Neoadjuvant therapy of esophageal squamous cell carcinoma: response evaluation by positron emission tomography

OBJECTIVE: To evaluate the use of positron emission tomography using [(18)F]-fluorodeoxyglucose (FDG-PET) to assess the response to neoadjuvant radiotherapy and chemotherapy in patients with locally advanced esophageal cancer. SUMMARY BACKGROUND DATA: Imaging modalities, including endoscopy, endoscopic ultrasound, computed tomography, and magnetic resonance imaging, currently used to evaluate response to neoadjuvant treatment in esophageal cancer do not reliably differentiate between responders and nonresponders. METHODS: Twenty-seven patients with histopathologically proven squamous cell carcinoma of the esophagus, located at or above the tracheal bifurcation, underwent neoadjuvant therapy consisting of external-beam radiotherapy and 5-fluorouracil as a continuous infusion. FDG-PET was performed before and 3 weeks after the end of radiotherapy and chemotherapy (before surgery). Quantitative measurements of tumor FDG uptake were correlated with histopathologic response and patient survival. RESULTS: After neoadjuvant therapy, 24 patients underwent surgery. Histopathologic evaluation revealed less than 10% viable tumor cells in 13 patients (responders) and more than 10% viable tumor cells in 11 patients (nonresponders). In responders, FDG uptake decreased by 72% +/- 11%; in nonresponders, it decreased by only 42% +/- 22%. At a threshold of 52% decrease of FDG uptake compared with baseline, sensitivity to detect response was 100%, with a corresponding specificity of 55%. The positive and negative predictive values were 72% and 100%. Nonresponders to PET scanning had a significantly worse survival after resection than responders. CONCLUSION: FDG-PET is a valuable tool for the noninvasive assessment of histopathologic tumor response after neoadjuvant radiotherapy and chemotherapy.     

Biomarkers for predicting the response of esophageal squamous cell carcinoma to neoadjuvant chemoradiation therapy

This review summarizes and evaluates the literature regarding the biomarkers for predicting the response and/or prognosis of esophageal squamous cell carcinoma (ESCC) patients treated with neoadjuvant chemoradiation therapy (CRT). There are seven categories of molecules known to correlate with the response and/or prognosis: tumor suppressors (p53, p21), cell cycle regulators (Cyclin D1, CDC25B, 14-3-3sigma), DNA repair molecules (p53R2, ERCC1), drug resistance proteins [metallothionein (MT)], angiogenic factors (VEGF), molecules involved in cell proliferation/invasion/metastasis (Ki-67, COX-2) and hedgehog signaling molecules (Gli-1). Of the above molecules, the tumor suppressor p53 is expected to be a representative biomarker for predicting the response and prognosis. The cell cycle markers CDC25B and 14-3-3sigma have potential as response biomarkers independent of the p53 status. The DNA repair markers, p53R2 or ERCC1, angiogenic molecule (VEGF), and hedgehog signaling pathway factor Gli-1 also have potential to predict the response and prognosis of ESCC. However, there are still many unanswered questions with regard to predicting the clinical effects of neoadjuvant CRT.     

FDG PET对骨肉瘤新辅助化疗疗效评估的初步研究

目的通过与病理学肿瘤坏死率相比较，评估18氟脱氧葡萄糖正电子发射断层显像（F-18-fluoro-2-deoxy—D—glucose positron emission tomography，FDG PET）对骨肉瘤新辅助化疗效果的判断价值。方法2004年4月至2006年12月，共有15例（女6例，男9例；年龄7～33岁，平均年龄17-3岁）行新辅助化疗的原发性骨肉瘤患者进行全身或局部FDGPET检查。所有患者均行化疗前和化疗后两次FDGPET检查。FDG—PET检查后，分别计算每例患者FDG的最大标准摄取值（SUV）和肿瘤／背景比值（TBR）。化疗结束后行保肢或者截肢手术，术后切除肿瘤按照Salzer-Kuntschik系统评估病理学肿瘤坏死率反应的化疗效果（I～Ⅲ级为效果良好，Ⅳ～Ⅵ级为效果差）。结果肿瘤坏死率评估显示：8例肿瘤坏死率大于90％，化疗效果良好；7例肿瘤坏死率小于90％，化疗效果不佳。统计学分析提示，化疗后与化疗前的最大标准摄取值之比（SUV2／SUVl）、肿瘤／背景比值之比（TBR2／TBRl）以及化疗后肿瘤背景比值（TRB2）均与肿瘤坏死率相关（P〈0．01，P〈0．001，P〈0．001）。所有化疗效果良好的患者TBR2／TBRl值小于0．46，化疗效果不良者均大于0．49。结论FDGPET为评价骨肉瘤患者化疗效果提供了一种可行的无创检查方法。肿瘤／背景比值与最大标准摄取值相比对评价骨肉瘤的化疗效果更有价值。     

