A case of complete pathological response after comprehensive treatment in a patient with pulmonary adenocarcinoma with synchronous solitary brain metastasis.

Systemic chemotherapy is the standard treatment for non-small cell lung cancer with distant metastases. However, additional local treatment for brain and thoracic lesions is recommended for patients with synchronous solitary brain metastases (SSBM). We report the case of a 71-year-old male diagnosed with pulmonary adenocarcinoma and SSBM. Pathological examination of the brain metastasis showed positive immunostaining for programmed cell death ligand 1 expression. After four cycles of chemotherapy with immune checkpoint inhibitors, right upper lobectomy with ND2a-1 was performed. Pathological examination revealed complete pathological response, and this patient is expected to experience long-term survival.

Neoadjuvant short-course radiotherapy followed by camrelizumab and chemotherapy in locally advanced rectal cancer (UNION): early outcomes of a multicenter randomized phase III trial.

BACKGROUND: Neoadjuvant short-course radiotherapy (SCRT) followed by CAPOX and camrelizumab (a PD-1 monoclonal antibody) has shown potential clinical activity for locally advanced rectal cancer (LARC) in a phase II trial. This study aimed to further confirm the efficacy and safety of SCRT followed by CAPOX and camrelizumab compared to long-course chemoradiotherapy (LCRT) followed by CAPOX alone as neoadjuvant treatment for LARC. PATIENTS AND METHODS: In this randomized, phase III trial, patients with T3-4/N+ rectal adenocarcinoma were randomly assigned (1:1) to receive SCRT or long-course chemoradiotherapy (LCRT), followed by 2 cycles of camrelizumab and CAPOX or CAPOX alone, respectively. After surgery, each arm underwent either 6 cycles of camrelizumab and CAPOX, followed by up to 17 doses of camrelizumab, or 6 cycles of CAPOX. The primary endpoint was pathological complete response (pCR) rate (ypT0N0) assessed by a blinded independent review committee. Key secondary endpoints tested hierarchically were 3-year event-free survival (EFS) rate and overall survival (OS). RESULTS: Between July 2021 and March 2023, the intention-to-treat population comprised 113 patients in experimental arm and 118 patients in control arm, with surgery performed in 92% and 83.9%, respectively. At data cutoff (July 11, 2023), the pCR rate were 39.8% (95% CI, 30.7 to 49.5) in experimental arm compared to 15.3% (95% CI, 9.3 to 23.0) in control arm (difference, 24.6%; odds ratio, 3.7; 95% CI, 2.0 to 6.9; p < 0.001). In each arm, surgical complication rates were 40.0% and 40.8%, grade ≥ 3 treatment-related adverse events were 29.2% and 27.2%. 3-year EFS rate and OS continue to mature. CONCLUSIONS: In LARC patients, neoadjuvant SCRT followed by camrelizumab plus CAPOX demonstrated a significantly higher pCR rate than LCRT followed by CAPOX, with a well-tolerated safety profile. SCRT followed by camrelizumab and chemotherapy can be recommended as a neoadjuvant treatment modality for these patients.

Neoadjuvant aumolertinib monotherapy for EGFR-mutant lung squamous cell carcinoma: a case report.

Background: Lung cancer is the malignant tumor with high incidence and mortality in China, and more than 30% of non-small cell lung cancer (NSCLC) patients are in the locally advanced stage at the first-time diagnosis. Currently, neoadjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) combined with radical surgery is effective in the treatment of unresectable stage III EGFR-mutated NSCLC (NSCLCm), and related studies are gradually increasing. But the feasibility of neoadjuvant EGFR-TKI combined with radical surgery for unresectable stage III EGFR-mutant lung squamous cell carcinoma (LUSQm) remains controversial. Case Description: This report presented a successful case of neoadjuvant target-therapy with aumolertinib, the third-generation EGFR-TKI, combined with radical surgery for a stage IIIA LUSQm female patient. After four cycles (28 days/cycle) of neoadjuvant target-therapy, the tumor had a partial response on imaging evaluation and pathological evaluation after surgery showed complete tumor response. The neoadjuvant target-therapy was well tolerated. All adverse events (AEs) that occurred during the treatment were grade I, including decreased platelets, impaired liver function, and diarrhea. The patient was instructed to continue taking Aumolertinib for 3 years after surgery. At the cut-off date of April 1, 2024, the patient had no recurrence after 20 months of treatment. Conclusions: The result of patient treatment demonstrated the potential feasibility of neoadjuvant Aumolertinib monotherapy for locally advanced LUSQm. The report provides some support for neoadjuvant target-therapy for LUSQm.

