a prospective, single-arm, single-center, phase 2 study. The primary endpoint was the R0 conversion rate, defined as the proportion of R0 surgical patients to the total number of patients treated. Of 56 patients screened, 47 were enrolled, received preoperative treatment, and were evaluated for tumor response. Most patients (28/47; 59.6%) had two or three unresectable factors. The objective response rate and disease control rate were 53.2% and 97.9%, respectively. Of the 46/47 patients who achieved disease control, 35 underwent surgery. The R0 conversion rate was 51.1% (24/47). A pathological complete response was observed in 14.3% (5/35) of patients. Median overall survival and event-free survival were 25.7 and 15.3 months, respectively. Overall survival and event-free survival were significantly better in surgical patients compared with non-surgical patients (p < 0.001). In the surgical population, R1/R2 resection was the only significant independent predictor of unfavorable event-free survival by multivariate analysis (p = 0.015). There were no chemotherapy- or perioperative-related deaths. The safety profile was manageable. Sintilimab plus chemotherapy and apatinib followed by conversional resection may be a new feasible and safe option for initially unresectable gastric cancer, potentially leading to long-term survival or even cure.

Stromal tumor infiltrating lymphocytes and TNBC-DX provide complementary prognostic information in triple-negative breast cancer.

Patients with triple-negative breast cancer (TNBC) who achieve pathologic complete response (pCR) to neoadjuvant systemic therapy have favorable survival, while those with residual disease have high recurrence risk. Stromal tumor infiltrating lymphocytes (sTILs) and TNBC-DX both predict pCR in TNBC. Whether these two biomarkers provide complementary information has not been tested. We evaluated sTILs and TNBC-DX in TNBC patients treated with docetaxel-carboplatin (TCb) on the MMJ-CAR-2014-01 study (NCT01560663) or TCb plus pembrolizumab (TCb+Pem) on the NeoPACT trial (NCT03639948). sTILs and TNBC-DX independently predicted pCR in patients treated with TCb+Pem. Patients with sTILs ≥ 30% and a TNBC-DX pCR-high genomic score achieved a pCR rate of 91.3% with TCb+Pem. An integrated classification incorporating sTILs and TNBC-DX identified approximately 40% of the NeoPACT cohort with a pCR rate exceeding 85%. The integrated classification was prognostic for event-free survival in patients treated with TCb+Pem. Integrating sTILs and TNBC-DX may facilitate chemoimmunotherapy escalation and de-escalation trials.

Development and validation of an interpretable machine learning model for diagnosing pathologic complete response in breast cancer.

Development and validation of an interpretable machine learning model for diagnosing pathologic complete response in breast cancer.

Self-supervised network predicting neoadjuvant chemoradiotherapy response to locally advanced rectal cancer patients.

Self-supervised network predicting neoadjuvant chemoradiotherapy response to locally advanced rectal cancer patients.

In Triple-Negative Breast Cancer: Correlation Among Metabolic Syndrome, S100A7/cPLA2 Expression and the Efficacy of Neoadjuvant Chemotherapy.

In Triple-Negative Breast Cancer: Correlation Among Metabolic Syndrome, S100A7/cPLA2 Expression and the Efficacy of Neoadjuvant Chemotherapy.

Patterns of care and surgical outcomes for early-stage rectal cancer in the United States.

Patterns of care and surgical outcomes for early-stage rectal cancer in the United States.

Response prediction for neoadjuvant treatment in locally advanced rectal cancer patients-improvement in decision-making: a systematic review

Response prediction for neoadjuvant treatment in locally advanced rectal cancer patients-improvement in decision-making: a systematic review

Circulating tumor DNA clearance as a predictive biomarker of pathologic complete response in patients with solid tumors treated with neoadjuvant immune checkpoint inhibitors: a systematic review and meta-analysis.

Circulating tumor DNA clearance as a predictive biomarker of pathologic complete response in patients with solid tumors treated with neoadjuvant immune checkpoint inhibitors: a systematic review and meta-analysis.

