Predictive and prognostic value of FDG-PET/CT imaging and different response evaluation criteria after primary systemic therapy of breast cancer.

OBJECTIVES: (1) To predict pathological complete remission (pCR) and survival after primary systemic therapy (PST) in patients diagnosed with breast cancer by using two different PET/CT based scores: a simplified PERCIST-based PET/CT score (Method 1) and a combined PET/CT score supplemented with the morphological results of the RECIST system (Method 2) and (2) to assess the effect of different breast carcinoma subtypes on tumor response and its evaluation. METHODS: Eighty-eight patients were enrolled in the study who underwent PET/CT imaging before and after PST. PET/CTs were evaluated by changes in maximum Standardized Uptake Value (SUVmax) and tumor size. Method 1 and 2 were applied to predict pathological complete remission (pCR). Kaplan-Meier analyses for survival were performed. Classification into biological subtypes was performed based on the pre-therapeutic tumor characteristics. RESULTS: A total of 30/88 patients showed pCR (34.1 %). Comparing pCR/non-pCR patient groups, significant differences were detected by changes in SUVmax (p < 0.001) and tumor size (p < 0.001) regarding the primary breast lesions. To predict pCR, Method 2 had higher sensitivity (72.4 % vs. 44.8 %) and negative predictive value (57.9 % vs. 45.8 %) with lower false negativity rate (16 vs. 32) than Method 1. pCR rate was higher in Her2-positive and triple negative tumors. Despite the significant differences detected between the biological subtypes regarding changes in primary tumor SUVmax (p = 0.007) and size (p = 0.015), the subtypes only had significant impact on response evaluation with Method 2 and not with Method 1. In our study, neither clinical nor pathological CR were predictors of longer progression-free survival. CONCLUSIONS: Our results suggest that combined PET/CT criteria are more predictive of pCR. The effect of biological subtypes is significant on pCR rate as well as on the changes in FDG-uptake and morphological tumor response. Response evaluation with combined criteria was also able to reflect the differences between the biological behavior of breast tumor subtypes.

Morphological and pathological response in primary systemic therapy of patients with breast cancer and the prediction of disease free survival: a single center observational study.

AIM: To identify breast cancer subtypes likely to respond to primary systemic therapy (PST or neoadjuvant therapy) and to assess the accuracy of physical examination (PE) and breast ultrasonography (US) in evaluating and predicting residual size of breast carcinoma following PST. METHODS: 116 patients who received at least two cycles of PST between 1998 and 2009 were selected from a prospectively collected clinical database. Radiological assessment was done by mammography and US. Prior to PST, tumors were subclassified according to core biopsy (NCB) and/or fine-needle aspiration-based immunohistochemical profiles of NCB. Pathological response rates were assessed following the surgeries by using Chevallier classification. Tumor measurements by PE and US were obtained before and after PST. Different clinical measurements were compared with histological findings. Disease-free survival (DFS) was assessed. RESULTS: Pathological complete remission (pCR=Chevallier I/II) was observed in 25 patients (21.5%), 44% of whom had triple negative histology, 28% Her2 positive and 76% had high-grade tumor. Of 116 patients, 24 received taxane-based PST, 48 combined taxane + anthracycline treatment, 8 trastuzumab combinations, 21 anthracycline-based treatments, and 15 other treatments. In the taxane treated group, the pCR rate was 30%, in the taxane + anthracycline group 25%, in the anthracycline group 9.5%, and in trastuzumab group 37.5%. After PST, PE and US were both significantly associated with pathology (P<0.001 and P=0.004, respectively). Concerning OS, significant difference was observed between the Chevallier III and IV group (P=0.031) in favor of Chevallier III group. In the pCR group, fewer events were observed during the follow-up period. CONCLUSIONS: Our results show that even limited, routinely used immunohistochemical profiling of tumors can predict the likelihood of pCR to PST: patients with triple negative and Her2-positive cancers are more likely to achieve pCR to PST. Also, PE is better correlated with pathological findings than US.

Complexity of Response Evaluation During Primary Systemic Therapy of Breast Cancer: Scoring Systems and Beyond-Preliminary Results.