Prediction of pathological complete response and prognosis in locally advanced rectal cancer.

BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

Effectiveness and safety of neoadjuvant therapy in triple-negative breast cancer in a real-world population. / [Artículo traducido] Efectividad y seguridad del tratamiento neoadyuvante del cáncer de mama triple negativo en la vida real.

OBJECTIVE: Triple-negative breast cancer is a subtype of aggressive breast cancer. Our aim is to evaluate the effectiveness and safety of neoadjuvant treatment in early-stage triple-negative breast cancer and to identify predictors of pathological complete response. METHODS: This is a single-center, retrospective study involving 79 patients with triple-negative breast cancer who initiated neoadjuvant treatment between January 2017 and October 2022. Descriptive analyses were performed as appropriate. Statistical analysis utilized bivariate logistic regression to explore the presence of factors related to pathological complete response, and the Kaplan-Meier method was employed for survival analysis. RESULTS: In the overall population, 27 patients (n = 78; 34.6%) achieved pathological complete response in the breast and axillary lymph nodes, and 31 (n = 73; 42.5%) achieved a grade 5 pathological complete response in the breast, according to the Miller and Payne classification. The addition of platinum to standard therapy improved both breast and axillary lymph node pathological complete response rates. Age less than 40 years was identified as a predictor of pathological complete response in our study population through bivariate analysis, while Ki67 levels lower than 70% were associated with a lower pathological complete response rate. Adverse events were reported in 72 patients (91.1%), with grade 3-5 adverse events observed in 33 (41.8%). There was a particularly notable increase in gastrointestinal and hematological adverse events when platinum was added. CONCLUSIONS: In this population, we observed moderate rates of pathological complete response with acceptable chemotherapy tolerance. Platinum-based chemotherapy appears to enhance the likelihood of achieving pathological complete response, albeit with a less favorable safety profile. Therefore, evaluating the benefit-risk balance is crucial when selecting the optimal chemotherapy regimen for individual patients.

Pathological complete response and associated factors in breast cancer after neoadjuvant chemotherapy: A retrospective study.

Objectives: This study aimed to determine clinical and pathological factors that identify a pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Material and Methods: A retrospective, single-center study was conducted in women over the age of 18 who had been diagnosed with pathologically confirmed invasive breast cancer and who had received NAC between July 2016 and October 2021. Patient demographics, clinical, radiological, treatment, and pathological data were reviewed from the electronic hospital records. The primary outcome of interest was pCR, defined as the absence of residual invasive breast cancer in both the breast and axillary lymph nodes. Multivariable logistic regression analysis was used to identify factors associated with pCR. Results: A total of 119 patients were included in the analysis. The distribution of age was 54.5 ± 11.5 years. pCR was observed in 33 (27.7%) patients. pCR for breast tissue was observed in 43 (36.1%) patients. There was no statistically significant relation between the clinical stage and pCR. Age, age at first labor, extent of disease in the breast, NAC completeness, clinical tumor size (cT) stage, clinical lymph node (cN) stage, and molecular subtype were analyzed in a multivariable model. Analysis showed that molecular subtype was the only independent factor related to pCR. pCR rates across molecular subtypes were: 8.7% in luminal-A, 10.8% in luminal-B, 54.5% in human epidermal growth factor receptor 2 (HER-2)-positive, 42.4% in luminal-B (HER-2 positive) and 46.7% in triple-negative. There was no statistically significant difference between luminal-A and luminal-B subgroups (odds ratio 1.15, 95% confidence interval, 0.19-9.35, p= 0.881). Despite the limited number of patients in HER2-positive and triple-negative groups, both demonstrated statistically significant higher odds compared to reference group. Conclusion: The presented study underscores the relevance of molecular subtypes in determining the response to neoadjuvant chemotherapy in breast cancer patients. Particularly HER2-positive and triple-negative subtypes may demonstrate more favorable response rates.

