Pathological Complete Remission Research Articles

Comprehensive Evaluation of a Levonorgestrel Intrauterine Device (LNG-IUD), Metformin, and Liraglutide for Fertility Preservation in Endometrial Cancer: Protocol for a Randomized Clinical Trial

Endometrial cancer is a leading gynecological malignancy, with obesity being a significant risk factor due to increased estrogen production in body fat. Current treatments often involve hysterectomy, which precludes fertility, thus highlighting the need for fertility-preserving options. This study aims to evaluate the combined efficacy of a levonorgestrel intrauterine device (LNG-IUD), metformin, and liraglutide for treating women with endometrial hyperplasia or early stage endometrial cancer while preserving fertility. The study will enroll 264 women aged 18–45 with a BMI > 30 who desire uterine preservation. Participants will be randomized into three groups: LNG-IUD alone, LNG-IUD plus metformin, and LNG-IUD plus metformin and liraglutide. Primary outcomes will include complete pathological remission, while secondary outcomes will assess histological changes, glucose, insulin levels, and weight changes over a 12-month period. This study protocol hypothesizes that LNG-IUD combined with metformin and liraglutide may potentially lead to higher regression rates of endometrial hyperplasia (EH) and early stage endometrial cancer (EC) compared to LNG-IUD alone. Furthermore, the protocol anticipates that these combination therapies will demonstrate good tolerability with minimal adverse effects, suggesting the potential benefit of integrating metabolic interventions with LNG-IUD to enhance treatment efficacy while preserving fertility in women with EH and EC.

Comparison of immunochemotherapy and chemotherapy alone in conversion therapy for locally advanced unresectable esophageal squamous cell carcinoma.

The clinical value of preoperative immunochemotherapy and simple chemotherapy induction regimen in the conversion therapy of locally advanced unresectable esophageal squamous cell carcinoma (ESCC) is still unclear. Retrospective analysis was conducted on patients with unresectable cT4b stage ESCC who underwent conversion surgery in our hospital from January 2020 to December 2022. According to the preoperative induction treatment plan, they were divided into induction immunochemotherapy group (iICT group) and induction chemotherapy group (iCT group). The conversion surgery rate, R0 resection rate, radiological and pathological tumor responses, safety, and short-term survival outcomes were analyzed. The results showed that a total of 199 patients with cT4b locally advanced unresectable ESCC who underwent preoperative induction therapy were included in this study. Among them, there were 64 cases (32.2%) in the iICT group, 135 cases (67.8%) in the iCT group. There was a statistically significant difference in objective response rate (73.5% vs 48.9%) and conversion surgery rate (81.3% vs 66.7%), between the iICT and iCT groups (P=0.001 and P=0.019). Among the two groups of patients who underwent surgery, there were statistically significant differences in R0 resection rate (94.2% vs 82.2%) and pathological complete remission rate (23.1% vs 6.7%) between the iICT and iCT groups (P=0.043 and P=0.004). And there was no statistically significant difference in the incidence of grade 3 and above between two groups (P=0.928). The 2-year EFS of the iICT group and iCT group were 76.4% and 42.4%, respectively, with statistically significant differences (P=0.006). Compared with simple chemotherapy, the combination of PD-1 inhibitors and chemotherapy can achieve better conversion surgery rate, tumor response and event-free survival in the conversion therapy of locally advanced unresectable ESCC.

Analysis of factors affecting complete pathological remission after neoadjuvant immunocombination chemotherapy treatment for locally advanced esophageal squamous carcinoma.

e16061 Background: Chemotherapy combined with immunotherapy for locally advanced esophageal squamous carcinoma has achieved a high rate of complete pathological remission, which is conducive to a better prognosis for patients; however, not all ESCC patients benefit from ICI therapy, so finding validated prognostic markers of efficacy will help us to screen for populations that are superior to neoadjuvant immunotherapy. Methods: Patients with locally advanced esophageal squamous carcinoma treated with neoadjuvant immune-combination chemotherapy followed by radical surgery from January 2019 to June 2023 at our institution were collected. The grouping was based on whether pathologic complete remission (pCR) was achieved after neoadjuvant therapy. Clinical and treatment-related data as well as hematologic, inflammatory, and nutritional indices within 1 week before neoadjuvant therapy and within 1 week after 2 cycles of neoadjuvant immune-combination chemotherapy treatment were collected from all patients, and univariate and multivariate analyses were performed to assess independent predictors of pCR. Results: Patients in both pCR and Non-pCR groups were more likely to obtain pCR if they had pre-treatment BMI > 21Kg/m2 vs BMI ≤21Kg/m2, number of neoadjuvant therapy cycles ≥3 cycles vs number of neoadjuvant therapy cycles = 2 cycles, and CYFRA21-1ng/ml < 3.28 vs ≥3.28 before neoadjuvant therapy (p < 0.05). Patients with albumin ≥40.10g/L vs albumin < 40.10g/L, NLR < 2.50 vs NLR ≥2.50, and NRI ≥98.06 vs NRI < 98.06 were more likely to achieve pCR before treatment in both groups (p < 0.05). SII ≥521.75 VS SII < 521.75 was more likely to achieve pCR after 2 cycles of treatment (p < 0.05). Univariate analysis of the comparison of dynamic changes in nutritional inflammatory indexes during treatment between the two groups of patients showed that pCR was more likely to be achieved in patients with persistently elevated eosinophil counts and NLR after 2 cycles of neoadjuvant immune-combination chemotherapy treatment (p < 0.05). The results of multifactorial analysis showed that pre-treatment BMI, SII after 2 cycles of treatment, and dynamic changes in eosinophils during neoadjuvant therapy were independent influences on complete pathological remission after neoadjuvant immune-combination chemotherapy treatment (p < 0.05). Conclusions: Complete pathological remission after neoadjuvant immune-combination chemotherapy treatment for esophageal squamous carcinoma was significantly correlated with the patient's pre-treatment BMI, Post-treatment SII, and eosinophil dynamics during treatment.