Lymph node staging for urinary bladder carcinoma with positron emission tomography (PET)

PET is a new method in nuclear medicine which examines the metabolism and not the morphology. Tumors show a higher rate of glycolysis than benign tissue and hence can be detected by radioactive glucose. This method has proved good for various tumors. In this study the lymph node staging of bladder cancer by PET was investigated. In 64 patients a PET of the pelvis after injection of fluorodeoxyglucose (FDG) was carried out preoperatively; the PET-results were compared with the histology of the OR specimen after classical pelvic lymphadenectomy. For lymph node staging positive nodes were found in 14 patients which was correct; a false-negative result was obtained in 7 patients. In 37 patients the PET-result was true-negative and in 6 patients false-positive resulting in a sensitivity of 67 %, a specificity of 86 % and an accuracy of 80 %. Therefore, our PET results are encouraging and seem to be better than those obtained by classical staging procedures such as CT or MRI.     

Lymph node staging for urinary bladder carcinoma with positron emission tomography (PET)

Summary PET is a new method in nuclear medicine which examines the metabolism and not the morphology. Tumors show a higher rate of glycolysis than benign tissue and hence can be detected by radioactive glucose. This method has proved good for various tumors. In this study the lymph node staging of bladder cancer by PET was investigated. In 64 patients a PET of the pelvis after injection of fluorodeoxyglucose (FDG) was carried out preoperatively; the PET-results were compared with the histology of the OR specimen after classical pelvic lymphadenectomy. For lymph node staging positive nodes were found in 14 patients which was correct; a false-negative result was obtained in 7 patients. In 37 patients the PET-result was true-negative and in 6 patients false-positive resulting in a sensitivity of 67 %, a specificity of 86 % and an accuracy of 80 %. Therefore, our PET results are encouraging and seem to be better than those obtained by classical staging procedures such as CT or MRI.      

Usefulness of positron emission tomography for assessing the response of neoadjuvant chemoradiotherapy in patients with esophageal cancer

BACKGROUND: In this study, we retrospectively assessed the performance of 18-F-fluorodeoxyglucose positron emission tomography (FDG-PET) compared with computed tomography (CT) and esophagography for assessing the response of advanced esophageal squamous cell carcinoma (SCC) to neoadjuvant chemoradiotherapy. METHODS: We studied 10 patients with thoracic esophageal SCC who received neoadjuvant chemoradiotherapy followed by surgery. Tumor response was assessed by CT, endoscopy, esophagography and FDG-PET before and after neoadjuvant treatment. RESULTS: Assessment of the rate of decrease in standardized uptake value (SUV) revealed a partial response (more than 50% decrease) in 5 (50%) of the patients, and assessment of length decrease of FDG uptake showed a partial response in 9 (90%) of the patients. Comparison of the histological response and the rate of decrease of various parameters revealed significant associations between histological response and tumor length (P <0.05), SUV after neoadjuvant therapy (P <0.05), and reduction in the extent of FDG uptake (P <0.01). However histological response was not significantly correlated with the rate of reduction of SUV, for both CT and esophagography. CONCLUSIONS: FDG-PET may be of considerable value for predicting the pathologic response of esophageal SCC to neoadjuvant therapy. Despite assessment of SUV before neoadjuvant therapy, low FDG uptake after therapy and reduction in the extent of FDG uptake may provide a reliable assessment of the response to therapy.     

PET在脊柱外科中的应用

1　ＰＥＴ介绍ＰＥＴ(派特 )是 ｐｏｓｉｔｒｏｎｅｍｉｓｓｉｏｎｔｏｍｏｇｒａｐｈｙ的简称 ,意为正质子发射计算机断层扫描 ,是目前核医学中唯一用解剖形态方式进行功能、代谢和受体显像的新技术。其集核物理、放射化学、医学影像新技术、分子生物学等高新技术之大成 ,被公认为当代医学高科技之冠。ＰＥＴ利用回旋加速器加速带电粒子 (如质子、氘核 )轰击靶核 ,通过核反应产生带正电子的放射性核素如 ,11Ｃ、13Ｎ、15Ｏ、18Ｆ等 ,这些核素在衰变过程中发射带正电荷的电子 ,这种正电子在组织中运行很短距离 (数毫米 )后 ,即与周围物质中…     

Endoscopic ultrasonography is useful for monitoring the tumor response of neoadjuvant chemoradiation therapy in esophageal squamous cell carcinoma

