Second Cycle Of Neoadjuvant Chemotherapy Research Articles

8099 Pembrolizumab Induced Autoimmune Diabetes: An Abrupt Virulent Onset

Abstract Disclosure: H.F. Belal: None. N. Shaykh: None. A. Rajesh: None. J.M. Chehade: None. Background: Pembrolizumab is a programmed cell death protein 1 inhibitors (PD-1i) approved for the treatment of many solid cancers. Although thyroid abnormalities are among the most common endocrine adverse effects associated with PD-1i, insulin-dependent diabetes mellitus can also occur in up to 1% of patients treated with PD1-i.[1] Clinical Case: A 70-year-old female with past medical history of non-toxic multi-nodular goiter and surgical hypothyroidism was diagnosed with gastric cancer. She had no pancreatic abnormality on PET scan. Her management included four cycles of neo-adjuvant chemotherapy: fluorouracil, cisplatin, trastuzumab and pembrolizumab. She had no personal history of gestational diabetes. Prior to initiating neo-adjuvant chemotherapy her A1c was 5.9%. She was not prescribed any anti-diabetic medications. Her grandmother had type 2 diabetes mellitus. On exam her BMI was 23.73 kg/m². She had no acanthosis nigrans, skin tags or abdominal striae. Eighteen days after completing her second cycle of neo-adjuvant chemotherapy, she presented to the emergency department with nausea, vomiting, polyuria and confusion and was found to be in DKA. Her A1c during admission was 7.1%. Imaging revealed no pancreatitis. Labs showed suppressed C-peptide <0.1 ng/mL (1.1-4.4) in the setting of blood glucose 283 mg/dL (71-99). Her GAD-65 antibody was elevated at 902 U/mL (0.0-5.0). She was diagnosed with PD-1i induced autoimmune diabetes mellitus (PD-1i DM) and subsequently treated with basal and prandial insulin. Conclusion: The mechanism of PD-1i DM is unclear. A proposed mechanism is aberrant T cell activation towards pancreatic islet cells. One study found that 59% of patients with PD-1i DM presented with DKA.[1] In this study, the median time of PD-1i DM onset was 20 weeks after the first treatment cycle. Additionally, 40% of these patient had at least one positive pancreatic autoantibody. A recent meta-analysis found the relative risk of PD-1i DM to be 1.56 (95% CI = 0.95-2.57, P = 0.08).2 This relative risk increased to 2.06 (95% CI = 0.48-8.86, P = 0.33) when PD-1i were combined with cytotoxic T lymphocyte antigen-4 inhibitors.

Early prediction of neoadjuvant chemotherapy efficacy for mass breast cancer based on dynamic contrast‐enhanced magnetic resonance imaging radiomics

AbstractRadiomics uses automated algorithms to extract high‐order features from images, which can contribute to clinical decisions such as therapeutic efficacy evaluation. We assessed the value of a dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI)‐based radiomics model for predicting pathological complete response (pCR) after a second cycle of neoadjuvant chemotherapy (NAC) in patients with mass breast cancer. We retrospectively analyzed data from 149 patients with mass breast cancer who underwent NAC between January 2017 and December 2022. Using DCE‐MRI, before NAC and after a second cycle of NAC, the least absolute shrinkage and selection operator and logistic regression (LR) algorithms were applied for feature selection and radiomics modeling. We found significant differences in two clinical imaging features (molecular subtypes, background parenchymal enhancement changes) and two radiomics features. Clinical and radiomics features were employed to build clinical, radiomics, and combined models to predict pCR. The LR model that combined clinical and radiomics features had an area under the curve of 0.811, higher than that for the imaging or radiomics model. Our findings suggest that a combined model based on imaging and radiomics features can improve early prediction of NAC efficacy for patients with mass breast cancer.

Early prediction of pathological response to neoadjuvant chemotherapy of breast tumors: a comparative study using amide proton transfer-weighted, diffusion weighted and dynamic contrast enhanced MRI.

