This study aims to evaluate the prognostic implications of pretreatment [18F]FDG-PET metrics in esophageal cancer patients through a meta-analysis of the existing literature.

We carefully searched electronic databases, including PubMed and Embase, from inception to April 1, 2024, to identify studies describing the prognostic value of pretreatment PET metrics for advanced esophageal cancer. Clinical endpoints examined were overall survival (OS), recurrence-free survival (RFS)/disease-free survival (DFS), and progression-free survival (PFS). Hazard ratios (HRs) for PFS and OS were taken directly from the original reports.

Forty-seven publications, including 5504 patients, were included in our analysis. OS and PFS were analyzed in 31 and nine studies, respectively, and DFS/RFS was analyzed in 16 studies. The comprehensive pooled analysis revealed significant associations between metabolic parameters derived from positron emission tomography (PET) imaging and clinical outcomes. Expressly, the pooled HR indicated that patients with higher SUVmax were significantly associated with poor PFS (HR: 1.06; 95% CI: 1.01-1.12, p = 0.011) and poor RFS/DFS (HR: 1.09; 95% CI: 1.02-1.18, p = 0.019). Patients with higher SUVmean were significantly associated with poorer OS (HR: 1.07; 95% CI: 1.01-1.14, p = 0.025). High MTV was significantly associated with inferior OS (HR: 1.02; 95% CI: 1.00-1.05, p = 0.049). High TLG was significantly associated with poorer RFS/DFS (HR: 2.02; 95% CI: 1.11-3.68, p = 0.022).

This study unveiled pretreatment FDG-derived parameters as valuable prognostic indicators in assessing esophageal cancer outcomes. Specifically, SUVmax is associated with PFS and RFS/DFS. SUVmean and MTV were correlated with OS, and TLG was only associated with RFS/DFS.

Question Inconsistent findings on the prognostic value of pretreatment [18F]FDG PET parameters in esophageal cancer require comprehensive analysis to clarify their role in outcome prediction. Findings Higher pretreatment [18F]FDG-PET metrics (SUVmax, SUVmean, MTV, TLG) are associated with poor survival outcomes, emphasizing their potential value in enhancing prognostic assessments for esophageal cancer. Clinical relevance This study highlights the prognostic significance of pretreatment [18F]FDG-PET metrics in esophageal cancer, providing valuable insights for patient outcome prediction and potentially guiding personalized treatment strategies.

In recent years, the utility of positron emission tomography/magnetic resonance imaging (PET/MRI) has become increasingly significant in diagnostic settings. This study provides a five-year follow-up on a previous pilot study that demonstrated the feasibility of PET/MRI in predicting the resectability of adenocarcinoma of the esophagogastric junction (AEG). We aimed to evaluate whether this imaging modality could further serve as a prognostic tool for survival in AEG patients.

A total of 22 patients were included in the initial pilot study, with 17 of them undergoing surgery. All patients underwent three series of neo-adjuvant chemotherapy (NT). This follow-up study retrospectively analyzed the correlation between the apparent diffusion coefficient (ADC) and standard uptake value (SUV) measurements of the primary tumor from the original study with overall survival and recurrence. ADC and SUV values were measured prior to initiation of NT, and again 17-21 days into the first cycle of NT-administration, and the differences between the scans were calculated as ∆SUVmax, ∆ADCb0, and ∆ADCb50. Early treatment response was assessed using the Response Evaluation Criteria In Solid Tumors (RECIST). Binary logistic regression was employed to evaluate the predictive values of ADC and SUV parameters, and receiver operating characteristic (ROC) curves were generated to determine sensitivity, specificity, and area under the curve (AUC).

As of January 7, 2022, 8 of the 22 patients were still alive. The AUC was calculated to assess the association of imaging parameters with long-term survival: ∆SUVmax: AUC = 0.74, sensitivity, 87.5%, specificity 62.5% (p = 0.037). ∆ADCb0: AUC = 0.62, sensitivity 85.7%, specificity 57.1% (p = 0.400). ∆ADCb50: AUC = 0.78, sensitivity 78.6%, specificity 85.7% (p = 0.011). Combining all three parameters yielded an AUC of 0.81, with a sensitivity of 78.6% and a specificity of 85.7% (p = 0.002). The results for individual measurements were: SUVmax(pre-NT): AUC = 0.56, sensitivity 78.6%, specificity 50% (p = 0.646). SUVmax(post-NT): AUC = 0.81, sensitivity 85.7%, specificity 87.5% (p = 0.002). ADCb0(pre-NT): AUC = 0.55, sensitivity 71.4%, specificity 62.5% (p = 0.682). ADCb0(post-NT): AUC = 0.63, sensitivity 78.6%, specificity 57.1% (p = 0.339). ADCb50(pre-NT): AUC = 0.51, sensitivity 85.7%, specificity 37.5% (p = 0.952). ADCb50(post-NT): AUC = 0.63, sensitivity 42.9%, specificity 100% (p = 0.279). No significant correlation was found between RECIST group and survival status (p = 0.15).