Prediction models of locally advanced rectal cancer prognosis incorporating perioperative longitudinal clinical data: A retrospective longitudinal cohort study.

e15624 Background: For locally advanced rectal cancer, neoadjuvant chemoradiation(CCRT) followed by surgery is a standard treatment. Clinical T/N stage, whether pathological complete remission (pCR) after neoadjuvant CCRT or not are well recognized tumor features that predict disease prognosis. Although the parameters that determine pathologic stage are the strongest predictors of postoperative outcome, other clinical, molecular, and histologic features may influence prognosis independent of stage. The aim is to compare the predictive efficiency, between different models for overall survival in rectal cancer patients. Methods: This retrospective study is approved by TMU-JIRB(Protocol Number: N201809032).This is also a single institute study. 175 newly-diagnosed patients with locally advanced rectal cancer were retrospectively enrolled between Jan.2011 and Dec.2016. Basic information include sex, age, body weight, body height, previous medical history were recorded. CEA level, chemotherapy regimen, type of surgery, and distance between tumor and anal verge were also collected. Chemotherapy regimen of CCRT including 5FU+LV, capecitabine (Xeloda), FOLFOX, and FOLFIRI are recorded. Surgical resection was then followed 4-8 weeks after completion of CCRT. The 2010 AJCC tumor response grading (TRG) system was used to report treatment response of proctectomy samples. The progression free survival (PFS) and overall survival (OS) are then calculated. PFS is defined as survival without any recurrence or distant metastasis before Dec 31st, 2023. A comprehensive evaluation was conducted by incorporating all these machine learning models together. The aim was to compare their predictive efficiency, with models such as Random Forest, Naïve Bayes, KNeighbor, SVM, Decision Tree, Logistic Regression, XGBoost, and LightGBM. Results: 175 patients (104 men and 71 women) were enrolled in this study. The median follow up time was 7.1 yrs. The BMI was 24.05 ± 0.03 for men and 24.20 ± 0.07 for women. 32 (17.3%) patients achieved pCR, TRG 0. Clinical staging cT3 (78.8%) and nodal positive (78.8%) are the most common tumor feature in this study group. The median age of male and female patient is 58.6 and 56.1 respectively. Upon applying various machine learning models, different predictive accuracies emerged. The Random Forest, KNeighbor, and SVM models all achieved an accuracy of 0.9250. Naïve Bayes had an accuracy of 0.8620, while the SVC model registered at 0.9310, and XGBoost was slightly behind at 0.9286. SVC model is marking the best-performing model in this evaluation. Conclusions: This multicenter retrospective data-driven deep learning prediction model informed that SVC model yielded the best predictive results. Further prospective clinical trials and external validation of this prediction model are needed to further reinforce our findings.

Trastuzumab, pertuzumab and nab-paclitaxel plus pyrotinib or not in neoadjuvant treatment of HER2-positive breast cancer: A multi-center, randomized, open-label, phase II study.

e12634 Background: Trastuzumab plus pertuzumab (TP) combined with chemotherapy is the standard neoadjuvant treatment regimen for HER2+ breast cancer. Anti-HER2 tyrosine kinase inhibitor, pyrotinib, shows great efficacy in HER2+ metastatic breast cancer, but lacking efficacy data on the basis of TP and chemotherapy in the neoadjuvant setting. This study aims to evaluate the efficacy and safety of TP plus nab-paclitaxel with or without pyrotinib as neoadjuvant treatment in HER2+ breast cancer. Methods: Stage II-III HER2+ breast cancer patients, stratified by disease stage (II vs. III) and hormone receptor (HR) status (positive vs. negative), were randomized 1:1 into the pyrotinib group or the control group. Both groups received a combination of 3-weekly TP and weekly nab-paclitaxel for 12 weeks. The pyrotinib group was concurrent given 320mg pyrotinib once daily. Primary endpoint was the total pathological complete remission (tpCR), defined as no invasive cancer in the breast and axillary lymph node. Results: From Nov 2020 to Apr 2023, a total of 109 patients were enrolled, with 108 receiving treatment: 55 in the pyrotinib group and 53 in the control group.The tpCR rate was 65.5% (95% CI: 51.4%, 77.8%) in the pyrotinib group, which shows no significant difference with the control group [60.4% (95% CI: 46.0%,73.5), P = 0.585). The breast pathological complete response (bpCR) rates were 70.9% (95% CI: 57.1%,82.4%) and 64.2%(95% CI: 49.8%,76.9%) in the pyrotinib and control group, respectively (P = 0.453). In the pyrotinib group, 52 (94.5%), 31 (56.4%), and 23 (41.8%) patients experienced dose-interruption, dose-reduction, and discontinuation of pyrotinib, respectively. The most common grade ≥3 adverse events in the pyrotinib and control groups were diarrhea (58.1% vs. 0%), decreased neutrophil count (23.6% vs. 15.1%), and decreased white blood cell count (16.4% vs. 7.5%). Conclusions: Our study showed pyrotinib didn’t significantly improve tpCR rate with pyrotinib on the basis of TP and nab-paclitaxel neoadjuvant therapy of HER2+ breast cancer. Concurrent pyrotinib treatment with TP was associated with a high rate of severe diarrhea. Further biomarker analyses are needed to identify which population would receive great benefit with neoadjuvant pyrotinib therapy in HER2+ breast cancer. Clinical trial information: NCT04398914 .