To examine amide proton transfer-weighted (APTw) combined with diffusion weighed (DWI) and dynamic contrast enhanced (DCE) MRI for early prediction of pathological response to neoadjuvant chemotherapy in invasive breast cancer. In this prospective study, 50 female breast cancer patients (49.58 ± 10.62 years old) administered neoadjuvant chemotherapy (NAC) were enrolled with MRI carried out both before NAC (T0) and at the end of the second cycle of NAC (T1). The patients were divided into 2 groups based on tumor response according to the Miller-Payne Grading (MPG) system. Group 1 included patients with a greater degree of decrease in major histologic responder (MHR, Miller-Payne G4-5), while group 2 included non-MHR cases (Miller-Payne G1-3). Traditional imaging protocols (T1 weighted, T2 weighted, diffusion weighted, and DCE-MRI) and APTw imaging were scanned for each subject before and after treatment. APTw value (APTw0 and APTw1), Dmax (maximum diameter, Dmax0 and Dmax1), V (3D tumor volume, V0 and V1), and ADC (apparent diffusion coefficient, ADC0 and ADC1) before and after treatment, as well as changes between the two times points (ΔAPT, ΔDmax, ΔV, ΔADC) for breast tumors were compared between the two groups. APT0 and APT1 values significantly differed between the two groups (p = 0.034 and 0.01). ΔAPTw values were significantly lower in non-MHR tumors compared with MHR tumors (p = 0.015). ΔDmax values were significantly higher in MHR tumors compared with non-MHR tumors (p = 0.005). ADC0 and ADC1 values were significantly higher in MHR tumors than in non-MHR tumors (p = 0.038 and 0.035). AUC (Dmax+DWI + APTw) = AUC (Dmax+APTw) > AUC (APTw) > AUC (Dmax+DWI) > AUC (Dmax). APTw imaging along with change of tumor size showed a significant potential in early prediction of MHR for NAC treatment in breast cancer, which might allow timely regimen refinement before definitive surgical treatment.

Longitudinal trajectory of amplitude of low-frequency fluctuation changes in breast cancer patients during neoadjuvant chemotherapy–A preliminary prospective study

Longitudinal trajectory of amplitude of low-frequency fluctuation changes in breast cancer patients during neoadjuvant chemotherapy–A preliminary prospective study

Early Assessment of Neoadjuvant Chemotherapy Response Using Multiparametric Magnetic Resonance Imaging in Luminal B-like Subtype of Breast Cancer Patients: A Single-Center Prospective Study

This study aimed to evaluate the performance of multiparametric breast magnetic resonance imaging (mpMRI) for predicting response to neoadjuvant chemotherapy (NAC) in patients with luminal B subtype breast cancer. The prospective study included thirty-five patients treated with NAC for both early and locally advanced breast cancer of the luminal B subtype at the University Hospital Centre Zagreb between January 2015 and December 2018. All patients underwent breast mpMRI before and after two cycles of NAC. Evaluation of mpMRI examinations included analysis of both morphological (shape, margins, and pattern of enhancement) and kinetic characteristics (initial signal increase and post-initial behavior of the time-signal intensity curve), which were additionally interpreted with a Göttingen score (GS). Histopathological analysis of surgical specimens included grading the tumor response based on the residual cancer burden (RCB) grading system and revealed 29 NAC responders (RCB-0 (pCR), I, II) and 6 NAC non-responders (RCB-III). Changes in GS were compared with RCB classes. A lack of GS decrease after the second cycle of NAC is associated with RCB class and non-responders to NAC.

Changes in the tumor oxygenation but not in the tumor volume and tumor vascularization reflect early response of breast cancer to neoadjuvant chemotherapy

BackgroundBreast cancer neoadjuvant chemotherapy (NACT) allows for assessing tumor sensitivity to systemic treatment, planning adjuvant treatment and follow-up. However, a sufficiently large number of patients fail to achieve the desired level of pathological tumor response while optimal early response assessment methods have not been established now. In our study, we simultaneously assessed the early chemotherapy-induced changes in the tumor volume by ultrasound (US), the tumor oxygenation by diffuse optical spectroscopy imaging (DOSI), and the state of the tumor vascular bed by Doppler US to elaborate the predictive criteria of breast tumor response to treatment.MethodsA total of 133 patients with a confirmed diagnosis of invasive breast cancer stage II to III admitted to NACT following definitive breast surgery were enrolled, of those 103 were included in the final analysis. Tumor oxygenation by DOSI, tumor volume by US, and tumor vascularization by Doppler US were determined before the first and second cycle of NACT. After NACT completion, patients underwent surgery followed by pathological examination and assessment of the pathological tumor response. On the basis of these, data regression predictive models were created.ResultsWe observed changes in all three parameters 3 weeks after the start of the treatment. However, a high predictive potential for early assessment of tumor sensitivity to NACT demonstrated only the level of oxygenation, ΔStO2, (ρ = 0.802, p ≤ 0.01). The regression model predicts the tumor response with a high probability of a correct conclusion (89.3%). The “Tumor volume” model and the “Vascularization index” model did not accurately predict the absence of a pathological tumor response to treatment (60.9% and 58.7%, respectively), while predicting a positive response to treatment was relatively better (78.9% and 75.4%, respectively).ConclusionsDiffuse optical spectroscopy imaging appeared to be a robust tool for early predicting breast cancer response to chemotherapy. It may help identify patients who need additional molecular genetic study of the tumor in order to find the source of resistance to treatment, as well as to correct the treatment regimen.

