Vascular Endothelial Growth Factor-C (VEGF-C) Expression Can Not Predict Pelvic Lymph Node Metastases and Response to Neo-adjuvant Chemotherapy in Bulky Cervical Cancer

Tumour Size ◽

Response To Treatment ◽

Chemotherapy Response ◽

The Difference ◽

Neo Adjuvant Chemotherapy ◽

Factor C

Objective: To assess whether VEGF-C expression can predict the response to neoadjuvant chemotherapy and pelvic lymphnode metastases in bulky cevical cancer. Methods: Seventeen cervical cancer stage IB2 and IIA2 cases during the period of July 2009 until June 2010 were collected consecutively and given neoadjuvant chemotherapy (NAC) PVB prior radical surgery. Response to treatment was evaluated based on the change of tumour size. VEGF-C expression was examined immunohistochemically at tumour biopsy before chemotherapy. The presence of lymphnode metastases histopathologically were obtained from pelvic lymphnode dissection. The difference and correlation of response and metastases on VEGF-C expression were analized statistically. The validity of the cut off percentage of immunopositive cells to VEGF-C to identify non responding and metastatic cases was calculated with the ROC. Multivariate analysis were done to determine the predictor of no response to chemotherapy. Results: Clinical response, using the RECIST version 1.1 criteria, was found in 41.18% cases and lymphnode metastases were found in 27.27% cases. VEGF-C was expressed in all cases. Statistically, there were no significant differences and correlation in response to treatment and pelvic lymphnode metastases on VEGF-C expression. At the cut off ≥ 76% immunopositivity to VEGF-C, the sensitivity to identify no response and the specificity to identify response to NAC are 70.00% and 71.43% respectively (LR+ 2.45 and LR- 0.42); whereas at the cut off ≥ 75% immunopositivity to VEGF-C, the sensitivity to identify lymphnode metastases and the specificity to identify no lymphnode metastases are 100.00% and 75.00% (LR+ 4.0 and LR- 0). With multivariate analysis using logistic regression, the cut off ≥ 76% immunopositive cells to VEGF-C were found to have positive coefficient, largest OR and statistic score, 1.93, 6.88 (96% CI OR 0.45; 104.34) and 41 respectively, to predict non responders in a prediction score model. Conclusion: VEGF-C expression on biopsy specimen bulky cervical cancers can not differentiate cases that respond to NAC and metastases to the pelvic lymphnode from that do not. The cut off ≥ 76% immunopositive cells to VEGF-C in a prediction model can be used as an alternative predictor to identify non responders. [Indones J Obstet Gynecol 2012; 36-3: 144-9] Keywords: bulky cervical cancer, neoadjuvant chemotherapy, response and metastases prediction, VEGF-C immunohistochemistry expression

Neoadjuvant Chemotherapy Followed by Surgery Versus Abdominal Radical Hysterectomy Alone for Oncological Outcomes of Stage IB3 Cervical Cancer—A Propensity Score Matching Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.730753 ◽

2021 ◽

Vol 11 ◽

Author(s):

Weili Li ◽

Wenling Zhang ◽

Lixin Sun ◽

Li Wang ◽

Zhumei Cui ◽

...

Keyword(s):