Preliminary results from a multi-center phase Ib/II study of RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2 positive locally advanced muscle-invasive urothelial bladder cancer (Hope-03).

e16595 Background: To evaluate the safety and efficacy of RC48-ADC, a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab, a PD-1 antibody, as a novel neoadjuvant treatment combination in patients with HER2 positive locally advanced muscle-invasive bladder cancer (MIBC). The study design has been presented at 2022 ESMO Asia meeting. The preliminary results would be reported this time. Methods: This is a Ib/II, multi-center, open-label, single-arm study (ChiECRCT20210564). 51 patients with pathological and imaging diagnosed cT2-4bN0-3M0-1a HER2 positive MIBC will be included. RC48-ADC is given every 2 weeks with a maximum dose of 120mg intravenously, and tislelizumab is given every three weeks at the dose of 200mg intravenously. Treatment efficacy will be performed by imaging and transurethral resection of tumors after the neoadjuvant treatment. Patients without disease progression will receive radical cystectomy or bladder-sparing therapies based on individual risk profiles and preferences. The primary endpoints are clinical complete remission rate (cCR, T0/Ta/Tis), pathological complete remission rate (pCR) and safety. The secondary endpoints are disease control rate (DCR), overall survival (OS), local recurrence free survival (LRFS), distant metastasis free survival (DMFS) and quality of life. Results: Until now, 18 patients were included successfully, with 3 female patients and 15 male patients. And the median age was 64.47 years old. Of them, 7 patients were HER2(2+), and 11 patients were HER2(3+). The clinical stages were T2-4aN0-3M1a. Sixteen patients had the primary efficacy evaluation by now. After the neoadjuvant treatment, 7 patients were T0, 4 patients Tis, 2 patients partial response (PR), 2 patients stable disease (SD) and 1 patient suffered from progress of local disease. Hence the cCR rate was 68.75%, and the DCR was 90.91%. Fourteen patients chose radiotherapy as bladder-sparing therapy and no evidence of tumor in 6 patients who received treatment efficacy after radiotherapy. Two patients received radical cystectomy and pT3N0M0 was achieved for both. No patient died so far. For safety analysis, 4 patients suffered from immune-related adverse event, namely, grade 2 myositis, grade 1 elevated transaminase and grade 1 hyperthyroidism which led to treatment interruption of tislelizumab. And 10 patients experienced RC48-ADC related toxicities, including grade 1 elevated transaminase, grade 1 erythra and grade 1 paresthesia. No treatment related dose reduction happened. Conclusions: The novel neoadjuvant combination of RC48-ADC and tislelizumab showed promising down stage efficacy in patients with HER2 positive locally advanced MIBC and the toxicities were manageable, which would be verified by the final analysis. Clinical trial information: ChiECRCT20210564.

Preliminary results from a multi-center phase Ib/II study of RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2 positive locally advanced muscle-invasive urothelial bladder cancer (Hope-03).