BACKGROUND: Precise and standardized response evaluation enables clinicians to tailor primary systemic therapy (PST). PATIENTS AND METHODS: Breast cancer patients underwent (18)F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) before and after PST. Response was assessed by maximal Standardized Uptake Value (SUVmax); morphological changes and Ki-67 labeling index (LI). In parallel response assessment was performed by European Organization for Research and Treatment of Cancer (EORTC); PET Response Criteria in Solid Tumors (PERCIST); World Health Organization (WHO); Response Evaluation Criteria in Solid Tumors (RECIST); Chevallier and Sataloff classifications, and by a novel Ki-67 score. Accuracy of different scoring systems was evaluated. RESULTS: In the 42 enrolled patients, SUVmax, size, and Ki-67 LI decreased significantly on PST. Significant differences between patients with versus those without pathological complete response were observed for pre-treatment Ki-67 LI and SUVmax and for post-treatment Ki-67 LI, SUVmax and size. Change in Ki-67 LI was the best predictor of pathological complete response. Correlation patterns of the directly measured metabolic, morphological, and proliferation responses differed from those determined by scoring methods. CONCLUSION: During PST, FDG-PET/CT enables for robust assessment of treatment efficacy, but more reliable scoring systems are still needed for more precise response evaluation.

Response evaluation after primary systemic therapy of Her2 positive breast cancer ­ an observational cross-sectional study.

AIM: To evaluate (I) trastuzumab-containing primary systemic therapy (PST) in human epidermal growth factor receptor 2 (Her2) overexpressing breast carcinomas.; (II) compare the patients who achieved and those who did not achieve pathological complete remission (pCR), and (III) analyze the accuracy of different clinical-imaging modalities in tumor response monitoring. METHODS: 188 patients who received PST between 2008 and 2014 were reviewed and 43 Her2 overexpressing breast cancer patients (28 Luminal B/Her2-positive and 15 Her2-positive) were enrolled. 26 patients received mostly taxane-based PST without trastuzumab (Group 1) and 17 patients received trastuzumab-containing PST (Group 2). We compared the concordance between pCR and complete remission (CR) defined by breast-ultrasound, CR defined by standard 18F-fluoro-deoxy-glucose positron emission tomography and computerized tomography (FDG-PET/CT) criteria (Method 1) and CR defined by a novel, breast cancer specific FDG-PET/CT criteria (Method 2). Sensitivity (sens), specificity (spec), and positive (PPV) and negative predictive values (NPV) were calculated. RESULTS: Ten patients (38.5%) in Group 1 and eight (47%) in Group 2 achieved pCR. pCR was significantly more frequent in Her2-positive than in Luminal B/Her2-positive tumors in both Group 1: (P=0.043) and Group 2: (P=0.029). PET/CT evaluated by the breast cancer specific criteria (Method 2) differentiated pCR from non-pCR more accurately in both groups (Group 1: sens=77.8%, spec=%, PPV=100%, NPV=71.4%; Group 2: sens=87.5%, spec=62.5%, PPV=70%, NPV=83.3%) than standard PET/CT criteria (Method 1) (Group 1: sens=22.2% spec=100% PPV=100% NPV=41.7%; in Group 2: sens=37.5%, spec=87.5%, PPV=75% NPV=58.3%) or breast ultrasound (Group 1, sens=83.3% spec=25% PPV=62.5% NPV=50%; Group 2, sens=100% spec=12.5% PPV=41.6% NPV=100%). CONCLUSION: The benefit of targeted treatment with trastuzumab-containing PST in Her2 overexpressing breast cancer was defined in terms of pCR rate. Luminal B/Her2-positive subtype needs further subdivision to identify patients who would benefit from PST. Combined evaluation of tumor response by our novel, breast cancer specific FDG-PET/CT criteria accurately differentiated pCR from non-pCR patients.

Primary systemic therapy for breast cancer: Does the patient's involvement in decision-making create a new future?

