Management of soft tissue sarcomas of the chest wall: a comprehensive overview.

Sarcomas of the chest wall are rare and their current treatment regimen is diverse and complex due to the heterogeneity of these tumors as well as the variations in tumor location and extent. They only account for 0.04% of newly diagnosed cancers of whom about 45% comprise soft tissue sarcomas. Larger cohort studies are scarce and often focus on one specific treatment item. We therefore aim to provide helicopter view for clinicians treating patients with sarcomas of the chest wall, focusing mainly on soft tissue sarcomas. This overview includes the value of neoadjuvant systemic or radiotherapy, surgical resection, approaches for thoracic wall reconstruction, and the need for follow-up. Provided the heterogeneity and relative rarity, we recommend that treatment decisions in soft tissue sarcoma of the chest wall are discussed in a multidisciplinary tumor board at a reference sarcoma center or within sarcoma networks to ensure personalized, rational decision making. A surgical oncologist specialized in sarcoma surgery is crucial, and for extensive resections involving the thoracic cavity we recommend involvement of a thoracic surgeon. In addition, a specialized medical- and radiation oncologist as well as a plastic surgeon is required to ensure the best multimodality treatment plan to optimize patient outcome.

Lipid profiling of electrosurgical vapors for real-time assistance of soft tissue sarcoma resection.

BACKGROUND: Soft tissue sarcomas (STS) constitute a heterogeneous group of rare tumor entities. Treatment relies on challenging patient-tailored surgical resection. Real-time intraoperative lipid profiling of electrosurgical vapors by rapid evaporative ionization mass spectrometry (REIMS) may aid in achieving successful surgical R0 resection (i.e., microscopically negative-tumor margin resection). Here, we evaluate the ex vivo accuracy of REIMS to discriminate and identify various STS from normal surrounding tissue. METHODS: Twenty-seven patients undergoing surgery for STS at Maastricht University Medical Center+ were included in the study. Samples of resected STS specimens were collected and analyzed ex vivo using REIMS. Electrosurgical cauterization of tumor and surrounding was generated successively in both cut and coagulation modes. Resected specimens were subsequently processed for gold standard histopathological review. Multivariate statistical analysis (principal component analysis-linear discriminant analysis) and leave-one patient-out cross-validation were employed to compare the classifications predicted by REIMS lipid profiles to the pathology classifications. Electrosurgical vapors produced during sarcoma resection were analyzed in vivo using REIMS. RESULTS: In total, 1200 histopathologically-validated ex vivo REIMS lipid profiles were generated from 27 patients. Ex vivo REIMS lipid profiles classified STS and normal tissues with 95.5% accuracy. STS, adipose and muscle tissues were classified with 98.3% accuracy. Well-differentiated liposarcomas and adipose tissues could not be discriminated based on their respective lipid profiles. Distinction of leiomyosarcomas from other STS could be achieved with 96.6% accuracy. In vivo REIMS analyses generated intense mass spectrometric signals. CONCLUSION: Lipid profiling by REIMS is able to discriminate and identify STS with high accuracy and therefore constitutes a potential asset to improve surgical resection of STS in the future.

The prognostic impact of BMI in patients with HR+/HER2- advanced breast cancer: a study of the SONABRE registry.

PURPOSE: This study determines the prognostic impact of body mass index (BMI) in patients with hormone receptor-positive/human epidermal growth factor receptor-2-negative (HR+/HER2-) advanced (i.e., metastatic) breast cancer (ABC). METHODS: All patients with HR+/HER2- ABC who received endocrine therapy +-a cyclin-dependent kinase 4/6 inhibitor as first-given systemic therapy in 2007-2020 in the Netherlands were identified from the Southeast Netherlands Advanced Breast Cancer (SONABRE) registry (NCT03577197). Patients were categorised as underweight (BMI: < 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese (≥ 30.0 kg/m2). Overall survival (OS) and progression-free survival (PFS) were compared between BMI classes using multivariable Cox regression analyses. RESULTS: This study included 1456 patients, of whom 35 (2%) were underweight, 580 (40%) normal weight, 479 (33%) overweight, and 362 (25%) obese. No differences in OS were observed between normal weight patients and respectively overweight (HR 0.99; 95% CI 0.85-1.16; p = 0.93) and obese patients (HR 1.04; 95% CI 0.88-1.24; p = 0.62). However, the OS of underweight patients (HR 1.45; 95% CI 0.97-2.15; p = 0.07) tended to be worse than the OS of normal weight patients. When compared with normal weight patients, the PFS was similar in underweight (HR 1.05; 95% CI 0.73-1.51; p = 0.81), overweight (HR 0.90; 95% CI 0.79-1.03; p = 0.14), and obese patients (HR 0.88; 95% CI 0.76-1.02; p = 0.10). CONCLUSION: In this study among 1456 patients with HR+/HER2- ABC, overweight and obesity were prevalent, whereas underweight was uncommon. When compared with normal weight, overweight and obesity were not associated with either OS or PFS. However, underweight seemed to be an adverse prognostic factor for OS.

