J Thorac Cardiovasc Surg 2008;136:205-212
© 2008 The American Association for Thoracic Surgery
Lack of fludeoxyglucose F 18 uptake in posttreatment positron emission tomography as a significant predictor of survival after subsequent surgery in multimodality treatment for patients with locally advanced esophageal squamous cell carcinoma
Ichirou Higuchi, MDa,
Takushi Yasuda, MDa,*,
Masahiko Yano, MDa,
Yuichirou Doki, MDa,
Hiroshi Miyata, MDa,
Mitsuaki Tatsumi, MDb,
Hironori Fukunaga, MDa,
Shuji Takiguchi, MDa,
Yoshiyuki Fujiwara, MDa,
Jun Hatazawa, MDb,
Morito Monden, MDa
a Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan
b Department of Nuclear Medicine and Tracer Kinetics, Graduate School of Medicine, Osaka University, Osaka, Japan
Received for publication June 19, 2007; revisions received January 25, 2008; accepted for publication February 15, 2008.
* Address for reprints: Takushi Yasuda, MD, Department of Surgery, School of Medicine, Kinki University, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka, 589-8511, Japan. (Email: tyasuda{at}surg.med.kindai.ac.jp).
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Abstract
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Objective: Patients with advanced esophageal squamous cell carcinoma receive neoadjuvant chemotherapy or chemoradiotherapy to improve survival, but benefits are observed only in those with histologic response. Positron emission tomography with fludeoxyglucose F 18 (INN fludeoxyglucose [18F]) detects accumulation of glucose analog in viable cancer cells. This study investigated the usefulness of positron emission tomography with fludeoxyglucose F 18 in assessment of response of advanced esophageal squamous cell carcinoma to neoadjuvant treatment to establish new criteria to predict postoperative long-term survival.
Methods: Fifty patients with locally advanced esophageal squamous cell carcinoma who received neoadjuvant therapy (chemotherapy 35, chemoradiotherapy 15) underwent positron emission tomography with fludeoxyglucose F 18 before surgical resection in evaluation of posttreatment maximum standardized uptake value, residual tumor size (maximum square area of longitudinal axis), histologic response, and postoperative survival.
Results: After treatment, uptake was not noted in 21 patients (posttreatment maximum standardized uptake value <2.5, negative) but was detected in 29 (
2.5, positive). Residual tumor size ranged from 0 to 54.0 mm2 for negative results and 55.0 to 676.0 mm2 for positive, clearly distinguishing histologic major response from nonresponse. The negative group demonstrated significantly higher 5-year cause-specific survival (67.7%) and lower hematogenous recurrence (4.8%) than the 36.5% and 37.0% values in the positive group, (P < .0042 and P = .0083, respectively). Univariate Cox regression analyses identified posttreatment maximum standardized uptake value (cutoff 2.5) as the only preoperative prognostic factor (P = .0071).
Conclusion: Posttreatment positron emission tomography with fludeoxyglucose F 18 reliably predicted histologic response and postoperative survival in advanced esophageal squamous cell carcinoma. This tool could potentially be used to tailor optimal treatment according to individual responses.
