Tumor Shrinkage Pattern Research Articles

Neoadjuvant Chemotherapy and Neoadjuvant Chemotherapy with Immunotherapy Result in Defferent Tumor Shrinkage Patterns in Triple-negative Breast Cancer.

This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change. Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p=0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p<0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p=0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI.

Neoadjuvant Chemotherapy and Neoadjuvant Chemotherapy With Immunotherapy Result in Different Tumor Shrinkage Patterns in Triple-Negative Breast Cancer.

This study aims to explore whether neoadjuvant chemotherapy with immunotherapy (NACI) leads to different tumor shrinkage patterns, based on magnetic resonance imaging (MRI), compared to neoadjuvant chemotherapy (NAC) alone in patients with triple-negative breast cancer (TNBC). Additionally, the study investigates the relationship between tumor shrinkage patterns and treatment efficacy was investigated. This retrospective study included patients with TNBC patients receiving NAC or NACI from January 2019 until July 2021 at our center. Pre- and post-treatment MRI results were obtained for each patient, and tumor shrinkage patterns were classified into three categories as follows: 1) concentric shrinkage (CS); 2) diffuse decrease; and 3) no change. Tumor shrinkage patterns were compared between the NAC and NACI groups, and the relevance of the patterns to treatment efficacy was assessed. Of the 99 patients, 65 received NAC and 34 received NACI. The CS pattern was observed in 53% and 20% of patients in the NAC and NACI groups, respectively. Diffuse decrease pattern was observed in 36% and 68% of patients in the NAC and NACI groups. The association between the treatment regimens (NAC and NACI) and tumor shrinkage patterns was statistically significant (p = 0.004). The postoperative pathological complete response (pCR) rate was 45% and 82% in the NAC and NACI groups (p < 0.001), respectively. In the NACI group, 17% of patients with the CS pattern and 56% of those with the diffuse decrease pattern achieved pCR (p = 0.903). All tumor shrinkage patterns were associated with achieved a high pCR rate in the NACI group. Our study demonstrates that the diffuse decrease pattern of tumor shrinkage is more common following NACI than that following NAC. Furthermore, our findings suggest that all tumor shrinkage patterns are associated with a high pCR rate in patients with TNBC treated with NACI. ClinicalTrials.gov Identifier: NCT04909554.

Impact of Tumor Shrinkage Pattern with Biweekly Triplet Gemcitabine+Cisplatin+S-1 Regimen for Biliary Tract Cancers: Implications for Neoadjuvant Therapy from the Data of KHBO1401 (KHBO1401-1A Study)

Introduction: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] vs. GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. Methods: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n = 183, 74%; GCS, n = 91; GC, n = 92). Results: The tumor shrinkage pattern could be divided into 4 categories based on the response at 100 days after enrollment: categories A (<–30% in size), B (−30–0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], p < 0.0001). Each category predicted the best response and overall survival (p < 0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was −53% in the GCS arm and −65% in the GC arm (p = 0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. Conclusion: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed regrowth after 6 cycles.

Multiparametric MRI radiomics fusion for predicting the response and shrinkage pattern to neoadjuvant chemotherapy in breast cancer.

During neoadjuvant chemotherapy (NACT), breast tumor morphological and vascular characteristics are usually changed. This study aimed to evaluate the tumor shrinkage pattern and response to NACT by preoperative multiparametric magnetic resonance imaging (MRI), including dynamic contrast-enhanced MRI (DCE-MRI), diffuse weighted imaging (DWI) and T2 weighted imaging (T2WI). In this retrospective analysis, female patients with unilateral unifocal primary breast cancer were included for predicting tumor pathologic/clinical response to NACT (n=216, development set, n=151 and validation set, n=65) and for discriminating the tumor concentric shrinkage (CS) pattern from the others (n=193; development set, n=135 and validation set, n=58). Radiomic features (n=102) of first-order statistical, morphological and textural features were calculated on tumors from the multiparametric MRI. Single- and multiparametric image-based features were assessed separately and were further combined to feed into a random forest-based predictive model. The predictive model was trained in the testing set and assessed on the testing dataset with an area under the curve (AUC). Molecular subtype information and radiomic features were fused to enhance the predictive performance. The DCE-MRI-based model showed higher performance (AUCs of 0.919, 0.830 and 0.825 for tumor pathologic response, clinical response and tumor shrinkage patterns, respectively) than either the T2WI or the ADC image-based model. An increased prediction performance was achieved by a model with multiparametric MRI radiomic feature fusion. All these results demonstrated that multiparametric MRI features and their information fusion could be of important clinical value for the preoperative prediction of treatment response and shrinkage pattern.