e16595 Background: To evaluate the safety and efficacy of RC48-ADC, a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab, a PD-1 antibody, as a novel neoadjuvant treatment combination in patients with HER2 positive locally advanced muscle-invasive bladder cancer (MIBC). The study design has been presented at 2022 ESMO Asia meeting. The preliminary results would be reported this time. Methods: This is a Ib/II, multi-center, open-label, single-arm study (ChiECRCT20210564). 51 patients with pathological and imaging diagnosed cT2-4bN0-3M0-1a HER2 positive MIBC will be included. RC48-ADC is given every 2 weeks with a maximum dose of 120mg intravenously, and tislelizumab is given every three weeks at the dose of 200mg intravenously. Treatment efficacy will be performed by imaging and transurethral resection of tumors after the neoadjuvant treatment. Patients without disease progression will receive radical cystectomy or bladder-sparing therapies based on individual risk profiles and preferences. The primary endpoints are clinical complete remission rate (cCR, T0/Ta/Tis), pathological complete remission rate (pCR) and safety. The secondary endpoints are disease control rate (DCR), overall survival (OS), local recurrence free survival (LRFS), distant metastasis free survival (DMFS) and quality of life. Results: Until now, 18 patients were included successfully, with 3 female patients and 15 male patients. And the median age was 64.47 years old. Of them, 7 patients were HER2(2+), and 11 patients were HER2(3+). The clinical stages were T2-4aN0-3M1a. Sixteen patients had the primary efficacy evaluation by now. After the neoadjuvant treatment, 7 patients were T0, 4 patients Tis, 2 patients partial response (PR), 2 patients stable disease (SD) and 1 patient suffered from progress of local disease. Hence the cCR rate was 68.75%, and the DCR was 90.91%. Fourteen patients chose radiotherapy as bladder-sparing therapy and no evidence of tumor in 6 patients who received treatment efficacy after radiotherapy. Two patients received radical cystectomy and pT3N0M0 was achieved for both. No patient died so far. For safety analysis, 4 patients suffered from immune-related adverse event, namely, grade 2 myositis, grade 1 elevated transaminase and grade 1 hyperthyroidism which led to treatment interruption of tislelizumab. And 10 patients experienced RC48-ADC related toxicities, including grade 1 elevated transaminase, grade 1 erythra and grade 1 paresthesia. No treatment related dose reduction happened. Conclusions: The novel neoadjuvant combination of RC48-ADC and tislelizumab showed promising down stage efficacy in patients with HER2 positive locally advanced MIBC and the toxicities were manageable, which would be verified by the final analysis. Clinical trial information: ChiECRCT20210564.

A randomized controlled study on perioperative treatment of esophageal squamous cell carcinoma with camrelizumab combined with nab-paclitaxel and cisplatin.

e16122 Background: Neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC) has received increasing acceptance due to its effectiveness being confirmed by several phase II studies. CheckMate 577 has determined the efficacy of adjuvant immunotherapy in ESCC patients (pts) with R0 resection after neoadjuvant chemoradiotherapy. However, in the era of neoadjuvant immunotherapy, the optimal adjuvant treatment regimen for pts with ESCC warrant further research. This study aims to explore the efficacy and safety of perioperative treatment with camrelizumab combined with nab-paclitaxel and cisplatin for potentially resectable ESCC. Methods: This study planned to enroll 190 pts with potentially resectable stage II/III/IVa (cT1b-4aN0-3M0) ESCC. Eligible pts received 2-cycle of neoadjuvant camrelizumab (200mg, d1, q3w) combined with nab-paclitaxel (125mg/m2, d1,8, q3w) and cisplatin (75mg/m2, d1, q3w). Pts who reached pathologic complete remission (pCR) were randomly assigned to the immunotherapy group (camrelizumab for 16 cycles) and the best supportive care (BSC) group. Pts who did not reach pCR were randomly assigned to the immunochemotherapy group (camrelizumab combined with nab-paclitaxel and cisplatin for 2-4 cycles and camrelizumab for 12-14 cycles) and the immunotherapy group. Primary endpoints were pCR rate and 3-year DFS rate. Secondary endpoints were major pathologic response (MPR) rate, objective response rate (ORR), disease free survival (DFS), overall survival (OS). Results: As of Jan. 9th 2024, 121 pts (83 males and 38 females) with a median age of 65 years were enrolled in the study. One hundred and thirteen pts completed neoadjuvant treatment and 102 pts were available for imaging evaluation, the ORR was 91.9% and the DCR was 98.9%. Ninety six pts underwent surgery, 95 (98.9%) pts had a R0 resection, 32 (33.3%) pts reached pCR, 33 (34.3%) pts reached MPR. TNM down-staging was observed in 74 (77%) pts. Of 81 pts who underwent randomization, 30 pts reached pCR, 14 pts were randomly assigned to immunotherapy group, and 16 were assigned to BSC group. For 51 pts who did not reach pCR, 26 were randomized to the immunochemotherapy group and 25 were assigned to the immunotherapy group. At date cutoff, 5 pts (distant recurrence) relapsed in the immunochemotherapy group and 2 pts (distant recurrence) relapsed in the immunotherapy group who did not reach pCR. One hundred and twtety-one of 123 pts had AEs, and 33 pts had grade ≥3 AEs. The most common grade ≥3 AEs were anemia (9.9%), decreased lymphocyte count (7.4%), leukopenia (4.1%). Conclusions: This ongoing study again confirmed the safety and efficacy of neoadjuvant immunochemotherapy for resectable ESCC. Further data on optimal adjuvant treatment regimen for pts with or without residual disease will be reported in the future. Clinical trial information: NCT05182944 .

