Locally advanced breast cancer: comparison of mammography,sonography and MR imaging in evaluation of residual disease in women receiving neoadjuvant chemotherapy

The accuracy of mammography, sonography and magnetic resonance imaging (MRI) in identifying residual disease after neoadjuvant chemotherapy is evaluated and imaging findings are correlated with pathologic findings. Fifteen patients enrolled in an experimental protocol of preoperative neoadjuvant chemotherapy underwent clinical examination, mammography, sonography and dynamic MRI, performed in this order, before and respectively after 2 and 4 cycles of neoadjuvant chemotherapy. Four radiologists, two for mammography, one for sonography and one for MR, examined the images, blinded to the results of the other examinations. All patients underwent radical or conservative surgery, and imaging findings were compared with pathologic findings. MRI identified 2/15 (13.3.%) clinically complete response (CR), 9/15 (60%) partial response (PR), 3/15 (20%) stable disease (SD) and 1/15 (6.7%) progressive disease. Mammography identified 1/15 (6.7%) clinically CR, 8/15 (53.3%) PR and 4/15 (27%) SD, and was not able to evaluate the disease in 2/15 (13%) cases. Sonography presented the same results as MRI. Therefore, MRI and sonography compared to mammography correctly identified residual disease in 100 vs. 86%. MRI resulted in two false-negative results because of the presence of microfoci of in situ ductal carcinoma (DCIS) and invasive lobular carcinoma (LCI). MRI was superior to mammography in cases of multifocal or multicentric disease (83 vs. 33%). Sonography performed after MRI improves the accuracy in evaluation of uncertain foci of multifocal disease seen on MR images with an increase of diagnostic accuracy from 73 to 84.5%. MRI assesses response to neoadjuvant chemotherapy better than traditional methods of physical examination and mammography.     

Imaging procedures for assessment of the response of mammary carcinoma to preoperative chemotherapy

Summary Neoadjuvant chemotherapy with epirubicin and cyclophosphamide makes breast conserving therapy possible in patients with large tumors, which are primarily not suited for this treatment. The regression of the tumor can be followed by mammography, ultrasound and MRI. Mammography is reproducible and easily available. Tumors, which cannot be measured mammographically, usually can be followed with ultrasound. MR allows imaging of the tumor independent of structure and density of the parenchyma. In addition the measurement of functional parameters is possible. – All methods are restricted in the imaging of tumor residuals after neoadjuvant chemotherapy, because imaging of small microscopic foci of invasive or even non invasive tumorresiduals is hardly possible. Of special concern are tumor specific microcalcifications, which only can be shown on mammograms, in this respect. They do not regress under chemotherapy, even if the invasive tumor regresses, and they typically hint for non invasive tumor residuals. For planning surgery the pretherapeutic tumor extent always has to be taken into account, because of the restricted ability to image small tumor residuals.      

Clinical and diagnostic value of preoperative MR mammography and FDG-PET in suspicious breast lesions

Dynamic enhanced magnetic resonance (MR) mammography and fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) of the breast were directly compared preoperatively in suspicious breast lesions. Forty-two breast lesions in 40 patients were examined with a three-dimensional dynamic MR imaging series and FDG-PET. The MR and PET examinations were evaluated separately and the results were compared with the histological findings. The sensitivity and specificity of each method were calculated. The diagnostic value of both modalities as single diagnostic tool and in combination was investigated. Nineteen malignant and 23 benign breast lesions were proven histologically. Magnetic resonance mammography and FDG-PET showed a sensitivity of 89 and 63%, respectively. The specificity was 74 and 91%, respectively. The combination of both imaging methods decreased the not-required biopsies from 55 to 17%. Only one false-negative finding—a patient pre-treated with chemotherapy—was observed in both methods. The combination of MR mammography and FDG-PET can help to decrease biopsies of benign breast lesions. Because of their high cost, these modalities should only be used in problematic cases to either rule out or to demonstrate malignancy. The best diagnostic strategy is achieved using MR mammography first. If the diagnosis is still questionable, FDG-PET can be performed. This article was presented in part at the 4th Annual Meeting of the ISMRM, New York, 1996     

Preoperative breast magnetic resonance imaging: applications in clinical practice

Results of large randomized trials have shown that survival rates after breast conserving surgery are equivalent to those obtained by radical mastectomy. Breast conserving surgery with wide local excision in women with early stage breast cancer who are thought to have a single and resectable tumour as determined by clinical examination and conventional imaging followed by postoperative irradiation is the standard of care in early breast cancer. Mapping of local disease is the key element to guide optimal surgery to obtain tumour-free margins, thereby decreasing risk of local recurrence. The usual preoperative workup of breast malignancy consists of clinical breast examination and mammography with or without ultrasound. However, mammography and ultrasound fail to accurately assess tumour extent in as many as a third of patients eligible for breast conserving therapy. It is well established that magnetic resonance imaging is far superior to mammography (with and without ultrasound) for mapping the local extent of breast cancer. Experts advocate its use despite its high costs, high number of false positive findings, and lack of evidence from randomized prospective trials and, notably, fear of "overtreatment." This article discusses the current role of breast magnetic resonance imaging with its clinical advantages and applications.     