Predictive Genetic Biomarkers for the Development of Peritoneal Metastases in Colorectal Cancer.

Metastatic colorectal cancer (CRC) is a common cause of cancer-related mortality, of which peritoneal metastases (PMs) have the worse outcome. Metastasis-specific markers may help predict the spread of tumor cells and select patients for preventive strategies. This exploratory pilot study aimed to gain more insight into genetic alterations in primary CRC tumors, which might be a predictive factor for the development of PM. Forty patients with T3 stage CRC were retrospectively divided in three groups: without metachronous metastases during 5-year follow-up (M0, n = 20), with metachronous liver metastases (LM, n = 10) and with metachronous PM (PM, n = 10). Patients with synchronous metastases were excluded. Primary formalin-fixed paraffin-embedded tumor samples were analyzed via comprehensive genome sequencing (TSO500 analysis) to identify DNA alterations and RNA fusion transcripts in 523 genes and 55 genes, respectively. Thirty-eight samples were included for final analysis. Four M0 tumors and one PM tumor were microsatellite instable. BRAF mutations were uniquely identified in three microsatellite-stable (MSS) PM tumors (37.5%, p = 0.010). RNA analysis showed an additional FAM198A-RAF1 fusion in one PM sample. BRAF p.V600E mutations were only present in PM patients with MSS tumors. Greater attention should be paid to BRAF-mutated tumors in relation to the development of metachronous PM.

Diagnostic Value of Four-Dimensional Dynamic Computed Tomography for Primary Hyperparathyroidism in Patients with Low Baseline Parathyroid Hormone Levels.

Low baseline levels of parathyroid hormone (PTH) are associated with a higher rate of multiglandular disease, lower localization rates of preoperative imaging modalities, and a higher rate of unsuccessful minimally invasive parathyroidectomies. The objective of this study is to assess the diagnostic value of four-dimensional dynamic computed tomography (4D-CT) in localizing primary hyperparathyroidism (pHPT) in patients with low baseline PTH levels, compared to patients with high baseline PTH levels. Patients with pHPT who received a 4D-CT scan as part of their standard diagnostic evaluation were divided into two groups based on the following criteria: (1) preoperative PTH levels less than 100 pg/mL and (2) patients with preoperative PTH levels greater than 100 pg/mL. All patients underwent parathyroidectomy based on 4D-CT findings, with intraoperative parathyroid hormone monitoring. The lesion-based sensitivity of 4D-CT was 88% in patients with low baseline PTH levels and 94.7% in patients with high baseline PTH levels (p = 0.33). However, the success rate of image-guided resection based on 4D-CT findings was 71.4% in the low baseline PTH group compared to 90.6% in the high baseline PTH group (p = 0.06). Our study demonstrated that 4D-CT has a high lesion-based sensitivity in patients with pHPT and low baseline PTH levels but led to a relatively low rate of successful image-guided resection in patients with low baseline PTH levels. Therefore, it is important to exercise increased caution during 4D-CT-guided surgical exploration of patients with low baseline PTH levels to ensure successful surgical resection of all parathyroid lesions.

Diagnostic Performance of Magnetic Resonance Imaging for Parathyroid Localization of Primary Hyperparathyroidism: A Systematic Review.