Abstract PS13-43: The utility of PET-CT after the second cycle of neoadjuvant chemotherapy for monitoring early metabolic change to predict pathologic response

Abstract INTRODUCTION Neoadjuvant chemotherapy (NAC) is increasingly utilized in the treatment of Breast Cancer to downsize the tumour, improve surgical outcome and to achieve a complete pathological response (pCR). Current regimes result in response rates of 40-80% depending on the subtype of the tumour and the presence of pCR, noted in 13-26% patients, is considered an indicator of excellent prognosis. An additional advantage of NAC is the assessment of the in vivo chemo-responsiveness of the tumor.FDG-PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) provides morphologic as well as functional imaging. Preliminary studies suggest it provides a more accurate evaluation of tumour response compared to other techniques. Moreover, studies suggest its utility in identifying non-responders early during NAC so as to enable a switch to an alternate more effective regimen, thereby preventing avoidable toxicity associated with an ineffective drug regimen.In this study, we evaluated metabolic changes on FDG-PET after 2 cycles of NAC to predict pathological response to NAC. PATIENTS AND METHODS A prospective cohort of patients with newly diagnosed, non-metastatic, T1-4, N1-2/3 breast cancer, undergoing NAC from October 2012 to December 2019 at a tertiary referral center, were entered in this study. The tumor size was assessed by the same surgeon at baseline and after every cycle of NAC. FDG-PET/CT was performed before commencement of NAC (PET1) and after the 2nd cycle of NAC (PET2) and the early metabolic response (ΔSUV max i.e. change in maximum standardized uptake value) was determined. All patients underwent surgery on completion of NAC and the pathological response following surgery served as the reference standard for the evaluation of the therapy response on FDG-PET/CT. Patients were classified into Responders [pCR and Minimal Residual Disease (MRD)] and Non-responders [Gross Residual Disease (GRD)] as per the classification of Honkoop et al. Receiver operating characteristic analysis was performed to identify an optimal threshold value of reduction rate (RR) of maximum standardized uptake values (ΔSUVmax) to accurately predict pathological response. RESULTS Out of 135 patients, 4 patients had bilateral cancer, resulting in 139 breast lesions assessed at baseline by FDG PET CT of which 51.07% were Luminal, 21.58% HER2 + and 27.34% TNBC. The mean age was 49 years (range 27-72), 54.81% were premenopausal, 45.19% post-menopausal, 85 (61.15%) were stage II cancers and 54 (38.84%) had stage III cancers. The overall pCR rate was 24.46%, 65 (46.76%) were Responders (pCR+MRD) and 74 (53.23%) Non-responders (GRD). The mean PET1 SUVmax of the tumors in Responder group was 14.5 and of Non-responder group was 9.4. The mean PET2 SUVmax for Responders was 4.28 and Non-responders was 7.52. The RR after the second course of NAC (ΔSUV), was significantly higher for Responders, 62.38% (+24.79) as compared to Non-responders 25.81% (+57.57), (p <0.0001). The optimal ΔSUV threshold to discriminate between Responders and Non-responders was 51% (69.35% sensitivity; 69.12% specificity) with area under the curve being 0.744. The negative predictive value for histopathologic Non-responders was 71.2 (CI 62.2- 78.8). CONCLUSIONS Metabolic change in FDG/PET-CT after 2 cycles of NAC can predict pathological response and, a ΔSUVmax of more than 51%, can differentiate Responders from Non- responders. Early determination of Non-responders could help identify a group which may benefit from an early change to an alternate regimen. Citation Format: Vinay Deshmane, Anuja Raniwala, Abhiyutthan Singh, Sachin Almel, Natasha Singh, Anita Bhaduri, Raj Jatale. The utility of PET-CT after the second cycle of neoadjuvant chemotherapy for monitoring early metabolic change to predict pathologic response [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-43.

Dysphagia predict the response to second cycle neoadjuvant chemotherapy in first cycle no response esophageal carcinoma.