Cervical Cancer ◽

Multivariate Analysis ◽

Radical Hysterectomy ◽

Protective Factor ◽

Postoperative Radiotherapy ◽

Disease Free Survival ◽

Oncological Outcomes ◽

Sensitive Group

ObjectiveTo compare the 5-year overall survival (OS) and disease-free survival (DFS) of patients with cervical cancer who received neoadjuvant chemotherapy followed by surgery (NACT) with those who received abdominal radical hysterectomy alone (ARH).MethodsWe retrospectively compared the oncological outcomes of 1410 patients with stage IB3 cervical cancer who received NACT (n=583) or ARH (n=827). The patients in the NACT group were divided into an NACT-sensitive group and an NACT-insensitive group according to their response to chemotherapy.ResultsThe 5-year oncological outcomes were significantly better in the NACT group than in the ARH group (OS: 96.2% vs. 91.2%, respectively, p=0.002; DFS: 92.2% vs. 87.5%, respectively, p=0.016). Cox multivariate analysis suggested that NACT was independently associated with a better 5-year OS (HR=0.496; 95% CI, 0.281-0.875; p=0.015), but it was not an independent factor for 5-year DFS (HR=0.760; 95% CI, 0.505-1.145; p=0.189). After matching, the 5-year oncological outcomes of the NACT group were better than those of the ARH group. Cox multivariate analysis suggested that NACT was still an independent protective factor for 5-year OS (HR=0.503; 95% CI, 0.275-0.918; p=0.025). The proportion of patients in the NACT group who received postoperative radiotherapy was significantly lower than that in the ARH group (p<0.001). Compared to the ARH group, the NACT-sensitive group had similar results as the NACT group. The NACT-insensitive group and the ARH group had similar 5-year oncological outcomes and proportions of patients receiving postoperative radiotherapy.ConclusionAmong patients with stage IB3 cervical cancer, NACT improved 5-year OS and was associated with a reduction in the proportion of patients receiving postoperative radiotherapy. These findings suggest that patients with stage IB3 cervical cancer, especially those who are sensitive to chemotherapy, might consider NACT followed by surgery.

Association between the nucleosome footprint of plasma DNA and neoadjuvant chemotherapy response for breast cancer

npj Breast Cancer ◽

10.1038/s41523-021-00237-5 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Xu Yang ◽

Geng-Xi Cai ◽

Bo-Wei Han ◽

Zhi-Wei Guo ◽

Ying-Song Wu ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Cell Receptor ◽

Chemotherapy Response ◽

Breast Cancer Patients ◽

Plasma Dna ◽

Transcription Start Sites ◽

Response To Chemotherapy

AbstractGene expression signatures have been used to predict the outcome of chemotherapy for breast cancer. The nucleosome footprint of cell-free DNA (cfDNA) carries gene expression information of the original tissues and thus may be used to predict the response to chemotherapy. Here we carried out the nucleosome positioning on cfDNA from 85 breast cancer patients and 85 healthy individuals and two cancer cell lines T-47D and MDA-MB-231 using low-coverage whole-genome sequencing (LCWGS) method. The patients showed distinct nucleosome footprints at Transcription Start Sites (TSSs) compared with normal donors. In order to identify the footprints of cfDNA corresponding with the responses to neoadjuvant chemotherapy in patients, we mapped on nucleosome positions on cfDNA of patients with different responses: responders (pretreatment, n = 28; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 12) and nonresponders (pretreatment, n = 10; post-1 cycle, post-3/4 cycles, and post-8 cycles of treatment, n = 10). The coverage depth near TSSs in plasma cfDNA differed significantly between responders and nonresponders at pretreatment, and also after neoadjuvant chemotherapy treatment cycles. We identified 232 TSSs with differential footprints at pretreatment and 321 after treatment and found enrichment in Gene Ontology terms such as cell growth inhibition, tumor suppressor, necrotic cell death, acute inflammatory response, T cell receptor signaling pathway, and positive regulation of vascular endothelial growth factor production. These results suggest that cfDNA nucleosome footprints may be used to predict the efficacy of neoadjuvant chemotherapy for breast cancer patients and thus may provide help in decision making for individual patients.

Squamous cell carcinoma antigen: prognostic significance and role in the monitoring of neoadjuvant chemotherapy response in cervical cancer.

10.1200/jco.1994.12.11.2309 ◽

1994 ◽

Vol 12 (11) ◽

pp. 2309-2316 ◽

Cited By ~ 54

Author(s):

G Scambia ◽

P Benedetti Panici ◽

E Foti ◽

M Amoroso ◽

G Salerno ◽

...