Breast MRI for Evaluating Residual Tumor Size Following Neoadjuvant Chemotherapy: Clinicopathologic Factors and MRI Imaging Features Affecting its Accuracy.

The aim of the study was to investigate the accuracy of breast Magnetic Resonance Imaging (MRI) for evaluating residual tumor size following Neoadjuvant Chemotherapy (NAC) and to identify clinicopathologic and MRI features affecting its accuracy. We retrospectively assessed 109 women who underwent preoperative Dynamic Contrast-Enhanced (DCE) MRI following NAC and subsequent surgery between April 2016 and August 2020. Preoperative MRI features, including Breast Imaging Reporting and Data System lexicon characteristics, size of residual enhancing lesion, tumor shrinkage pattern, and clinicopathologic features, were investigated, and MRI and pathology findings were compared. Residual tumor size on MRI showed high agreement with residual invasive tumor size on pathologic examination (ICC, 0.808, p<0.001). The residual tumor size measured by MRI and final pathologic size were concordant in 63/109 cases (57.8%), while MRI overestimated the size in 35/109 cases (32.1%). For estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, MRI tended to underestimate the residual tumor size compared with HER2-positive cancers (p=0.002) and triple-negative cancers (p=0.12). On MRI, tumors with concentric shrinkage patterns after NAC showed less size discrepancy with final pathologic tumor size than those with non-concentric patterns (p=0.026). In ER-positive/HER2-negative cancers, MRI tends to underestimate the residual tumor size, compared to in other subtypes. Tumors with concentric shrinkage patterns after NAC showed less MRI/pathology size discrepancy.

Prediction of Tumor Shrinkage Pattern to Neoadjuvant Chemotherapy Using a Multiparametric MRI-Based Machine Learning Model in Patients With Breast Cancer.

Aim: After neoadjuvant chemotherapy (NACT), tumor shrinkage pattern is a more reasonable outcome to decide a possible breast-conserving surgery (BCS) than pathological complete response (pCR). The aim of this article was to establish a machine learning model combining radiomics features from multiparametric MRI (mpMRI) and clinicopathologic characteristics, for early prediction of tumor shrinkage pattern prior to NACT in breast cancer.Materials and Methods: This study included 199 patients with breast cancer who successfully completed NACT and underwent following breast surgery. For each patient, 4,198 radiomics features were extracted from the segmented 3D regions of interest (ROI) in mpMRI sequences such as T1-weighted dynamic contrast-enhanced imaging (T1-DCE), fat-suppressed T2-weighted imaging (T2WI), and apparent diffusion coefficient (ADC) map. The feature selection and supervised machine learning algorithms were used to identify the predictors correlated with tumor shrinkage pattern as follows: (1) reducing the feature dimension by using ANOVA and the least absolute shrinkage and selection operator (LASSO) with 10-fold cross-validation, (2) splitting the dataset into a training dataset and testing dataset, and constructing prediction models using 12 classification algorithms, and (3) assessing the model performance through an area under the curve (AUC), accuracy, sensitivity, and specificity. We also compared the most discriminative model in different molecular subtypes of breast cancer.Results: The Multilayer Perception (MLP) neural network achieved higher AUC and accuracy than other classifiers. The radiomics model achieved a mean AUC of 0.975 (accuracy = 0.912) on the training dataset and 0.900 (accuracy = 0.828) on the testing dataset with 30-round 6-fold cross-validation. When incorporating clinicopathologic characteristics, the mean AUC was 0.985 (accuracy = 0.930) on the training dataset and 0.939 (accuracy = 0.870) on the testing dataset. The model further achieved good AUC on the testing dataset with 30-round 5-fold cross-validation in three molecular subtypes of breast cancer as following: (1) HR+/HER2–: 0.901 (accuracy = 0.816), (2) HER2+: 0.940 (accuracy = 0.865), and (3) TN: 0.837 (accuracy = 0.811).Conclusions: It is feasible that our machine learning model combining radiomics features and clinical characteristics could provide a potential tool to predict tumor shrinkage patterns prior to NACT. Our prediction model will be valuable in guiding NACT and surgical treatment in breast cancer.