After the first-cycle of neoadjuvant chemotherapy (NAC), many patients with esophageal squamous cell carcinoma (ESCC) experience a stable disease (SD)/progressive disease (PD) response. Clinically, SD patients are recommended to receive a second cycle of NAC, and PD patients are recommended to undergo surgery if possible. However, we found some PD tumors shrank after a second-cycle of NAC. Some first-cycle SD patients may develop PD after second-cycle NAC and lose the chance of surgery. Thus, how to predict the response to second-cycle NAC for first-cycle SD/PD patients is important for clinical practice. This retrospective single-center study was approved by the Institutional Review Board at the Affiliated Cancer Hospital of Zhengzhou University/Henan Cancer Hospital. We retrospectively reviewed patients with ESCC who had NAC and evaluated SD by computed tomography (CT) scan after the first-cycle between March 9, 2013 and October 24, 2016. Univariate and multivariate analyses of the clinical parameters were performed to identify markers predictive of a clinically response by using IBM-SPSS version 23. There were 64 patients included in the study. Thirty-one first-cycle NAC-SD/PD patients (48.4%) showed a response after second-cycle NAC, which was significantly correlated with alleviated dysphagia (P=0.006) and smoking (P=0.025). In the multivariate analyses, alleviated dysphagia [odds ratio (OR) 3.978; 95% confidence interval (CI), 1.335-11.856; P=0.013] was identified as the only independent predictive factor for tumor response after second-cycle of NAC for first-cycle SD/PD patients. Alleviated dysphagia might be a useful factor to predict the response to second-cycle NAC for first-cycle SD/PD patients.

Influence of incomplete neoadjuvant chemotherapy on esophageal carcinoma.

Neoadjuvant chemotherapy (NAC) involving two cycles of cisplatin plus fluorouracil is recommended in Japan as a standard treatment for resectable, locally advanced esophageal squamous cell carcinoma (ESCC). We have encountered patients who were administered incomplete chemotherapy because of adverse events or the patient's refusal of treatment. Here, we retrospectively investigated the influence on perioperative outcomes and long-term prognosis of patients with ESCC who underwent complete (two cycles) or incomplete (one cycle) NAC. We retrospectively investigated 133 patients with locally advanced ESCC of the thoracic esophagus who underwent NAC. We compared the perioperative results and prognoses of patients who underwent complete or incomplete NAC because of adverse events or the patient's refusal of treatment. Of 133 patients, 37 patients did not receive the second cycle of NAC; the remaining 96 patients received the second cycle of NAC as scheduled. There were no significant differences in the clinical backgrounds, surgical results, or operative morbidity rates between the groups. Patients in both groups were similarly administered postoperative chemotherapy regimens. There was no significant difference in disease-free survival or overall survival. We suggest that perioperative outcomes and long-term prognosis of patients with locally advanced ESCC were not significantly influenced, even if the patients did not receive a complete cycle of NAC. When certain adverse events occur after the first cycle of NAC, we believe that it is nevertheless possible to discontinue chemotherapy.

Early Prediction of Response to Neoadjuvant Chemotherapy Using Dynamic Contrast-Enhanced MRI and Ultrasound in Breast Cancer.

ObjectiveTo determine the diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and DCE ultrasound (DCE-US) for predicting response to neoadjuvant chemotherapy (NAC) in breast cancer patients.Materials and MethodsThis Institutional Review Board-approved prospective study was performed between 2014 and 2016. Thirty-nine women with breast cancer underwent DCE-US and DCE-MRI before the NAC, follow-up DCE-US after the first cycle of NAC, and follow-up DCE-MRI after the second cycle of NAC. DCE-MRI parameters (transfer constant [Ktrans], reverse constant [kep], and leakage space [Ve]) were assessed with histograms. From DCE-US, peak-enhancement, the area under the curve, wash-in rate, wash-out rate, time to peak, and rise time (RT) were obtained. After surgery, all the imaging parameters and their changes were compared with histopathologic response using the Miller-Payne Grading (MPG) system. Data from minor and good responders were compared using Wilcoxon rank sum test, chi-square test, or Fisher's exact test. Receiver operating characteristic curve analysis was used for assessing diagnostic performance to predict good response.ResultsTwelve patients (30.8%) showed a good response (MPG 4 or 5) and 27 (69.2%) showed a minor response (MPG 1–3). The mean, 25th, 50th, and 75th percentiles of Ktrans and Kep of post-NAC DCE-MRI differed between the two groups. These parameters showed fair to good diagnostic performance for the prediction of response to NAC (AUC 0.76–0.81, p ≤ 0.007). Among DCE-US parameters, the percentage change in RT showed fair prediction (AUC 0.71, p = 0.023).ConclusionQuantitative analysis of DCE-MRI and DCE-US was helpful for early prediction of response to NAC.

Decreased background parenchymal enhancement of the contralateral breast after two cycles of neoadjuvant chemotherapy is associated with tumor response in HER2-positive breast cancer.