Monitoring response to treatment in patients utilizing PET

Establishing new surrogate end points for monitoring response to treatment is needed for current therapy modalities and for new therapeutic strategies including molecular targeted cancer therapies. PET as a functional imaging technology provides rapid, reproducible, noninvasive in vivo assessment and quantification of several biologic processes targeted by these therapies. PET is useful in a variety of clinical relevant applications, including distinguishing between radiation necrosis and tumor recurrence, determining the resectability of recurrent tumor, and evaluating response to therapy. FDG-PET has demonstrated efficacy for monitoring therapeutic response in a wide range of cancers, including breast, esophageal, lung, head and neck, and lymphoma. FDG-PET can assess tumor glucose use with high reproducibility. Following therapy, the decrease of glucose use correlates with the reduction of viable tumor cells. FDG-PET allows the prediction of therapy response early in the course of therapy and determining the viability of residual masses after completion of treatment. The molecular basis for the success of FDG-PET is the rapid reduction of tumor glucose metabolism in effective therapies. Of even higher clinical relevance is the accurate identification of nonresponders in patients without a significant change in tumor glucose metabolism after initiation of therapy. PET imaging can easily visualize these changes in metabolic activity and indicate, sometimes within hours of the first treatment, whether or not a patient will respond to a particular therapy. In contrast to CT, MR imaging, or ultrasound, PET imaging allows identification of responding and nonresponding tumors early in the course of therapy. With this information, physicians can rapidly modify ineffective therapies for individual patients and thereby potentially improve patient outcomes and reduce cost. One of the major limitations for the routine application of FDG-PET imaging for therapy monitoring is that no generally accepted cutoff values have been established to differentiate optimally between responders and nonresponders. The patient series are still relatively small and frequently consist of different tumor types and different therapy regimens. Prospective studies including a sufficient number of patients are needed to define cutoff values to differentiate between responder and nonresponder for different tumors and different treatment regimes. In the future, PET imaging can also serve in the evaluation of new therapeutic agents, new experimental treatments, and specifically in monitoring clinical phase II studies.     

18F-FDG-PET zur Therapieverlaufskontrolle beim Ösophaguskarzinom

PET imaging with the glucose analog fluorodeoxyglucose (FDG-PET) has been evaluated in several studies to monitor tumor response in patients undergoing chemo- and radiotherapy. The clinical value of FDG-PET for differentiation of residual tumor and therapy induced fibrosis has been documented for esophageal cancer. Furthermore, there are now several reports suggesting that quantitative assessment of therapy induced changes in tumor FDG-uptake may allow prediction of tumor response and patient outcome very early in the course of therapy. This suggests that FDG-PET may be used to identify non-responders early during neoadjuvant chemoradiotherapy allowing for early modifications of the treatment protocol.     

Atypical growth on MRI in a case of Ewing’s sarcoma despite lower SUV on PET

Ewing’s sarcoma is a rare primary bone malignancy of small round blue cells. Treatment typically consists of neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy. The disease response to chemotherapy can be followed with fluorodeoxyglucose (FDG) positron emission tomography (PET), which measures the metabolic activity of the tumor, and by magnetic resonance imaging (MRI), which measures tumor size. We present a unique case in which the tumor grew in size following neoadjuvant chemotherapy but decreased in metabolic activity, making it difficult to judge efficacy of the chemotherapy. An atypical response to chemotherapy in this case caused tumor growth due to a fibrotic reaction while viable tumor cells were eradicated. This case highlights the ability of FDG-PET scan to identify the uncommon situation in which a tumor that increased in size may have had a favorable response to chemotherapy. This possibility should be considered in similar cases in which FDG-PET scan shows diminishing metabolic activity despite tumor growth.     