Recurrence patterns and long-term survival of locally advanced esophageal cancer patients with pathological complete response after different neoadjuvant therapies followed by surgery

BackgroundAchieving pathological complete response (pCR) after neoadjuvant therapy is associated with improved survival in patients with esophageal squamous cell carcinoma (ESCC). However, the recurrence patterns and survival outcomes of pCR patients who received neoadjuvant chemotherapy (NAC), chemoradiotherapy (NCRT), or immunochemotherapy (NICT) remain unclear.MethodsThis retrospective cohort study included 250 ESCC patients who achieved pCR after neoadjuvant therapy (119 in the NAC group, 61 in the NCRT group, and 70 in the NICT group). The aim was to compare the effects of the three neoadjuvant modalities on recurrence patterns and overall survival (OS) in pCR patients.ResultsUnder multimodal neoadjuvant therapy, there was no significant difference in recurrence rates among the three groups (NAC: 5.88% vs. NICT: 7.14% vs. NCRT: (9.84%,P = 0.624). Distant metastasis was the predominant pattern in the NAC (71.4%) and NCRT (80.0%) groups, while the NICT group exhibited a higher proportion of local recurrence (80.0%,P = 0.208); most recurrences occurred at a single site. The 5-year OS rates were 87.0% in the NAC group, 76.7% in the NCRT group, and not evaluable in the NICT group, with no statistical difference among groups (P = 0.189). Event-free survival (EFS) also showed no significant difference (P = 0.076). Intergroup differences were observed in the incidence of postoperative complications including Pneumonia (P < 0.05).ConclusionNo statistical differences in OS or EFS were found among pCR patients treated with different neoadjuvant modalities (P > 0.05), but recurrence patterns varied across groups: distant metastasis was more common in the NAC/NCRT groups, whereas the NICT group had a higher frequency of local recurrence. Multicenter long-term follow-up studies are warranted to validate these findings.

Efficacy and safety of small-molecule TKIs in neoadjuvant treatment of HER2-positive breast cancer: a systematic review and network meta-analysis

ObjectiveThis study aimed to evaluate the efficacy and safety of small-molecule TKIs in neoadjuvant treatment of HER2-positive breast cancer using a network meta-analysis approach.MethodsA systematic literature search was conducted in the Medline, Embase, and Web of Science databases. Eligible studies that included HER2-positive breast cancer patients receiving neoadjuvant treatment with small-molecule TKIs before surgery were included. A Bayesian framework within a random-effects model was used for network meta-analysis to summarize direct and indirect evidence. Outcome measures included breast pathological complete response (breast pCR), total pathological complete response (total pCR) of the breast and lymph nodes, and selected safety endpoints.ResultsEight eligible studies involving a total of 1,841 participants were included. The most common treatment regimens were Trastuzumab (n = 8), Lapatinib (n = 6), and Lapatinib plus Trastuzumab (n = 6), while there were fewer studies on Pyrotinib plus Trastuzumab (n = 2). No studies about tucatinib and neratinib were enrolled. The rankings of efficacy for the breast pCR and total pCR endpoints were as follows: (i) Pyrotinib plus Trastuzumab, (ii) Lapatinib plus Trastuzumab, (iii) Trastuzumab, (iv) Lapatinib. Regarding safety endpoints of grade 3 or higher diarrhea, neutropenia, fatigue, and skin disorders, the rankings were as follows: (i) Trastuzumab, (ii) Lapatinib, (iii) Lapatinib plus Trastuzumab, (iv) Pyrotinib plus Trastuzumab for diarrhea; (i) Pyrotinib plus Trastuzumab, (ii) Trastuzumab, (iii) Lapatinib plus Trastuzumab, (iv) Lapatinib for neutropenia; (i) Lapatinib plus Trastuzumab, (ii) Trastuzumab, (iii) Lapatinib for fatigue; (i) Trastuzumab, (ii) Lapatinib plus Trastuzumab, (iii) Lapatinib for skin disorders.ConclusionFor HER2-positive breast cancer patients, the use of small-molecule TKIs in combination with trastuzumab as neoadjuvant treatment has certain advantages in improving the rate of pathological response. Dual-targeted therapy with pyrotinib shows objective efficacy and acceptable safety; however, further research is still needed to confirm these findings.

Posttreatment MRI to Predict Pathologic Complete Response of Triple-Negative Breast Cancer to Neoadjuvant Chemoimmunotherapy.