Background Several recent studies have focused on the association between background parenchymal enhancement (BPE) and tumor response to neoadjuvant chemotherapy (NAC), but early prediction of tumor response based on BPE has yet not been investigated. Purpose To retrospectively investigate whether changes in the BPE of the contralateral breast following NAC could help predict tumor response in early stage HER2-positive breast cancer. Material and Methods Data from 71 patients who were diagnosed with unilateral HER2 positive breast cancer and then underwent NAC with trastuzumab before surgery were analyzed retrospectively. Two experienced radiologists independently categorized the patients' levels of BPE of the contralateral breast into four categories (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) at baseline and after the second cycle of NAC. After undergoing surgery, 34 patients achieved pathologic complete response (pCR) and 37 patients had residual disease (non-pCR). The association between BPE and histopathologic tumor response was analyzed. Result The level of BPE was higher in premenopausal than post-menopausal women both at baseline and after the second cycle of NAC ( P < 0.005). A significant reduction in BPE ( P < 0.001) was observed after the second NAC cycle; however, a more obvious decrease in BPE was identified in premenopausal relative to post-menopausal women ( P = 0.041). No significant association was identified between pCR and baseline BPE ( P = 0.287). However, after the second NAC cycle, decreased BPE was significantly associated with pCR ( P = 0.003). Conclusion For HER2-positive patients, changes in BPE may serve as an additional imaging biomarker of treatment response at an early stage.

Texture analysis based on contrast-enhanced MRI can predict treatment response to neoadjuvant chemotherapy of breast cancer

Objective: To investigate whether texture analysis based on contrast-enhanced MRI can predict pathological complete response of locally advanced breast cancer undergoing neoadjuvant chemotherapy(NAC). Methods: Forty-seven patients with breast cancer undergone neoadjuvant chemotherapy from January 2015 to February 2016 were divided into pathological complete response (pCR) group or non-pathological complete response (non-pCR) group based on surgical pathology. Their parameters of texture analysis based on MRI before neoadjuvant chemotherapy and after 2 cycles of treatment were analyzed. Parameters(Energy, Entropy, Inertia, Correlation, Inverse Difference Moment)before and after 2 cycles of NAC between pCR and non-pCR groups were compared using Student t or Wilcoxon rank sum test. The diagnostic performance of different parameters was judged by the receiver-operating characteristic (ROC) curve analysis. Results: The post-NAC value was significantly different from that of pre-NAC (all P<0.05). Pre-treatment parameters (Energy, Entropy, Inertia, Correlation, Inverse Difference Moment) were 78.58×10(-5)(55.64×10(-5), 135.23×10(-5)), 10.06 ± 1.02, 7 993.91±2 428.10, (4.76±0.99) ×10(-5) and (18.10±4.13) ×10(-3) in pCR group, and 76.84×10(-5) (48.68×10(-5), 154.15×10(-5)), 10.28±1.26, 7 184.77 (4 938.03, 9 974.04), (5.21±2.01) ×10(-5) and (17.68±5.87) ×10(-3) in non-pCR group. No significant difference was found between both groups. (P>0.05 for all). At the end of the second cycle of NAC, parameters(Energy, Entropy, Inertia, Correlation, Inverse Difference Moment) were (542.11±361.04) ×10(-5,) 7.95±1.28, 16 765.08±97 06.56, (0.43±0.07) ×10(-5,) and (12.18±9.82) ×10(-3) in pCR group, and 133.00×10(-5) (79.80×10(-5,) 239.00×10(-5)), 9.29±1.46, 7 916.64(6 418.89, 10 934.40), (0.38±0.08) ×10(-5) and (14.80±5.06) ×10(-3) in non-pCR group. At the end of the second cycle of NAC, there was significant difference in the parameters (Energy, Entropy, Inertia, Correlation) and Δparameters (ΔEnergy, ΔEntropy, ΔInertia, ΔInverse Difference Moment) between both groups (P<0.05 for all). The area under curve (AUC) of post-treatment ΔEntropy was 0.81, which was the largest one among parameters. Sensitivity of ΔEntropy for predicting pCR was 75.0% and specificity was 85.7%, respectively. Conclusion: Texture analysis based on dynamic contrast-enhanced MRI can predict early treatment response in primary breast cancer.

Thermal tomography for monitoring tumor response to neoadjuvant chemotherapy in women with locally advanced breast cancer.