乳腺癌肿瘤浸润性淋巴细胞水平的影像评估进展

肿瘤浸润性淋巴细胞（TIL）是肿瘤免疫中最受关注的生物标志物,TIL对乳腺癌新辅助化疗和免疫治疗有协同作用,可改善临床疗效。目前采用的评估TIL的方法不能全面反映TIL在肿瘤组织中分布的时间和空间异质性,而影像学具有无创、简便和整体性的特点,被预期为评估乳腺癌TIL水平的有效方法。就乳腺MRI、超声以及PET/CT和PET/MRI等影像学方法评估乳腺癌TIL水平的研究进展予以综述。     

F-18 fluorodeoxyglucose-positron emission tomography imaging for primary breast cancer and loco-regional staging

Breast cancer is the most common female malignancy in Western countries. The limitations of mammography, ultrasound and MRI do not allow reliable identification of primary breast cancer at early stages. Functional breast imaging with positron emission tomography (PET) and F-18 fluorodeoxyglucose (FDG) enables the visualization of increased glucose metabolism of breast cancer. However, despite the successful identification of primary breast cancer, FDG-PET provides a low sensitivity to detect small tumors. Therefore, FDG-PET does not allow screening of asymptomatic women and cannot be used to exclude breast cancer in patients with suspicious breast masses or abnormal mammography. FDG-PET is a powerful tool for staging of breast cancer patients, but does not detect micrometastases and small tumor infiltrated lymph nodes. Nevertheless, in patients with locally advanced breast cancer, PET accurately determines the extent of disease, particularly the loco-regional lymph node status. Advances in technology, for example the development of dedicated breast imaging devices such as positron emission mammography, hold promise to improve the detection of primary tumors in the future.     

Imaging findings of a biopsy-proven desmoid tumor of the axilla in a young female

Desmoid tumors (fibromatoses) are rare but locally aggressive tumors that do not metastasize. They are non-encapsulated, well-differentiated lesions made of fibroblasts and collagen, which mainly appear in the mesentery and abdominal wall. Rarely, these tumors can also occur in breasts, making up approximately 0.2% of all breast neoplasms. Treatment typically includes surgical excision and/or medical management.We describe a case of a 31-year-old female presenting with a mass in her left axilla that was biopsy proven to be a desmoid tumor. In this case report, we discuss the various imaging findings present on ultrasound, mammography, computed tomography, and magnetic resonance imaging.     

FDG-PET and CT in Evaluation of Chemotherapy in Advanced Head and Neck Cancer

Purpose: To compare [18F]2-deoxy-2-fluoro-D-glucose-positron emission tomography (FDG-PET) and computed tomography (CT) scans in assessment of response to neoadjuvant chemotherapy in advanced head and neck cancer.Materials and Methods: In a prospective clinical study, advanced head and neck cancer patients were enrolled in a neoadjuvant organ preservation protocol and received CT and FDG-PET scans prior to and after 2 or 3 rounds of chemotherapy. All patients had prechemotherapy and postchemotherapy tissue biopsies within the tumor region. Patients were then classified as pathologic complete response (PCR) or residual disease (RD) based on biopsies. Analysis of the tumor activity, using FDG-PET, was performed using standardized uptake ratios (SUR) in the region of the primary tumor. Analysis of the tumor size, using contrast enhanced CT, was performed using measurements of the primary tumor in 3 dimensions.Results: Nineteen of the 28 patients with stage III and IV cancer of the head and neck enrolled between December 1994 and May 1996 completed the study. Three patients were PCR and had a mean SUR reduction of 82% by positron emission tomography (PET) and volume reduction of 80% by CT. Sixteen patients had RD after chemotherapy, their SUR and volume reductions were 32% and 41%, respectively. Reduction in SUR with PET was significant. The mean tumor volume reduction by CT approached statistical significance. There was a positive correlation between the percent reduction in tumor volume and SUR (P < 0.004).Conclusion: FDG-PET and CT imaging are at least equivalent in correctly assessing tumor response to chemotherapy with a trend toward better performance by PET.     

Wertigkeit von Mammographie, Sonographie und MRT zur Verlaufsbeurteilung der neoadjuvanten Chemotherapie bei lokal fortgeschrittenem Mammakarzinom

Purpose

The aim of this study is to give an overview on the surveillance of response to neoadjuvant chemotherapy in locally advanced breast cancer with mammography, ultrasound and breast MRI.

Material and methods

The results of a recently presented study on surveillance in the course of chemotherapy with contrast-enhanced MRI are compared with ratings based on mammography and ultrasound.