GSDME-mediated pyroptosis promotes anti-tumor immunity of neoadjuvant chemotherapy in breast cancer.

Paclitaxel and anthracycline-based chemotherapy is one of the standard treatment options for breast cancer. However, only about 6-30% of breast cancer patients achieved a pathological complete response (pCR), and the mechanism responsible for the difference is still unclear. In this study, random forest algorithm was used to screen feature genes, and artificial neural network (ANN) algorithm was used to construct an ANN model for predicting the efficacy of neoadjuvant chemotherapy for breast cancer. Furthermore, digital pathology, cytology, and molecular biology experiments were used to verify the relationship between the efficacy of neoadjuvant chemotherapy and immune ecology. It was found that paclitaxel and doxorubicin, an anthracycline, could induce typical pyroptosis and bubbling in breast cancer cells, accompanied by gasdermin E (GSDME) cleavage. Paclitaxel with LDH release and Annexin V/PI doubule positive cell populations, and accompanied by the increased release of damage-associated molecular patterns, HMGB1 and ATP. Cell coculture experiments also demonstrated enhanced phagocytosis of macrophages and increased the levels of IFN-γ and IL-2 secretion after paclitaxel treatment. Mechanistically, GSDME may mediate paclitaxel and doxorubicin-induced pyroptosis in breast cancer cells through the caspase-9/caspase-3 pathway, activate anti-tumor immunity, and promote the efficacy of paclitaxel and anthracycline-based neoadjuvant chemotherapy. This study has practical guiding significance for the precision treatment of breast cancer, and can also provide ideas for understanding molecular mechanisms related to the chemotherapy sensitivity.

Successful treatment of enormous locally advanced breast cancer through neoadjuvant chemotherapy and surgical intervention: a case report.

Background: Breast cancer has become a critical international healthcare issue. Specifically, among the different subtypes, breast cancer marked by human epidermal growth factor receptor 2 (HER2)-overexpression usually correlates with low survival and a poor prognosis and poses challenges in treatment, thus leading to high mortality. Case Description: A 54-year-old female patient was diagnosed with a large T4cN2aM0 stage IIIB breast tumor with HER2 overexpression. The tumor size was large, and there was a lack of opportunity for surgery. However, after neoadjuvant chemotherapy (NACT), the size of the tumor continuously shrank, and the patient successfully underwent a modified radical mastectomy. Even though a certain amount of mass remained and she did not complete six courses of NACT, our patient's postoperative pathological result still revealed that a pathological complete response (pCR) was achieved. The appropriate time window for choosing surgical intervention should be determined based on the patient's general condition instead of complying with the treatment guidelines. Also, imaging findings may be misleading in patients who have undergone NACT. Moreover, the regimen should be chosen flexibly. Conclusions: Patients with locally advanced breast cancer can still achieve a radical surgical resection following appropriate comprehensive treatment. Hopefully, this case can provide new ideas for surgeons when they face similar conditions.

Predicting pathological complete response after neoadjuvant chemotherapy in breast cancer by clinicopathological indicators and ultrasound parameters using a nomogram.

The study explored the impact of pretreatment serum albumin-to-alkaline phosphatase ratio (AAPR) and changes in tumor blood supply on pathological complete response (pCR) in breast cancer (BC) patients following neoadjuvant chemotherapy (NACT). Additionally, a nomogram for predicting pCR was established and validated. The study included BC patients undergoing NACT at Yongchuan Hospital of Chongqing Medical University from January 2019 to October 2023. We analyzed the correlation between pCR and clinicopathological factors, as well as tumor ultrasound features, using chi-square or Fisher's exact test. We developed and validated a nomogram predicting pCR based on regression analysis results. The study included 176 BC patients. Logistic regression analysis identified AAPR [odds ratio (OR) 2.616, 95% confidence interval (CI) 1.140-5.998, P = 0.023], changes in tumor blood supply after two NACT cycles (OR 2.247, 95%CI 1.071-4.716, P = 0.032), tumor histological grade (OR 3.843, 95%CI 1.286-10.659, P = 0.010), and HER2 status (OR 2.776, 95%CI 1.057-7.240, P = 0.038) as independent predictors of pCR after NACT. The nomogram, based on AAPR, changes in tumor blood supply after two NACT cycles, tumor histological grade, and HER2 status, demonstrated a good predictive capability.