BackgroundRecently, neoadjuvant chemoradiation therapy (CRT) has been introduced for treatment of esophageal squamous cell carcinoma (ESCC). This study was performed to investigate the usefulness of endoscopic ultrasonography (EUS) in comparison with EUS findings before and after CRT, and histologic findings.MethodsThere were 33 patients with potentially resectable ESCC who underwent neoadjuvant CRT. Preoperative EUS and histologic findings were compared. EUS criteria were established on the basis of low and high echoic regions. Resected specimens were examined by hematoxylin-eosin, azan, and cytokeratin immunohistochemical staining.ResultsAzan and cytokeratin staining clearly delineated fibrous changes and residual tumor. Low echoic regions corresponded to residual tumor and high echoic spots corresponded to fibrosis. All 12 patients classified as grade 1 on EUS diagnosis had histologic grade 1 tumors. Nineteen of 21 cases that presented with high echo were grade 2 or 3. The prognosis according to EUS diagnosis was similar to the histologic effect.ConclusionsPreoperative EUS findings reflected the histologic effect after neoadjuvant CRT. EUS is a useful tool to assess the effect for CRT and to predict the prognosis in ESCC patients.     

Evolving role of positron emission tomography (PET) in urological malignancy

We present a review on the increasing indications for the use of positron emission tomography (PET) in uro‐oncology. In this review we describe the details of the different types of PET scans, indications for requesting PET scans in specific urological malignancy and the interpretation of the results.     

Characterization of tumor thrombus in renal cell carcinoma with prostate specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT)

IntroductionVenous tumor thrombus (TT) occurs as part of the natural history of renal cell carcinoma (RCC) local progression in a small minority of cases. MRI is currently the most accurate imaging modality for determining TT extent. PSMA PET/CT may improve RCC staging and IVC TT characterization. The objective of this study was to investigate the role of PSMA PET/CT in defining superior extent of TT in RCC and TT IVC tributary vessel spread, with comparative accuracy vs. MRI, to assess suitability for resection and inform preoperative surgical planning.MethodsPatients who underwent PSMA PET/CT for assessment of renal malignancy with TT from 2015 to 2020 at 3 tertiary hospitals in Brisbane, Australia, were retrospectively identified. TT extent was classified using Mayo Clinic levels and compared according to imaging modality.ResultsFourteen patients were included, all of which were clear cell RCC. Ten patients also underwent MRI, 6 of which were concordant in extent according to MRI and PSMA PET. Discordant extent occurred in 4 patients, of which 2 patients had non-PSMA avid thrombus (Mayo level 0 and level 3 on MRI). Further discordance was seen in a patient with adrenal vein and lumbar vein TT only seen on MRI and PSMA PET/CT, respectively. Finally, discordant extent was seen in another patient with Mayo level 4 TT without lumbar vein involvement on MRI vs. level 3 on PSMA PET/CT with lumbar vein involvement.ConclusionsPSMA PET/CT can provide additional information about TT extent in RCC which may not be seen on MRI. Additional information from PSMA PET/CT in this setting may assist surgical planning, in addition to detection of metastatic disease.     

Evaluation of lymph node metastases in squamous cell carcinoma of the esophagus with positron emission tomography

BACKGROUND: Previous studies suggest positron emission tomography (PET) may improve staging accuracy of esophageal cancer compared with conventional methods, especially in detecting occult distant metastases. We evaluated the accuracy of PET in the detection of lymph node metastasis prospectively with pathologic findings. METHODS: Fifty-three patients with squamous cell carcinoma underwent whole-body PET scan and chest computed tomography (CT). The findings of PET and chest CT of 50 patients who underwent curative esophagectomy with radical lymph node dissection were compared with the pathologic findings. RESULTS: Among 53 primary esophageal tumors, PET detected 51 (96.2%) and CT detected 49 (92.5%) tumors correctly. Nodal metastases were present in 108 of 436 dissected lymph node groups. PET detected 56 metastatic node groups (51.9% sensitivity, 94.2% specificity, 83.7% accuracy), compared with CT, which detected 16 (14.8% sensitivity, 96.7% specificity, 76.6% accuracy; sensitivity: p < 0.005). CONCLUSIONS: PET was more sensitive than CT in the detection of nodal metastases and may improve staging of squamous cell carcinoma of the esophagus.     

Diagnosis of esophageal cancer using positron emission tomography

Fluorodeoxyglucose positron emission tomography (FDG-PET) is more accurate than computed tomography (CT) for evaluating lymph node metastases and for N staging, but less accurate than combined CT and endoscopic ultrasonography (EUS). Lymph nodes located adjacent to the primary lesion tend to be false negatives. We consider that combined FDG-PET and EUS is the most accurate for the detection of lymph node metastasis in esophageal cancer. FDG-PET is also more accurate than CT for detecting distant metastases and improves the detection of stage IV disease compared with the conventional staging modalities. For the diagnosis of recurrence except for perianastomotic recurrence, FDG-PET provides additional information and is more sensitive than conventional work-ups. FDGPET is a valuable tool for the noninvasive assessment of tumor response after neoadjuvant therapy. 11C-methionine (MET) is another tracer for PET that can be used to assess the metabolism of amino acids, since MET accumulates in esophageal malignant tumors. Choline-PET is more accurate than FDG-PET for the detection of mediastinal lymph node metastases.     