Impact of treatment interval between neoadjuvant immunochemotherapy and surgery in lung squamous cell carcinoma

ObjectiveThe optimal timing for surgery following neoadjuvant immunochemotherapy for lung squamous cell carcinoma appears to be a topic of limited data. Many clinical studies lack stringent guidelines regarding this timing. The objective of this study is to explore the effect of the interval between neoadjuvant immunochemotherapy and surgery on survival outcomes in patients with lung squamous cell carcinoma.MethodsThis study conducted a retrospective analysis of patients with lung squamous cell carcinoma who underwent neoadjuvant immunochemotherapy between January 2019 and October 2022 at The First Affiliated Hospital, Zhejiang University School of Medicine. Patients were divided into two groups based on the treatment interval: ≤33 days and > 33 days. The primary observational endpoints of the study were Disease-Free Survival (DFS) and Overall Survival (OS). Secondary observational endpoints included Objective response rate (ORR), Major Pathological Response (MPR), and Pathological Complete Remission (pCR).ResultsUsing the Kaplan-Meier methods, the ≤ 33d group demonstrated a superior DFS curve compared to the > 33d group (p = 0.0015). The median DFS for the two groups was 952 days and 590 days, respectively. There was no statistical difference in the OS curves between the groups (p = 0.66), and the median OS was not reached for either group. The treatment interval did not influence the pathologic response of the tumor or lymph nodes.ConclusionsThe study observed that shorter treatment intervals were associated with improved DFS, without influencing OS, pathologic response, or surgical safety. Patients should avoid having a prolonged treatment interval between neoadjuvant immunochemotherapy and surgery.

Abstract PO4-01-04: Clinical significance of Circulating tumor DNA (ctDNA) analysis in predicting pathologic complete remission in HER2-positive Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NACT) combined with dual anti-HER2 agents followed by surgical resection is the standard treatment for stage II-III HER2-positive breast cancer. Despite the availability of effective therapies as an adjuvant treatment such as ado-trastuzumab emtansine (T-DM1) and neratinib, pathologic complete remission (pCR) strongly predicts survival. This study aimed to investigate the role of ctDNA analysis in predicting pCR and clinical outcome using comprehensive ctDNA analysis. Methods: A total of 34 HER2-positive breast cancer patients who underwent NACT combined with dual anti-HER2 agents and surgical resection were enrolled, including 22 clinical stage II and 12 III patients. Plasma samples were collected at four-time points: before neoadjuvant chemotherapy, after 3 cycles, at the completion of neoadjuvant chemotherapy, and after surgery. low-pass whole-genome sequencing (lpWGS) and whole exome sequencing (WES) in evaluating blood copy-number burden (bCNB), genomic alterations, mutational signatures, blood tumor mutational burden (bTMB). Mutations selected from the baseline sample were monitored for Molecular residual disease (MRD) monitoring. lpWGS yielded negative results, targeted NGS sequencing was conducted. Results: Among the enrolled patients (N=34), 21 patients (61.8%) had nodal metastasis and 22 patients (64.7%) were hormone receptor-positive. A total 26 patients (76.5%) achieved pCR. Positive ctDNA was detected in 20 patients (58.8%) at baseline. Higher nodal stage was significantly associated with ctDNA positivity at baseline. After surgery, MRD positivity was observed in 3 patients (8.8%). Among the 26 patents who acheived pCR, only 1 patient (3.8%) showed MRD positivity, while 2 non-pCR patients (25%) demonstrated MRD positivity. Conclusion: The presence of MRD was significantly associated with non-pCR status. The presence of ctDNA at baseline was associated with a higher nodal stage, suggesting its potential as a prognostic marker. Further studies with larger cohorts are warranted to validate these findings and explore the utility of ctDNA analysis for personalized treatment decisions in HER2-positive breast cancer. Citation Format: Byeongju Kang, Soo Jung Lee, Jeeyeon Lee, In Hee Lee, Jee-Young Park, Ho Yong Park, Tiantian Zheng, Lu Tan, Liam Il-Young Chung, Shidong Jia, Pan Du, Young Kwang Chae, Yee Soo Chae. Clinical significance of Circulating tumor DNA (ctDNA) analysis in predicting pathologic complete remission in HER2-positive Breast Cancer Patients Undergoing Neoadjuvant Chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-04.

Clinical factors and major pathological response after neoadjuvant chemoimmunotherapy in potentially resectable lung squamous cell carcinoma.

Major pathological response (MPR) helps evaluate the prognosis of patients with lung squamous cell carcinoma (LUSC). However, the clinical factors that affect the achievement of MPR after neoadjuvant chemoimmunotherapy (NCIO) in patients with LUSC remain unclear. This study aimed to explore the clinical factors affecting the MPR after NCIO in patients with potentially resectable LUSC. This retrospective study included patients with stage IIB-IIIC LUSC who underwent surgical resection after receiving NCIO at a center between March 2020 and November 2022. In addition to the postoperative pathological remission rate, sex, age, body mass index (BMI), smoking history, TNM stage, hematological and imaging test results, and other indicators were examined before NCIO. According to the pathological response rate of the surgically removed tumor tissue, the patients were split into MPR and non-MPR groups. In total, 91 LUSC patients who met the study's eligibility criteria were enrolled: 32 (35%) patients in the non-MPR group and 59 (65%) in the MPR group, which included 43 cases of pathological complete remission (pCR). Pre-treatment lymphocyte level (LY) (odds ratio [OR] =5.997), tumor burden (OR=0.958), N classification (OR=15.915), radiographic response (OR=11.590), pulmonary atelectasis (OR=5.413), and PD-L1 expression (OR=1.028) were independently associated with MPR (all P < 0.05). Based on these six independent predictors, we developed a nomogram model of prediction having an area under the curve (AUC) of 0.914 that is simple to apply clinically to predict the MPR. The MPR group showed greater disease-free survival (DFS) than the non-MPR group, according to the survival analysis (P < 0.001). The MPR rate of NCIO for potentially resectable LUSC was 65%. LY, tumor burden, N classification, radiographic response, pulmonary atelectasis, and PD-L1 expression in patients with LUSC before NCIO were the independent and ideal predictors of MPR. The developed nomogram demonstrated a good degree of accuracy and resilience in predicting the MPR following NCIO, indicating that it is a useful tool for assuring customized therapy for patients with possibly resectable LUSC.

