Effect Of Neoadjuvant Chemotherapy Research Articles

Neoadjuvant chemotherapy may be the best neoadjuvant therapy modality for non-metastatic pancreatic cancer: a population based study.

Currently, there are no studies showing which neoadjuvant therapy modality can provide better prognosis for patients after pancreatic cancer surgery. This study explores the optimal neoadjuvant therapy model by comparing the survival differences between patients with non-metastatic pancreatic cancer (cT1-4N0-1M0) who received neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NARCT). We retrospectively analyzed the clinical data of 723 patients with cT1-4N0-1M0 pancreatic cancer who received neoadjuvant therapy before surgery from the Surveillance, Epidemiology, and End Results (SEER) database. After propensity score matching (PSM), we compared the effects of NACT and NARCT on overall survival (OS) and cancer-specific survival (CSS) in patients with non-metastatic pancreatic cancer, and then performed subgroup analyze. Finally, we used univariate and multivariate Cox regression analysis to explore potential risk factors for OS and CSS in patients with non-metastatic pancreatic cancer treated with preoperative neoadjuvant therapy. Before PSM, mOS (30.0 months VS 26.0 months, P=0.122) and mCSS (30.0 months VS 26.0 months, P=0.117) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, but this was not statistically significant (P>0.05). After PSM, mOS (30.0 months VS 25.0 months, P=0.032) and mCSS (33.0 months VS 26.0 months, P=0.028) were better in patients with non-metastatic pancreatic cancer treated with NACT compared with NARCT, and this difference was statistically significant (P<0.05). Multivariate Cox regression analysis results showed that age, lymph node positivity, and NARCT were independent adverse prognostic factors for OS and CSS in patients with non-metastatic pancreatic cancer. The study results show that compared with NARCT, NACT is the best preoperative neoadjuvant therapy mode for patients with non-metastatic pancreatic cancer. This result still needs to be confirmed by more prospective randomized controlled trials.

Evaluation of Conservative Breast Surgery After Neoadjuvant Chemotherapy in Early Breast Cancer

Background: The breast cancer is a frequent type of cancers. It is associated with high mortality related to cancer in women. The treatment options transferred from radical surgery to less invasive operations. This was attributed to surgical advance and available neoadjuvant chemotherapy. Objective: This work aimed to evaluate the conservative breast surgery feasibility and outcome for early breast cancer received neoadjuvant chemotherapy (NACT) for downstaging. Patients and Methods: Thirty women (30) with early breast cancer were included between November 2022 and May 2023. All women were assessed in systematic manner by history, clinical, laboratory and radiological investigations before chemotherapy, before and after surgery. A true cut biopsy was drawn to estimate the histopathological nature. All surgeries were performed one and half months after the last session of NACT. A regular postoperative follow up was carried out up to six months. Any complications were recorded. Effect of NACT on the tumor grading was the primary outcome, while cosmetic results and patient satisfaction were the secondary outcomes. Results: Complications were in the form of wound infection, seroma and hematoma in 6.7%, 13.3% and 3.3% respectively. These were mild and treated conservatively. The excellent cosmetic result was achieved for 80.0% and excellent patient satisfaction was recorded for 60.0%. The effect of chemotherapy showed significant improvement of clinical and pathological post chemotherapy tumor size values when compared to clinical tumor size values before chemotherapy, the T1 grade (≤2cm) increased from 50% to 66.7%, while the T2 grade (&gt; 2cm &lt;5 cm) decreased from 50% to33.3%. Conclusion: NACT was associated with excellent response regarding tumor size reduction, negativity of lymph nodes as well as pathological response of early breast cancer, before breast conservation surgery (BCS). The BCS after NACT could be considered as a safe option with acceptable aesthetic outcome.

Assessment of Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Carcinoma Using Image-Guided Clip Placement.