Our results indicate that PET/MRI is feasible for predicting long-term survival in AEG patients. The highest AUCs were achieved when combining SUV and ADC parameters, and when using post-NT SUVmax alone.

The purpose of this study is to assess the correlation between metabolic response with fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and pathological response in patients with locally advanced esophageal cancer treated with neoadjuvant chemoradiotherapy and to study FDG-PET parameters for the prediction of pathological response and outcome.

Twenty-five patients with locally advanced esophageal cancer underwent two FDG-PET/CT scans for initial staging and after neoadjuvant chemoradiotherapy. FDG uptake in the primary tumor was calculated in both scans (SUVmax, SULpeak, and TLG). Metabolic response was assessed according to the reduction of PET parameters: complete response (mCR = 100%), partial response (mPR ≥50%), and no response (mNR ≤50%). Pathological response was also classified as complete (pCR), partial (pPR), or no response (pNR). Patients were followed up (range, 8-99 months) determining free-disease interval (FDI) and overall survival (OS).

Two patients were excluded due to exitus for nonesophageal-related causes. The metabolic response was observed in 18/23 remaining patients (3mCR, 15 mPR), of which 12/18 patients showed a pathological response (3 pCR, 9 pPR). A major discrepancy was observed in 2 mNR patients who achieved pPR. FDI and OS were longer in patients with metabolic response than nonresponders, but no statistical difference was found. No significant correlation was found between PET parameters and pathological response, FDI, and OS.

FDG-PET/CT is a useful technique to assess response to neoadjuvant chemoradiotherapy in esophageal cancer. Although in this preliminary study, no correlation between metabolic and pathologic response was found and no statistical differences between responders and nonresponders were observed, a tendency of longer FDI and OS was apparently found in responders patients.

Locally advanced esophageal adenocarcinomas (EACs) are treated with multimodal therapy, namely surgery, neoadjuvant chemotherapy (NAC) or chemoradiotherapy (CRT) depending on patient and tumor level factors. Yet, there is little consensus on choice of the optimum systemic therapy. To compare the pathological complete response (pCR) after FLOT, non-FLOT-based chemotherapy and chemoradiotherapy regimes in patients with EACs. A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review and Scopus databases. Studies were included if they had investigated the use of chemo(radio)therapy regimens in the neoadjuvant setting for EAC and reported the pCR rates. A meta-analysis of proportions was performed to compare the pooled pCR rates between FLOT, non-FLOT and CRT cohorts. We included 22 studies that described tumor regression post-NAC. Altogether, 1,056 patients had undergone FLOT or DCF regimes, while 1,610 patients had received ECF or ECX. The pCR rates ranged from 3.3% to 54% for FLOT regimes, while pCR ranged between 0% and 31% for ECF/ECX protocols. Pooled random-effects meta-meta-analysis of proportions showed a statistically significant higher incidence of pCR in FLOT-based chemotherapy at 0.148 (95%CI: 0.080, 0.259) compared with non-FLOT-based chemotherapy at 0.074 (95%CI: 0.042, 0.129). However, pCR rates were significantly highest at 0.250 (95%CI: 0.202, 0.306) for CRT. The use of enhanced FLOT-based regimens have improved the pCR rates for chemotherapeutic regimes but still falls short of pathological outcomes from CRT. Further work can characterize clinical responses to neoadjuvant therapy and determine whether an organ-preservation strategy is feasible.

Definitive chemoradiation therapy avoids the perioperative and long-term morbidity of esophagectomy and is the standard of care for cervical esophageal cancer. There are significant differences in tumor response to chemoradiation and recurrence patterns between squamous cell cancer and adenocarcinoma of the esophagus. Multimodality therapy for esophageal cancer continues to progress, now with the widespread use of PET scanning and possible active surveillance in patients with complete clinical response to chemoradiation. As drug development and targeted therapy trials continue to expand, our understanding of tumor biology and precision medicine will continue to refine the treatment of esophageal cancer.