Results

Contrast-enhanced MRI correlates best with the histological tumor size when compared with mammography and ultrasound. Tumors with a high HER2 score (2+ with positive FISH test or 3+) show a significantly higher response compared to tumors with a lower HER2 score: size p <0.01, maximum enhancement p <0.01 and area under the curve (AUC) p <0.05. Reduction of tumor size and enhancement are complementary parameters and are not correlated to each other (r=0.22).

Discussion

Contrast-enhanced MRI of the breast is a reliable method for quantification of the response to neoadjuvant chemotherapy. The reductions of tumor size and of tumor enhancement are not correlated. Therefore, it may be reasonable to take both aspects for quantification of therapy response into account. Further studies are needed for evaluation of the value of breast MRI as a prognostic factor.     

Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET).

Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patient's tumor and to predict the response to treatment at the earliest possible time. Since the development of neoadjuvant chemotherapy, PET has been proved to be the most sensitive and accurate imaging technique for early therapy response evaluation of breast tumors. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. The role of PET in the context of patient management and the cost-effectiveness of this approach needs further evaluation. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these.     

Response prediction by FDG-PET after neoadjuvant radiochemotherapy and combined regional hyperthermia of rectal cancer: correlation with endorectal ultrasound and histopathology

Accurate response assessment after neoadjuvant therapy is essential in patients with rectal cancer. The aim of this study was to assess the value of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting response of locally advanced rectal cancer to preoperative multimodal treatment. Twenty-two consecutive patients with locally advanced (uT3/4) primary rectal cancer were entered in this prospective pilot study. FDG-PET was performed before and after neoadjuvant radiochemotherapy (RCT) with combined regional hyperthermia (RHT). Treatment consisted of external-beam radiotherapy (45 Gy), chemotherapy (folinic acid and 5-fluorouracil) and regional pelvic hyperthermia followed by curative tumour resection 6–8 weeks later. Semi-quantitative measurements (SUV) of tumour FDG uptake were made before and 2–4 weeks after completion of neoadjuvant treatment. Two patients who did not receive post-therapeutic restaging by FDG-PET were excluded from the analysis. Results were correlated with findings on endorectal ultrasound (EUS, n=17 patients) and histopathology. Histopathological evaluation of the resected tumour revealed complete response in one patient, partial response in 12 and stable disease in seven. SUV reduction in tumours was significantly greater in responders than in non-responders [60% (±15%) vs 30% (±18%), P=0.003, CI=95%). Using a minimum post-therapeutic SUV reduction of 36% to define response, FDG-PET revealed a sensitivity of 100% (EUS: 33%) and a specificity of 86% (EUS: 80%) in response prediction; the corresponding positive and negative predictive values were 93% (EUS: 80%) and 100% (EUS: 33%), respectively. FDG-PET results were statistically significant (P<0.001, CI=95%). FDG-PET has great potential in the assessment of tumour response to neoadjuvant RCT in combination with RHT and is superior to EUS for this purpose.     

磁共振灌注成像对局部进展期乳腺癌新辅助化疗疗效的评价

目的:探讨磁共振T1WI首次通过灌注成像时局部进展期乳腺癌新辅助化疗疗效评价及其作为化疗反应预测因子的可行性.方法:根据新辅助化疗后体积改变将10例乳腺癌分为反应组和无反应组,比较分析化疗前后肿瘤体积、最大信号丢失率变化及化疗前最大信号丢失率与肿瘤缩退率间的相关关系.结果:化疗前两组体积及最大信号丢失率差异均无统计学意...     

乳腺良性叶状肿瘤术中乳腺内整形术10例分析

目的探讨乳腺良性叶状肿瘤临床诊断和治疗方法。方法回顾分析经手术病理确诊为乳腺良性叶状肿瘤10例患者的病历资料。结果乳腺肿块为首发症状且增长快速,术前超声、钼靶、核磁共振等影像学检查准确率50%,空芯针活检术前病理与术后病理相符率90%。局部扩大切除术随访至今未见复发,术中乳腺内成型能保证乳房的外形。结论术前空芯针活检是明确诊断的标准,局部扩大切除术可以作为乳腺良性叶状肿瘤的标准术式,术中乳腺瓣成型术能维持乳房的基本外形,值得推荐。     