Background The present study aims to evaluate the response of locally advanced breast carcinoma (LABC) to neoadjuvant chemotherapy (NACT) using image-guided clip placement based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Methods Thirty-four patients with LABC were included in the study. Consent for three-dimensional titanium clip placement (400/300/200 mm Liga clips) under local anesthesia with USG guidance was obtained. Serial sonographic/X-ray evaluations of tumor bed size were conducted before every cycle of NACT. All data were recorded in millimeters of concentric tumor regression/non-regression. Tumor regression in a concentric or Swiss cheese pattern and non-responders were evaluated. Assessment of the response to NACT was performed using RECIST criteria, dividing it into four categories. Tumor response was confirmed with computerized tomography (CT) conducted before and after the completion of NACT. Patients underwent surgical management, mostly modified radical mastectomy (MRM), as they had locally advanced breast carcinoma. Following MRM, the clips in the specimen guided the original site of the tumor for histopathological evaluation and response to chemotherapy. Results Tumor response was classified into four types: complete response (CR), partial response (PR), progressive disease (PD), and stable disease. RECIST 1.1 criteria were elaborated and defined. Data for all patients were entered into an Excel sheet (Microsoft Corporation, Redmond, Washington)to prepare a master chart, and the following observations were made and analyzed using SPSS software. The duration of chemotherapy for the study population ranged from 32 to 206 days, with a mean (±SD) of 111.82 (± 52.64) days and a median (IQR) of 81 (63, 158) days. The mean period between clip insertion and completion of NACT was 111.82 days. The baseline sum diameters and post-NACT diameters of the tumors were 70.50 (±13.60) mm before NACT and 17.75 (±17.20) mm after NACT. Hence, the mean size of the lump was statistically significantly lower after NACT, with a mean difference of 52.75 (p<0.05). The mean rate of reduction in tumor diameter was found to be 74.32% (±23.44%) based on RECIST 1.1 criteria. Pathological response was observed in all patients except for 8.8% of the patients. Clinical complete response was seen in 35.29% of patients, and partial response was observed in 52.92% of the patients based on RECIST 1.1 criteria. The study thus demonstrates the effectiveness of NACT in LABC, with a mean reduction in tumor diameter of 74.32%, assessed with the help of RECIST 1.1 criteria. Conclusion NACT for patients with LABC has shown a significant reduction in tumor size. NACT should be the initial mode of management for patients with LABC. RECIST 1.1 criteria are effective and can be used to assess tumor response to NACT. This has aided in the stratification of the response of NACT for further management through systemic therapy (adjuvant chemotherapy) after the surgical excision of the tumor.

Systematic Review of the Survival Outcomes of Neoadjuvant Chemotherapy in Women with Malignant Ovarian Germ Cell Tumors.

Randomized clinical trials assessing the efficacy of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer have predominantly included women with high-grade serous carcinomas. The response rate and oncological outcomes of NACT for malignant ovarian germ cell tumors (MOGCT) are poorly understood. This study aimed to examine the effects of NACT on women with MOGCT by conducting a systematic review of four public search engines. Fifteen studies were identified, and a further descriptive analysis was performed for 10 original articles. In those studies, most women were treated with a bleomycin, etoposide, and cisplatin regimen, and one to three cycles were used in most studies. Four studies comparing NACT and primary debulking surgery showed similar complete response rates (n = 2; pooled odds ratio [OR] 0.90, 95% confidence interval [CI] 0.15-5.27), comparable overall survival (n = 3; 87.0-100% versus 70.0-100%), disease-free survival (n = 3; 87.0-100% versus 70.0-100%), recurrence rate (n = 1; OR 3.50, 95%CI 0.38-32.50), and adverse events rate from chemotherapy between the groups. In conclusion, NACT may be considered for the management of MOGCT; however, possible candidates for NACT use and an ideal number of NACT cycles remain unknown. Further studies are warranted to validate the efficacy of NACT in advanced MOGCT patients.

Locally advanced thymoma; does neoadjuvant chemotherapy make a difference?

BackgroundRegardless of its rare occurrence, Thymoma remains the most frequently encountered primary tumor of the anterior mediastinum comprising about 50% of all masses in the region. Surgical resection, via thymectomy, remains the mainstay treatment modality. In locally advanced and borderline resectable tumors, neoadjuvant chemotherapy (NACT) may be utilized to increase the chance of R0 resection, raising the question of its efficacy and safety.MethodsDemographic and clinical data from patients who presented to a tertiary cancer center between January 2015–October 2021 with a diagnosis of thymoma and underwent curative surgical resection was collected. Computed tomography scan was used to delineate clinical staging, tumor size and to detect post-therapeutic variations in tumor burden. The response evaluation criteria in solid tumors (RECIST) was used to classify the effect of NACT on tumor burden. The pathological response was determined by measuring the percentage of necrotic tissue.ResultsA total of 23 patients were diagnosed with thymoma. Most patients were male with a mean age 46 (± 15) years at diagnosis. The most common clinical stage was stage II with 5 patients (22%). A total of 12 patients had NACT as compared to 11 patients who had upfront surgery. The mean change in tumor volume was 165 cm3 (p = 0.079) and the change in and maximum diameter was 1.53 ± 1.49 cm (p < 0.01). The effect of NACT on tumor burden based on RECIST criteria was minimal as 8 patients had stable disease. Based on pathological findings, the average necrotic portion of the tumor was 39.5% (p = 0.152). The overall survival rate is 95.65%, mean survival was 115 months (4–125). Recurrence occurred in 5 patients. The NACT group had a higher risk for recurrence (4; 33.3%) with a mean survival of 43.8 months compared to 59.6 months in those who did not receive induction therapy.ConclusionsThe exact role of induction chemotherapy in locally advanced thymoma patients remains controversial. NACT effect after utilizing radiological and pathological assessment tools was not found to significantly improve oncological outcomes compared to upfront surgery in locally advanced disease, with minimal radiologic and pathologic effect. To further demonstrate the impact of induction chemotherapy, we recommend multicentric collaborative studies.