Up to 32% of patients with esophageal cancer show a pathological complete response (ypCR) after neoadjuvant therapy. To prevent overtreatment, the indication to perform esophagectomy in these patients should be reconsidered. Implementing an organ-preserving strategy for patients with ypCR requires an accurate assessment of residual disease after neoadjuvant treatment. The aim of this study was to systematically review the effectiveness of imaging techniques used for detection of ypCR after neoadjuvant therapy but before resection in patients with esophageal cancer.

A systematic literature search of the Medline, Embase, and Cochrane Library databases was performed from January 1, 2000, to December 13, 2017. Eligible studies were diagnostic studies that compared results of imaging modalities after neoadjuvant therapy to histopathological findings in the resection specimen after esophagectomy. Methodological quality was assessed by the Cochrane Quality Assessment of Diagnostic Accuracy Studies, version 2, model. Primary outcome measures were true positive, false-positive, false-negative, and true negative values of imaging techniques predicting ypCR. A meta-analysis was performed by pooling sensitivities and specificities by using a bivariate model.

A total of 4420 articles were identified. After exclusion of irrelevant titles and abstracts, 360 articles were reviewed in full text. In total, four imaging modalities (computed tomography [CT], positron emission tomography [PET-CT], endoscopic ultrasound [EUS], and magnetic resonance imaging [MRI]) were used for restaging. The meta-analysis was conducted with data from 56 studies involving 3625 patients. The pooled sensitivities of CT, PET-CT, EUS, and MRI for detecting ypCR were 0.35, 0.62, 0.01 and 0.80, respectively, whereas the pooled specificities were 0.83, 0.73, 0.99, and 0.83, respectively. The positive predictive value in detecting ypCR was 0.47 for CT, 0.41 for PET-CT, not applicable for EUS, and 0.61 for MRI.

Current imaging modalities such as CT, PET-CT, and EUS seem to be insufficiently accurate to identify complete responders. More accurate diagnostic tests are needed to improve restaging accuracy for patients with esophageal cancer.

Esophageal cancer is known as one of the malignant cancers with poor prognosis. To improve the outcome, combined multimodality treatment is attempted. On the other hand, advances in genomics and other "omic" technologies are paving way to the patient-oriented treatment called "personalized" or "precision" medicine. Recent advancements of imaging techniques such as functional imaging make it possible to use imaging features as biomarker for diagnosis, treatment response, and prognosis in cancer treatment. In this review, we will discuss how we can use imaging derived tumor features as biomarker for the treatment of esophageal cancer.

Neoadjuvant chemotherapy (NAC) is a promising treatment strategy for advanced esophageal cancer. However, measures of NAC response assessment and prognostic prediction have not yet been established. The aim of this study was to evaluate the usefulness of combined ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT). A total of 77 patients with stage IB-IV esophageal cancer who were treated with NAC followed by curative resection were retrospectively analyzed. PET/CT was performed before and after NAC and 56 patients were clinical responders. The pretreatment maximal standardized uptake value (pre-SUV_max), post-SUV_max and %SUV_max were 11.3±5.8, 5.1±4.8 and 49.0±35.1%, respectively, for the main tumors (T) and 4.3±2.8, 2.5±1.9 and 67.0±39.6%, respectively, for the metastatic nodes (N). Among the preoperatively available factors, clinical response (P=0.018), post-SUV_max-N (P=0.0001) and %SUV_max-T (P=0.0031) were significant prognostic factors by univariate analysis. The multivariate analysis identified post-SUV_max-N as the only significant prognostic predictor (P=0.0254). Patients with a post-SUV_max-N of <3.0 exhibited significantly fewer pathological metastatic nodes and better disease-free survival compared with patients with a post-SUV_max-N >3.0. Therefore, post-SUV_max-N may be a useful prognostic predictor in patients with advanced esophageal cancer who are treated with NAC followed by surgery.

Preoperative therapy is the gold standard for esophageal or gastroesophageal junction adenocarcinoma. Positron emission tomography (PET) is not only essential for tumor staging, but changes in glucose consumption correspond with response to therapy and correlated with prognosis. Therefore, with further refinement, PET parameter can serve as a tool for personalized therapy. For instance, the Municon trials suggested the possibility of PET-response guided therapy for esophageal adenocarcinoma (EAC) patients, however there are limitations. New PET parameters such as total lesion glycolysis (TLG) or magnetic resonance imaging (MRI) may provide better response prediction. Furthermore, PET parameters combined with genomic profiling might enhance better treatment selection, prediction, and prognostication. Here, we summarized the current state of understanding and future possibilities.

