Impact of factors affecting the residual tumor size diagnosed by MRI following neoadjuvant chemotherapy in comparison to pathology.

BACKGROUND AND OBJECTIVES: To investigate accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: Ninety-eight patients were studied. Several MRI were performed during NAC for response monitoring, and the residual tumor size was measured on last MRI after completing NAC. Covariates, including age, tumor characteristics, biomarkers, NAC regimens, MRI scanners, and time from last MRI to operation, were analyzed. Univariate and Multivariate linear regression models were used to determine the predictive value of these covariates for MRI-pathology size discrepancy as the outcome measure. RESULTS: The mean (±SD) of the absolute difference between MRI and pathological residual tumor size was 1.0 ± 2.0 cm (range, 0-14 cm). Univariate regression analysis showed tumor type, morphology, HR status, HER2 status, and MRI scanner (1.5 T or 3.0 T) were significantly associated with MRI-pathology size discrepancy (all P < 0.05). Multivariate regression analyses demonstrated that only tumor type, tumor morphology, and biomarker status considering both HR and HER-2 were independent predictors (P = 0.0014, 0.0032, and 0.0286, respectively). CONCLUSION: The accuracy of MRI in evaluating residual tumor size depends on tumor type, morphology, and biomarker status. The information may be considered in surgical planning for NAC patients.

Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile.

BACKGROUND: This study aimed to evaluate the influence of hormone receptor (HR) and Ki-67 proliferation markers in predicting the accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in patients with HER2-negative (HER2(-)) breast cancer receiving neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Fifty-four women were studied. Patients received AC (doxorubicin (Adriamycin)/cyclophosphamide) and/or taxane-based regimens. The accuracy of MR-determined clinical complete response (CCR) was compared to pathological complete response (pCR). The size of detectable residual tumor on MRI was correlated with pathologically diagnosed tumor size using the Pearson correlation. RESULTS: MRI correctly diagnosed 16 of the 17 cases of pCR. There were 8 false-negative diagnoses: 7 HR(+) and 1 HR(-). The overall sensitivity, specificity, and accuracy of MRI were 78%, 94%, and 83%, respectively. The positive predictive value was 97% and the negative predictive value was 67%. For MRI vs. pathologically determined tumor size correlation, HR(-) cancers showed a higher correlation (R = 0.79) than did HR(+) cancers (R = 0.58). A worse MRI/pathology size discrepancy was found in HR(+) cancer than in HR(-)cancer (1.6 ± 2.8 cm vs. 0.56 ± 0.9 cm; P = .05). Tumors with low Ki-67 proliferation (< 40%) showed a larger size discrepancy than did those with high Ki-67 proliferation (≥ 40%) (1.2 ± 2.0 cm vs. 0.4 ± 0.8 cm; P = .05). CONCLUSIONS: The results showed that the diagnostic performance of MRI for patients with breast cancer undergoing NAC is associated with a molecular biomarker profile. Among HER2(-)tumors, the accuracy of MRI was worse in HR(+)cancers than in HR(-)cancers and was also worse in low-proliferation tumors than in high-proliferation tumors. These findings may help in surgical planning.

Breast cancer: evaluation of response to neoadjuvant chemotherapy with 3.0-T MR imaging.

PURPOSE: To assess how the molecular biomarker status of a breast cancer, including human epidermal growth factor receptor 2 (HER2), hormone receptors, and the proliferation marker Ki-67 status, affects the diagnosis at 3.0-T magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Fifty patients (age range, 28-82 years; mean age, 49 years) receiving neoadjuvant chemotherapy were monitored with 3.0-T MR imaging. The longest dimension of the residual cancer was measured at MR imaging and correlated with pathologic findings. Patients were further divided into subgroups on the basis of HER2, hormone receptor, and Ki-67 status. Pathologic complete response (pCR) was defined as when there were no residual invasive cancer cells. The Pearson correlation was used to correlate MR imaging-determined and pathologic tumor size, and the unpaired t test was used to compare MR imaging-pathologic size discrepancies. RESULTS: Of the 50 women, 14 achieved pCR. There were seven false-negative diagnoses at MR imaging. The overall sensitivity, specificity, and accuracy for diagnosing invasive residual disease at MR imaging were 81%, 93%, and 84%, respectively. The mean MR imaging-pathologic size discrepancy was 0.5 cm ± 0.9 (standard deviation) for HER2-positive cancer and 2.3 cm ± 3.5 for HER2-negative cancer (P = .009). In the HER2-negative group, the size discrepancy was smaller for hormone receptor-negative than for hormone receptor-positive cancers (1.0 cm ± 1.1 vs 3.0 cm ± 4.0, P = .04). The size discrepancy was smaller in patients with 40% or greater Ki-67 expression (0.8 cm ± 1.1) than in patients with 10% or less Ki-67 expression (3.9 cm ± 5.1, P = .06). CONCLUSION: The diagnostic accuracy of breast MR imaging is better in more aggressive than in less aggressive cancers. When MR imaging is used for surgical planning, caution should be taken with HER2-negative hormone receptor-positive cancers.

Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment.

Approximately 8-20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.

Impact of MRI-evaluated neoadjuvant chemotherapy response on change of surgical recommendation in breast cancer.

OBJECTIVE: To investigate how MRI imaging of neoadjuvant chemotherapy (NAC) tumor response affects the recommendation for optimal breast cancer surgery, both before and after NAC. SUMMARY BACKGROUND DATA: Understanding how imaging findings are incorporated into surgeons' decision-making processes will help establish appropriate imaging guidelines for recommending breast conservation surgery (BCS) after the NAC. METHODS: Seventy-six breast cancer patients undergoing NAC with MRI follow-up studies were analyzed. Two experienced breast surgeons reviewed all cases. An initial surgical recommendation was made based on the pre-NAC lesion presentation; a subsequent surgical recommendation was made based on the post-NAC tumor response. Finally, the pathology results were disclosed and the surgeons were asked to decide on the optimal definitive surgical procedure. MRI findings throughout the entire course of the NAC were analyzed to understand how they affected different recommendations. RESULTS: Before the NAC, a large tumor size or extent of disease were the primary determinant factors for mastectomy. In this study, the mean tumor size was 5.3 +/- 3.4 cm (RECIST) in the mastectomy group and 3.2 +/- 1.6 cm in the lumpectomy group (P = 0.0001). After the NAC, based on consensus recommendations, 21 mastectomy candidates remained for mastectomy, with tumor size decreasing from 7.4 +/- 4.5 to 1.5 +/- 2.5 cm, and 22 mastectomy candidates were changed to lumpectomy, with tumor size decreasing from 4.2 +/- 2.1 to 0.4 +/- 0.6 cm. When the final pathology revealed pCR or minimal residual disease, the surgeons agreed that BCS is the optimal procedure. On the other hand, for a large extent of residual disease, mastectomy should be performed. CONCLUSION: In patients who had more extensive pretreatment disease, despite an excellent response to NAC, the surgeons still tended to apply an aggressive approach and recommended mastectomy. Given that the confirmation of pCR or minimal residual disease would change surgeons' recommendations for less aggressive, conservation surgery, the maturity of MRI for NAC response prediction may provide reliable staging information to aid in the recommendation of the optimal surgical procedure.

The predictive value of sentinel lymph node biopsy in locally advanced breast cancer patients who have undergone neoadjuvant chemotherapy.

With the increasing usage of neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC), there is the need to investigate the routine axillary node dissections performed in this group of patients. Controversy exists about the utility of sentinel node biopsy (SNB), either before or after NAC. With the addition of trastuzumab in the treatment of Her2/neu-positive LABC patients, the validity of SNB in this subset population needs to be investigated. A retrospective study of 20 patients who underwent NAC for LABC was undertaken. The pathology of the axillary nodes, sentinel nodes, and primary tumor after neoadjuvant chemotherapy were examined. Twenty patients underwent NAC with doxorubicin and cyclophosphamide, followed sequentially by paclitaxel and carboplatin, with or without trastuzumab based on Her2/neu status. Post chemotherapy, 20 patients underwent mastectomy or lumpectomy with SNB with axillary node dissections. The overall accuracy of SNB was 95 per cent with a false-negative rate of 14 per cent (1/7). In Her2/neu-positive patients, overall accuracy was 100 per cent (8/8) and a false-negative rate of zero per cent. Sentinel node biopsy is a viable option in patients who have undergone NAC. Her2/neu-positive patients who had undergone NAC with trastuzumab had comparable accuracy for sentinel node biopsy in predicting axillary node status.

Predicting nodal status using dynamic contrast-enhanced magnetic resonance imaging in patients with locally advanced breast cancer undergoing neoadjuvant chemotherapy with and without sequential trastuzumab.