Abbreviations and Acronyms FDG = fludeoxyglucose F 18; PET = positron emission tomography; SCC = squamous cell carcinoma; SUVmax
= maximum standardized uptake value
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Introduction
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Neoadjuvant chemotherapy and chemoradiotherapy have been used to improve the survival of patients with locally advanced esophageal carcinoma. No survival benefits have been observed, however, in patients without histologic response.1-6
It is important to distinguish those with histologic response and to tailor subsequent treatment. Treatment response has been evaluated clinically by detection of relative morphologic changes in tumor size with computed tomography, barium study, and endoscopic ultrasonography. All these diagnostic modalities are inadequate for use in clinical decision making, however, because local fibrosis and cicatricial stenosis often hinder accurate assessment, diluting any correlation with histologic response.7-10
Positron emission tomography (PET) with fludeoxyglucose F 18 (FDG, INN fludeoxyglucose [18F]) is a metabolic imaging modality that allows detection and visualization of accumulated glucose analogs in viable malignant tumor cells. FDG uptake reflects the volume and activity of viable cancer cells, even after neoadjuvant treatment. Thus the difference in uptake before and after treatment should reflect clinical response, and the posttreatment FDG uptake should indicate residual tumor volume and viability (histologic response). Several preliminary studies have suggested the usefulness of FDG-PET for evaluation of the response to chemotherapy or chemoradiotherapy in esophageal carcinoma.11-24 Most of these have been preliminary reports of small-scale studies, however, so the usefulness of FDG-PET in response evaluation has not yet been established. Furthermore, the studies have examined mainly patients with adenocarcinoma, not with squamous cell carcinoma (SCC), which is the most common cell type in Japan. To our knowledge, there has been no large-scale report of patients with esophageal SCC.
The purpose of this study was to investigate whether FDG-PET could predict histologic response and postoperative survival in large number of patients with esophageal SCC and to establish a new, distinct standard for FDG-PET assessment. We prospectively evaluated pretreatment and posttreatment FDG-PET scans and compared the findings with residual tumor volume, histologic response, postoperative survival, and failure pattern.
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Materials and Methods
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Study Design and Patients
This study was a single-arm, prospective, single-institution clinical trial. Patients with histologically confirmed T3 SCC tumors without hematogenous metastasis were eligible for enrollment. Of M1 lymph nodes, supraclavicular and celiac artery lymph nodes that existed in the region of three-field lymphadenectomy were included. To compare FDG uptake of PET and histologic response, we excluded patients with unresectable T4 tumors. Other exclusion criteria were diabetes mellitus, history of previous treatment of the same disease, presence of another active malignant disease, and severe functional visceral or mental disorder. Of 356 patients with esophageal SCC who were treated at Osaka University Hospital between March 2000 and August 2004, a total of 50 patients who fulfilled these criteria were enrolled in this study (Table E1). Patients underwent conventional staging with barium esophagography, gastroesophageal endoscopy, and computed tomography, followed by FDG-PET. These patients then received either neoadjuvant chemotherapy or chemoradiotherapy, followed by repeated conventional staging and FDG-PET approximately 2 or 4 weeks after completion of chemotherapy or chemoradiotherapy, respectively. Finally, patients underwent surgical resection within 2 weeks after the second FDG-PET. Initial and repeated conventional staging, second FDG-PET, and neoadjuvant treatment were completed in all cases. The pretreatment FDG-PET could not be performed in 7 cases, however, because of inconvenient examination schedules. Informed consent was obtained from all patients, and the study was approved by the High-Degree Advanced Medical Committee of Osaka University Hospital.
Neoadjuvant Treatment
Patients confirmed to have no FDG uptake in any lymph node on PET underwent chemoradiotherapy, whereas those with FDG accumulation in any lymph node received chemotherapy for systemic and local control. The regimen of chemoradiotherapy consisted of concurrent external beam radiotherapy (4 weeks, 5 d/wk, 40 Gy total), bolus infusion of cisplatin at a dose of 7 mg/m2, and continuous infusion of fluorouracil at 350 mg/m2 (4 weeks, 5 d/wk). The radiation field included all regional lymph node areas. The chemotherapy consisted of two cycles of combination protocol of bolus infusion of cisplatin at 70 mg/m2 and doxorubicin at 30 mg/m2 on day 1 and continuous infusion of fluorouracil at 1000 mg/d on days 1 to 7. The courses were repeated twice every 28 days.
FDG-PET Imaging
Whole-body FDG-PET imaging was performed as reported previously.25-27 Briefly, each patient fasted for at least 4 hours before intravenous administration of approximately 370 MBq FDG. Serum glucose levels were determined just before FDG injection. All patients were normoglycemic (blood glucose <150 mg/dL). Simultaneous emission and transmission PET scans were acquired 1 hour after FDG injection (transmission source 68Ge-68Ga line source). Then imaging was performed with a dedicated PET scanner (HEADTOME/SET 2400W; Shimadzu Co, Kyoto, Japan).