Biomarker dynamics affecting neoadjuvant therapy response and outcome of HER2-positive breast cancer subtype

HER2+ breast cancer (BC) is an aggressive subtype genetically and biologically heterogeneous. We evaluate the predictive and prognostic role of HER2 protein/gene expression levels combined with clinico-pathologic features in 154 HER2+ BCs patients who received trastuzumab-based neoadjuvant chemotherapy (NACT). The tumoral pathological complete response (pCR) rate was 40.9%. High tumoral pCR show a scarce mortality rate vs subjects with a lower response. 93.7% of ypT0 were HER2 IHC3+ BC, 6.3% were HER2 IHC 2+/SISH+ and 86.7% of ypN0 were HER2 IHC3+, the remaining were HER2 IHC2+/SISH+. Better pCR rate correlate with a high percentage of infiltrating immune cells and right-sided tumors, that reduce distant metastasis and improve survival, but no incidence difference. HER2 IHC score and laterality emerge as strong predictors of tumoral pCR after NACT from machine learning analysis. HER2 IHC3+ and G3 are poor prognostic factors for HER2+ BC patients, and could be considered in the application of neoadjuvant therapy. Increasing TILs concentrations, lower lymph node ratio and lower residual tumor cellularity are associated with a better outcome. The immune microenvironment and scarce lymph node involvement have crucial role in clinical outcomes. The combination of all predictors might offer new options for NACT effectiveness prediction and stratification of HER2+ BC during clinical decision-making.

The effect of neoadjuvant chemotherapy on surgical site wound infection after immediate breast reconstruction in patients with breast cancer: A meta-analysis.

Using a meta-analysis approach, we conducted a comprehensive evaluation of the effect of neoadjuvant chemotherapy (NACT) on the incidence of surgical site wound infection during immediate breast reconstruction (IBR) following breast cancer. The aim was to provide evidence-based support for the prevention of wound surgical site infection during IBR after breast cancer surgery. Relevant literature on the effects of NACT on IBR in patients with breast cancer published up until May 2023, was retrieved from various databases, including PubMed, Cochrane Library, EMBASE, China National Knowledge Infrastructure (CNKI), Wanfang databases, and China Biology Medicine Database. Two researchers performed the literature screening, data collection, and quality assessment of the included studies independently. The meta-analysis was conducted using Stata version 17.0. Fourteen studies involving 3401 patients (599 in the intervention group and 2802 in the control group) were included in the analysis. The incidence of surgical site infection in the NACT group was higher than that in the control group, but the difference between the two groups was not statistically significant (7.17% vs. 4.85%, odds ratio: 1.02, 95% confidence interval: 0.70-1.50, p = 0.902). These findings suggest that NACT does not increase the risk of surgical site infection during IBR. However, owing to the variation in sample size and literature quality among the included studies, randomised controlled trials are needed to confirm the safety of IBR in patients receiving neoadjuvant chemotherapy.

Genomic and transcriptomic characterization of ovarian cancer under neoadjuvant and adjuvant chemotherapy.