Evolution of neoadjuvant therapy for breast cancer regimens over 12 years and pathologic response rates according to tumor subtypes and clinical stage: A single-center retrospective study.

Given the evolution of neoadjuvant therapy (NAT) for breast cancer, this study aimed to analyze trends in NAT regimens over time and patients' pathological responses, tumor stages, and subtypes. Data were analyzed for 548 patients with cT1-4N0-3M0 breast cancer who received NAT at Shandong Cancer Hospital between 2011 and 2022. The 12-year study period was divided into six 2-year periods termed P1 to P6. From P1 to P6, the proportion of stage II patients treated with NAT increased from 6.4% to 33.8% compared with same-stage operable breast cancer (r = 0.228, P < 0.001), while the proportion of the full-course group increased from 50.0% to 99.0% (r = 0.354, P < 0.001). The pathologic complete remission (pCR) rate in the full-course group increased from 30.8% to 54.6% (r = 0.248, P < 0.001). In the full-course human epidermal growth factor receptor-2 positive (HER2+) group, the proportion of chemotherapy combined with inhibition therapy increased from 33.3% to 100% (r = 0.530, P < 0.001). Furthermore, dual inhibition therapy increased from 0 to 98.9%. The proportion of the nonanthracycline group (dual inhibition) increased from 56.0% at P5 to 76.6% at P6 (r = 0.190, P = 0.042). In the full-course Triple-Negative Breast Cancer (TNBC) group, the proportion of platinum therapy increased from 0 to 41.9% (r = 0.324, P < 0.001) and immune drugs increased from 0 to 53.2% (r = 0.500, P < 0.001). Overall, the results indicate an increasing proportion of patients receiving NAT therapy over time. Furthermore, there were increases in HER2 + patients receiving inhibition therapy (especially dual inhibition) and TNBC patients receiving platinum and immune therapy as part of NAT. Notably, these changes were associated with improved outcomes.

Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer

Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894–0.4706, p < 0.0001) and enhanced infiltration of adaptive immune cells. Biomolecular analysis showed that high TLS-score was strongly associated with more infiltration of immune cells and increased activation of immune-related pathways. TLS+ tumors in pre-treatment specimens were associated with a higher proportion of good respond (62.5% vs. 29.8%, p < 0.0002) and pathological complete remission (pCR) (40.0% vs. 11.1%, p < 0.0001), and significantly increased RFS (HR 0.3574 95%CI 0.1489–0.8578 p = 0.0213) compared with TLS- tumors in the neoTx cohort, which was confirmed in GSE119409 and GSE150082. Further studies showed that neoTx significantly reduced TLS density and maturity, and abolished the prognostic value of TLS. Our study illustrates that TLS may have a key role in mediating the T-cell-inflamed tumor microenvironment, which also provides a new direction for neoTx, especially neoadjuvant immunotherapy, in LRAC patients.

Vasohibin-1 Expression Can Predict Pathological Complete Remission of Advanced Bladder Cancer with Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) is a well-established standard practice in invasive bladder cancer (BCa), however patient selection remains challenging. High expression of vasohibin-1 (VASH1), an endogenous regulator of angiogenesis, has been reported in high-grade and advanced BCa; however, its prognostic value for chemotherapy outcomes remains unexplored. In this study, we sought to identify biomarkers of chemotherapy response focusing on the relationship between angiogenesis and tissue hypoxia. Forty Japanese patients with BCa who underwent NAC and radical cystectomy were included in the present analysis. We compared the immunohistochemical expression of CD34, VASH1, and carbonic anhydrase 9 (CA9) between patients who achieved tumor clearance at operation (ypT0) and those with residual disease after cystectomy. There were 19 patients in the ypT0 group, while the remaining 21 patients had residual tumors at operation. Patients in the ypT0 group had high microvessel density (p=0.031), high VASH1 density (p<0.001), and stronger CA9 staining (p=0.046) than their counterparts. Multivariate analysis identified microvessel and VASH1 density as independent predictive factors for pathological ypT0 disease (p=0.043 and 0.002, respectively). The 5-year recurrence-free survival rate was higher in the high VASH1 density group than in the low VASH1 density group (66.3% vs. 33.3%, p=0.036). VASH1 density is a potential therapeutic biomarker for chemotherapy response in BCa.