Keyword(s):

Cervical Cancer ◽

Squamous Cell Carcinoma ◽

Response To Neoadjuvant Chemotherapy

Squamous Cell ◽

Locally Advanced ◽

Chemotherapy Response ◽

Advanced Cervical Cancer ◽

Squamous Cell Carcinoma Antigen ◽

Locally Advanced Cervical Cancer ◽

PURPOSE The aim of the study was to investigate the role of squamous cell carcinoma antigen (SCC) in the management of patients with locally advanced cervical cancer treated by neoadjuvant chemotherapy and radical surgery. PATIENTS AND METHODS SCC assay was performed with a radioimmunoassay kit in a series of 102 patients with locally advanced cervical cancer. The values of 2.5, 5, and 7 ng/mL were used to define SCC antigen positivity. The chi 2 and Fisher's exact test and the stepwise logistic regression were used to evaluate the distribution of marker values. Analysis of survival was performed using the Kaplan and Meier test and Cox multivariate regression analysis. RESULTS SCC levels were elevated in 65%, 45%, and 32% of patients with primary tumors for cutoff values of 2.5, 5, and 7 ng/mL, respectively. SCC pretreatment levels correlated with stage, tumor volume and lymph node status. In the multivariate analysis, SCC expression proved to be an independent predictor of response to neoadjuvant chemotherapy. SCC posttreatment levels were strongly related to chemotherapy response. Moreover, the overall correlation between the clinical course of the disease and the variation of SCC levels was 83%. In patients with squamous cell tumors, survival was significantly longer in SCC-negative cases compared with SCC-positive cases (P = .04). Moreover, in patients undergoing surgery after response to neoadjuvant chemotherapy, low SCC values were associated with better prognosis (P = .02). In the multivariate analysis, parametrial involvement and SCC status proved to retain an independent prognostic value. CONCLUSION Our data show that SCC assay may provide useful information to improve the prognostic characterization and disease monitoring of patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy.

Contrast-enhanced spectral mammography in the radiological assessment of response to neoadjuvant chemotherapy in breast cancer

Journal of Medical Science ◽

10.20883/medical.e521 ◽

2021 ◽

pp. e521

Author(s):

Anna Grażyńska ◽

Sofija Antoniuk ◽

Katarzyna Steinhof-Radwańska

Keyword(s):

Breast Cancer ◽

Magnetic Resonance Imaging ◽

Magnetic Resonance ◽

Residual Disease ◽

Tumour Size ◽

Breast Cancer Diagnosis ◽

Chemotherapy Response ◽

Resonance Imaging ◽

Contrast Enhanced

Accurate morphological assessment and measurement of the residual disease following neoadjuvant chemotherapy are vital for the effective surgical treatment in patients with breast cancer. Neoadjuvant chemotherapy response is measured by RECIST 1.1 criteria (Response Evaluation Criteria in Solid Tumors), and the classification of the specific therapeutic responses is based on the difference in the tumour size prior to and after chemotherapy. There are currently a few methods of imaging used in the assessment of the neoadjuvant chemotherapy response. Conventional mammography remains the most popular method, whereas magnetic resonance imaging is considered the most effective ones. Nonetheless, the available methods tend to be imperfect and limited, and therefore, new methods are constantly investigated. Contrast-enhanced spectral mammography is a relatively new method used in breast cancer diagnosis, which involves the phenomenon of neoangiogenesis of cancerous tumours, allowing contrast enhancement in the areas of vessel proliferation in the background of the surrounding breast tissue. Contrast-enhanced spectral mammography presents sensitivity similar to magnetic resonance imaging in breast cancer detection, and can be an efficient method used in monitoring neoadjuvant chemotherapy response.

Chemotherapy-elicited exosomal miR-378a-3p and miR-378d to promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling.

10.1200/jco.2021.39.15_suppl.e12615 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12615-e12615

Author(s):

Jin Zhang

Keyword(s):