OBJECTIVE: Primary systemic therapy (PST) followed by surgery is the standard initial treatment for locally advanced breast cancer (LABC). However, some patients are averse to mastectomy or breast-conserving surgery and do not consent to these procedures. The reasons for this controversial decision, the factors influencing the decision-making and optimal solutions for decision aiding need to be investigated. METHODS: We addressed these questions by a review of literature on the possibilities associated with different patient choices and subsequent treatment options in relation to LABC. RESULTS: A total of 5 reviews and 22 clinical studies were summarized in relation to decision making and the most successful decision aids. A discussion is given of the issues of those few patients who cannot be convinced to undergo surgery. CONCLUSION: Currently there is no guideline for the treatment of patients who reject the surgical procedures after PST. Medical oncologists should be able to apply decision aid modalities in a personalized manner to give all needed information to their patients thereby ensuring a deliberate decision-making process, facilitating acceptance of a need for surgery, and thus improving the chances of prolonged survival. PRACTICE IMPLICATIONS: Currently multidisciplinary tumor boards are the most suitable decision aids in oncological practice.

[The role of FDG-PET-CT in the evaluation of primary systemic therapy in breast cancer: links between metabolic and pathological remission]. / Az FDG-PET-CT szerepe az emlorák primer szisztémás kezelése során: a metabolikus változások és a patológiai remisszió összefüggései.

INTRODUCTION: FDG-PET-CT is highly sensitive in detection of viable tumour tissue, giving an importance for that in oncological diagnostics. AIM: The authors analysed retrospectively the relationship between metabolic response and changes in Ki-67, a proliferation marker. METHODS: Staging FDG-PET-CT scans (before and after therapy) SUVs (Standardized Uptake Value), and morphological changes in the primary tumour and axillary lymph node region were evaluated in 30 patients with breast cancer. Calculated ΔSUV were compared with Ki-67 proliferation marker (measured in biopsies and surgical specimens). RESULTS: The decrease of SUV and size were significant in the primary tumour and the axillary lymph node region. Decrease of Ki-67 was significant. Significant correlation was found between Ki-67 and SUV before therapy, initial Ki-67 and ΔSUV, and ΔKi-67 and ΔSUV. CONCLUSIONS: The metabolic changes were more sensitive in the measurement of the therapeutic response than morphological remission, and they correlated well with the pathological response, in not standardized clinical conditions even.

[Comparison of breast cancer in young and old women based on clinicopathological features]. / A fiatal- és idoskori emlorák összehasonlítása klinikopatológiai jellemzok alapján.

The two far ends of the age at the diagnosis of breast cancer are the age of younger than 35, and that of older than 70. Most probably, these two groups of patients differ in many ways. The aim of our present study was to underline the fact that age at the diagnosis of breast cancer is indeed a prognostic factor. Between October 1995 and March 2009, 80 old and 51 young breast cancer patients were treated at the Department of Diagnostic Radiology and Oncotherapy, Semmelweis University, Budapest. The prognostic and predictive factors of the tumors were analysed together with the disease-free and overall survival data. There were statistically significant differences between the two groups concerning the menstrual and reproductive factors, histological characteristics and immunophenotype of the tumors. Tumor size, nodal status and the Nottingham Prognostic Index did not show statistically significant differences. A trend to a shorter disease-free survival, higher rate of distant metastases and disease-specific death was seen in the group of young patients, but it was not significant. Overall survival was significantly shorter in the group of young patients. Therefore, we can state that young patients have a more aggressive disease and worse outcome. There is an increased importance of self examination in these groups, since both age groups are beyond the age limits of the screening population in Hungary. The media and primary school education as well should be involved in educating women concerning this aspect. The individual follow-up of young patients with positive family history should also be established.

[Chemotherapy for advanced gastric cancer--our possibilities in 2007]. / Az elôrehaladott gyomorrák gyógyszeres kezelésének lehetôségei 2007-ben.

Gastric cancer is the fourth most common malignancy in Hungary. Surgery remains the mainstay of any curative treatment, however, approximately two-thirds of patients diagnosed with gastric cancer have unresectable (locally advanced and/or metastatic) disease. In that stage, palliative chemotherapy is of crucial importance. Gastric cancer is heterogeneous regarding location, etiology, histology and natural course. This diversity is reflected in the results of randomized controlled trials as well. Patient selection, location of primary, stage and pretreatment of the tumor, as well as the reference treatment, patient stratification and endpoints have varied among trials. Based on the results of the clinical trials of the past decades, gastric cancer is chemosensitive, however, patient prognosis remains very poor, with a median survival of less than one year, and therapy-associated toxicity remains an issue. Based on the aforementioned, no standard regimens have yet been established worldwide. New compounds and targeted biological treatment make the development of more effective, less toxic, individualized treatment modalities possible.