Clinical Analysis of the Efficacy and Safety of Different Neoadjuvant Strategies in the Treatment of Locally Advanced Rectal Cancer.

OBJECTIVE: In this study, we retrospectively analysed the efficacy and safety of three treatment models, namely, short-course radiotherapy sequential XELOX chemotherapy, neoadjuvant mFOLFOX6 concurrent radiotherapy and long-course concurrent radiotherapy with total mesorectal excision (TME) after treatment of locally advanced rectal cancer with high-risk factors. METHODS: We collected clinical data on 177 patients with locally advanced rectal cancer (cT3-4 and/or cN+) who were treated at the Department of Abdominal Oncology of the Affiliated Cancer Hospital of Guizhou Medical University from December 2017 to December 2022.All patients were associated with 2-3 risk factors [T4b, N2, Extramural Vascular Invasion (EMVI), Mesorectal Fascia (MRF) positivity], positive lateral lymph nodes. Among them, there were 45 cases in the short course radiotherapy sequential XELOX chemotherapy group (RT + XELOX group); 64 cases in the neoadjuvant mFOLFOX6 concurrent radiotherapy group (mFOLFOX6 + CRT group); and 68 cases in the long course concurrent radiotherapy group (CRT group). The RT + XELOX group and mFOLFOX6 + CRT group completed radiotherapy and 4 cycles of neoadjuvant chemotherapy, respectively, and then rested for 1-2 weeks before TME surgery; the CRT group completed concurrent radiotherapy and then rested for 6-8 weeks before TME surgery.Adjuvant chemotherapy was conducted after surgery in each of the three groups: 2 cycles of adjuvant chemotherapy with XELOX regimen in the RT + XELOX group, 4-6 cycles of adjuvant chemotherapy with mFOLFOX6 in the mFOLFOX6 + CRT group, and 8-12 cycles of adjuvant chemotherapy with mFOLFOX6 in the CRT group.The pathological complete response rate (pCR rate), tumour downstage rate, tumour complete resection rate (R0 resection rate), local recurrence rate, distant metastasis rate, overall survival rate, incidence of adverse reactions, surgical complications and completion rate of perioperative systemic chemotherapy were compared among patients in the three groups of cases after TME. RESULTS: The pCR rate (21.95% vs 17.24% vs 5.00%, p = 0.034) and and tumour downstage rate (78.05% vs 68.97% vs 53.33%, p = 0.029) were higher in the RT + XELOX group and mFOLFOX6 + CRT group compared to the CRT group. The RT + XELOX group had a lower 3-year distant metastasis rate (14.63% vs 36.67%, p = 0.048) and improved 3-year overall survival (76.57% vs 48.56%, p < 0.001) compared to the CRT group. There was no significant reduction in the 3-year distant metastasis rate in the mFOLFOX6 + CRT group versus the CRT group (27.59% vs 36.67%, p = 0.719), and the 3-year overall survival was similar (51.23% vs 48.56%, p = 0.35). Multi-logistic regression analysis and stratified analysis showed that patients in the RT + XELOX group and mFOLFOX6 + CRT group were more likely to achieve pCR than the CRT group (RT + XELOX group: OR 7.3, 95% CI [2.6-20.8], p < 0.001; mFOLFOX6 + CRT group OR 2.9, 95% CI [1.1-7.9], p = 0.036). The completion rates of perioperative systemic chemotherapy in the RT + XELOX, mFOLFOX6 + CRT, and CRT groups were 82.93% vs. 84.48% vs. 61.67% (χ2=9.95, p = 0.007), respectively. And there were significant differences in grade 3-4 leukopenia and thrombocytopenia (incidence of leukopenia: 15.50% vs. 7.81% vs. 1.47%, p = 0.045; incidence of thrombocytopenia: 13.33% vs 7.81% vs 1.47%, p = 0.027). There was no significant difference in the incidence of intraoperative and postoperative complications among the three groups (p > 0.05). CONCLUSIONS: RT + XELOX group and mFOLFOX6 + CRT group significantly improved the near-term outcome (e.g., pCR rate) in patients with locally advanced rectal cancer with high-risk factors compared with CRT group. The RT + XELOX group also reduced the 3-year distant metastasis rate, increased the 3-year overall survival rate, and did not increase the incidence of perioperative surgical complications. It provides an effective means for the comprehensive treatment of locally advanced rectal cancer and has important clinical guidance and application value.