Efficacy of radiotherapy in combined treatment of hepatocellular carcinoma patients with portal vein tumor thrombus: a real-world study

Background and aimsHepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) has an extremely poor prognosis. A previous study proved that low-dose radiotherapy (RT) could prolong the prognosis of HCC patients with PVTT. This study aims to explore the sensitivity of PVTT to RT treatment.MethodsPatients were selected based on imaging diagnosis of HCC accompanied by PVTT and received combined treatment of radiotherapy, antiangiogenic drugs and immune checkpoint inhibitors, followed by hepatectomy or liver transplantation from January 2019 to August 2022. The efficacy was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines and pathological assessment. The sensitivity of tumor cells to the treatment was compared between the primary tumor (PT)and PVTT by analyzing their residual tumor and pathologic complete remission (PCR) incidence.ResultsData from 14 patients were collected in the study. After combined treatment, the size of PVTT decreased more significantly than that of the primary tumor in the imaging study (p < 0.05). The residual cancer was significantly more restrictive than that of primary tumor in paired patients based on pathological measurement (p = 0.008). The PCR incidence of the primary tumor (21.42%) was significantly lower (p = 0.008) than that of PVTT in the pathologic study (78.57%).ConclusionPVTT is more sensitive to radiotherapy treatment than the primary tumor in patients with HCC. This combination therapy might be an effective option as a downstaging therapy for patients with HCC with PVTT.

Evaluation of neoadjuvant immunotherapy in resectable gastric/gastroesophageal junction tumors: a meta-analysis and systematic review.

Neoadjuvant therapy for resectable gastric cancer/gastroesophageal junction tumors is progressing slowly. Although immunotherapy for advanced gastric cancer/gastroesophageal junction tumors has made great progress, the efficacy and safety of neoadjuvant immunotherapy for locally resectable gastric cancer/gastroesophageal junction tumors have not been clearly demonstrated. Here, we conducted a systematic review and meta-analysis to assess the efficacy and safety of neoadjuvant immunotherapy and advance the current research. Original articles describing the safety and efficacy of neoadjuvant immunotherapy for resectable gastric cancer/gastroesophageal junction tumors published up until October 15, 2023 were retrieved from PubMed, Embase, the Cochrane Library, and other major databases. The odds ratios (OR) and 95% confidence intervals (CIs) were calculated for heterogeneity and subgroup analysis. A total of 1074 patients from 33 studies were included. The effectiveness of neoadjuvant immunotherapy was mainly evaluated using pathological complete remission (PCR), major pathological remission (MPR), and tumor regression grade (TRG). Among the included patients, 1015 underwent surgical treatment and 847 achieved R0 resection. Of the patients treated with neoadjuvant immunotherapy, 24% (95% CI: 19%-28%) achieved PCR and 49% (95% CI: 38%-61%) achieved MPR. Safety was assessed by a surgical resection rate of 0.89 (95% CI: 85%-93%), incidence of ≥ 3 treatment-related adverse events (TRAEs) of 28% (95% CI: 17%-40%), and incidence of ≥ 3 immune-related adverse events (irAEs) of 19% (95% CI: 11%-27%). Neoadjuvant immunotherapy, especially neoadjuvant dual-immunotherapy combinations, is effective and safe for resectable gastric/gastroesophageal junction tumors in the short term. Nevertheless, further multicenter randomized trials are required to demonstrate which combination model is more beneficial. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=358752, identifier CRD42022358752.

RC48-ADC combined with tislelizumab as neoadjuvant treatment in patients with HER2-positive locally advanced muscle-invasive urothelial bladder cancer: a multi-center phase Ib/II study (HOPE-03).

Bladder cancer with high expression of human epidermal growth factor receptor-2 (HER2) is related to pathological malignancy and poor prognosis. The standard care for muscle-invasive urothelial bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph node dissection. For HER2-positive MIBC, the efficacy of cisplatin-based NAC is unsatisfactory, and adverse reactions are inevitable or even intolerable. New regimens with higher efficiency and lower toxicity need to be explored in the neoadjuvant setting for this population. HOPE-03 is a multi-center, open-label, single-arm, phase Ib/II study aiming to evaluate the safety and efficacy of RC48-ADC (disitamab vedotin (DV)), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E, and tislelizumab (PD-1 antibody) as a novel neoadjuvant treatment combination in patients with HER2-positive locally advanced urothelial MIBC. Fifty-one patients with cT2-4bN0-3M0-1a pathology- and imaging-diagnosed HER2 positive (immunohistochemistry status 3+ or 2+ or 1+) MIBC were recruited. Of these patients, six were enrolled in the dose-escalation phase (three patients in the RC48-ADC 1.5 mg/kg group and three patients in the 2.0 mg/kg group), and 45 patients were enrolled in the phase II study (the expected recommended phase II dose for RC48-ADC was 2.0 mg/kg). Patients without disease progression received radical cystectomy or bladder-sparing therapies as their preference after neoadjuvant treatment. The primary endpoints were clinical complete remission rate (cCR rate; T0/Ta/Tis), pathological complete remission rate (pCR rate), and safety. The secondary endpoints were overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and quality of life. The HOPE-03 trial provides a description of the safety profile of RC-48 and tislelizumab combination in the neoadjuvant treatment of HER2-positive locally advanced urothelial MIBC, and the efficacy is explored as well in this population. https://www.chictr.org.cn/showproj.html?proj=137111, identifier ChiCTR2200060153.