e17571 Background: Neoadjuvant chemotherapy (NACT) has become a routine selection for late-staged ovarian cancer patients to reduce the tumor load before debulking surgery; and chemotherapy remains as the mainstream therapy for ovarian cancer. However, the effects of NACT on the cancer genome and the molecular determinates of tumor response to chemotherapy in ovarian cancer have not been characterized systematically. Methods: We obtained 121 clinical samples from 44 ovarian cancer patients (19 underwent NACT and 25 did not) and collected the key clinical features for these samples such as age, tumor stage, platinum-free interval, and platinum response. We then performed whole-exome sequencing for all the 121 samples and RNA-sequencing for 54 samples. We conducted a systematic comparative analysis between samples collected from the patients with and without NACT to characterize the effects of NACT on the cancer genome and transcriptomes. Focusing on the genomic and transcriptomic differences of treatment-naive samples between platinum sensitive and resistant patients, we also did a comparative analysis to identify molecular features that can predict the response to platinum. Results: We observed significantly elevated mutational signatures associated with platinum chemotherapy in the samples from patients who have undergone NACT. We also found increased microsatellite instability (MSI) in the post-NACT primary samples compared to treatment-naive ones. Interestingly, the prevalence of CCNE1 amplification significantly decreased in the post-NACT metastatic samples of patients. Consistently, the mRNA expression of CCNE1 appeared to down-regulated in such samples. Furthermore, the expression signature of cancer hallmarks related to this gene decreased in post-NACT metastatic samples, such as E2F targets, G2M checkpoint, and mitotic spindle. Remarkably, we found that homologous recombination deficiency (HRD) is a strong indicator for platinum sensitivity, which was also supported by HRD-associated mutational signatures. The expression signature of immune-related hallmarks was significantly upregulated in sensitive primary samples, including interferon alpha response, interferon gamma response, and IL6 JAK STAT3 signaling. Conclusions: Based on comprehensive profiling for genomic and transcriptomic characterization of a large cohort of ovarian cancer patients, we found that (i) NACT likely increased MSI and decreased prevalence of CCNE1 amplification; and (ii) a high HRD score and elevated immune-related expression signatures can strongly predict the sensitivity to platinum-based chemotherapy. These results lays a key foundation for develop novel, effective therapies for ovarian cancer.

Trends in the use of neoadjuvant chemotherapy for low-grade serous ovarian cancer in the United States.

5581 Background: Following the publication of randomized trials demonstrating its noninferiority, the use of neoadjuvant chemotherapy (NACT) for the treatment of advanced stage epithelial ovarian cancer has increased substantially in the United States. However, low-grade serous ovarian cancers (LGSOC) respond poorly to chemotherapy compared with high-grade serous carcinoma. For LGSOC, clinical guidelines favor surgical resection prior to adjuvant therapy. This study seeks to describe patterns and temporal trends in the use of NACT for LGSOC. Methods: This cohort study identified women treated for stage III or IV LGSOC in a Commission on Cancer accredited cancer program between January 1, 2004, to December 31, 2020. We fit Poisson regression models to evaluate temporal trends in the use of NACT and cytoreductive outcomes, and to identify factors associated with receipt of NACT. We considered age, race/ethnicity, Charlson Comorbidity Index, year of diagnosis, insurance status, income, facility type, census region, and stage as potentially associated with NACT. Due to the high rate of missingness in data describing cytoreductive outcomes after surgery, we undertook both multiply imputed and complete case analyses. Results: A total of 3,343 patients received treatment for LGSOC during the study period. The mean age at diagnosis was 54.8 year (SD 15.5) and most patients (82%) were white. The most commonly observed upfront treatment strategies were cytoreductive surgery followed by adjuvant chemotherapy (63.7%) and surgery without chemotherapy (19.2%). Treatment with NACT followed by interval cytoreductive surgery (13.0%) or chemotherapy alone (4.1%) were less common. The proportion of patients who received NACT increased from 9.5% in 2004 to 25.9% in 2020, corresponding to a statistically significant annual percent change (APC) of 7.2% (95% CI 5.6-8.9). Increasing decade of age (risk ratio [RR] 1.15; 95% CI 1.09-1.23), increasing calendar year of diagnosis (RR 1.07; 95% CI 1.05-1.08) and stage IV disease (RR 2.66; 95% CI 2.3-3.07) were associated with a higher probability of receiving NACT. Other variables were not associated with receipt of NACT. Among patients who underwent cytoreductive surgery, the proportion who achieved no gross residual disease remained stable over the course of the study period in both complete case (APC 0.5%; 95% CI -1.8 to 0.9) and multiply imputed (APC -0.1%; 95% CI -1.6 to 1.3) analyses. Conclusions: The use of NACT for patients with LGSOC increased substantially from 2004 to 2020. Despite increased utilization of NACT, the rate of complete cytoreduction has not improved over the study period, possibly calling into question the effectiveness of NACT in reducing tumor burden in this setting.