HYPOTHESIS: Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) is a reliable and accurate method for monitoring primary tumor response in the breast and can be used as a surrogate to predict final axillary nodal status. DESIGN: Retrospective study (October 1, 2004, through February 28, 2006) of 46 patients with clinically staged locally advanced breast cancer. SETTING: Comprehensive cancer center. PATIENTS: Forty-six patients with locally advanced breast cancer. INTERVENTIONS: Neoadjuvant chemotherapy (NAC), DCE-MRI, mastectomy and lumpectomy, and axillary lymph node dissection. MAIN OUTCOME MEASURES: The DCE-MRI results and pathologic response of the breast and axillary lymph nodes. RESULTS: Forty-six patients underwent NAC with doxorubicin hydrochloride and cyclophosphamide, followed by paclitaxel and carboplatin, with or without trastuzumab based on human epidermal growth factor receptor 2 (HER2/neu) status. Twenty-one patients (46%) had a complete pathologic response. For the HER2/neu-positive patients, the complete pathologic response rate was 70% (14/20). The accuracy, sensitivity, and specificity of the primary tumor response in predicting the axillary nodal status were 78%, 88%, and 72%, respectively. The accuracy, sensitivity, and specificity of the DCE-MRI-measured response in the primary tumor in predicting axillary nodal status were 74%, 62%, and 82%, respectively. For the HER2/neu-positive patients, the accuracy, sensitivity, and specificity improved to 80%, 75%, and 82%, respectively. CONCLUSIONS: The results of DCE-MRI of the primary tumor can be predictive of axillary nodal status, especially in patients receiving trastuzumab who are HER2/neu positive. The HER2/neu-positive patients with a complete clinical response on DCE-MRI are highly unlikely to benefit from an axillary lymph node dissection. For HER2/neu-negative patients, sentinel lymph node sampling is warranted.

Hepatobiliary cystadenoma: a case report and a review of the literature.

BACKGROUND: Hepatic cystic lesions are rare; however, their management and treatment is dependent on early recognition and diagnosis. METHODS: In this report, the authors discuss a 72-year-old woman who presented to their clinic for treatment of a hepatocystadenoma. RESULTS: The history, physical examination, and diagnostic modalities lead to surgical intervention despite an unclear diagnosis. CONCLUSIONS: This case illustrates an unusual hepatic lesion in which the diagnosis was not known until the time of laparotomy. However, diagnostic modalities were important in establishing the need for surgical intervention. The authors offer a pertinent review of the literature and discuss current treatment modalities.

Duodenocaval fistula: a late complication of retroperitoneal irradiation and vena cava replacement.

Duodenocaval fistula (DCF), an unusual pathology, is associated with a 40% mortality rate in the 36 patients previously reported. Although migrating or ingested foreign bodies, trauma, and peptic ulcer disease are often described etiologies, 11 patients have been described who developed DCF after resection of retroperitoneal tumors, 9 of whom also had postoperative radiotherapy. We report two patients who developed DCF after resection of retroperitoneal tumors followed by radiation therapy. The first patient, a 56-year-old female, presented with upper gastrointestinal hemorrhage requiring transfusion caused by a duodenoprosthetic caval fistula 7 years after successful resection of a retroperitoneal leiomyosarcoma and replacement of the inferior vena cava followed by radiation and chemotherapy. The second patient, a 37-year-old male who had previously undergone resection of a retroperitoneal sarcoma followed by external radiotherapy, developed massive upper and lower gastrointestinal bleeding secondary to a duodenocaval fistula. The etiology, diagnosis, and treatment of DCF are analyzed with an emphasis on DCF following resection and irradiation of retroperitoneal tumors. In most patients, "spontaneous" DCF have occurred as a late complication of high-dose radiation for carcinoma of the right kidney or retroperitoneal structures.

Microsatellite instability in Japanese vs European American patients with gastric cancer.

BACKGROUND: The stage-stratified survival following gastrectomy for gastric cancer is far better in Japan than in the United States. The process of carcinogenesis may differ in gastric cancers from Japan and the United States, accounting for prognostic differences, as patients of Asian descent treated in United States also exhibit superior survival in comparison with non-Asian patients. HYPOTHESIS: The phenotype of gastric cancer differs between Japanese and American patients. DESIGN: Retrospective case-case (blinded) study. SETTING: University hospitals in Japan and the United States. PATIENTS AND METHODS: We compared the frequency of microsatellite instability (MSI) at 7 loci from formalin-fixed paraffin-embedded gastrectomy specimens, between cases of gastric cancer at Hitachi General Hospital (N = 18) and in US patients of European descent treated in Orange County, Calif (N = 20). Microsatellite instability, Lauren classification, and T stage were determined without knowledge of the country of origin of the specimens. MAIN OUTCOME MEASURE: The frequency of MSI in Japanese vs European American gastric cancer specimens. RESULTS: The frequency of MSI in Japanese gastric carcinoma specimens was higher than in specimens from American patients of European descent (39% vs 20%, respectively). In contrast, a high frequency of MSI was demonstrated in only 3 European American specimens (15% of all specimens in this group). Tumors from Japanese and American men were more likely to demonstrate MSI than those from women (50% vs 5.6%, respectively; P =.004). Among advanced-stage tumors, Japanese specimens were significantly more likely to demonstrate MSI (55%) than European American specimens (7.1%; P =.02). Specimens from Japan and America demonstrating MSI were equally likely to be from men, involve the gastroesophageal junction, and demonstrate intestinal histologic abnormalities. CONCLUSIONS: Advanced gastric cancers from Japan are more likely to demonstrate MSI. These data warrant a study of larger numbers of patients to assess whether differences in MSI expression correlates with prognostic differences between gastric carcinoma in patients in Japan vs the United States.