Accurate preoperative localization is crucial for successful minimally invasive parathyroidectomy in primary hyperparathyroidism (PHPT). Preoperative localization can be challenging in patients with recurrent and/or multigland disease (MGD). This has led clinicians to investigate multiple imaging techniques, most of which are associated with radiation exposure. Magnetic resonance imaging (MRI) offers ionizing radiation-free and accurate imaging, making it an attractive alternative imaging modality. The objective of this systematic review is to provide an overview of the diagnostic performance of MRI in the localization of PHPT. PubMed and Embase libraries were searched from 1 January 2000 to 31 March 2023. Studies were included that investigated MRI techniques for the localization of PHPT. The exclusion criteria were (1) secondary/tertiary hyperparathyroidism, (2) studies that provided no diagnostic performance values, (3) studies published before 2000, and (4) studies using 0.5 Tesla MRI scanners. Twenty-four articles were included in the systematic review, with a total of 1127 patients with PHPT. In 14 studies investigating conventional MRI for PHPT localization, sensitivities varied between 39.1% and 94.3%. When employing more advanced MRI protocols like 4D MRI for PHPT localization in 11 studies, sensitivities ranged from 55.6% to 100%. The combination of MR imaging with functional techniques such as 18F-FCH-PET/MRI yielded the highest diagnostic accuracy, with sensitivities ranging from 84.2% to 100% in five studies. Despite the limitations of the available evidence, the results of this review indicate that the combination of MR imaging with functional imaging techniques such as 18F-FCH-PET/MRI yielded the highest diagnostic accuracy. Further research on emerging MR imaging modalities, such as 4D MRI and PET/MRI, is warranted, as MRI exposes patients to minimal or no ionizing radiation compared to other imaging modalities.

Detection of differentiated thyroid carcinoma in exhaled breath with an electronic nose.

This proof-of-principle study investigates the diagnostic performance of the Aeonose in differentiating malignant from benign thyroid diseases based on volatile organic compound analysis in exhaled breath. All patients with a suspicious thyroid nodule planned for surgery, exhaled in the Aeonose. Definitive diagnosis was provided by histopathological determination after surgical resection. Breath samples were analyzed utilizing artificial neural networking. About 133 participants were included, 48 of whom were diagnosed with well-differentiated thyroid cancer. A sensitivity of 0.73 and a negative predictive value (NPV) of 0.82 were found. The sensitivity and NPV improved to 0.94 and 0.95 respectively after adding clinical variables via multivariate logistic regression analysis. This study demonstrates the feasibility of the Aeonose to discriminate between malignant and benign thyroid disease. With a high NPV, low cost, and non-invasive nature, the Aeonose may be a promising diagnostic tool in the detection of thyroid cancer.

Axillary Pathologic Complete Response After Neoadjuvant Systemic Therapy by Breast Cancer Subtype in Patients With Initially Clinically Node-Positive Disease: A Systematic Review and Meta-analysis.

Importance: An overview of rates of axillary pathologic complete response (pCR) for all breast cancer subtypes, both for patients with and without pathologically proven clinically node-positive disease, is lacking. Objective: To provide pooled data of all studies in the neoadjuvant setting on axillary pCR rates for different breast cancer subtypes in patients with initially clinically node-positive disease. Data Sources: The electronic databases Embase and PubMed were used to conduct a systematic literature search on July 16, 2020. The references of the included studies were manually checked to identify other eligible studies. Study Selection: Studies in the neoadjuvant therapy setting were identified regarding axillary pCR for different breast cancer subtypes in patients with initially clinically node-positive disease (ie, defined as node-positive before the initiation of neoadjuvant systemic therapy). Data Extraction and Synthesis: Two reviewers independently selected eligible studies according to the inclusion criteria and extracted all data. All discrepant results were resolved during a consensus meeting. To identify the different subtypes, the subtype definitions as reported by the included articles were used. The random-effects model was used to calculate the overall pooled estimate of axillary pCR for each breast cancer subtype. Main Outcomes and Measures: The main outcome of this study was the rate of axillary pCR and residual axillary lymph node disease after neoadjuvant systemic therapy for different breast cancer subtypes, differentiating studies with and without patients with pathologically proven clinically node-positive disease. Results: This pooled analysis included 33 unique studies with 57 531 unique patients and showed the following axillary pCR rates for each of the 7 reported subtypes in decreasing order: 60% for hormone receptor (HR)-negative/ERBB2 (formerly HER2)-positive, 59% for ERBB2-positive (HR-negative or HR-positive), 48% for triple-negative, 45% for HR-positive/ERBB2-positive, 35% for luminal B, 18% for HR-positive/ERBB2-negative, and 13% for luminal A breast cancer. No major differences were found in the axillary pCR rates per subtype by analyzing separately the studies of patients with and without pathologically proven clinically node-positive disease before neoadjuvant systemic therapy. Conclusions and Relevance: The HR-negative/ERBB2-positive subtype was associated with the highest axillary pCR rate. These data may help estimate axillary treatment response in the neoadjuvant setting and thus select patients for more or less invasive axillary procedures.