Abstract LB195: Immunotherapies that repolarize macrophages and CD4 T cells enhance the effect of chemotherapy in high-grade serous ovarian cancer

Abstract We asked if single-cell RNA sequencing (scRNA-seq) analysis of tumor immune cells in high-grade serous ovarian cancer (HGSOC) would reveal ways to enhance effects of neo-adjuvant chemotherapy (NACT). Analysis of 64,097 immune cells from seven HGSOC omental metastases showed that positive effects of NACT on immune responses were counterbalanced by induction of immunosuppressive mechanisms, especially related to antigen presentation and Treg activity. We identified stabilin-1 (Clever-1) on macrophages and FOXP3 in Tregs as targets and validated actions of their inhibitors in vitro. ScRNA-seq analysis of 69,781 cells from chemotherapy-treated syngeneic mouse HGSOC tumors showed significant agreement with the patient results. Combinations of chemotherapy with anti-stabilin1 antibody and/or FOXP3 inhibitor (AZD8701), FOXP3i, significantly increased median survival of mice with established peritoneal disease. Long-term survivors (300 days+) were resistant to tumor rechallenge. Analysis of bulk RNA sequencing data from treated murine tumors confirmed our hypothesis and suggested potential mechanisms to explain the anti-tumor response seen in the murine models. Tumors treated with chemotherapy plus anti-stabilin1 antibody showed significant enrichment of anti-tumor macrophage signature and antigen presentation pathway compared to chemotherapy alone. Tumors treated with chemotherapy plus FOXP3i in combination with anti-stabilin1 antibody showed significant upregulation of antigen presentation, T cell activation and cytotoxicity and T helper 1 differentiation pathways. There was significant reduction in FOXP3 positive cells and significant increase of Tbet positive cells in FOXP3i treated murine tumors suggesting repolarization of naive T cells in the tumor microenvironment towards a more anti-tumor T helper phenotype. As there are early phase clinical trials of FOXP3 inhibitor and anti-stabilin1 (Clever-1) antibody in patients with advanced cancer, these results suggest ways of improving response to chemotherapy not only in HGSOC but in other cancers that are treated by NACT. Citation Format: Samar Elorbany, Chiara Berlato, Larissa Carnevalli, Eleni Maniati, Jun Wang, Simon Barry, Ranjit Manchanda, Julia Kzhyshkowska, Frances Balkwill. Immunotherapies that repolarize macrophages and CD4 T cells enhance the effect of chemotherapy in high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB195.

DNA Methylation and Prospects for Predicting the Therapeutic Effect of Neoadjuvant Chemotherapy for Triple-Negative and Luminal B Breast Cancer.

Despite advances in the diagnosis and treatment of breast cancer (BC), the main cause of deaths is resistance to existing therapies. An approach to improve the effectiveness of therapy in patients with aggressive BC subtypes is neoadjuvant chemotherapy (NACT). Yet, the response to NACT for aggressive subtypes is less than 65% according to large clinical trials. An obvious fact is the lack of biomarkers predicting the therapeutic effect of NACT. In a search for epigenetic markers, we performed genome-wide differential methylation screening by XmaI-RRBS in cohorts of NACT responders and nonresponders, for triple-negative (TN) and luminal B tumors. The predictive potential of the most discriminative loci was further assessed in independent cohorts by methylation-sensitive restriction enzyme quantitative PCR (MSRE-qPCR), a promising method for the implementation of DNA methylation markers in diagnostic laboratories. The selected most informative individual markers were combined into panels demonstrating cvAUC = 0.83 (TMEM132D and MYO15B markers panel) for TN tumors and cvAUC = 0.76 (TTC34, LTBR and CLEC14A) for luminal B tumors. The combination of methylation markers with clinical features that correlate with NACT effect (clinical stage for TN and lymph node status for luminal B tumors) produces better classifiers, with cvAUC = 0.87 for TN tumors and cvAUC = 0.83 for luminal B tumors. Thus, clinical characteristics predictive of NACT response are independently additive to the epigenetic classifier and in combination improve prediction.

Neoadjuvant chemotherapy in advanced epithelial ovarian cancer by histology: A SEER based survival analysis.

To evaluate the prognostic effect of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC) patients with different histological subtype. Stage III/IV EOC patients diagnosed between 2010 and 2018 were identified from the surveillance, epidemiology, and end results database (SEER) database and stratified by histological subtype. Kaplan-Meier analysis was used for the assessment of overall survival (OS) cause-specific survival (CSS) before and after matching for baseline characteristics between NACT and primary debulking surgery (PDS) groups. Cox proportional risk model was conducted to identify independent prognostic factors. A total of 13,582 patients were included in the analysis. Of them, 9505 (74.50%) received PDS and 3253 (25.50%) received NACT. Overall, an inferior OS and CSS was observed among patients with high-grade serous carcinoma (HGSC) receiving NACT, while NACT served as a protective factor in clear cell carcinoma and carcinosarcoma in both original cohorts and adjusted cohorts. For other histo-subtypes, PDS showed survival benefit over NACT in certain cohorts of models. Prognostic effect of NACT in advanced EOC differed from pathological subtypes. Although it served as a risk factor for HGSC, patients with less common subtypes may benefit from NACT.