Breast Cancer ◽

Drug Resistance ◽

Pathologic Complete Response ◽

Chemotherapeutic Agents ◽

Cell Counting ◽

Chemotherapy Response ◽

Mouse Tumor ◽

Serum Exosomes

e12615 Background: Not all breast cancer (BC) patients who receive neoadjuvant chemotherapy achieve a pathologic complete response (pCR), but the reasons for this are unknown. Previous studies have shown that exosomes produced in the tumor microenvironment in response to chemotherapy promote a chemotherapy-resistant phenotype in tumors. However, the role of BC chemo-elicited exosomes in regulating chemoresistance is poorly understood. Methods: Using commercial kits, serum exosomes were extracted from patients before neoadjuvant chemotherapy, after one cycle of chemotherapy and after four cycles of chemotherapy consisting of doxorubicin (DOX) and paclitaxel (PTX). Their miRNAs were sequenced, and the correlation between the sequencing results and chemotherapy effects was further verified by RT-qPCR using patient serum exosomes. Cell Counting Kit-8 (CCK-8) was used to detect chemosensitivity. Stemness was assessed by CD44+/CD24- population analysis and mammosphere formation assays. Chromatin immunoprecipitation (ChIP) experiments were performed to verify the binding of signal transducer and activator of transcription 3 (STAT3) to the promoter of miRNAs. Results: Here, we provide clinical evidence that chemotherapy-elicited exosomal miR-378a-3p and miR-378d are closely related to the chemotherapy response and that exosomes produced by BC cells after stimulation with DOX or PTX deliver miR-378a-3p and miR-378d to neighboring cells to activate WNT and NOTCH stemness pathways and induce drug resistance by targeting Dickkopf 3 (DKK3) and NUMB. In addition, STAT3, which is enhanced by zeste homolog 2 (EZH2), bound to the promoter regions of miR-378a-3p and miR-378d, thereby increasing their expression in exosomes. More importantly, chemotherapeutic agents combined with the EZH2 inhibitor tazemetostat reversed chemotherapy-elicited exosome induced drug resistance in a nude mouse tumor xenograft model. Conclusions: This study revealed a novel mechanism of acquired chemoresistance whereby chemotherapy activates the EZH2/STAT3 axis in BC cells, which then secrete chemotherapy-elicited exosomes enriched in miR-378a-3p and miR-378d. These exosomes are absorbed by chemotherapy-surviving BC cells, leading to activation of WNT and NOTCH stem cell pathways via the targeting of DKK3 and NUMB and subsequently resulting in drug resistance. Therefore, blocking this adaptive mechanism during chemotherapy may reduce the development of chemotherapy resistance and maximize the therapeutic effect.

Size of cervical lesion in locally advanced carcinoma cervix and response to neoadjuvant chemotherapy

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20194607 ◽

2019 ◽

Vol 8 (11) ◽

pp. 4254

Author(s):

Neetu Ahirwar

Keyword(s):

Tumour Size ◽

Locally Advanced ◽

Vascular Supply ◽

Cervical Lesion ◽

Carcinoma Cervix ◽

Advanced Carcinoma ◽

Treatment Volume ◽

Pre Treatment

Background: Recently neoadjuvant chemotherapy has started being considered for advanced stage of carcinoma cervix. Drug delivery to pelvic tumour is optimal with neoadjuvant chemotherapy since tumour vascular supply has not been damaged by any previous pelvic interference. Tumor size and parametrial involvement have been reported to be important predictor of NACT response. Objective of this study was to find out association between size of cervical lesion in locally advanced carcinoma cervix and response to neoadjuvant chemotherapy.Methods: The present prospective cohort study was carried out in the Department of Obstetrics and Gynaecology with the collaboration of Department of Radiotherapy, Chhatrapati Shahuji Maharaj Medical University Lucknow for a period of 1-year august 2010 to august 2011. 26 patients with histologically proven locally advanced carcinoma cervix were studied. In all cases Cisplatin 75 mg/m2 and paclitaxel 135 mg/m2 on day one was given at 14 days interval up to maximum of three courses. Evaluation of operability status was done two weeks after second course of chemotherapy. Those found operable were taken up for radical hysterectomy and rest were given 3rd course of chemotherapy. After two weeks of 3rd course again operability assessment was done and patient was taken up either for surgery or radiotherapy.Results: It was observed that out of 14 patients who had tumour size <4 cm, 9 (64.2%) responded completely (CR), 2 (14.2%) responded partially and 3 (21.4%) responded as SD while in 12 patients with tumour size >4 cm, 4 (33.3%) responded completely (CR) and rest 8 (66.6%) response was partial (PR).Conclusions: Response to chemotherapy was modified by pre-treatment volume of the tumour.