Dynamic Contrast-Enhanced MRI Evaluation of Pathologic Complete Response in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer After HER2-Targeted Therapy

Pathologic complete response (pCR) in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer after HER2-targeted therapy correlates increased disease-free survival and decreased mastectomy rates. The aim of this study was to explore tumor shrinkage patterns and initial tumor enhancement with pCR in HER2-positive breast cancer. This was an institutional review board-approved retrospective analysis of 51 HER2 positive breast cancer patients with breast MRI both pre- and post-HER2-targeted therapy. Initial enhancement ratio (IER, initial enhancement percentage over baseline at first postcontrast imaging), pattern of tumor shrinkage, and Dynamic contrast enhanced (DCE)-MRI imaging features were assessed. Wilcoxon rank, Spearman correlation, Fisher's exact, and Mann-Whitney tests were used to correlate MRI imaging features with pCR. IER reader agreement was evaluated by intraclass correlation. Binary logistic regression was used to evaluate multivariate associations with pCR. 56.9% (29/51) of patients had pCR at surgery. Concentric tumor shrinkage pattern was associated with pCR (p = 0.001, Area under the curve (AUC) 0.778): accuracy 80.4%, specificity 96.6%, and sensitivity of 59.1%. There was no association with pCR and imaging response as defined by RECIST criteria (p = 0.169), pretreatment IER (Reader 1 (R1) p = 0.665, Reader 2 (R2) p = 0.766), or lesion size (p = 0.69). IER was associated with axillary metastases (R1 p = 0.016, R2 < 0.001) and ki-67 (R1 r = 0.52, p = 0.008, R2 r = -0.44, p = 0.028). The shrinkage pattern of HER2-positive tumors after targeted therapy may be associated with pCR. There was no association between IER and pCR. Future studies evaluating the correlation of shrinkage patterns to texture radiomics are of interest.

Impact of tumor shrinkage pattern by biweekly triplet gemcitabine/cisplatin/s-1 for biliary tract cancers: Implication for neoadjuvant therapy (KHBO1401-1A study).

4093 Background: There have not been any new evidenced regimen for biliary tract cancers (BTC) after ABC-02 study, we conducted biweekly triplet gemcitabine/cisplatin/s-1 regimen (GCS) and compared with conventional doublet gemcitabine/cisplatin regimen (GC) as phase III (KHBO1401) study. Biweekly GCS was proved not only to prolong patients’ survival (HR 0.791 (90% C.I. 0.628-0.996), one-sided P = 0.046) but also to achieve high response rate (42% versus 15%, P &lt; 0.001) and good conversion rate (2.5% versus 0.0%), and would be good for neoadjuvant therapy. Herein, we investigated tumor shrinkage pattern to explore possibilities of neoadjuvant therapy. Methods: Totally 246 patients were enrolled in multi-center phase III KHBO1401 study between 2014 and 2016. Tumor shrinkage pattern (best response, timing, response at 100 days (14 weeks, approx. 6 cycles in GCS and 4 cycles in GC), etc.) and survival were investigated in the patients with measurable BTC (n = 183, 74%, 91 in GCS and 92 in GC) as sub-analysis. P &lt; 0.05 was considered statistically significant. Results: Tumor shrinkage pattern could be divided to 4 categories by the response at 100 days after enrollment; category A ( &lt; -30% in size), B (-30% to 0%), C (0% to +20%), and D ( &gt; +20%). GCS arm contained more category A &amp; B (61 (67%) vs. 33 (36%), P &lt; 0.0001). Each category predicted best response and overall survival (p &lt; 0.0001). Timing for maximum tumor response were different among categories, category A achieved maximum tumor shrinkage at 165 +/- 76 days in GCS and 225 +/- 190 days in GC, category B at 139 +/- 78 versus 154 +/- 82 days, and category C and D did not achieve tumor shrinkage. Maximum tumor shrinkage in category A was -53% in GCS versus -65% in GC (P = 0.0892), and 20% patients in GCS underwent tumor regrowth 154 +/- 143 days later. Conclusions: GCS provided faster and more tumor shrinkage with better survival in the comparison of GC, although it had 20% risk of re-growth after 6 cycles.