Dedicated Axillary MRI-Based Radiomics Analysis for the Prediction of Axillary Lymph Node Metastasis in Breast Cancer.

Radiomics features may contribute to increased diagnostic performance of MRI in the prediction of axillary lymph node metastasis. The objective of the study was to predict preoperative axillary lymph node metastasis in breast cancer using clinical models and radiomics models based on T2-weighted (T2W) dedicated axillary MRI features with node-by-node analysis. From August 2012 until October 2014, all women who had undergone dedicated axillary 3.0T T2W MRI, followed by axillary surgery, were retrospectively identified, and available clinical data were collected. All axillary lymph nodes were manually delineated on the T2W MR images, and quantitative radiomics features were extracted from the delineated regions. Data were partitioned patient-wise to train 100 models using different splits for the training and validation cohorts to account for multiple lymph nodes per patient and class imbalance. Features were selected in the training cohorts using recursive feature elimination with repeated 5-fold cross-validation, followed by the development of random forest models. The performance of the models was assessed using the area under the curve (AUC). A total of 75 women (median age, 61 years; interquartile range, 51-68 years) with 511 axillary lymph nodes were included. On final pathology, 36 (7%) of the lymph nodes had metastasis. A total of 105 original radiomics features were extracted from the T2W MR images. Each cohort split resulted in a different number of lymph nodes in the training cohorts and a different set of selected features. Performance of the 100 clinical and radiomics models showed a wide range of AUC values between 0.41-0.74 and 0.48-0.89 in the training cohorts, respectively, and between 0.30-0.98 and 0.37-0.99 in the validation cohorts, respectively. With these results, it was not possible to obtain a final prediction model. Clinical characteristics and dedicated axillary MRI-based radiomics with node-by-node analysis did not contribute to the prediction of axillary lymph node metastasis in breast cancer based on data where variations in acquisition and reconstruction parameters were not addressed.

Applying the electronic nose for pre-operative SARS-CoV-2 screening.

BACKGROUND: Infection with SARS-CoV-2 causes corona virus disease (COVID-19). The most standard diagnostic method is reverse transcription-polymerase chain reaction (RT-PCR) on a nasopharyngeal and/or an oropharyngeal swab. The high occurrence of false-negative results due to the non-presence of SARS-CoV-2 in the oropharyngeal environment renders this sampling method not ideal. Therefore, a new sampling device is desirable. This proof-of-principle study investigated the possibility to train machine-learning classifiers with an electronic nose (Aeonose) to differentiate between COVID-19-positive and negative persons based on volatile organic compounds (VOCs) analysis. METHODS: Between April and June 2020, participants were invited for breath analysis when a swab for RT-PCR was collected. If the RT-PCR resulted negative, the presence of SARS-CoV-2-specific antibodies was checked to confirm the negative result. All participants breathed through the Aeonose for five minutes. This device contains metal-oxide sensors that change in conductivity upon reaction with VOCs in exhaled breath. These conductivity changes are input data for machine learning and used for pattern recognition. The result is a value between - 1 and + 1, indicating the infection probability. RESULTS: 219 participants were included, 57 of which COVID-19 positive. A sensitivity of 0.86 and a negative predictive value (NPV) of 0.92 were found. Adding clinical variables to machine-learning classifier via multivariate logistic regression analysis, the NPV improved to 0.96. CONCLUSIONS: The Aeonose can distinguish COVID-19 positive from negative participants based on VOC patterns in exhaled breath with a high NPV. The Aeonose might be a promising, non-invasive, and low-cost triage tool for excluding SARS-CoV-2 infection in patients elected for surgery.

Stromal vapors for real-time molecular guidance of breast-conserving surgery.