For semiquantitative analysis, regions of interest were selected semiautomatically at the most intense area of FDG accumulation in the primary tumor on the PET image, and the maximum standardized uptake value (SUVmax) was calculated according to the following formula: PET count at most intense point x calibration factor (MBq/kg)/injection dose (MBq)/body weight (kg). Primary tumors with SUVmax at least 2.5 were considered to have a positive result, because FDG uptake at SUVmax less than 2.5 is invisible. When there was no visible FDG uptake, the fusion images combined with PET images and computed tomographic images were composed with our previously described method, regions of interest were drawn exactly on the area corresponding to the primary tumor, and the SUVmax was calculated.26
Surgical Treatment
The surgical procedure consisted of transthoracic subtotal esophagectomy and reconstruction of the gastric tube in tumors of the thoracic esophagus. Three-field lymphadenectomy was performed for patients with upper-third thoracic tumors or lymph node metastases along the recurrent laryngeal nerves,28 and two-field lymphadenectomy was performed for the remaining patients. Patients with cervical tumors underwent partial esophageal resection and bilateral neck lymphadenectomy, followed by reconstruction with a free jejunal graft.
Histopathologic Evaluation
Resected primary tumors were embedded in paraffin after fixation with formaldehyde, and serial sections of each block were cut and stained with hematoxylin and eosin. Conventional histologic examination was performed in all cases. Histopathologic response was classified in accordance with the guidelines of the Japanese Society for Esophageal Diseases29 as follows: grade 3 was complete disappearance of cancer cells, grade 2 was more than two-thirds disappearance, grade 1 was less than one-third disappearance, and grade 0 was no disappearance. Histologically good response was defined as grade 2 or 3 response; this definition was based on our previous results of patients with clinical T4 esophageal SCC who underwent surgery after chemoradiotherapy with 3-year survivals of 85.7% for grade 3, 45.8% for grade 2, and 0% for grade 1.2
Tumor size was expressed as the square area of the longitudinal maximum dimension of the tumor. A photograph of the maximal section was stored in the computer as an image file, and tumor size was measured with appropriate software (NIH Image 1.62 for the Mac. Download at http://rsb.info.nih.gov/nih-image).
Statistical Analysis
The relationship between FDG uptake (SUVmax) and tumor size was determined with the Pearson correlation coefficient. Comparisons of histologic responses according to posttreatment FDG-PET results were analyzed with the Mann—Whitney U test. Independent predictive factors for survival were determined with Cox regression analysis. Univariate analyses and comparisons of the two groups with regard to patterns of failure were performed with the 
2 test. Survival was calculated from the initial date of treatment to the occurrence of the event or date of the most recent follow-up visit. Cause-specific and disease-free survivals were calculated by the Kaplan–Meier method. The significances of prognostic variables for outcome were calculated by log-rank test.
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Results
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Patient Characteristics
Fifty patients were included in this study (Table E1). The median age was 62.2 years (range 44–77 years). Cervical esophageal tumors were observed in 11 patients, with the remaining tumors located in the thoracic esophagus (upper in 5 patients, middle in 17, and lower in 17). The initial clinical stage was III or more, with T3 tumors in all 50 patients (III in 24 patients, IVA in 11, and IVB in 15). On the basis of the pretreatment diagnosis of lymph node metastases, 15 patients received chemoradiotherapy; the remaining 35 patients underwent chemotherapy followed by surgery. R0 resection was performed in 48 cases, with only 2 patients undergoing R2 resection because of invasion of the right pulmonary vein in 1 case and the left main bronchus in the other. There were no postoperative deaths.