Rhabdomyosarcoma of the breast

AIM: The aim of this study was to describe the first imaging studies of a primary embryonal rhabdomyosarcoma of the breast in an adult woman. PATIENT: This 45-year-old woman was seen for investigation of a palpable mass in the left breast. Examinations included mammography, Doppler ultrasound, and MRI. The diagnosis was made after surgical biopsy. Treatment consisted in neoadjuvant chemotherapy, followed by quadrantectomy and interstitial curietherapy. Imaging studies were performed both prior to and during therapy (i.e., after three then after six courses of chemotherapy). Imaging findings were correlated with histopathological findings. RESULTS: Mammography was not very contributive as the breasts were dense, particularly in the external left quadrants. On ultrasound, the mass had a tissue density and sharp contours; the mass was not highly vascularized on Doppler. MRI revealed a mass that enhanced markedly on both early and late contrast-enhanced T1-weighted sequences and was hyperintense on T2-weighted sequences. MRI appeared to be the best technique for the evaluation of the residual tissue. CONCLUSION: Rhabdomyosarcoma is a rare tumor in adults; to our knowledge, this is the first report describing the imaging features and value of MRI for the work-up and follow-up of mammary rhabdomyosarcoma.     

Gastrointestinal tract malignancies and positron emission tomography: an overview

(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is highly accurate in restaging colorectal cancer, esophageal cancer, and gastrointestinal stromal tumors. Overall, it compares favorably with anatomical imaging in the evaluation of tumor recurrence because metabolic abnormalities usually precede a structural change. Initial staging of these malignancies with PET is best used in patients with locally advanced disease who may benefit from curative resection if distant metastases are not found. It also appears to have great potential in predicting histopathologic response to neoadjuvant therapy and in monitoring the success of radiofrequency ablation and (90)Y microspheres radioembolization soon after intervention. FDG-PET can be used in other gastrointestinal malignancies as a prognostic tool and to detect distant disease but its role has not yet been well defined.     

Contrast-enhanced MRI in breast cancer patients eligible for breast-conserving therapy: complementary value for subgroups of patients

The aim of this study was to identify patients prior to breast-conserving therapy (BCT) who have complementary value of contrast-enhanced magnetic resonance imaging (MRI) over conventional imaging in the assessment of tumor extent. All patients were eligible for BCT according to conventional imaging, and underwent preoperative MRI as part of this study. One hundred and sixty-five patients (166 tumors) were included. MRI was defined to have complementary value if conventional imaging underestimated or overestimated tumor extent (by more than 10 mm compared to histology) and MRI assessed the extent accurately. Logistic regression was employed to identify characteristics that are predictive of the complementary value of preoperative MRI. MRI had complementary value in 39 cases (23%). Patients <58 years old with irregular lesion margins at mammography and discrepancy in tumor extent by more than 10 mm between mammography and ultrasonography had a 3.2× higher chance of accurate assessment at MRI (positive predictive value 50%, negative predictive value 84%, p=0.0002). Preoperative MRI in patients eligible for BCT is more accurate than conventional imaging in the assessment of tumor extent in approximately one out of four patients. Subgroups of patients in whom MRI has complementary value may be defined by the differences in clinical and imaging features.     

Evaluation of chemotherapy response in osteosarcoma with FDG-PET

Objective  The objective of this study is to evaluate the utility of positron emission tomography (PET) with 2-deoxy-[¹⁸F] fl uoro-D-glucose (FDG) in the assessment of the chemotherapy response of osteosarcoma when compared with the degree of necrosis determined histologically. Methods  Whole-body FDG-PET scan was performed on 11 patients with osteosarcoma. All patients received neoadjuvant chemotherapy. The tumor size changes on magnetic resonance imaging; FDG-PET standardized uptake values prior to (SUV₁) and following (SUV₂) chemotherapy were analyzed and correlated with response to chemotherapy as assessed using histopathology in surgically excised tumors. Nine patients underwent FDG-PET scan both prior to and following neoadjuvant chemotherapy. The remaining two patients were examined only prior to surgery. Results  Histologically, five patients had a good histologic response to chemotherapy (≧90% necrosis). The changes in tumor size did not correlate with histologic response (P > 0.05). SUV₂ with good response was significantly lower than that with poor response (1.93 ± 0.50, 5.86 ± 2.55, respectively). Both the positive and negative predictive values of the SUV₂ of less than 2.5 for a good response were 100%. Patients with good response showed a significantly higher ratio of SUV2 to SUV1 (SUV_2:1) than patients with poor response (0.74 ± 0.11, 0.26 ± 0.39, respectively, P < 0.05). The positive and negative predictive values of SUV_2:1 ≤ 0.5 for good and poor responses were 80% and 100%, respectively. Conclusions  FDG-PET imaging of osteosarcoma correlates positively with histologic response to neoadjuvant chemotherapy. SUV₂ and SUV_2:1 could be feasible as non-invasive surrogate predictors of response in osteosarcoma patients.