Validating a Predictive Atlas of Tumor Shrinkage for Adaptive Radiotherapy of Locally Advanced Lung Cancer

To cross-validate and expand a predictive atlas that can estimate geometric patterns of lung tumor shrinkage during radiation therapy using data from 2 independent institutions and to model its integration into adaptive radiation therapy (ART) for enhanced dose escalation. Data from 22 patients at a collaborating institution were obtained to cross-validate an atlas, originally created with 12 patients, for predicting patterns of tumor shrinkage during radiation therapy. Subsequently, the atlas was expanded by integrating all 34 patients. Each study patient was selected via a leave-one-out scheme and was matched with a subgroup of the remaining 33 patients based on similarity measures of tumor volume and surroundings. The spatial distribution of residual tumor was estimated by thresholding the superimposed shrinkage patterns in the subgroup. A Bayesian method was also developed to recalibrate the prediction using the tumor observed on the midcourse images. Finally, in a retrospective predictive treatment planning (PTP) study, at the initial planning stage, the predicted residual tumors were escalated to the highest achievable dose while maintaining the original prescription dose to the remainder of the tumor. The PTP approach was compared isotoxically to ART that replans with midcourse imaging and to PTP-ART with the recalibrated prediction. Predictive accuracy (true positive plus true negative ratios based on predicted and actual residual tumor) were comparable across institutions, 0.71 versus 0.73, and improved to 0.74 with an expanded atlas including 2 institutions. Recalibration further improved accuracy to 0.76. PTP increased the mean dose to the actual residual tumor by an averaged 6.3Gy compared to ART. A predictive atlas found to perform well across institutions and benefit from more diversified shrinkage patterns and tumor locations. Elevating tumoricidal dose to the predicted residual tumor throughout the entire treatment course could improve the efficacy and efficiency of treatment compared to ART with midcourse replanning.

Spontaneous shrinkage of solitary osteochondromas.

Osteochondromas are the most common benign bone tumors, and thus far, their spontaneous shrinkage is considered a rare phenomenon. This study was designed to investigate the exact ratio of remission to progressive or stable cases and analyze the mechanism of tumor regression on the basis of existing theories. We retrospectively collected images of solitary osteochondromas in patients from 1992 to 2013, excluding cases involving short-term follow-up periods and follow-up periods that ended before growth plate closure. A total of 121 patients were diagnosed and screened for study inclusion. Tumor shrinkage was measured by assessing three points on tumor contours to determine if they had regressed or vanished. Patterns of shrinkage were further divided on the basis of mechanisms described as incorporation, absorption, and fracture. Seventeen patients (mean age at initial diagnosis 13.1years) met the study inclusion criteria. Tumor morphological classifications were pedunculated (10 cases) and sessile (7 cases). Osteochondroma shrinkage was the most common outcome (8 cases), followed by stable osteochondromas (6 cases), and osteochondromas that had progressed (3 cases). Tumors with sessile morphology were more prone to shrinkage (6 of 7 cases) compared with those of pedunculated morphology (2 of 10 cases; p=0.015). Among pedunculated cases, tumor shrinkage was via absorption. The timing of tumor growth cessation was related to the pattern of tumor shrinkage. Absorption mostly followed tumor growth cessation, whereas incorporation mostly preceded tumor growth cessation. The shrinkage of osteochondromas appears less rare than was originally thought.

Pattern of Tumor Shrinkage during Neoadjuvant Chemotherapy Is Associated with Prognosis in Low-Grade Luminal Early Breast Cancer.

Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P < .001 and P < .001, respectively). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .001) and OS (P = .009) rate. In the validation set, the median follow-up period was 56.9 months. Recurrence was observed in 20 patients (16.5%) and eight (6.6%) deaths were related to breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months; P ≤ .001). The CS pattern was associated with an excellent prognosis (median OS, 80.6 months; 95% CI: 79.3, 81.8 months vs 65.0 months; 95% CI: 60.1, 69.8 months; P = .004). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .007) and OS (P = .037) rates. Conclusion The CS pattern as revealed at MR imaging during NAC had the only significant independent association with prognosis in patients with low-grade luminal breast cancer. © RSNA, 2017.