Background & AimsThis study aims to analyze the feasibility and predictive value of thermal tomography (TT) for monitoring early treatment response in patients with locally advanced breast cancer (LABC) receiving neoadjuvant chemotherapy (NAC).MethodsPatients with LABC who were due to receive six cycles of NAC were examined by TT prior to NAC, the second cycle of NAC, the fourth cycle of NAC and surgery. Changes in TT parameters and ultrasonography were correlated with pathologic response to NAC, and the predictive value was assessed.ResultsForty-four patients were evaluable for response (25 pathologic responders and 19 nonresponders). As early as after the first cycle of NAC, changes in the TT parameters ΔTs, ΔTn, and ΔTa correlated significantly with pathologic response (P < 0.05). The best predictor of pathologic response after the 6th cycle of NAC was TT (area under the receiver operating characteristic curve, 0.794), as opposed to cross-sectional areas and the longest diameter by ultrasonography.ConclusionsTT allows for monitoring early tumor response to NAC and can predict pathologic response in the early stages of therapy. Therefore, TT could be used as a novel imaging modality to monitor NAC treatment.

Early Evaluation of Relative Changes in Tumor Stiffness by Shear Wave Elastography Predicts the Response to Neoadjuvant Chemotherapy in Patients With Breast Cancer.

Neoadjuvant chemotherapy plays an important role in comprehensive therapy for breast cancer, but response prediction is imperfect. Shear wave elastography (SWE) is a novel technique that can quantitatively evaluate tissue stiffness. In this study, we sought to investigate the application value of SWE for early prediction of the response to neoadjuvant chemotherapy in patients with breast cancer. We prospectively evaluated tumor stiffness in 62 patients with breast cancer using SWE, which was performed at baseline and after the second cycle of neoadjuvant chemotherapy. After chemotherapy, all of the patients underwent surgery. We investigated the correlations between the relative changes in tumor stiffness (Δ stiffness) after 2 cycles of chemotherapy and the pathologic response to the therapy. Compared with baseline values, tumor stiffness after 2 cycles of neoadjuvant chemotherapy was significantly decreased in responders (P < .001) but not in nonresponders (P = .172). The Δstiffness was significantly higher in responders (-42.194%) than in nonresponders (-23.593%; P = .001). As determined at either the baseline or after the second cycle of chemotherapy, tumor stiffness was significantly lower in responders than in nonresponders (P = .033 and .009, respectively). The Δ stiffness threshold for distinguishing between responders and nonresponders was -36.1% (72.92% sensitivity and 85.71% specificity). Furthermore, correlating Δ stiffness with clinical and pathologic characteristics, we found that estrogen and progesterone receptor expression showed statistically significant correlations with Δ stiffness (estrogen receptor, P = .008; progesterone receptor, P = .023). Early evaluation of relative changes in tumor stiffness using SWE could effectively predict the response to neoadjuvant chemotherapy in patients with breast cancer and might indicate better therapeutic strategies on a timelier basis.

Role of the Intravoxel Incoherent Motion Diffusion Weighted Imaging in the Pre-treatment Prediction and Early Response Monitoring to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

The aim of this study was to explore whether intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) can probe pre-treatment differences or monitor early response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC).Thirty-six patients with locally advanced breast cancer were imaged using multiple-b DWI with 12 b values ranging from 0 to 1000 s/mm2 at the baseline, and 28 patients were repeatedly scanned after the second cycle of NAC. Subjects were divided into pathologic complete response (pCR) and nonpathologic complete response (non-pCR) groups according to the surgical pathologic specimen. Parameters (D, D∗, f, maximum diameter [MD] and volume [V]) before and after 2 cycles of NAC and their corresponding change (Δparameter) between pCR and non-pCR groups were compared using the Student t test or nonparametric test. The diagnostic performance of different parameters was judged by the receiver-operating characteristic curve analysis.Before NAC, the f value of pCR group was significantly higher than that of non-pCR (32.40% vs 24.40%, P = 0.048). At the end of the second cycle of NAC, the D value was significantly higher and the f value was significantly lower in pCR than that in non-pCR (P = 0.001; P = 0.015, respectively), whereas the D∗ value and V of the pCR group was slightly lower than that of the non-pCR group (P = 0.507; P = 0.676, respectively). ΔD was higher in pCR (−0.45 × 10–3 mm2/s) than that in non-pCR (−0.07 × 10−3 mm2/s) after 2 cycles of NAC (P < 0.001). Δf value in the pCR group was significantly higher than that in the non-pCR group (17.30% vs 5.30%, P = 0.001). There was no significant difference in ΔD∗ between the pCR and non-pCR group (P = 0.456). The prediction performance of ΔD value was the highest (AUC [area under the curve] = 0.924, 95% CI [95% confidence interval] = 0.759–0.990). When the optimal cut-off was set at −0.163 × 10−3 mm2/s, the values for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were up to 100% (95% CI = 66.4–100), 73.7% (95% CI = 48.8–90.9), 64.3% (95% CI = 35.6–86.0), and 100% (95% CI = 73.2–99.3), respectively.IVIM-derived parameters, especially the D and f value, showed potential value in the pre-treatment prediction and early response monitoring to NAC in locally advanced breast cancer. ΔD value had the best prediction performance for pathologic response after NAC.