Background Neoadjuvant chemoimmunotherapy (NACI) has substantially improved pathologic complete response (pCR) rates in early triple-negative breast cancer (TNBC). However, the predictive accuracy of posttreatment MRI remains unexplored. Purpose To assess the performance of posttreatment MRI in the prediction of pCR in participants with TNBC treated with NACI. Materials and Methods In this prospective multicenter study (August 2021-June 2024), women with early TNBC were recruited from three centers (training set: Institut Curie; test set: Institut Godinot and Institut Oscar Lambret). Post-NACI dynamic contrast-enhanced MRI scans from multiple vendors were analyzed. Radiologic complete response (rCR)-defined as no enhancement in the tumor bed-was evaluated for predicting pCR. A multivariable logistic regression model incorporating rCR, nodal involvement, and Ki-67 index was developed and externally validated. In cases with residual enhancement (non-rCR), a radiomic score using shape and first-order features was tested. Results A total of 175 women were included in the training set (mean age, 49 years ± 11 [SD]) and 84 women in the external test set (mean age, 52 years ± 12). The rCR at MRI was predictive of pCR, with an area under the receiver operating characteristic curve (AUC) of 0.83 (95% CI: 0.75, 0.92). The combined model (rCR + nodal status + Ki-67) yielded an AUC of 0.88 (95% CI: 0.81, 0.96) in the test set. In node-negative patients with Ki-67 greater than 30%, the rCR false-discovery rate (ie, the proportion of rCR cases that were actually non-pCR or residual disease missed at breast MRI) was 3.6% (two of 56) in the training set and 3.5% (one of 29) in the test set; all cancers were limited to residual cancer burden I. In non-rCR cases, a model incorporating the radiomics score and lesion count achieved an AUC of 0.80 (95% CI: 0.69, 0.90). Conclusion Posttreatment rCR at MRI demonstrated strong predictive value for pCR in early TNBC following NACI. © RSNA, 2025 Supplemental material is available for this article. See also the editorial by Onishi in this issue.

Neoadjuvant ARX788 plus pyrotinib versus trastuzumab, pertuzumab, docetaxel and carboplatin for HER2-positive breast cancer: a randomised phase 2b trial

Antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) are widely used for HER2-positive metastatic breast cancer, but their efficacy in the neoadjuvant setting remains under investigation. The MUKDEN 06 trial (NCT05426486), a multicentre, randomised, phase 2b study, compared ARX788 (anti-HER2 ADC) plus pyrotinib (TKI) with the standard neoadjuvant regimen of docetaxel, carboplatin, trastuzumab, and pertuzumab (TCbHP) in female patients with early or locally advanced HER2-positive breast cancer. The primary endpoint was the pathological complete response (pCR, ypT0/is, ypN0) rate, analyzed in the intention-to-treat population. pCR was achieved in 70.6% (48/68) of patients receiving ARX788 plus pyrotinib, compared to 51.5% (35/68) in the TCbHP group, with a significant absolute difference of 19.1% (95% CI, 2.7–34.6; p = 0.023). No treatment-related deaths occurred. The most common grade 3–4 adverse events were diarrhea and hepatic dysfunction in the ARX788 plus pyrotinib group, and fatigue, nausea and anorexia in the TCbHP group. Interstitial lung disease (ILD)/pneumonitis and ocular events were observed with ARX788 plus pyrotinib, indicating a distinct safety profile. These findings offer clinical insights into the potential of dual HER2-targeted blockade with an ADC and TKI as an optional neoadjuvant strategy for patients with early or locally advanced HER2-positive breast cancer.

Outcomes of neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Outcomes of neoadjuvant immunochemotherapy and neoadjuvant chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Correlations Between Mammographic Breast Density and Outcomes After Neoadjuvant Chemotherapy in Patients with Locally Advanced Breast Cancer

Introduction: An inverse association between high mammographic breast density (MBD) and pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) for early breast cancer (EBC) has been reported. However, the relationship of MBD to relapse-free (RFS) and breast cancer-specific survival (BCSS) is unexplored. This study aims to validate the relationship between MBD and NAC pCR in EBC and to assess correlations with RFS and BCSS. Materials &amp; Methods: MBD was measured on contralateral mammograms in 127 women before NAC using Cumulus software. The percent dense area was correlated with patient and tumour characteristics, pCR, RFS and BCSS. Results: Mean MBD was higher in relapsing patients (p = 0.041) but did not vary by pCR or BC-deaths. As a dichotomous variable, no difference was seen between high and low MBD cohorts for pCR (17.5 vs. 25.0%, p = 0.15), BC relapse (38 vs. 30%, p = 0.15) or BC death (32 vs. 25%, p = 0.20). A planned analysis by body mass index (BMI) demonstrated high MBD associated with lower pCR (0% vs. 28.1%, p = 0.036) and trends for higher relapse (56% vs. 28%, p = 0.063) and BC deaths (56 vs. 28%, (p = 0.071)) in obese patients. No relationship was observed in non-obese patients. Conclusions: Obesity and high MBD may interact to cause chemoresistance. Further research in these patients is warranted.