Achieving radical tumor resection while preserving disease-free tissue during breast-conserving surgery (BCS) remains a challenge. Here, mass spectrometry technologies were used to discriminate stromal tissues reported to be altered surrounding breast tumors, and build tissue classifiers ex vivo. Additionally, we employed the approach for in vivo and real-time classification of breast pathology based on electrosurgical vapors. Breast-resected samples were obtained from patients undergoing surgery at MUMC+. The specimens were subsequently sampled ex vivo to generate electrosurgical vapors analyzed by rapid evaporative ionization mass spectrometry (REIMS). Tissues were processed for histopathology to assign tissue components to the mass spectral profiles. We collected a total of 689 ex vivo REIMS profiles from 72 patients which were analyzed using multivariate statistical analysis (principal component analysis-linear discriminant analysis). These profiles were classified as adipose, stromal and tumor tissues with 92.3% accuracy with a leave-one patient-out cross-validation. Tissue recognition using this ex vivo-built REIMS classification model was subsequently tested in vivo on electrosurgical vapors. Stromal and adipose tissues were classified during one BCS. Complementary ex vivo analyses were performed by REIMS and by desorption electrospray ionization mass spectrometry (DESI-MS) to study the potential of breast stroma to guide BCS. Tumor border stroma (TBS) and remote tumor stroma (RTS) were classified by REIMS and DESI-MS with 86.4% and 87.8% accuracy, respectively. We demonstrate the potential of stromal molecular alterations surrounding breast tumors to guide BCS in real-time using REIMS analysis of electrosurgical vapors.

Diagnostic performance of standard breast MRI compared to dedicated axillary MRI for assessment of node-negative and node-positive breast cancer.

OBJECTIVES: To investigate whether breast MRI has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. METHODS: Forty-seven patients were included. All had undergone both breast MRI and dedicated axillary MRI, followed by surgery. All included breast MRI exams had complete field of view (FOV) of the axillary region. First, unenhanced T2-weighted (T2W) and subsequent diffusion-weighted (DW) images of both MRI exams were independently analyzed by two breast radiologists using a confidence scale and compared to histopathology. ADC values were measured by two researchers independently. Diagnostic performance parameters were calculated on a patient-by-patient basis. RESULTS: T2W breast MRI had the following diagnostic performance: sensitivity of 50.0% and 62.5%, specificity of 92.3%, PPV of 57.1% and 62.5%, NPV of 90.0% and 92.3%, and AUC of 0.72 for reader 1 and 0.78 for reader 2. T2W dedicated axillary MRI had the following diagnostic performance: sensitivity of 37.5% and 62.5%, specificity of 82.1% and 92.3%, PPV of 44.6% and 50.0%, NPV of 87.8% and 91.4%, and AUC of 0.65 for reader 1 and 0.73 for reader 2. In both evaluations, addition of DW images resulted in comparable diagnostic performance. For both breast MRI and dedicated axillary MRI, there was no significant difference between mean ADC values of benign and malignant lymph nodes. CONCLUSIONS: T2W breast MRI with complete FOV of the axillary region has comparable diagnostic performance as T2W dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. Optimization of T2W breast MRI protocol by including a complete FOV of the axillary region can, therefore, be recommended in clinical practice. KEY POINTS: • Breast MRI with complete field of view of the axillary region has comparable diagnostic performance as dedicated axillary MRI regarding assessment of node-negative and node-positive breast cancer. • Optimization of breast MRI protocol by including a complete field of view of the axillary region is recommended in clinical practice. • For both breast MRI and dedicated axillary MRI, DW imaging (including ADC measurements) is of no added value.

MRI predicts increased eligibility for sphincter preservation after CRT in low rectal cancer.

Chemoradiation increases the eligibility for sphincter preservation in low rectal cancer, as assessed by MRI. INTRODUCTION: We evaluated whether MRI can predict sphincter preservation after chemoradiation (CRT), and whether the feasibility of sphincter preservation increases after CRT, when compared with MRI before neoadjuvant treatment. METHODS: 85 patients with low rectal tumour (≤5 cm from anorectal junction (ARJ)) were included. Radiologist and a surgeon measured the tumour distance to ARJ, and assigned confidence level scores (CLS) for the feasibility of sphincter preserving surgery on MRI. Reference standard was the type of surgery, sphincter preserving vs. non-preserving. RESULTS: Tumour distance from the ARJ increased after CRT by 9 mm (p < 0.001). Eligibility for sphincter preservation increased by 21% for the radiologist and 25% for the surgeon, based on CLS. Cut-off for distance to the ARJ after CRT was 28 mm, aiming for optimal specificity. Diagnostic performance after CRT based on CLS yielded an AUC of 0.81 [95%CI 0.70-0.91] for the radiologist and 0.82 [95%CI 0.72-0.92] for the surgeon (p = 0.78). AUCs for tumour distance to the ARJ were 0.85 [95%CI 0.77-0.94] and 0.84 [95%CI 0.75-0.94], respectively (p = 0.84). Interobserver agreement for CLS was moderate before CRT (Κ 0.51; 95%CI 0.36-0.66) and after (K 0.54; 95%CI 0.39-0.69). Measurement of tumour distance to ARJ showed good agreement before (ICC 0.76; 95%CI 0.65-0.84) and after CRT (ICC 0.77; 95%CI 0.66-0.84). CONCLUSION: MRI can be a valuable adjunct in the decision making for sphincter preservation after CRT, with distance from the tumour to the ARJ as an accurate and reliable factor. CRT increases the tumour distance to the ARJ, leading to an estimated increase of sphincter preserving surgery in up to 21-25% of patients.