Prognostic Impact of Inflammation-Based Factors in Patients with Esophageal Squamous Cell Carcinoma Achieving Pathological Complete Response After Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Patients achieving pathological complete response (pCR) post-neoadjuvant chemoradiotherapy (nCRT) and surgery for locally advanced esophageal squamous cell carcinoma (ESCC) have a favorable prognosis. However, recurrence occurs in approximately 20-30% of all patients, with few studies evaluating their prognostic factors. We identified these prognostic factors, including inflammation-based markers, in patients with ESCC showing pCR after nCRT and surgery. PATIENTS AND METHODS: Patients with ESCC undergoing esophagectomy post-nCRT (January 2007-August 2017) were studied. Survival analysis evaluated 5-year overall (OS) and recurrence-free survival (RFS). Risk factors, including inflammation factors, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (PLR), were analyzed using Cox-proportional hazards model. RESULTS: Overall, 123patients participated herein. After a median follow-up duration of 67 months (44-86 months), 17 patients (12.3%) had recurrent disease. The 5-year OS and RFS rates were 71.6% and 68.0%, respectively. In the multivariable analysis, older age ( ≥ 60 years) [hazard ratio (HR) 3.228, 95% confidence interval (CI) 1.478-7.048, p = 0.003], higher pretreatment T stage (≥ T3; HR 2.563, 95% CI 1.335-4.922, p = 0.005), nonapplication of induction chemotherapy (HR 2.389, 95% CI 1.184-4.824, p = 0.015), and higher post-nCRT PLR (≥ 184.2; HR 2.896, 95% CI 1.547-5.420, p = 0.001) were poor independent prognostic factors for 5-year RFS. The patient group with three to four identified factors with poor outcomes exhibited a 5-year RFS rate of 46.2%. CONCLUSIONS: Significant prognostic factors include higher post-nCRT PLR, older age, higher clinical T stage, and nonapplication of induction chemotherapy. Identifying higher recurrence risk patients is crucial for tailored follow-up and treatment.

Predictive model based on multiple immunofluorescence quantitative analysis for pathological complete response to neoadjuvant immunochemotherapy in lung squamous cell carcinoma.

Objective: This study aims to establish a prediction model for neoadjuvant immunochemotherapy (NICT) in lung squamous cell carcinoma to guide clinical treatment. Methods: This retrospective study included 50 patients diagnosed with lung squamous cell carcinoma who received NICT. The patients were divided into the pathological complete response (PCR) group and the non-PCR group. HE staining and multiple immunofluorescence (mIF) techniques were utilized to analyze the differences in the immune microenvironment between these groups. LASSO regression and optimal subset regression were employed to identify the most significant variables and construct a prediction model. Results: The PCR group showed higher densities of lymphocyte nuclei and karyorrhexis based on HE staining. Furthermore, based on mIF analysis, the PCR group showed higher cell densities of CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region, while showing lower cell densities of CD3+Foxp3+, Foxp3+, and CD163+. Logistic univariate analysis revealed CD8+PD-L1+, PD-L1+, CD8+, CD4+LAG-3+, lymphocyte nuclei, and karyorrhexis as significant factors influencing PCR. By using diverse screening methods, the three most relevant variables (CD8+, PD-L1+, and CD8+PD-L1+ in the tumor region) were selected to establish the prediction model. The model exhibited excellent performance in both the training set (AUC=0.965) and the validation set (AUC=0.786). In the validation set, In comparison to the conventional TPS scoring criteria, the model attained superior accuracy (0.85), specificity(0.67), and sensitivity (0.92). Conclusion: NICT treatment might induce anti-tumor effects by enriching immune cells and reactivating exhausted T cells. CD8+, PD-L1+, and CD8+PD-L1+ cell abundances within the tumor region have been closely associated with therapeutic efficacy. Incorporating these three variables into a predictive model allows accurate forecasting of treatment outcomes and provides a reliable basis for selecting NICT treatment strategies.