Compliance With Neoadjuvant Chemotherapy in T4 Oral Cancers: Place, Person, Socioeconomic Status, or Assistance

PurposeApproximately 15% to 20% of our patients with head and neck cancer receiving neoadjuvant chemotherapy (NACT) discontinue therapy because of various nonmedical reasons. We sought to analyze the factors associated with treatment default and noncompliance among these patients.Patients and MethodsWe performed a retrospective analysis of patients with T4 oral cancer treated with NACT between January 2011 and December 2012. We included patients who discontinued treatment for nonmedical reasons before the second cycle of NACT. The factors analyzed were income, education, socioeconomic status, age, sex, place of residence, habits, and payment pattern (government supported or personal capacity). Pearson χ2 test was used to identify significant factors associated with noncompliance.ResultsOf 486 patients, 91 patients (18.7%) were noncompliant. Percentages of noncompliant patients in the age groups < 30, between 30 and 60, and > 60 years were 25.0%, 17.4%, and 25.5%, respectively (P = .27). Percentages of noncompliance in patients residing within the city, same state, or different state were 20.7%, 20.9%, and 17.1%, respectively (P = .44). Noncompliance rates were 20.3%, 15.7%, 18.1%, and 22.5% in upper middle, lower middle, upper lower, and lower economic strata, respectively (P = .60). Similarly, there was no significant difference in noncompliance according to occupation, education level, payment pattern, sex, or habits.ConclusionOur analysis failed to identify any specific significant factor associated with noncompliance with NACT among our patients with T4 oral cancers.

Correlation between the expression of S100A4 and the efficacy of TAC neoadjuvant chemotherapy in breast cancer.

The aim of this study was to investigate the correlation between the expression of S100A4 and the efficacy of neoadjuvant chemotherapy in breast cancer. A total of 65 patients with invasive breast cancer were treated with neoadjuvant chemotherapy using the TAC regimen. The expression of S100A4 was detected by an immunohistochemical two-step method prior to treatment, after 2 cycles of chemotherapy and after 4 cycles of chemotherapy. Pathological evaluations of the chemotherapy were performed using the Miller and Payne (MP) grading system and their correlation with the changes of S100A4 expression during and after the treatment were explored. Between pre-neoadjuvant chemotherapy and 4 cycles post-chemotherapy, there was a significant difference in the expression of S100A4 (P<0.05); S100A4 expression was associated with neoadjuvant chemotherapy. However, between pre-neoadjuvant chemotherapy and 2 cycles post-chemotherapy, there was no significant difference in the expression of S100A4 (P>0.05). The intensity and changes of S100A4 expression were positively correlated with the efficacy of neoadjuvant chemotherapy (r=0.259, P<0.05). When patients with an MP grade of I or II following the second cycle of neoadjuvant chemotherapy were continually treated with the original chemotherapy for another 2 cycles, the desired effect was generally not achieved. S100A4 may be used as a predictor of the efficacy of neoadjuvant chemotherapy in breast cancer, guiding the formulation of individualized programs to improve the effectiveness of the treatment. For patients with an MP grade level of I or II after 2 cycles of neoadjuvant chemotherapy, the use of alternative chemotherapy regimens should be considered.

⁹⁹mTc-3PRGD₂ SPECT to monitor early response to neoadjuvant chemotherapy in stage II and III breast cancer.