FDG Uptake and Tumor Size
We first examined the correlation between posttreatment SUVmax of the primary tumor measured by FDG-PET and the square area of the longitudinal maximum dimension of the resected tumor (tumor size). The posttreatment SUVmax, as shown in
Figure 1, correlated significantly with the residual tumor size (r = 0.898, P < .0001), with a regression equation of y = 0.025 x x + 1.634. This result suggests that residual tumor size could be predicted by posttreatment SUVmax.
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Figure 1. Correlation between tumor size (maximum cross-sectional area of resected tumor) and posttreatment maximum standardized uptake value (SUVmax) in primary tumor. Posttreatment maximum standardized uptake value and tumor size ranged from 1.03 to 25.62 and from 0 mm2 to 676.0 mm2, respectively n = 50, y = 0.025 x x + 1.634, r = 0.898, R
2 = 0.806, P < .0001).
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Histologic Response and Residual Tumor Size
Histologic response grades were as follows: 8 patients with grade 0, 22 with grade 1, 14 with grade 2, and 6 with grade 3 (Figure E1). As mentioned in the Methods section, a histologic response of at least grade 2 was necessary for long survival, as described in our previous report.2
Figure E1 shows the distribution of residual tumor size according to the histologic response. The tumor size ranged from 55 to 672 mm2 for grade 0, 1.3 to 676 mm2 for grade 1, 0.9 to 102 mm2 for grade 2, and was defined as 0 mm2 for grade 3 (no tumor), demonstrating a distinct difference between grade 1 or lower nonresponse and grade 2 or better response. When the cutoff value was set at 33 mm2, as shown in Figure E1, the sensitivity and specificity for accuracy of histologic response were the highest, 94.7% and 93.5%, respectively, suggesting that posttreatment residual tumor size less than 33 mm2 might indicate grade 2 or better histologic response.
Posttreatment PET Diagnosis
To determine the standard value of FDG-PET to predict histologic response, we calculated posttreatment SUVmax corresponding to residual tumor of 33 mm2 according to the formula of the expression of regression obtained in Figure 1. The result was 2.459, but FDG accumulation with SUVmax less than 2.5 cannot be detected by PET. We therefore classified patients with posttreatment SUVmax less than 2.5 as having a response. This response evaluation could be assessed by visual inspection, and posttreatment SUVmax values less than 2.5 and greater than or equal to 2.5 were designated as negative (Figure E2) and positive PET results, respectively.
Posttreatment PET Diagnosis and Histologic Response
All 50 patients were assessed again with this new standard of treatment response evaluation. They were classified as 21 with negative PET (response, chemotherapy 13, chemoradiotherapy 8) and 29 with positive PET (nonresponse, chemotherapy 22, chemoradiotherapy 7). The residual tumor size ranged from 0 to 54 mm2 (average 12.8 mm2) in the negative PET group and 55 to 676.0 mm2 (average 238.8 mm2) in the positive PET group (
Table 1). Negative PET results indicated that residual tumor was less than 55 mm2. With regard to the grade of histologic response, 18 (85.7%) patients of the negative PET group showed grade 2 or better histologic response, whereas only 2 in the positive PET group showed such high histologic response (6.9%, P < .0001; Table 1). Consequently, the sensitivity, specificity, and accuracy of posttreatment PET diagnosis for prediction of grade 2 or better histologic major response were 85.7%, 93.1%, and 90.0%, respectively.
Posttreatment PET Diagnosis and Survival After Surgery
We evaluated the ability of posttreatment SUVmax to predict postoperative long-term survival. The median follow-up was 26.5 months (range 5.4–84.2 months). During this period, 4 patients died of other diseases without recurrence: 3 in the negative PET group of aneurysm, pneumonia, and hepatocellular carcinoma and 1 in the positive PET group of pneumonia. Tumor recurrence was identified in 25 patients, 7 in the negative PET group and 18 in the positive PET group. All patients, with recurrence, were dead at the end of the follow-up period, except for 1 in the negative PET group. Especially of note, 7 patients, with recurrence, in the positive PET group died within 1 year after initiation of neoadjuvant therapy.