Assessing the Efficacy of Radioactive Iodine Seed Localisation in Targeted Axillary Dissection for Node-Positive Early Breast Cancer Patients Undergoing Neoadjuvant Systemic Therapy: A Systematic Review and Pooled Analysis.

Targeted axillary dissection (TAD), employing marked lymph node biopsy (MLNB) alongside sentinel lymph node biopsy (SLNB), is increasingly recognised for its efficacy in reducing false negative rates (FNRs) in node-positive early breast cancer patients receiving neoadjuvant systemic therapy (NST). One such method, 125I radioactive seed localisation (RSL), involves implanting a seed into a biopsy-proven lymph node either pre- or post-NST. This systematic review and pooled analysis aimed to assess the performance of RSL in TAD among node-positive patients undergoing NST. Six studies, encompassing 574 TAD procedures, met the inclusion criteria. Results showed a 100% successful deployment rate, with a 97.6% successful localisation rate and a 99.8% retrieval rate. Additionally, there was a 60.0% concordance rate between SLNB and MLNB. The FNR of SLNB alone was significantly higher than it was for MLNB (18.8% versus 5.3%, respectively; p = 0.001). Pathological complete response (pCR) was observed in 44% of cases (248/564). On average, the interval from 125I seed deployment to surgery was 75.8 days (range: 0-272). These findings underscore the efficacy of RSL in TAD for node-positive patients undergoing NST, enabling precise axillary pCR identification and facilitating the safe omission of axillary lymph node dissection.

CT-based quantification of intratumoral heterogeneity for predicting pathologic complete response to neoadjuvant immunochemotherapy in non-small cell lung cancer.

Objectives: To investigate the prediction of pathologic complete response (pCR) in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant immunochemotherapy (NAIC) using quantification of intratumoral heterogeneity from pre-treatment CT image. Methods: This retrospective study included 178 patients with NSCLC who underwent NAIC at 4 different centers. The training set comprised 108 patients from center A, while the external validation set consisted of 70 patients from center B, center C, and center D. The traditional radiomics model was contrasted using radiomics features. The radiomics features of each pixel within the tumor region of interest (ROI) were extracted. The optimal division of tumor subregions was determined using the K-means unsupervised clustering method. The internal tumor heterogeneity habitat model was developed using the habitats features from each tumor sub-region. The LR algorithm was employed in this study to construct a machine learning prediction model. The diagnostic performance of the model was evaluated using criteria such as area under the receiver operating characteristic curve (AUC), accuracy, specificity, sensitivity, positive predictive value (PPV), and negative predictive value (NPV). Results: In the training cohort, the traditional radiomics model achieved an AUC of 0.778 [95% confidence interval (CI): 0.688-0.868], while the tumor internal heterogeneity habitat model achieved an AUC of 0.861 (95% CI: 0.789-0.932). The tumor internal heterogeneity habitat model exhibits a higher AUC value. It demonstrates an accuracy of 0.815, surpassing the accuracy of 0.685 achieved by traditional radiomics models. In the external validation cohort, the AUC values of the two models were 0.723 (CI: 0.591-0.855) and 0.781 (95% CI: 0.673-0.889), respectively. The habitat model continues to exhibit higher AUC values. In terms of accuracy evaluation, the tumor heterogeneity habitat model outperforms the traditional radiomics model, achieving a score of 0.743 compared to 0.686. Conclusion: The quantitative analysis of intratumoral heterogeneity using CT to predict pCR in NSCLC patients undergoing NAIC holds the potential to inform clinical decision-making for resectable NSCLC patients, prevent overtreatment, and enable personalized and precise cancer management.