Feasibility of indocyanine green fluorescence imaging for intraoperative identification of parathyroid glands during thyroid surgery.

BACKGROUND: This study assessed the feasibility of near-infrared fluorescence imaging with indocyanine green (ICG) to identify the parathyroid glands (PGs) intraoperatively and to assess their perfusion after thyroid resection. METHODS: Patients undergoing elective thyroidectomy were enrolled in this prospective study. An intravenous bolus of 7.5 mg ICG was administered twice: the first bolus to identify the PGs before resection of the thyroid and the second to assess vascularization of the PGs after resection. RESULTS: A total of 30 operations in 26 patients were included. In 17 surgeries (56.7%), fluorescence imaging was of added value, especially to confirm the presence of a suspected PG. No intraoperative or postoperative complications occurred because of the use of ICG. CONCLUSION: Near-infrared fluorescence imaging with the use of ICG for intraoperative identification of the PGs and the assessment of its vascularization is feasible and safe and can provide more certainty about the location of the PGs.

Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer.

PURPOSE: Neoadjuvant chemoradiotherapy for rectal cancer can result in complete disappearance of tumor and involved nodes. In patients without residual tumor on imaging and endoscopy (clinical complete response [cCR]) a wait-and-see-policy (omission of surgery with follow-up) might be considered instead of surgery. The purpose of this prospective cohort study was to evaluate feasibility and safety of a wait-and-see policy with strict selection criteria and follow-up. PATIENTS AND METHODS: Patients with a cCR after chemoradiotherapy were prospectively selected for the wait-and-see policy with magnetic resonance imaging (MRI) and endoscopy plus biopsies. Follow-up was performed 3 to 6 monthly and consisted of MRI, endoscopy, and computed tomography scans. A control group of patients with a pathologic complete response (pCR) after surgery was identified from a prospective cohort study. Functional outcome was measured with the Memorial Sloan-Kettering Cancer Center (MSKCC) bowel function questionnaire and Wexner incontinence score. Long-term outcome was estimated by using Kaplan-Meier curves. RESULTS: Twenty-one patients with cCR were included in the wait-and-see policy group. Mean follow-up was 25 ± 19 months. One patient developed a local recurrence and had surgery as salvage treatment. The other 20 patients are alive without disease. The control group consisted of 20 patients with a pCR after surgery who had a mean follow-up of 35 ± 23 months. For these patients with a pCR, cumulative probabilities of 2-year disease-free survival and overall survival were 93% and 91%, respectively. CONCLUSION: A wait-and-see policy with strict selection criteria, up-to-date imaging techniques, and follow-up is feasible and results in promising outcome at least as good as that of patients with a pCR after surgery. The proposed selection criteria and follow-up could form the basis for future randomized studies.

Accuracy of gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer.

OBJECTIVE: To prospectively assess the accuracy of gadofosveset-enhanced magnetic resonance imaging (MRI) for nodal staging and restaging in rectal cancer. BACKGROUND: Accurate preoperative assessment of nodal disease in rectal cancer impacts treatment management. Staging with modern imaging techniques (computed tomography, MRI and endorectal ultrasound) is insufficiently accurate for clinical decision making. This study aims to assess the accuracy of MRI using a novel lymph node magnetic resonance contrast, gadofosveset, for nodal staging and restaging in rectal cancer using a per node comparison with histology as the reference standard. METHODS: Sixty-eight patients underwent gadofosveset-enhanced MRI at 1.5T. Twenty-six patients (primary staging group I) were treated with total mesorectal excision (with or without preoperative 5 × 5 Gy) and 42 (restaging group II) underwent a long course of chemoradiation followed by a restaging MRI and resection. Nodes were scored as benign or malignant by 2 radiologists (experienced and junior reader) first on standard MRI, then on gadofosveset-enhanced MRI. For group I the primary staging MRI was compared with histology. In group II the second, restaging MRI was compared with histology. RESULTS: For the experienced reader, sensitivity, specificity, and area under the ROC-curve (AUC) improved from 76%, 82% and 0.84 on standard MRI to 80%, 97% and 0.96 on gadofosveset-MRI (P < 0.001). For the junior reader results improved from 69%, 85%, and 0.85 on standard MRI to 70%, 95%, and 0.93 on gadofosveset-MRI (P = 0.03). Interobserver agreement was good on both standard MRI (κ 0.73) and gadofosveset-MRI (κ 0.71). CONCLUSIONS: This study shows high reproducibility and significantly improved accuracy compared to standard MRI for gadofosveset-enhanced MRI for nodal staging and restaging in rectal cancer.