Postoperative therapy of recurrent esophageal squamous cell carcinoma

Some 218 resected cases and 43 autopsied cases after resection during the last 13 years were analyzed with regard to the mode of recurrence and survival. Several factors were investigated with the following results. 1) Extensive clearance of upper mediastinal lymph nodes during radical surgery may reduce the incidence of tumor recurrence. It is preferable to remove the cervical lymph node, however, after positive metastasis to cervical lymph node. 2) Beginning in 1981, interstitial brachytherapy of 192Ir seed assemblies using afterloading techniques was administered to two patients with esophageal carcinoma infiltrating the aorta and four patients infiltrating the trachea and main bronchus which were not completely resected in either case due to invasion of adjacent organs. No significant difference in life-prolongation was observed, but it may have been effective for prevention of localized recurrence in cases with aortic infiltration and with infiltration of the trachea and bronchus. 3) From 1984, eleven patients with recurrent squamous cell esophageal carcinoma were treated with combination chemotherapy sandwiched with irradiation (CDDP/5FU-RT-CDDP/5FU). Eight patients (73%) had complete or partial response, and six patients survived over one year after combination chemotherapy sandwiched with irradiation. Combination chemotherapy sandwiched with irradiation appears to be effective in the treatment of patients with recurrent squamous cell carcinoma of the esophagus. Toxic effects are moderate and manageable.     

Prospective evaluation of positron emission tomography in the preoperative staging of esophageal carcinoma

HYPOTHESIS: Positron emission tomography (PET) is a useful tool in the selection of patients with esophageal cancer who may not benefit from esophageal resection. DESIGN: Case series. SETTING: Tertiary care hospital. PATIENTS: Eighty-one patients with newly diagnosed esophageal cancer who underwent PET and computer tomography (CT) of the chest and abdomen (and of the neck in 45 patients) within 45 days were included. MAIN OUTCOME MEASURES: We calculated the sensitivity and specificity in detecting metastatic sites on the basis of 31 histologically verified lesions. In addition to results obtained on CT, the information provided by PET was evaluated with a view to the choice of management strategies. RESULTS: The PET findings had a higher specificity (89% vs 11%) but a lower sensitivity (38% vs 63%) than CT findings in the detection of metastatic sites. The CT results showed greater agreement with histopathological findings than did PET results. In 8 patients (10%), PET detected distant metastases that were not identified with CT. In 4 patients (5%), PET detected bone metastases only, but in all of these patients metastases in other locations were detected by CT. Although PET led to upstaging (M1) in 2 patients (2%), it did not enable the exclusion of esophageal resection. CONCLUSIONS: Preoperative PET was not characterized by greater accuracy in the detection of metastatic sites previously identified by CT. Therefore, PET did not lead to a change in the indication for esophagectomy. An increase in the sensitivity and the combined use of CT and PET may lead to new indications for this staging procedure.     

Use of positron emission tomography (PET) in stereotactic conditions for brain biopsy

Summary In order to take advantage of the metabolic information provided by positron emission tomography (PET) in cases of brain tumour, we have developed a technique to integrate PET images routinely in the planning of stereotactic brain biopsy. We used stereotactic PET with [¹⁸F]-labelled fluorodeoxyglucose (PET-FDG) in 38 patients undergoing brain biopsy. To evaluate the contribution of PET-FDG in guiding brain biopsy, we analyzed the diagnosis provided by the 78 Stereotactic trajectories obtained in these patients.We found that stereotactic PET-FDG seemed to provide more information in cases of anaplastic astrocytomas and glioblastomas than in low-grade gliomas. Our results also show that biopsy trajectories performed in areas where increased FDG uptake is found within the lesion boundaries always provide interpretable specimens; this was not the case for trajectories guided by CT only. Therefore, the routine integration PET-FDG in the planning of stereotactic brain biopsy may lead to a reduction in sampling. Recently, we also tested consecutive stereotactic PET with [¹¹C]-labelled methionine (PET-Met) and PET-FDG. This technique allowed us to compare accurately the tumoural glucose metabolism and protein synthesis.Our results suggest that stereotactic PET may increase the diagnostic yield of brain biopsy and may improve the understanding of PET in neuro-oncology.