Risk model and factors for prediction of response to neoadjuvant chemotherapy in patients with advanced gastric cancer-a two-center cohort study

ObjectiveDue to inconsistency in neoadjuvant chemotherapy (NACT) response in advanced gastric cancer (GC), the indications remain the source of controversy. This study focused on identifying factors related to NACT chemosensitivity and providing the best treatment for GC cases.MethodsClinical data in 867 GC cases treated with neoadjuvant chemotherapy were downloaded from two medical centers between January 2014 and December 2020, and analyzed by logistic regression and the least absolute shrinkage and selection operator (LASSO) for identifying potential factors that predicted NACT response and might be incorporated in constructing the prediction nomogram.ResultsAfter the inclusion and exclusion criteria were applied, totally 460 cases were enrolled, among which, 307 were males (66.74%) whereas 153 were females (33.26%), with the age of 24–77 (average, 59.37 ± 10.60) years. Consistent with RECIST standard, 242 patients were classified into effective group (PR or CR) while 218 were into ineffective group (PD or SD), with the effective rate of 52.61%. In training set, LASSO and logistic regression analysis showed that five risk factors were significantly associated with NACT effectiveness, including tumor location, Smoking history, T and N stages, and differentiation. In terms of our prediction model, its C-index was 0.842. Moreover, calibration curve showed that the model-predicted results were in good consistence with actual results. Validation based on internal and external validation sets exhibited consistency between training set results and ours.ConclusionsThis study identified five risk factors which were significantly associated with NACT response, including smoking history, clinical T stage, clinical N stage, tumor location and differentiation. The prediction model that exhibited satisfying ability to predict NACT effectiveness was constructed, which may be adopted for identifying the best therapeutic strategy for advanced GC by gastrointestinal surgeons.

Neoadjuvant chemotherapy for patients with international federation of gynecology and obstetrics stages IB3 and IIA2 cervical cancer: a multicenter prospective trial

BackgroundPreoperative neoadjuvant chemotherapy (NACT) has been widely used in developing countries for the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB3 and IIA2 cervical cancer. However, the effectiveness of NACT and treatment options for NACT-insensitive patients have been concerning. This study will assess prognostic differences between NACT and primary surgery treatment (PST), determine factors associated with prognosis, and explore better adjuvant treatment modalities for NACT-insensitive patients.MethodsThis study analyzed clinical characteristics, pathological characteristics, treatment options, and follow-up information of 774 patients with FIGO stages IB3 and IIA2 cervical cancer from 28 centers from January 2016 to October 2019 who participated in a multicenter, prospective, randomized controlled trial.ResultsFor patients undergoing NACT, the 5-year OS and PFS rate was 85.8 and 80.5% respectively. They were similar in the PST group. There was no significant difference in OS and PFS between clinical response (CR)/partial response (PR) groups and stable disease (SD)/progressive disease (PD) groups. Apart from deep cervical invasion (p = 0.046) affecting OS for patients undergoing NACT, no other clinical and pathological factors were associated with OS. 97.8% of NACT-insensitive patients opted for surgery. If these patients did not have intermediate- or high-risk factors, whether they had undergone postoperative adjuvant therapy was irrelevant to their prognosis, whereas for patients with intermediate- or high-risk factors, adjuvant chemotherapy resulted in better PFS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.019) and OS (chemotherapy vs. no therapy, p < 0.001; chemotherapy vs. radiotherapy, p = 0.002).ConclusionsNACT could be a choice for patients with FIGO stages IB3 and IIA2 cervical cancer. The main risk factor influencing prognosis in the NACT group is deep cervical invasion. After systematic treatment, insensitivity to NACT does not indicate a poorer prognosis. For NACT-insensitive patients, Chinese prefer surgery. Postoperative adjuvant therapy in patients with no intermediate- or high-risk factors does not improve prognosis, and chemotherapy in patients with intermediate- and high-risk factors is more effective than radiation therapy and other treatments.Trial registrationThe study was prospectively registered on ClinicalTrials.gov (NCT03308591); date of registration: 12/10/2017.

560P Neoadjuvant camrelizumab plus chemotherapy in patients with locally advanced cervical cancer (NACI): A prospective, single-arm, phase II trial

Neoadjuvant chemotherapy (NACT) is an emerging approach for locally advanced cervical cancer (LACC), while two-thirds of patients (pts) respond to it and pts without response benefit little. PD-1 inhibitors have exhibited promising role in recurrent or metastatic cervical cancer. Additionally, preclinical evidence for the activation and synergistic effects of NACT on PD-1 inhibitors supports the superiority of neoadjuvant immunotherapy. We designed this phase II study to evaluated the efficacy and safety of preoperative PD-1 inhibitor camrelizumab combined chemotherapy in pts with LACC.