The cause-specific median survival was longer than 84.2 months in the negative PET group and was 18.2 months in the positive PET group. The 1-, 3- and 5-year cause-specific survivals were 95.0%, 73.9%, and 67.7%, respectively, in the negative PET group, compared with 75.9%, 41.1%, and 36.5%, respectively, in the positive PET group (P = .0042;
Figure 2, A). The 1-, 3- and 5-year disease-free survivals that could be analyzed in 48 patients, excluding 2 with R2 resection, were 90.2%, 65.2%, and 65.2%, respectively, in the negative PET group, compared with only 48.1%, 37.0%, and 37.0%, respectively, in the positive PET group (P = .0219; Figure 2, B). These results indicate that posttreatment PET diagnosis could distinguish patients with response who had postoperative long-term survival from those without response who had a poor prognosis.
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Figure 2. Correlation between posttreatment positron emission tomographic (PET) diagnosis at primary tumor site and postoperative survival by Kaplan–Meier analysis in neoadjuvant group. A, Cause-specific survival from data of all 50 patients. B, Disease-free survival from data of 48 patients, excluding 2 cases of noncurative resection (R2).
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Posttreatment PET Diagnosis and Patterns of Failure
The patterns of failure are shown in
Table 2. There was no significant difference in local recurrence rate between positive PET (14.8%) and negative PET (9.5%) groups (P = .5782). On the other hand, the proportion of patients with distant metastasis in the positive PET group (48.1%) was more than twice that in the negative PET group (23.8%), although the difference did not reach statistical significance (P = .08). Hematogenous spread was significantly lower in the negative PET group (4.8%) than in the positive PET group (37.0%, P = .0083). Furthermore, there were no differences in tumor recurrence rate according to neoadjuvant treatment modality (chemotherapy vs chemoradiotherapy) between the positive and negative PET groups (Table 2).
Posttreatment PET Diagnosis and Prediction of Long-term Outcome
We examined the usefulness of posttreatment PET diagnosis for clinical prediction of long-term survival after surgery. First, we determined the preoperative risk factors for long-term survival with univariate Cox regression analysis (
Table 3). The hazard ratio of posttreatment SUVmax greater than or equal to 2.5 versus less than 2.5 was 3.628 (P = .0071), indicating a strong correlation with postoperative survival. In comparison, pretreatment clinical stage and clinical response did not correlate with survival. Furthermore, pretreatment SUVmax values (range of tested cutoff levels 4–15)19,21 did not correlate with survival, nor were reduction in SUVmax after treatment (range of tested cutoff levels 30%–80%)11-13,16-18,20,21 and posttreatment SUVmax value less than 4,23 which were previously reported to be associated with good prognosis.11-13,16,18 Consequently, posttreatment PET diagnosis by SUVmax with a cutoff of 2.5 was the only significant preoperative prognostic factor.
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Discussion
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The aims of multimodality cancer treatment are local control of the tumor by reducing its size, systemic control by eliminating micrometastases, and improvement in survival. Thus the response to preoperative therapy should have an impact on the prognosis after surgery. The response to cancer therapy has been evaluated by morphologic assessment of the relative change in tumor size before and after treatment. Many clinical studies of neoadjuvant therapy, however, have reported a lack of improvement of survival in patients with clinically complete or partial response measured by change in size, although such improvement has been noted in patients with a complete or nearly complete histologic response.3-6 These results suggest that treatment response should be assessed by the absolute volume of posttreatment residual tumor, rather than by relative change in tumor volume. Assessment of the posttreatment residual tumor has been conducted to date by conventional modalities; however, none seems satisfactory.7-10 How to predict preoperatively information that is otherwise obtained by pathologic examination after surgery is the greatest challenge.