Esophageal cancer commonly has a poor prognosis, which requires an accurate diagnosis and early treatment to improve outcome. Other modalities for staging, such as endoscopic ultrasound imaging and computed tomography (CT) scans, have a role in diagnosis and staging. However, PET with fluorine-18 fluoro-2-deoxy-d-glucose/CT (FDG PET/CT) scanning allows for improved detection of distant metastatic disease and can help to prevent unnecessary interventions that would increase morbidity. FDG PET/CT scanning is valuable in the neoadjuvant chemotherapy assessment and predicting survival outcomes subsequent to surgery. FDG PET/CT scanning detects recurrent disease and metastases in follow-up.

We retrospectively evaluated the value of PET/CT in predicting survival and histopathological tumour-response in patients with distal oesophageal and gastric adenocarcinoma following neoadjuvant treatment.

Twenty-one patients with resectable distal oesophageal adenocarcinoma and 14 with gastric adenocarcinoma between January 2002 and December 2011, who had undergone serial PET before and after neoadjuvant therapy followed by surgery, were enrolled. Maximum standard uptake value (SUVmax) and metabolic tumour volume were measured and correlated with tumour regression grade and survival.

Histopathological tumour response (PR) is a stronger predictor of overall and disease-free survival compared to metabolic response. ∆%SUVmax ≥70% was the only PET metric that predicted PR (82.4% sensitivity, 61.5% specificity, p = 0.047). Histopathological non-responders had a higher risk of death (HR 8.461, p = 0.001) and recurrence (HR 6.385, p = 0.002) and similarly in metabolic non-responders for death (HR 2.956, p = 0.063) and recurrence (HR 3.614, p = 0.028). Ordinalised ∆%SUVmax showed a predictive trend for OS and DFS, but failed to achieve statistical significance.

PR was a stronger predictor of survival than metabolic response. ∆%SUVmax ≥70% was the best biomarker on PET that predicted PR and survival in oesophageal and gastric adenocarcinoma. Ordinalisation of ∆%SUVmax was not helpful in predicting primary outcomes.

Although change in standardized uptake value (SUV) measures and PET-based textural features during treatment have shown promise in tumor response prediction, it is unclear which quantitative measure is the most predictive. We compared the relationship between PET-based features and pathologic response and overall survival with the SUV measures in esophageal cancer.

Fifty-four esophageal cancer patients received PET/CT scans before and after chemoradiotherapy. Of these, 45 patients underwent surgery and were classified into complete, partial, and non-responders to the preoperative chemoradiation. SUVmax and SUVmean, two cooccurrence matrix (Entropy and Homogeneity), two run-length matrix (RLM) (high-gray-run emphasis and Short-run high-gray-run emphasis), and two size-zone matrix (high-gray-zone emphasis and short-zone high-gray emphasis) textures were computed. The relationship between the relative difference of each measure at different treatment time points and the pathologic response and overall survival was assessed using the area under the receiver-operating-characteristic curve (AUC) and Kaplan-Meier statistics, respectively.

All Textures, except Homogeneity, were better related to pathologic response than SUVmax and SUVmean. Entropy was found to significantly distinguish non-responders from the complete (AUC = 0.79, p = 1.7 × 10(-4)) and partial (AUC = 0.71, p = 0.01) responders. Non-responders can also be significantly differentiated from partial and complete responders by the change in the run-length and size-zone matrix textures (AUC = 0.71-0.76, p ≤ 0.02). Homogeneity, SUVmax, and SUVmean failed to differentiate between any of the responders (AUC = 0.50-0.57, p ≥ 0.46). However, none of the measures were found to significantly distinguish between complete and partial responders with AUC <0.60 (p = 0.37). Median Entropy and RLM textures significantly discriminated patients with good and poor survival (log-rank p < 0.02), while all other textures and survival were poorly related (log-rank p > 0.25).

For the patients studied, temporal changes in Entropy and all RLM were better correlated with pathological response and survival than the SUV measures. The hypothesis that these metrics can be used as clinical predictors of better patient outcomes will be tested in a larger patient dataset in the future.