Abstract P4-02-13: The pattern of tumor shrinkage is associated with prognosis in low grade luminal early breast cancer during neoadjuvant chemotherapy

Abstract BACKGROUND: In neoadjuvant chemotherapy (NAC) for early breast cancer, the pathological response rate in estrogen receptor (ER)-positive tumors has been low in comparison with those of ER-negative tumors. Therefore, surrogate makers other than the pCR rate are needed during NAC for luminal breast cancer. Using MRI, we analyzed the patterns of tumor shrinkage after NAC as a surrogate prognostic factor in low grade luminal breast cancer. METHODS: Of 854 patients who had received NAC in a single institute from Jan. 2000 to Dec. 2009, 183 patients with low grade luminal breast cancer were retrospectively evaluated for this study. They were defined as ER and/or PgR positive in more than 10% of cancer cells and HER2 negative (IHC 0, 1+ or FISH &amp;lt;2.0) with nuclear grade 1 and 2. RESULTS: The median observation period was 67.9 months following surgery, and recurrence was observed in 31 patients (16.9%). The median age was 49 (22-76) years. One hundred eighty patients received anthracycline-containing chemotherapy, and 158 received taxane. There were 16 deaths (8.7%) related to breast cancer. We categorized the patterns of tumor shrinkage by MRI into 6 types: concentric shrinkage (CS), diffuse decrease (DD), reduction to small foci (RSF), decrease of intensity only (DIO), no change (NC), and enlargement (EL). According to our categorization, CS occurred in 97 (53.0%), RSF in 7 (3.8%), DD in 62 (33.9%), DIO in 7 (3.8%), NC in 5 (2.7%), and EL in 5 (2.7%). As expected, there were statistically significant differences in both the median DFS and OS in each pattern of tumor shrinkage (p &amp;lt;0.001 and p=0.001, respectively); in particular, the CS pattern had excellent prognosis. Multivariate analysis demonstrated that concentric shrinkage was the only significant good prognostic factor for OS (p=0.015). CONCLUSIONS: Tumor shrinkage patterns as revealed by MRI could be important surrogate prognostic factors for NAC in early low grade luminal breast cancer. Citation Format: Fukada I, Araki K, Kobayashi K, Gomi N, Horii R, Akiyama F, Takahashi S, Iiwase T, Ohno S, Ito Y. The pattern of tumor shrinkage is associated with prognosis in low grade luminal early breast cancer during neoadjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-02-13.

Abstract P1-14-22: Neo-adjuvant chemotherapy for the treatment of breast cancer exterts a selection pressure toward luminal phenotype

Abstract The effect of anthracycline and taxane based chemotherapy on biological features of residual disease after neo-adjuvant therapies in breast cancer patients is poorly described. PATIENTS AND METHODS: We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neo-adjuvant chemotherapy at INT, Milan, Italy, between January 2010 and March 2015. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation including the shrinking pattern (scattered or concentric); ER, PgR, HER2 and Ki-67 expression were evaluated both at diagnostic biopsy and at final surgery. McNemar's test was used to compare paired proportions. RESULTS: We identified a total of 325 patients. Median age was 51 yrs (range: 23 - 85 yrs). 304 (93%) pts received anthracycline and taxane containing chemotherapy for a median number of 6 (range 2-18) cycles. Radical modified mastectomy was performed in 68% of cases. Scattered residual disease was diagnosed in 112 (34%) cases. HER2 over-expression in diagnostic biopsy was significantly associated to scattered response (OR 1.94, CI 1.13 – 3.36, p= 0.017). 11/220 pts (5%) with ER-positive diagnostic biopsy had ER-negative residual tumor; 9/54 pts (17%) with initial ER-negative tumors became ER-positive. 34/183 (19%) pts with initial positive PgR at diagnostic biopsy had PgR-negative residual tumor; whereas, 17/86 pts (20%) with negative PgR became positive. The HER2 expression changed from positive to negative in 9/49 (18%) cases and from negative to positive in 7/190 (4%) cases. The Ki-67 expression changed from &amp;gt; or =20% to &amp;lt;20% in 63/175 (36%) cases and vice-versa in 14/54 (26%) cases. Compared to diagnostic biopsy, the rate of PgR-positive tumors decreased from 68 to 62% (p= 0.024) and the rate of Ki67&amp;lt;20% tumors increased from 24 to 45% (p=&amp;lt;0.001) in surgical specimen. Subtype changes at surgery occurred in 37/245 (15%) of cases, i.e. none in triple negative, 8/20 (10%) in HER2 positive, and 29/202 (14%) in luminal tumors. 73% of cases that changed after treatment showed a trend towards luminal differentiation. There was no significant correlation between pre- and post-treatment biological characteristics and the type of tumor shrinkage. CONCLUSION: Anthracycline and taxane-based neo-adjuvant chemotherapy induces loss of PgR and Ki-67 in breast cancer. These changes are independent of the pattern of tumor shrinkage. The subtype switching toward more luminal phenotype suggest an endocrine effect of chemotherapy and paves the way to possible combinatorial approach of chemo- and hormone-therapy. Citation Format: Galli G, Porcu L, Baili P, Hade A, Di Salvo F, Bregni G, Agresti R, Gennaro M, De Santis MC, Ferrari B, de Braud F, Di Cosimo S. Neo-adjuvant chemotherapy for the treatment of breast cancer exterts a selection pressure toward luminal phenotype. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-22.