MRI after chemoradiotherapy of rectal cancer: a useful tool to select patients for local excision.

PURPOSE: If identification of good responders to neoadjuvant chemoradiotherapy in rectal cancer is possible, there might be opportunities for local excision in selected patients. The aim of this study was to determine whether postchemoradiation MRI in rectal cancer can accurately identify ypT0 to 2/ypN0, because both features are essential for identification of good responders. METHODS: Seventy-nine patients (4 hospitals) underwent postchemoradiation MRI, 62 received a lymph node-specific contrast agent (ultrasmall superparamagnetic iron oxide). An expert and general radiologist prospectively predicted whether the tumor penetrated the mesorectal fat and whether nodes were sterilized after chemoradiation. Histology was the reference standard. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: For prediction of whether a tumor penetrated the bowel wall, there was an negative predictive value of 0.90 and 0.76 for the expert and general radiologist, respectively. The negative predictive value for prediction of nodal status was 0.95 and 0.85 for expert and general radiologist, respectively. CONCLUSION: This prospective multicenter study demonstrates that MRI with a lymph node-specific contrast agent interpreted by an expert radiologist can select ypT0 to 2/ypN0 rectal cancer with low risk of undetected nodal metastases or invasion through the bowel wall. These patients could thus have been selected for local excision. However, future studies will have to prove equal outcome of such a modified surgical approach compared with current practice.

Locally advanced rectal cancer: MR imaging for restaging after neoadjuvant radiation therapy with concomitant chemotherapy. Part I. Are we able to predict tumor confined to the rectal wall?

PURPOSE: To retrospectively assess accuracy of magnetic resonance (MR) imaging after radiation therapy with concomitant chemotherapy for downsizing of the primary lesion to ypT0-2 tumor confined to rectal wall in locally advanced rectal cancer, with histopathologic findings as reference standard, and to evaluate additional value of volumetric analysis. MATERIALS AND METHODS: The institutional review board approved the study and waived informed consent. Sixty-seven patients met criteria of the study. T2-weighted MR images obtained before and after radiation therapy with concomitant chemotherapy were assessed for tumor stage by expert abdominal radiologist, colorectal surgeon, and general radiologist. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated; tumor volume was measured (compared with Mann-Whitney U test). Findings were correlated with histopathologic findings. RESULTS: Sixty-seven patients (38 men, 29 women; mean age, 63 years) who underwent radiation therapy with concomitant chemotherapy and surgery (all but one) were evaluated. The PPV for prediction of tumor confined to rectal wall (ypT0-2) was 91% (10 of 11), 86% (six of seven), and 88% (seven of eight) for expert abdominal radiologist, surgeon, and general radiologist, respectively. In 24 patients, sensitivity was 42% (10), 25% (six), and 29% (seven). ypT0-2 tumors had significantly smaller volumes than did ypT3-4 tumors before radiation therapy with concomitant chemotherapy (55 vs 92 cm(3), P = .038). Volume reduction rates were significantly higher in ypT0-2 than in ypT3-4 tumors (89% vs 61%, P < .001). If volume before radiation therapy with concomitant chemotherapy was 50 cm(3) or smaller and volume reduction rate was 75% or higher, excised tumor was always confined to rectal wall (ypT0-2). By using these criteria, 43% (six of 14) of cases with overstaging could have been predicted to be ypT0-2 tumors correctly. CONCLUSION: Downsizing to ypT0-2 tumors can be accurately predicted by combining morphologic tumor staging predictions with results from volumetric analyses. MR images obtained after radiation therapy with concomitant chemotherapy might be helpful in more individualized treatment planning.

Locally advanced rectal cancer: MR imaging for restaging after neoadjuvant radiation therapy with concomitant chemotherapy. Part II. What are the criteria to predict involved lymph nodes?