A Comparison Between Neoadjuvant Chemotherapy and Neoadjuvant Chemoradiotherapy in Treating Esophageal Carcinoma: A Study at a Tertiary Care Cancer Center in Suburban India.

Background and objectiveEsophageal carcinoma remains a disease associated with high mortality rates among patients even after receiving treatment. Management with surgery alone offers a five-year survival of only 20%. Hence adjuvant and neoadjuvant therapies were instituted to treat this condition along with surgery. Neoadjuvant chemoradiotherapy (NACRT) followed by surgery is currently the standard of care. Neoadjuvant chemotherapy (NACT) is also recommended by some authors as a method of adequate care. There is a scarcity of studies in the literature comparing NACRT with NACT. In light of this, we employed the criteria of pathological response as a primary endpoint to compare the effectiveness of NACT and NACRT in treating esophageal carcinoma.Materials and methodsA total of 50 patients with esophageal cancer having Eastern Cooperative Oncology Group (ECOG) scores 0-2 with cancer stages cT2-T4a, cN0-N1, and cM0 were enrolled. The patients were further classified into two groups of 25 each. While one group received chemotherapy using inj. paclitaxel and carboplatin (NACT group), the other was managed with inj paclitaxel and carboplatin as well as 42 Gy of fractionated irradiation (NACRT group). Six weeks after the last dose of radiation or three weeks after chemotherapy, they were evaluated and offered transthoracic esophagectomy (TTE).ResultsSquamous cell carcinoma was found in 39 (78%) cases and 11 (22%) cases had adenocarcinoma. Pathologically complete or near-complete responses were seen in 42% of patients in the NACRT group and 22% in the NACT group.ConclusionWhile NACT and NACRT are both effective therapies for esophageal cancers, NACRT offers better tumor regression compared to NACT. Given the higher rates of complete or near-complete response in the NACRT group, NACRT is likely to offer higher overall survival rates than NACT.

Abstract 6106: The effect of neoadjuvant chemotherapy on tumor immune microenvironment in ovarian cancer

Abstract Background: Ovarian cancer (OC) is a highly lethal gynecologic malignancy, neoadjuvant chemotherapy (NACT) with interval de-bulking surgery (IDS) is an established strategy for woman with advanced epithelial ovarian cancer (EOC). Tumor infiltrating lymphocytes (TILs) play an important role in the pathogenesis of OC. However, the effect of NACT on tumor immune microenvironment (TIME) has not been evaluated. Methods: All patients underwent NACT with IDS. Formalin-fixed paraffin-embedded tissue samples were collected from biopsy specimens and the corresponding post-NACT surgical specimens. The densities and percentage of specific TILs [CD8+, CD3+, CD4+, CD20+, tumor associated macrophages (TAMs), dim CD56+NK, bright CD56+NK, PD-1+ etc.] within the TIME were analyzed by multiplex immunohistochemistry (3DMedcines Inc.). Serum CA 125 was measured 3-weekly per protocol and evaluated the response to NACT using GCIG CA125 response criteria. Results: A total of 28 patients were enrolled in this study with planned IDS after NACT. Of 25 patients evaluated by GCIG CA125 response criteria, 76% (19/25) had a CA125 response. In CA125 response patients, we observed significant recruitments of the densities and percentage of CD8+ in tumor, percentage of PD-1+ cell in tumor after-NACT vs before-NACT (34.85/mm3 vs 110.54/mm3, p=0.0258; 0.50% vs 1.73%, p=0.0132; 0.53% vs 2.66%, p=0.0576, respectively), while no significant change was found in TAMs, NK cells and CD20+ cells. However, in CA125 non-response patients, the TILs in tumor did not change significantly. Conclusion: NACT could release the tumor associated antigen by killing tumor cells for uptake by tumor-infiltrating dendritic cells and promote the infiltration of CD8+ and PD-1+ T lymphocyte in CA125 response OC patients. Given the limited clinical prognostic information and the number of patients in this study, the results of this study will need confirmation in larger studies in the future. Citation Format: Guangming Cao, Dingchao Hua, Lina Cui, Xiaochen Zhao, Shuzhen Wang, Lei Zhu. The effect of neoadjuvant chemotherapy on tumor immune microenvironment in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6106.