Feasibility of breast conservation after neoadjuvant taxae-based chemotherapy in locally advanced breast cancer

10.1200/jco.2009.27.15_suppl.e11627 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e11627-e11627

Author(s):

M. A. Aboziada ◽

M. I. El-Sayed ◽

D. W. Maximous ◽

M. E. Abdel-Wanis ◽

M. M. Bakr

Keyword(s):

Metastatic Cancer ◽

Locally Advanced Breast Cancer ◽

Tumour Size ◽

Locally Advanced ◽

Breast Conservation ◽

Hormonal Treatment ◽

Standard Of Care ◽

Cancer Breast ◽

Response To Chemotherapy

e11627 Background: Neoadjuvant chemotherapy is the standard of care of locally advanced cancer breast. Our study was aiming to evaluate the feasibility of breast conversation (BC) after neoadjuvant chemotherapy. Methods: Forty five patients had stage IIB and stage IIIA were selected to 3 cycles taxane-based neoadjuvant chemotherapy. Patient who had tumours ≤ 5cm underwent BC while patients who had tumour size >5cm underwent radical surgery. Negative margin is essential for BC. Adjuvant chemotherapy and 3-D radiotherapy ± hormonal treatment were given to all patients. Results: Thirty four patients had BC. Response to chemotherapy was the only statistically significant factor which influences the BC. Incidence of local recurrence was 5.9% for patients who had BC at a median follow up 24 months. Conclusions: Breast conservation is feasible in selected cases of locally advanced, non metastatic cancer breast. We recommend that patients who have tumour size ≤ 4cm after chemotherapy are the best candidates for BC. No significant financial relationships to disclose.

Neoadjuvant chemotherapy in operable breast cancer with docetaxel, doxorubicin, and cyclophosphamide (TAC) or TAC followed by vinorelbine and capecitabine (NX): Final results and analysis of markers predicting response to treatment

10.1200/jco.2009.27.15_suppl.524 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 524-524

Author(s):

J. Huober ◽

G. von Minckwitz ◽

C. Denkert ◽

A. Kleine-Tebbe ◽

E. Weiss ◽

...

Keyword(s):

Multivariate Analysis ◽

Clinical Response ◽

Remission Rate ◽

Univariate Analysis ◽

Early Response ◽

Response To Treatment ◽

Lymph Node Status ◽

Study Population ◽

Her 2

524 Background: The aim of this analysis was to determine the pathological complete remission rate (pCR) for the entire Gepartrio study population and to identify markers predicting response to NACT. Methods: The design of the Gepartrio study was described elsewhere (von Minckwitz et al.). Age at diagnosis, tumor size, lymph node status, estrogen (ER), progesterone (PgR), HER-2 status, histological type, and grade were assessed in uni- and multivariate analysis. Clinical response after 2 cycles TAC and pCR at surgery were used as efficacy endpoints. Results: 2072 pts were randomized depending on response after 2 cycles TAC. 1122 pts (54.2%) had a clinical response after 2 cycles and 385 (18.6 %) pCR. The highest pCR rate (60%) was observed in pts with triple neg tumors and < 40 years. In the HR pos/HER-2 pos pts the pCR rates were 17.6% vs. 9% for HR pos/HER-2 neg pts (p<0.001). In the HR neg subset absence of HER-2 overexpression (“triple neg tumors”) resulted in significantly improved pCR rates compared to the HR neg HER-2 pos subset (40.7% versus 31.6%, p=0.041). In univariate analysis predictors for both an early response and a pCR at surgery were age < 40 years, non T4 tumor, grade 3, neg hormone receptors (HR) and a triple neg status. Non lobular histology was only predictive for a pCR in univariate analysis. In multivariate analysis independent factors for early response were non T4 tu, tumors ≥ 40 mm, poor grading and neg HRs. Independent predictors for a pCR remained age < 40 years, poor grading, a non lobular subtype and triple neg tumors. Conclusions: The pCR rate for the whole study population of the Gepartrio trial was comparable to other neoadjuvant regimens. Markers identified as independent predictors may help in decision making for pts being considered for neoadjuvant chemotherapy. [Table: see text]