Impact of adjuvant chemotherapy on survival after pathological complete response in rectal cancer: a meta-analysis of 31,558 patients.

BACKGROUND: Locally advanced rectal cancer (LARC) typically involves neoadjuvant chemoradiotherapy (nCRT) followed by surgery (total mesorectal excision, TME). While achieving a complete pathological response (pCR) is a strong indicator of a positive prognosis, the specific benefits of adjuvant chemotherapy after pCR remain unclear. To address this knowledge gap, we conducted a systematic review and meta-analysis to assess the potential advantages of adjuvant therapy in patients who achieve pCR. METHODS: In this study, we searched Medline, Embase, and Web of Science databases for relevant research. We focused on binary outcomes, analyzing them using odds ratios (ORs) with 95% confidence intervals (CIs). To account for potential variability between studies, all endpoints were analyzed with DerSimonian and Laird random-effects models. We assessed heterogeneity using the I2 statistic and employed the R statistical software (version 4.2.3) for all analyses. RESULTS: Thirty-four studies, comprising 31,558 patients, were included. The outcomes demonstrated a significant difference favoring the AC group in terms of overall survival (OS) (HR 0.75; 95% CI 0.60-0.94; p = 0.015; I2 = 0%), and OS in 5 years (OR 1.65; 95% CI 1.21-2.24; p = 0.001; I2 = 39%). There was no significant difference between the groups for disease-free survival (DFS) (HR 0.94; 95% CI 0.76-1.17; p = 0.61; I2 = 17%), DFS in 5 years (OR 1.19; 95% CI 0.82-1.74; p = 0.36; I2 = 43%), recurrence-free survival (RFS) (HR 1.10; 95% CI 0.87-1.40; p = 0.39; I2 = 0%), and relapse-free survival (OR 1.08; 95% CI 0.78-1.51; p = 0.62; I2 = 0%). CONCLUSION: This systematic review and meta-analysis found a significant difference in favor of the ACT group in terms of survival after pCR. Therefore, the administration of this treatment as adjuvant therapy should be encouraged in clinical practice.

CT-based delta-radiomics nomogram to predict pathological complete response after neoadjuvant chemoradiotherapy in esophageal squamous cell carcinoma patients.

BACKGROUND: This study developed a nomogram model using CT-based delta-radiomics features and clinical factors to predict pathological complete response (pCR) in esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (nCRT). METHODS: The study retrospectively analyzed 232 ESCC patients who underwent pretreatment and post-treatment CT scans. Patients were divided into training (n = 186) and validation (n = 46) sets through fivefold cross-validation. 837 radiomics features were extracted from regions of interest (ROIs) delineations on CT images before and after nCRT to calculate delta values. The LASSO algorithm selected delta-radiomics features (DRF) based on classification performance. Logistic regression constructed a nomogram incorporating DRFs and clinical factors. Receiver operating characteristic (ROC) and area under the curve (AUC) analyses evaluated nomogram performance for predicting pCR. RESULTS: No significant differences existed between the training and validation datasets. The 4-feature delta-radiomics signature (DRS) demonstrated good predictive accuracy for pCR, with α-binormal-based and empirical AUCs of 0.871 and 0.869. T-stage (p = 0.001) and differentiation degree (p = 0.018) were independent predictors of pCR. The nomogram combined the DRS and clinical factors improved the classification performance in the training dataset (AUCαbin = 0.933 and AUCemp = 0.941). The validation set showed similar performance with AUCs of 0.958 and 0.962. CONCLUSIONS: The CT-based delta-radiomics nomogram model with clinical factors provided high predictive accuracy for pCR in ESCC patients after nCRT.