O1-15-1 - The Pattern of Tumor Shrinkage is Associated with Prognosis in Luminal Breast Cancer During Neoadjuvant Chemotherapy

Background and Objective: Understanding neoadjuvant chemotherapy (NAC) for early breast cancer, the pathological response rate in estrogen receptor (ER)-positive has been low in comparison with those of ER-negative. Therefore, the luminal breast cancer (LBC) must have heterogeneity in response to NAC. We analyzed the patterns of tumor shrinkage after NAC as a surrogate prognostic factor in LBC using MRI.Methods and Results: Of 854 patients who had received NAC in the single institute from Jan. 2000 to Dec. 2009, 265 LBC were retrospectively evaluated for this study. The LBC was defined as ER and/or PgR positive in more than 10% of cancer cells and HER2 negative (IHC 0, 1+ or FISH <2.0). Before and after NAC, the primary lesions were evaluated by MRI in 230 patients. The median observation period was 67.3 months from operation, and recurrence was observed in 43 patients (18.7%). The median age was 49.5 (25-76) years. 227 patients received anthracycline-containing chemotherapy and 200 patients received taxane. There were 24 deaths (10.4%) related to breast cancer. We categorized the patterns of tumor shrinkage by MRI into 6 types; the concentric shrinkage (CS), diffuse decrease (DD), reduction to small foci (RSF), decrease of intensity only (DIO), no change (NC), and enlargement (EL). According to our categorization, the CS was shown in 123 (54.5%), RSF in 9 (3.9%), DD in 76 (33.0%), DIO in 8 (3.5%), NC in 6 (2.6%), and EL in 8 (3.5%), respectively. As expected, there were statistically significant differences in both the median DFS and OS in each patterns of tumor shrinkage (p < 0.001), especially CS pattern had excellent prognosis.Discussion: The tumor shrinkage pattern of MRI could be an important surrogate prognostic factor for NAC in early LBC. Our results suggest that the LBC with non-CS pattern may have the higher heterogeneity which associated with chemotherapy-resistant residual cancer cells.

O3-12-3 - Survival Outcome Assessed According to Tumor Response and Shrinkage Pattern in Egfr(+)Nsclc Treated with Egfr-Tki

Introduction: Somatic mutations in the epidermal growth factor receptor gene (EGFR) are associated with a marked therapeutic response to EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC). Clinical indicators of the likely survival benefit of EGFR-TKI treatment in NSCLC patients with EGFR mutations have not been identified, however. We therefore evaluated progression-free survival (PFS) and overall survival (OS) according to tumor response and tumor shrinkage pattern in such patients.Methods: Among 145 EGFR mutation-positive NSCLC patients treated with EGFR-TKIs, 68 individuals were selected for analysis.Results: Of the 68 selected patients, 6 achieved a complete response (CR), 42 a partial response (PR), and 14 stable disease (SD). Both PFS and OS were significantly longer in patients who achieved a CR or PR than in those who experienced SD. Multivariate analysis showed that a response (CR or PR) to EGFR-TKIs was significantly associated with both PFS and OS. Among the CR/PR group, the median maximal tumor shrinkage relative to baseline was 56%, and the median time to response (TTR) was 4.2 weeks. The subsets of these patients who experienced rapid tumor regression (TTR of =< 4.2 weeks) or a high degree of tumor shrinkage (=> 56%) did not show a more favorable PFS or OS compared with those who experienced slow tumor regression or a low degree of tumor shrinkage.Conclusion: Response (CR or PR) may represent the optimal surrogate for efficacy among EGFR mutation positive NSCLC patients treated with EGFR-TKIs.