FDG-PET is a distinct new metabolic diagnostic modality. This study revealed that FDG-PET was directly predictive of posttreatment residual tumor volume. FDG uptake correlated with tumor size even after treatment (Figure E1), and a posttreatment SUVmax less than 2.5, meaning no FDG accumulation (negative), corresponded to grade 2 or better histologic major response. Negative results of PET were correlated with a residual tumor size smaller than 55 mm2 in all patients, clearly distinguishing histologic response from nonresponse (Table 1). Moreover, the negative PET group showed a significantly better survival than did the positive PET group in the analysis of median survival, cause-specific survival (P = .0042), and disease-free survival (P = .0219; Figure 2). Thus posttreatment FDG-PET diagnosis appears to be preoperatively predictive of both histologic major response and postoperative survival.
Table 4 summarizes the results of 15 clinical studies of response evaluation to neoadjuvant therapy by FDG-PET in patients with esophageal carcinoma. The studies are divided into two groups according to the criteria of response to such therapy. The first group consists of 12 studies that assessed the response by measuring FDG uptake before and after treatment (reduction rate group),11-22 whereas the second group comprises 3 studies, including our own, that examined the response by measuring posttreatment SUVmax (posttreatment group).23,24 We reviewed the results of assessment of FDG-PET as a tool for evaluating the histologic response to neoadjuvant therapy (complete or nearly complete response) and postoperative survival. The former was examined in 11 studies (10 studies in rate of reduction of FDG uptake, references 11-15, and 17-21; 1 study in posttreatment, our study), and the latter was investigated in 8 studies (5 studies in reduction rate, references 11-13, 16, and 18; 3 studies in posttreatment, references 23, and 24). The results showed that 8 of 11 histologic response studies 7 studies in reduction rate, references 11-14, 17, 18, and 20; 1 study in posttreatment, our study) and 7 of 8 survival-outcome studies (4 studies in reduction rate, references 11-13, and 18; 3 studies in posttreatment, references 23, and 24) agreed on the suitability of FDG-PET for predicting the histologic response and survival after neoadjuvant therapy, despite the use of different response criteria in these studies. Except for 2 studies, however, all other studies11-14,17,18,20,23,24 included small population samples of 17 to 37 patients who underwent surgery. Thus relatively large-scale analyses were limited to 2 studies only: the report of Swisher and colleagues23 for 71 patients with mainly adenocarcinoma and our own report of 50 patients with SCC. Both studies emphasized the usefulness of posttreatment SUVmax as an indicator for response evaluation. The cutoff values for major response were 4.0 in the study of Swisher and colleagues23 and 2.5 in our own study. This difference may result from the difference in cell type. Univariate Cox regression analysis demonstrated that posttreatment SUVmax (cutoff value 2.5) was the only preoperative prognostic factor for esophageal SCC in our study, although other response criteria reported previously, such as reduction rate of SUVmax, were included in our analysis (Table 3). Consequently, posttreatment SUVmax is the most promising noninvasive parameter for accurate, objective, and preoperative prediction of histopathologic response to preoperative treatment and prognosis. Moreover, to our knowledge, ours is the first report of a large-scale analysis of the response evaluation by FDG-PET for patients with esophageal SCC.
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Table 4 Summary of reported studies that evaluated response to neoadjuvant therapy by positron emission tomography with fludeoxyglucose F 18 in patients with esophageal carcinoma
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Failure pattern analyses revealed that the negative PET group showed a lower rate of distant metastases, especially an extremely lower rate of hematogenous metastases (4.8%), than did the positive PET group (37.0%, P = .0083; Table 2). Therefore responses such as disappearance of FDG uptake after treatment might suggest downstaging from systemic disease to local disease as a result of control of potential systemic micrometastases by first-line therapy. In this context, patients with negative posttreatment PET results could be good candidates for subsequent surgery. On the other hand, patients with positive posttreatment PET results showed high tumor recurrence (63.0%); in other words, both the local and systemic controls were insufficient. From this point of view, additional preoperative chemotherapy or chemoradiotherapy might lead to improvement in outcome, although the optimal treatment for patients without response is still unclear. Nevertheless, FDG-PET is helpful for predicting histologic response versus nonresponse before surgery, allowing selection of the ensuing clinical management according to the expected response.