MRP1 but Not MDR1 Is Associated with Response to Neoadjuvant Chemotherapy in Breast Cancer Patients

Disease Markers ◽

10.1155/2013/728410 ◽

2013 ◽

Vol 34 (6) ◽

pp. 387-393 ◽

Cited By ~ 18

Author(s):

Mohsen Taheri ◽

Frouzandeh Mahjoubi

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Cancer Patients ◽

Histological Grade ◽

Chemotherapeutic Agents ◽

Response To Treatment ◽

Breast Cancer Patients ◽

Mrp1 Expression

A major problem in the treatment of breast cancer is the development of resistance to chemotherapeutic agents. Although the role of multidrug resistance 1 (MDR1) and multidrug resistance associated protein 1 (MRP1) in inducing drug resistance in many cancers has been widely investigated the clinical significance of expression of these genes in breast cancer remains unclear and the data is still controversial. We investigated the expression of MDR1 and MRP1 in breast cancer patients as well as the possible correlation between MDR1 and MRP1 and clinical response to chemotherapy. In the present study, MDR1 and MRP1 gene expression were investigated by real time reverse transcription polymerase chain reaction (RT-PCR) assay in 54 breast cancer tumors and in corresponding adjacent normal tissues before neoadjuvant chemotherapy. The expression level of MDR1 and MRP1 were significantly higher in breast tumors than normal breast tissues. Although a significant relationship was found between the MRP1 expression and response to treatment no association was observed between MDR1 expression and response to treatment. MDR1 and MRP1 expression levels have been shown to be independent of tumor size, histological grade and the status of progesterone or estrogen receptor.

Analysis of factors related to recurrence of paediatric hepatoblastoma -A single centre retrospective study

10.21203/rs.2.14548/v2 ◽

2019 ◽

Author(s):

Wei Yang ◽

Yiwei Chen ◽

Yijin Huang ◽

Huanmin Wang

Keyword(s):

Risk Factors ◽

Multivariate Analysis ◽

Retrospective Study ◽

Tumor Recurrence ◽

Tumour Size ◽

Alpha Fetoprotein ◽

Therapeutic Effects ◽

Significant Difference ◽

Prognostic Risk Factors

Abstract Purpose: This study was performed to identify risk factors associated with recurrence of hepatoblastoma. Methods: A retrospective study was conducted on 56 patients with hepatoblastoma from 2012 to 2015 in Beijing Children’s Hospital. PRETEXT stage, serum alpha fetoprotein (AFP) value, change trend of tumors after treatment and some other clinical characteristics were collected and analyzed. The comparison of independent variables that were not distributed normally was performed with the log-rank test. Results: 28 patients with tumor recurrence and 28 non-recurrence patients were included in this study, the median age at presentation was 46.5 (26, 71.5) months. There was a significant difference in the 3-year recurrence free survival (RFS) probability between the patients over 54 months and those younger than 54 months (p=0.007). After neoadjuvant chemotherapy, the chance of recurrence in PR patients was shown to be significantly lower than that in SD patients (p=0.004). The 3-year RFS of patients with a decrease in AFP of more than 60% after neoadjuvant chemotherapy was significantly higher than that of patients with a decrease rate of less than 60% (p=0.005). Postoperative follow-up revealed that patients whose postoperative AFP fell to normal levels within six months of the start of treatment had a three-year RFS of 68.6%, which is higher than that of patients whose AFP fell below the normal range after six months (p=0.0005). Finally, multivariate analysis by Cox regression showed that AFP that decreased by less than 60% and tumour size that decreased by less than 50% after neoadjuvant chemotherapy were significant independent prognostic risk factors for 3-year RFS. Other clinical features were not significantly associated with tumor recurrence in this study. Conclusion: Through this study, we concluded that the prognosis of childhood HB is related to the age at presentation and the response of chemotherapy. The results of the multivariate analysis showed that AFP that decreased by less than 60% and tumour size that decreased by less than 50% after neoadjuvant chemotherapy were significant independent prognostic risk factors. These findings can be helpful to evaluate therapeutic effects and predict prognosis. Key words: hepatoblastoma; alpha fetoprotein; risk factor