Survival Outcome Assessed According to Tumor Response and Shrinkage Pattern in Patients with EGFR Mutation–Positive Non–Small-Cell Lung Cancer Treated with Gefitinib or Erlotinib

Introduction:Somatic mutations in the epidermal growth factor receptor gene (EGFR) are associated with a marked therapeutic response to EGFR–tyrosine kinase inhibitors (TKIs) in patients with advanced non–small cell lung cancer (NSCLC). Clinical indicators of the likely survival benefit of EGFR-TKI treatment in NSCLC patients with EGFR mutations have not been identified, however. We therefore evaluated progression-free survival (PFS) and overall survival (OS) according to tumor response and tumor shrinkage pattern in such patients.Methods:Among 145 EGFR mutation–positive NSCLC patients treated with EGFR-TKIs, 68 individuals were selected for analysis.Results:Of the 68 selected patients, 6 achieved a complete response (CR), 42 a partial response (PR), and 14 stable disease (SD). Both PFS and OS were significantly longer in patients who achieved a CR or PR than in those who experienced SD. Multivariate analysis showed that a response (CR or PR) to EGFR-TKIs was significantly associated with both PFS and OS. Among the CR/PR group, the median maximal tumor shrinkage relative to baseline was 56%, and the median time to response (TTR) was 4.2 weeks. The subsets of these patients who experienced rapid tumor regression (TTR of ≤4.2 weeks) or a high degree of tumor shrinkage (≥56%) did not show a more favorable PFS or OS compared with those who experienced slow tumor regression or a low degree of tumor shrinkage.Conclusion:Response (CR or PR) may represent the optimal surrogate for efficacy among EGFR mutation–positive NSCLC patients treated with EGFR-TKIs.

Magnetic resonance imaging with concentric shrinkage as a prognostic factor in patients with luminal breast cancer during neoadjuvant chemotherapy.

e11587 Background: The important characteristics of breast cancer is its tumor heterogeneity and response to neoadjuvant chemotherapy (NAC). We analyzed the patterns of tumor shrinkage as a prognostic indicator after NAC for luminal breast cancer. Methods and Results. Methods: Of 854 patients who had received NAC in the single institute between January 2000 and December 2009, 265 luminal breast cancerwere retrospevively examined. Luminal breast cancer was defined as ER and/or PgR positive in more than 10% of cancer cells and HER2 negative (IHC 0, 1+ or FISH &lt;2.0). Before and after NAC, the primary lesion was evaluated by enhanced MRI in 235 patients. Results: The median follow-up period was 51.4 months. 38 patients(16.2%) experienced recurrence after a median DFI of 49.1 months. The median age was 50 and 232 patients received anthracycline containing chemotherapy and 179 patients received taxane. 120 out of 235 patients exhibited concentric shrinkage pattern. Multivariate analysis for DFS identified Age(49&gt;), strong ER/PgR positivity and concentric shrinkage as significantly favorable, and lymph node metastases as significantly unfavorable prognostic factors. Multivariate analysis for OS identified tumor size as significantly unfavorable prognostic factors(p=0.012). Conclusions: the tumor shrinkage pattern could be an important prognostic factor for luminal breast cancer and this suggests that a concentric shrinkage pattern of response may be infrequently associated with chemotherapy-resistant residual cancer cells.

Survival versus intrinsic and acquired resistance in advanced non-small cell lung cancer.

e19066 Background: While advanced NSCLC responds to platinum-based therapy (PBT), intrinsic and acquired resistance limits efficacy. We assessed impact of resistance patterns on overall survival (OS). Methods: Using serial measurements of tumor diameters from 130 NSCLC patients on PBT, we calculated % incremental change in tumor size compared to the most recent prior scan and % overall change from pre PBT. Results: 98/130 (75%) had measurable tumor shrinkage (TS) at 1st repeat scan (RS) post 2 cycles, of whom 81 had a 2nd RS post 4 cycles. Of these, 20 (25%) had tumor growth (TG) at the 2nd RS. Only 1 had initial TG then followed by TS. Of 41 with a 3rd RS &lt;4 weeks post cycle 6, 13/41 (32%) had TG. The greatest % incremental TS (compared to most recent prior scan) was seen early (at 1st RS) for 76% of patients. Rate of TS decreased with later cycles in these patients. 11 patients had rapid TS on 1st RS, then gradual further shrinkage over &gt;3 subsequent scans, while 15 had progressive gradual TS over &gt;4 scans without initial rapid TS. By Spearman coefficients, maximum % TS from pre PBT over all scans correlated with OS (r=0.46, p&lt;0.0001), time to progression (TTP) (r=0.69, p&lt;0.0001) and post-progression survival (PPS) (r=0.30, p=0.001). TTP also correlated with OS (r=0.63, p&lt;0.0001), TTP correlated with PPS (r=0.44, p&lt;0.0001), and OS correlated with PPS (r=0.95, p&lt;0.0001). Median OS (11.0 months for all patients) varied with TS pattern (p&lt;0.0001): OS for patients with first TG at 1st, 2nd, 3rd and 4th RS was 5.9, 10.8, 10.5 and 15.1 months. OS was 18.2 months in patients with most TS at 1st RS followed by gradual further TS over later scans, and was 30.5 months with progressive gradual TS without rapid TS at 1st RS. OS with RECIST partial response (23% of patients), minor TS (52%), minor TG (13%) and RECIST progressive disease (13%) was 16.9, 12.4, 9.8 and 4.0 months (p&lt;0.0001). Conclusions: OS, TTP and PPS correlate strongly with response (degree of TS/TG) and with resistance pattern. OS is longest with progressive further TS over multiple scans. Within this group, partial acquired resistance (decreased TS rate after initial rapid TS) has shorter OS than with sustained incremental TS. The underlying biological factors driving clinical resistance remain undefined.