Delta-radiomics features combined with haematological index predict pathological complete response after neoadjuvant immunochemotherapy in resectable non-small cell lung cancer.

Delta-radiomics features combined with haematological index predict pathological complete response after neoadjuvant immunochemotherapy in resectable non-small cell lung cancer.

Long and short-term efficacy and safety comparison of nab-paclitaxel versus paclitaxel combined with trastuzumab and pertuzumab for neoadjuvant treatment of HER2-positive breast cancer: A systematic review and meta-analysis.

Long and short-term efficacy and safety comparison of nab-paclitaxel versus paclitaxel combined with trastuzumab and pertuzumab for neoadjuvant treatment of HER2-positive breast cancer: A systematic review and meta-analysis.

Comparison of 10-Year Survival Between Patients With Axillary Pathologic Complete Response After Neoadjuvant Chemotherapy and Patients With Initially Negative Nodes in Breast Cancer.

Comparison of 10-Year Survival Between Patients With Axillary Pathologic Complete Response After Neoadjuvant Chemotherapy and Patients With Initially Negative Nodes in Breast Cancer.

Predict status of axillary lymph node after neoadjuvant chemotherapy with dual-energy CT in breast cancer

BackgroundA proportion of breast patients achieve axillary pathological complete response (pCR) following NAC. However, few studies have investigated the potential of quantitative parameters derived from dual-energy CT (DECT) for predicting axillary lymph node (ALN) downstaging after NAC.MethodsThis study included a prospective training and retrospective validation cohort from December 2019 to June 2022. Both groups enrolled invasive breast cancer with biopsy-proved metastatic ALNs who underwent contrast-enhanced DECT and NAC followed by surgery. A metastatic ALN, named target lymph node (TLN), was marked with metal clip at baseline. Quantitative DECT parameters and size of TLN, and clinical information were compared between pCR and non-pCR node group referring to postoperative pathology. Three predictive models, clinical, quantitative CT, and combinational models, were built by logistic regression and nomogram was drawn accordingly. The performance was evaluated by the receiver operator characteristic curve and clinical usefulness was assessed by decision curve analysis.ResultsA total of 75 and 53 patients were included in training and validation cohort respectively. Of them, 34 (45.3%) and 22 (41.5%) patients achieved nodal pCR in the two sets. Multivariable analyses revealed that negative estrogen receptor expression, parenchyma thickness and the iodine concentration of TLN at post-NAC CT were independently predictive factors for pCR. The combinational model showed discriminatory power than the single clinical model (AUC, 0.724; p = 0.003) and quantitative CT model (AUC, 0.728; p = 0.030) with AUC of 0.847 and 0.828 in training and validation cohort. It provided enhanced net benefits within a wide range of threshold probabilities.ConclusionQuantitative DECT parameters can be used to evaluate axillary nodal status after NAC and guide personalized treatment strategies.

Protein-Level Analysis of Differential Response to Chemotherapy in Triple-Negative Breast Cancer Identifies CYP1B1 as a Biomarker for Chemotherapy Resistance

Resistance to chemotherapy is a critical challenge in triple-negative breast cancer (TNBC). In this study, the proteomes of pretreatment core biopsy samples from 16 patients with TNBC with differential response to neoadjuvant chemotherapy (NAC) were analyzed by nanoLC/MS-MS to identify biomarkers of intrinsic chemotherapy resistance. This led to the identification of cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) and 71 additional proteins as significantly more abundant in chemoresistant than chemosensitive TNBC. IHC analysis of 80 TNBC samples confirmed an association between elevated tumor cell CYP1B1 and residual cancer burden class 2/3 disease after NAC in T cell–excluded (TCE) TNBC (P < 0.01) but not in T cell–infiltrated (TCI) TNBC. The frequency of complete pathologic response in TCE-TNBC with elevated CYP1B1 was 18% versus 56% in TCE-TNBC with low CYP1B1 and 75% in TCI-TNBC. Retrospective review of the chemotherapy regimens suggested that TCE-TNBC with elevated CYP1B1 was particularly resistant to doxorubicin/cyclophosphamide. This study is the first to associate resistance to NAC in TNBC with elevated CYP1B1.Significance:This retrospective analysis of pretreatment TNBC core biopsies found that elevation of CYP1B1, a drug-metabolizing enzyme in tumor cells, was associated with resistance to NAC in patients with TNBC treated initially with doxorubicin. If confirmed, this pattern of chemotherapy resistance could guide future clinical trials.