PURPOSE: To prospectively determine diagnostic performance of predictive criteria for nodal restaging after radiation therapy with concomitant chemotherapy by using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging in patients with rectal cancer. MATERIALS AND METHODS: After institutional review board approval and informed consent were obtained, 39 patients (24 men, 15 women; mean age, 64 years) with rectal cancer underwent USPIO-enhanced two-dimensional (2D) T2-weighted fast spin-echo, three-dimensional (3D) T1-weighted gradient-echo, and 3D T2*-weighted MR for restaging. Two observers evaluated nodes for border irregularity, short- and long-axis diameters, and estimated percentage of white region (<30%, 30%-50%, or >50%) within the node (3D T2*-weighted images). Ratio of the measured surface area of the white region within the black node to the measured surface area of the total node (Ratio(A)) was calculated. Signal intensity (SI) in gluteus muscle (SI(GM)) and in total node (SI(TN)) were used to calculate SI(TN)/SI(GM) ratio. Histopathologic findings were reference standard. Receiver operating characteristic (ROC) curves were compared and interobserver agreement was determined. RESULTS: Lesion-by-lesion analysis was feasible in 201 lymph nodes. Area under the ROC curve (AUC) of border and short- and long-axis diameters for observer 1 were 0.85, 0.87, and 0.88 and for observer 2 were 0.70, 0.89, and 0.87, respectively. AUC for estimated percentage of white region within the node, Ratio(A), and SI(TN)/SI(GM) ratio for observer 1 were 0.98, 0.99, and 0.62 and for observer 2 were 0.97, 0.98, and 0.65, respectively. AUC for USPIO-enhanced MR criteria was significantly better than AUC for conventional MR criteria (P < .01). All criteria except border irregularity and SI(TN)/SI(GM) ratio showed high interobserver agreement (kappa > 0.79). CONCLUSION: The most reliable predictors for identifying benign nodes after radiation therapy with concomitant chemotherapy by using USPIO-enhanced MR imaging for restaging in patients with rectal cancer were estimated percentage of white region within the node and Ratio(A). Measurements on standard 2D T2-weighted fast spin-echo images versus primary staging results offer reasonably good accuracy to identify benign lymph nodes after therapy.

USPIO-enhanced MR imaging for nodal staging in patients with primary rectal cancer: predictive criteria.

PURPOSE: To prospectively determine diagnostic performance of predictive criteria for nodal staging with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging in primary rectal cancer patients, with histopathologic findings as reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty-eight rectal cancer patients (18 men, 10 women; mean age, 68 years) underwent USPIO-enhanced MR. Two observers with different experience evaluated each node on three-dimensional T2*-weighted images for border irregularity, short- and long-axis diameter, and estimated percentage (<30%, 30%-50%, or >50%) of white region within the node. Ratio of measured surface area of white region within the node to measured surface area of total node (ratio(A)) was calculated. Signal intensity (SI) of gluteus muscle (SI(GM)), total node (SI(TN)), and white (SI(WR)) and dark (SI(DR)) regions within the node were used to calculate SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios. Lesion-by-lesion, receiver operating characteristic curve, and interobserver agreement analyses were performed. The most accurate and practical criterion was evaluated by observer 3. RESULTS: In 28 patients, 236 lymph nodes were examined. Area under the receiver operating characteristic curve (AUC) of estimated percentage of white region and ratio(A) were 0.96 and 0.99 (observer 1) and 0.95 and 0.97 (observer 2), respectively. AUC of estimated percentage criterion for observer 3 was 0.96. AUC of border, short- and long-axis diameter, and SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios were 0.65, 0.75, 0.79, 0.85, and 0.75 (observer 1) and 0.58, 0.75, 0.79, 0.89, and 0.79 (observer 2), respectively. Interobserver agreement (kappa value) for estimated white region between observers 1 and 2, 1 and 3, and 2 and 3 were 0.77, 0.79, and 0.84, respectively. For observers 1 and 2, kappa value for border was 0.28. For observers 1 and 2, intraclass correlation coefficient for short- and long-axis diameters, ratio(A), and SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios were 0.91, 0.96, 0.91, 0.72, and 0.92, respectively. CONCLUSION: Estimated percentage of white region and measured ratio(A) are the most accurate criteria for predicting malignant nodes with USPIO-enhanced MR imaging; the first criterion is the most practical.