A nomogram to predict the pathological complete response in patients with breast cancer based on the TILs-US score.

BACKGROUND: The tumor-infiltrating lymphocytes-ultrasonography score is a calculation system for predicting lymphocyte-predominant breast cancers in surgical specimens. A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score was developed to predict the pathological complete response in breast cancer treated with neoadjuvant chemotherapy. METHODS: A retrospective evaluation was conducted on 118 patients with breast cancer treated with neoadjuvant chemotherapy at Hiroshima University Hospital. Tumor-infiltrating lymphocytes-ultrasonography scores ≥4 were classified as high. A nomogram was developed using a stepwise logistic regression model for pathological complete response (ypT0 ypN0), based on the smallest Akaike information criterion. The predictive ability and clinical usefulness of the nomogram were also evaluated. RESULTS: Among 118 patients, 34 (28.8%) achieved a pathological complete response, and 52 (44.1%) exhibited high tumor-infiltrating lymphocytes-ultrasonography. In multivariate logistic regression analysis, high tumor-infiltrating lymphocytes-ultrasonography (odds ratio, 6.01; P < 0.001), clinical complete response (odds ratio, 4.83; P = 0.004) and hormone receptor (odds ratio, 3.48; P = 0.038) were independent predictors of pathological complete response. A nomogram based on tumor-infiltrating lymphocytes-ultrasonography score, clinical complete response, hormone receptor and clinical N status was developed. The nomogram showed an area under the curve of 0.831 and a bias-corrected area under the curve of 0.809. The calibration plot showed a good fit between the expected and actual pathological complete response values. Decision curve analysis also showed the clinical utility of the nomogram for predicting pathological complete responses. CONCLUSIONS: A nomogram based on the tumor-infiltrating lymphocytes-ultrasonography score exhibited a favorable predictive ability for pathological complete response in patients with breast cancer, which can be useful in predicting the residual disease status after neoadjuvant chemotherapy.

In situ HER2 RNA expression as a predictor of pathologic complete response of HER2-positive breast cancer patients receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment.

BACKGROUND: Immunohistochemistry (IHC) and in situ hybridization (ISH) remain standard biomarkers for therapeutic decisions in human epidermal growth factor 2 (HER2)-positive breast cancers (BCs); however, they are insufficient to explain the heterogeneous anti-HER2 response. METHODS: We aimed to investigate the correlation of in situ HER2 RNA expression (isHRE), using RNAscope, with HER2 biomarkers and the impact of isHRE on the pathological complete response (pCR) rates of 278 patients with HER2 IHC/fluorescence ISH (FISH)-positive BC receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment (NCTT). RESULTS: We validated HER2 RNAscope scoring as a semiquantitative method to determine isHRE and showed a positive correlation between RNAscope scores and pCR rates, with particularly different rates between patients with a score of 5 versus 1-4 BCs (66.7% vs. 15.9%, p < 0.0001). There were higher RNAscope scores and pCR rates in patients with HER2 IHC 3 + versus IHC 2+/FISH + BCs and HER2 RNAscope scores and pCR rates showed similar non-linear positive correlations with HER2 copy numbers and HER2/centromere 17 ratios. Moreover, in each HER2-positive IHC/FISH category, higher pCR rates were observed in patients with RNAscope scores of 5 versus 1-4 BC. Patients achieving pCR had BCs with notably higher HER2 RNAscope scores. Multivariate analysis identified HER2 RNAscope 5 as a strong pCR predictor [odds ratio = 10.865, p < 0.001]. The combined impact of multivariate analysis-defined pCR predictors demonstrated that a higher pCR rate was observed in patients with a score of 5 versus a score of 1-4 BCs regardless of the status of hormone receptor and mono-or dual anti-HER2 blockade. CONCUSIONS: Our results demonstrated that high isHRE (RNAscope score 5) is a strong pCR predictor in patients with HER2-positive BCs receiving NCTT, highlighting the complementary role of isHRE in stratifying HER2 status in tissue. Such stratification is relevant to anti-HER2 therapeutic efficacy, particularly using the cutoff of score 1-4 versus 5.