The tumor immune microenvironment correlates with neoadjuvant chemotherapy response in high-grade serous ovarian cancer.

e17605 Background: Platinum-based neoadjuvant chemotherapy (NACT) plus interval debulking surgery (IDS) and adjuvant chemotherapy has been an established alternative for advanced epithelial ovarian cancer (EOC). The chemotherapy response score (CRS) has been applied to assess the efficacy of NACT in high-grade serous ovarian cancer (HGSOC). The purpose of this study was to assess the effect of NACT on tumor immune microenvironment (TIME) of HGSOC, and the correlation between the TIME and CRS. Methods: All patients underwent NACT with IDS. Formalin-fixed paraffin-embedded tissue samples were collected from pretreatment biopsy specimens and the corresponding post-NACT surgical specimens. The densities and percentage of various cell populations within the TIME were analyzed by multiplex immunohistochemistry (3DMedcines Inc.), including specific tumor infiltrating lymphocytes (TILs) (CD8+T cell, FOXP3+CD4+Treg cell and CD20+B cell), tumor associated macrophages (TAMs), NK cells (CD56 dim and CD56 bright). Patients were divided into three groups according to CRS based on pathological reaction of surgical specimens: CRS1 shows no or minimal response, CRS2 shows moderate response and CRS3 usually shows complete or near-complete response. Statistical analyses were performed using GraphPad Prism 7.0. P &lt; 0.05 was considered statistically significant. Results: A total of 25 HGSOC patients were enrolled in this study, 32% (8/25) of patients with CRS 1, 64% (16/25) with CRS 2, and 4% (1/25) with CRS 3. After NACT, patients with CRS 2 or 3 had a significant increase of the densities of CD20+B cells in stroma (pre-NACT 15.71/mm3 vs. post-NACT 87.82/mm3, p = 0.048). We also observed borderline significant increases of percentage of CD20+B cells, the densities and percentage of CD8+T cells in stroma after NACT (pre-NACT vs. post-NACT, 0.32% vs.1.54%, 56.35/mm3 vs. 311.35/mm3, 0.95% vs. 5.48%, respectively). Meanwhile, no significant change in CD4+T, TAMs and NK cells. In patients with CRS 1, we observed a significant increase of the densities and percentage of CD4+FOXP3+Treg in stroma (pre-NACT vs. post-NACT, 1.38/mm3 vs. 19.75/mm3, p = 0.01; 0.04% vs. 0.41%, p = 0.017, respectively), while CD8+T, CD20+B, TAMs and NK cells did not change significantly. Additionally, we found a significant difference in CD56 bright NK infiltration when comparing CRS 2 or 3 group with CRS1 group in post-NACT (0.5/mm3 vs.12/mm3, p = 0.049; 0.005% vs. 0.23%, p = 0.048). Conclusions: These data suggest immune infiltrate in TIME may serve as a biomarker to predict response to NACT in HGSOC. The infiltration of CD8+ T and CD20+ B cell was more pronounced in CRS2 or 3, while the enhanced infiltration of FOXP3+CD4+Treg cells is associated with immunosuppressive TIME and poor response (CRS1). The mechanism of lymphocyte regulation is not completely understood, thereby deserving further investigation.

Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers

Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR-negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time.This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails.

Breast Thermography as an Adjunct Tool to Monitor the Chemotherapy Response in a Triple Negative BIRADS V Cancer Patient: A Case Study.

Prior studies have reported that breast thermography is a potential adjunct tool to mammography in early cancer detection, especially in developing countries with limited medical facilities. This non-invasive, safe, and painless screening tool can reduce the mortality due to cancer by early detection and monitoring. This prospective study aims to analyze changes in static breast thermograms of a BIRADS V category breast cancer patient to assess the response to Neoadjuvant chemotherapy (NACT) in locally advanced cancer and to compare with thermograms of a BIRADS II category benign patient. Breast thermograms of the malignant and benign patients in five different views were taken using FLIR E40 thermal camera under strict acquisition protocols. Details of the patient along with the thermograms were recorded pre and post NACT. There is a qualitative reduction in the warm region of the surface after the first cycle of chemotherapy treatment. Thermal, fractal, and statistical analysis of thermograms is performed for both patients. In the patient with aggressive ductal carcinoma, the difference in the mean surface temperature between contralateral breasts is high, which is reduced after the first cycle of NACT. This preliminary study indicates that breast thermography can potentially be used as an effective non-invasive, non-contact, and radiation-free tool to analyze the effect of NACT on patients with different stages of breast cancer. This study also signifies the role of the thermography technique in reaching a largely rural population with limited medical resources for early cancer screening.