Equivalent prognosis with no lymph node metastasis to pathological complete remission in patients with localized advanced esophageal cancer after neoadjuvant triplet chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by curative surgery: a single-center retrospective cohort study.

Adjuvant nivolumab therapy has become the standard therapy for patients with localized advanced esophageal cancer with non-pathological complete response after neoadjuvant chemoradiotherapy followed by curative surgery. However, the necessity of this therapy for patients after neoadjuvant chemotherapy (NAC) with docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen followed by surgery is unclear, and the prognosis of grouping based on the presence or absence of pathological tumor and lymph node findings has not been analyzed. Therefore, our study aimed to address these questions. This retrospective cohort study included patients with cT1N1-3M0 and cT2-3N0-3M0 esophageal cancer according to the Japanese Classification of Esophageal Cancer, 11th edition, who received NAC with DCF followed by curative surgery between 2008 and 2020 at Jichi Medical University Hospital. We divided patients with ypT0-3N0-3M0 into four histological groups, namely ypT0N0, ypT+N0, ypT0N+, and ypT+N+, and we evaluated overall survival as the primary outcome and the prognostic relationship of lymph node metastasis as the secondary outcome. A total of 101 patients were included in this study. Kaplan-Meier analysis showed that the curves of the ypT0N0 and ypT+N0 groups were almost identical, while they differed from the other two groups. The hazard ratio of ypN+ was 4.44 (95% confidence interval: 2.03-9.71; P<0.001). The prognosis of the ypT+N0 group after NAC with DCF followed by surgery was similar to that of pathological complete remission. Grouping patients according to pathological lymph node status is a reasonable predictor of prognosis.

Addition of immune checkpoint inhibitors to chemotherapy versus chemotherapy alone in patients with triple-negative breast cancer: A systematic review and meta-analysis.

Triple-negative breast cancer (TNBC) is a relatively common malignant tumor with high mortality rates. There are limited treatment options and current therapy regimens often fall short of providing positive outcomes. The development of immune checkpoint inhibitors (ICIs) have provided a vital treatment option although efficacy has varied. Here, we review patient response to current TNBC treatment with and without the addition of ICIs. A systematic search of PubMed, Cochrane, and EMBASE library databases was done to search eligible studies published from their inception through April 3, 2022. The primary outcome indicators used were progression-free survival (PFS), overall survival (OS), pathological complete response rate (pCR) and objective remission rate (ORR), while adverse events (AEs) were also analyzed. Publication bias and sensitivity analyses and were performed to evaluate the quality of assessment. Overall, the meta-analysis looked at seven randomized controlled trials (RCTs) that included 4631 patients with TNBC. Results showed an improvement in PFS for patients receiving ICI in addition to chemotherapy (CT) in both the intent-to-treat (ITT) population and PD-L1 positive patients. Increased pCR rates were observed in all patients irrespective of PD-L1 status as well as increased ORR in the ITT which was more notable in PD-L1 positive subjects. While significant improvement in OS was observed only in PD-L1 positive individuals, the use of ICIs plus CT resulted in severe adverse reactions, specifically immune-related. This study supports the increased efficacy of ICIs in combination with CT compared to CT alone in patients with TNBC, with the most notable benefit observed in PD-L1 positive patients. However, combination therapy increases the risk of adverse reactions which warrants further investigation.

Complete pathological remission and tertiary lymphoid structures are associated with the efficacy of resectable NSCLC receiving neoadjuvant chemoimmunotherapy: A double-center retrospective study

ABSTRACT This study aimed to investigate the relationship between complete pathological remission (PCR), tertiary lymphoid structure (TLS) maturation and expression and clinical outcomes of patients with resectable non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. Totally 80 patients with resectable NSCLC (stage IB-IIIB) receiving neoadjuvant chemoimmunotherapy were analyzed. We used the Kaplan-Meier method to plot survival curves and the log-rank test to compare differences. Among all patients included, 45 patients (56.25%) achieved major pathological response (MPR), including 30 patients (37.50%) with PCR. The proportion of patients diagnosed with stage IB, II, IIIA and IIIB was 1.25%, 10.00%, 52.50% and 36.25%, respectively. We divided patients into PCR group and non-PCR group respectively according to whether they achieved PCR. We found that patients achieving PCR had significantly improved disease-free survival (DFS) (mDFS: NR vs. 20.24 months, P = .020). TLS expression was low in 43 cases (53.75%) and high in 37 cases (46.25%). TLS maturation was low in 55 cases (68.75%) and high in 25 cases (31.25%). The DFS of patients with TLS high-maturation (34.07 vs. 22.30 months, P = .024) and TLS high-expression (34.07 vs. 22.30 months, P = .041) was significantly longer. In most subgroups, the PCR, TLS high-maturation and TLS high-expression group respectively achieved a better clinical outcome relative to the non-PCR, TLS low-maturation and TLS low-expression group. In patients with resectable NSCLC receiving neoadjuvant chemoimmunotherapy, the acquirement of PCR may predict better DFS. In addition, high expression and maturation of TLS may be prognostic factors.