O3-023 - Concentric Tumor Shrinkage by Chemotherapy is a Good Prognostic Factor in Neoadjuvant Chemotherapy for Luminal Breast Cancer

ABSTRACT Background and objective The important characteristics of breast cancer is its heterogeneity and attitude of response to neoadjuvant chemotherapy (NAC). We analyzed the patterns of tumor shrinkage as a prognostic indicator after NAC for luminal breast cancer. Methods and results Of the 503 patients who had received NAC in our hospital between January 2000 and December 2007, 142 luminal breast cancer were included in this study. Luminal breast cancer was defined as ER and/or PgR-positive in more than 10% of cancer cells and HER2 negative (IHC 0, 1+ or FISH Discussion The results suggest that concentric tumor shrinkage tends to be associated with a favorable prognosis, whereas scattered residual cancer cells are resistant to chemotherapy.

Magnetic Resonance Imaging Patterns of Tumor Regression After Neoadjuvant Chemotherapy in Breast Cancer Patients

The objectives of the study were to analyze the tumor shrinkage pattern on magnetic resonance imaging (MRI) after neoadjuvant chemotherapy and to evaluate whether there is any difference in shrinkage pattern between pathological responder and nonresponder groups. In addition, we wanted to compare tumor diameter obtained from MRI with histological diameter according to the tumor shrinkage pattern. Between July 2008 and December 2010, 55 consecutive patients (56 lesions) with pathologically proven breast cancer who underwent neoadjuvant chemotherapy followed by surgery were retrospectively enrolled. The shrinkage pattern was classified into 4 categories: I (concentric shrinkage without surrounding lesion), II (concentric shrinkage with surrounding lesions), III (shrinkage with residual multinodular lesions, and IV (diffuse contrast enhancement in whole quadrants). Histological regression was scored on a 5-point scale regarding tumor cellularity reduction (Miller-Payne grading system). Patients with Miller-Payne grade 1 or 2 were classified into the nonresponder group, and patients with grade 3, 4, or 5 were in the responder group. Of 56 lesions, pattern I was seen in 29 lesions, pattern II in 13 lesions, pattern III in 5 lesions, and pattern IV in 4 lesions. Three lesions were not visualized on MRI after neoadjuvant chemotherapy, and 2 lesions were increased in size. There was a statistically significant difference in the tumor shrinkage pattern between responder and nonresponder groups (P = 0.017). All 5 lesions with type III shrinkage pattern were found in the responder group, and all 4 lesions with pattern IV were in the nonresponder group. Magnetic resonance imaging diameter of lesions with types I, II, and IV patterns showed significant correlation with the histological diameter. Among them, the correlation factor was highest in pattern IV (ρ = 0.94, P < 0.001) followed by pattern I (ρ = 0.67, P < 0.01) and pattern II (ρ = 0.502, P = 0.08). However, in type III shrinkage pattern, tumor size measured on MRI was not significantly correlated with histological size (P = 0.87). Types III and I shrinkage patterns were more frequently observed in the pathological responder group, and type IV was more frequently noted in the nonresponder group. Tumor diameter measured on MRI showed strong correlation with histological diameter in lesions with types I and IV shrinkage patterns, whereas lesions with type III did not show significant correlation. Type II pattern showed similar frequencies between the 2 groups and moderate correlation between sizes obtained from MRI and histology.