Also, FDG-PET has another advantage of possibly checking the presence or absence of distant metastases by whole-body scanning. Surgical indication in multimodality treatment has three conditions. First is that micrometastases outside the surgically resectable field be eliminated, second is that there are no distant metastases in the whole body, and last is that long-term survival after surgery be anticipated. FDG-PET can provide important and definitive information for all conditions preoperatively, accurately, and noninvasively.
Even FDG-PET, however, could not predict pathologically complete response. As shown in Table 1, residual tumors measuring less than 55 mm2 cannot be visualized by FDG-PET, and thus it is impossible to distinguish pathologically complete response from minimal residual tumor smaller than 55 mm2. If pathologically complete response could be predicted accurately, there would be no need for surgery in such cases. Previous studies, however, reported that false-negative results in patients with minimal residual tumors despite of lack of FDG uptake constituted 29% to 82% of negative PET results.11-15,17-19,21 Molecular biologic approaches may provide useful information but need to be investigated thoroughly in future studies. Esophagectomy should therefore still be considered the therapeutic choice, as long as microscopic residual tumor cannot be ruled out completely.
We treated malignant tumors of heterogeneous biological activity and patients with heterogeneous immunologic response. Nevertheless, treatment was applied with a uniform protocol, as though all patients were from a homogeneous population. Survival benefits of such regimens are observed only in those with response, whereas the prognosis of those without a response seems to be even worse than that of patients treated by surgery alone. It is therefore indispensable for improvement of treatment outcome and quality of life to predict the response to first-line therapy and tailor the second-line therapy according to the response. In this context, posttreatment FDG-PET can have an impact on any decision either for or against additional preoperative treatment in individual cases. Further large-scale multicenter studies are needed to investigate the feasibility of FDG-PET as the optimal standard for evaluation of response to chemotherapy and chemoradiotherapy.
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Figure E1
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Relationship between histologic response grade in primary tumor after chemoradiotherapy and residual tumor size. Size of 33 mm2, indicated by arrow, represents cutoff value used to distinguish between grade 1 or worse histologic nonresponse and grade 2 or better histologic response.
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Figure E2
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Example of positron emission tomographic imaging before (A) after (B) chemotherapy, with histologic finding of residual tumor (C). Maximum standardized uptake value of primary tumor decreased from 15.59 to 1.63 after therapy. Size of residual tumor was 1.3 mm2, and histologic response was assessed as grade 2.
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Table E1
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Patient characteristics
| Patients (No.) |
50 |
| Sex ratio (male/female) |
41:9 |
| Age (y, median and range) |
62.2 (44–77) |
| Location (No.) |
| Cervical |
11 |
| Upper thoracic |
5 |
| Middle thoracic |
17 |
| Lower thoracic |
17 |
| Pretreatment clinical stage (No.) |
| I |
0 |
| IIA |
0 |
| IIB |
0 |
| III |
24 |
| IVA |
11 |
| IVB |
15 |
| Preoperative treatment (No.) |
| Chemoradiotherapy |
15 |
| Chemotherapy |
35 |
| Surgery (No.) |
| Cervical esophagectomy |
11 |
| Subtotal esophagectomy |
39 |
| Resectability (No.) |
| R0 |
48 |
| R1 |
0 |
| R2 |
2 |
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R0, No residual tumor cell; R1, microscopic residual tumor cells; R2, macroscopic residual tumor cells.
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R. M. Kwee
Prediction of Tumor Response to Neoadjuvant Therapy in Patients with Esophageal Cancer with Use of 18F FDG PET: A Systematic Review
Radiology,
March 1, 2010;
254(3):
707 - 717.
[Abstract]
[Full Text]
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Abstract
Introduction