Monitoring of response to neoadjuvant chemotherapy (NCT) is important for optimal management of patients with breast cancer. (99m)Tc-3PRGD2 SPECT is a newly developed imaging modality for evaluating tumor vascular status. In this study, we investigated the application of (99m)Tc-3PRGD2 SPECT in evaluating therapy response to NCT in patients with stage II or III breast cancer. Thirty-three patients were scheduled to undergo (99m)Tc-3PRGD2 SPECT at baseline, after the first and second cycle of NCT. Four patients had extremely low (99m)Tc-3PRGD2 uptake at baseline, and were not included in the subsequent studies. Changes in tumor to nontumor (T/N) ratio were compared with pathological tumor responses classified using the residual cancer burden system. Receiver operator characteristic analysis was used to compare the power to identify responders between the end of the first and the end of the second cycle of NCT. The impact of breast cancer subtype on (99m)Tc-3PRGD2 uptake was evaluated. The correlation between (99m)Tc-3PRGD2 uptake and pathological tumor response was also evaluated in each breast cancer subtype. Surgery was performed after four cycles of NCT and pathological analysis revealed 18 responders and 15 nonresponders. In patients with clearly visible (99m)Tc-3PRGD2 uptake at baseline, the sensitivity, specificity, and negative predictive value of (99m)Tc-3PRGD2 SPECT were 86.7 %, 85.7 % and 86.7 % after the first cycle of NCT, and 92.9 %, 93.3 % and 93.3 % after the second cycle, respectively. Among these patients, the HER-2-positive group demonstrated both higher T/N ratios and a greater change in T/N ratio than patients with other breast cancer subtypes (P < 0.05). A strong correlation was found between changes in T/N ratio and pathological tumor response in the HER-2-positive group (P < 0.03). (99m)Tc-3PRGD2 SPECT seems to be useful for determining the pathological tumor response in patients with stage II or III breast cancer undergoing NCT, especially those with the HER-2-positive subtype.

Can FDG-PET/CT predict early response to neoadjuvant chemotherapy in breast cancer?

Can FDG-PET/CT predict early response to neoadjuvant chemotherapy in breast cancer?

Abstract P4-02-03: FDG PET/CT for early monitoring of response to neoadjuvant chemotherapy in breast cancer patients.

Abstract Introduction: Neoadjuvant chemotherapy (NAC), initially used only for locally advanced breast cancer, is now commonly used in patients with operable but large breast cancer or unfavorable tumor/breast size index because increases the chances of performing breast conservative surgery (BCS) instead of mastectomy in this group of patients. Patients and Methods: This is a prospective unicenter trial. FDG PET/CT were performed in 40 patients at baseline and after the second cycle of NAC. The level and relative changes in standardized uptake value (SUV) of FDG uptake were assessed regarding their ability to predict histopathologic response. Pathologic complete response (pCR) was defined as no malignant cells (no invasive ductal carcinoma and no ductal carcinoma in situ) identifiable in sections from the site of the tumor in the breast and in the axillary lymph node. Results: This prospectively study analyzed forty patients undergoing NAC, all female, age ranged 27–64 years (mean 41.0 years and median 38 years), all tumors were invasive ductal carcinoma, histological tumor grade 1, 2 and 3 were present respectively at 5%, 38.5% and 100% of the sample and nuclear grade 2 and 3 were present respectively at 12.5% and 87.5%. Estrogen receptor was positive in 60% of patients and the progesterone receptor was positive in 47.5% of patients. Her 2 was overexpressed in 12 patients (30%). Phenotype in this sample had the following distribution: 12.5% luminal A (5 patients), 50% Luminal B (20 patients: 14 patients with Ki-67&amp;gt; 14% and 6 cases with HER 2 overexpression), 15 % HER 2 (6 patients) and cases triple negative 9 (22.5%). size of the primary tumor ranged from 4.10 cm to 12.0 cm (mean 7.10 cm). The size of the primary tumor ranged from had a mean of 6.7 cm and a median of 6.0 cm. This group showed great uniformity in relation to primary chemotherapy. NAC with cyclophosphamide and adriamycin were administered to 38 patients. In this study, pCR was obtained in 12 patients (30%). Baseline FDG SUV referring to pCR group was 11.26 and 7.26 in non-pCR group (p = 0.04). FDG SUV after second cycle was 2.73 in pCR group and 4.64 in non-pCR group (p = 0.048). When analyzing ΔSUV (difference between baseline SUV and SUV after second cycle), pCR group had a mean reduction of 81.58% and non-pCR group had a mean reduction of 81.58% (p = 0.001). Receiver operating curve analyses were performed to deter mine optimal differentiation cut-off values of ΔSUV for differentiation of pCR and non-pCR. After two courses of NAC the optimal cutoff value to early differentiation between pCR from non-pCR were 59,1% in decrease of SUV. The sensitivity and specificity were 64,3% and 100,0%, respectively. Conclusion: The optimum role of FDG PET in predicting the response of breast cancers to neoadjuvant chemotherapy is still not clearly defined and the SUV cut-off needs to be validated. FDG-PET allows for prediction of treatment response by the level of FDG uptake in terms of SUV at baseline and after two cycles of chemotherapy and FDG-PET may be helpful for individual treatment stratification in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-03.