Perioperative or preoperative radiochemotherapy (RCTx) is nowadays standard for locally advanced esophageal cancer in Europe, as randomized studies have shown a significant survival benefit for patients with multimodal treatment. As responders and nonresponders have a significantly different prognosis, a response-based tailored preoperative treatment would be of utmost interest. An established method is a metabolic response evaluation by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). The level of metabolic response is known to be dependent on the localization, tumor entity and type of preoperative treatment. Association of FDG-PET with later response and prognosis was shown for absolute standardized uptake values (SUV) or a decrease of SUV levels before and after therapy but there are also contradictory findings in the literature and no prospective validation. However, neither time points nor cut-off for metabolic response evaluation have been defined so far. The most interesting approach seems to be early response monitoring during preoperative chemotherapy, which has shown promising results in prospective single center trials (MUNICON I/II) during chemotherapy of adenocarcinoma of the esophagogastric junction (AEG), but needs to be validated in prospective multicenter trails.

We studied the predictive value of [(18) F]fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) for assessing disease-free (DFS) and overall survival (OS) in esophageal and esophagogastric junction cancer.

A literature search (PUBMED/MEDLINE, EMBASE, Cochrane) was performed to identify full papers with (18)FDG-PET and survival data, using indexing terms and free text words. Studies with >10 patients with locally advanced esophageal cancer, presenting sequential or at least one post-adjuvant treatment (18)FDG-PET data and Kaplan-Meier survival curves with >6 months median follow-up period were included. We performed a meta-analysis for DFS and OS using the hazard ratio (HRs) as outcome measure. Sources of heterogeneity study were also explored.

We identified 26 eligible studies including a total of 1,544 patients (average age 62 years, 82% males). The TNM distribution was as follows: stage I 7%, II 24%, III 53% and IV 15%. The pooled HRs for complete metabolic response versus no response were 0.51 for OS (95% CI, 0.4-0.64; P < 0.00001) and 0.47 for DFS (95% CI, 0.38-0.57; P < 0.00001), respectively. No statistical heterogeneity was present. To explore sources of clinical heterogeneity, we also realised subgroup and regression analyses. Taken into account the moderate correlation between OS and DFS (ρ = 0.54), we used joint bivariate random regression model. These analyses did not show a statistically significant impact of study characteristics and PET modalities on the pooled outcome estimates.

Despite methodological and clinical heterogeneity, metabolic response on (18)FDG-PET is a significant predictor of long-term survival data.

(18)F-FDG-PET is potentially useful for evaluating response to neoadjuvant therapy for esophageal cancer. However, the optimal (18)F-FDG-PET parameter for evaluating the response to therapy and survival has not been established. This study aimed to select the best of the two parameters of fluorodeoxyglucose ((18)F-FDG)-positron emission tomography (PET): decreased ratio of maximal standardized uptake (SUVmax-DR) or absolute value of posttreatment SUVmax (post-SUVmax), in predicting response and survival of patients with esophageal cancer who underwent neoadjuvant chemotherapy.

The study subjects were 211 consecutive patients with esophageal cancer who received neoadjuvant chemotherapy followed by surgery. (18)F-FDG-PET was performed before and 2-3 weeks after completion of neoadjuvant chemotherapy in assessment with pretreatment SUVmax (pre-SUVmax), post-SUVmax and SUVmax-DR.

The mean SUVmax decreased during neoadjuvant chemotherapy from 11.4 to 5.8, and the mean SUVmax-DR was 49.4%. Both post-SUVmax and SUVmax-DR correlated significantly with pathological response, although neither post-SUVmax nor SUVmax-DR could distinguish pathological complete response from pathological good response. The 5-year survival rate was significantly higher in patients with SUVmax-DR of >50% than those with <50% (56.5 vs. 39.6 %, p = 0.0137), and also significantly higher in patients with post-SUVmax of <3.5 than those with >3.5 (62.2 vs. 35.1%, p < 0.0001). Multivariate analysis identified post-SUVmax value, but not SUVmax-DR, as an independent prognostic factor in patients who underwent neoadjuvant chemotherapy.

Post-SUVmax is more useful for predicting survival of patients with esophageal cancer who undergo neoadjuvant therapy followed by surgery, although both SUVmax-DR and post-SUVmax equally correlate with pathological response.

Positron emission tomography scanning is used to assess response to induction therapy after treatment of esophageal cancer. A decrease in standardized uptake value has been correlated with response to therapy, with a standardized uptake value of zero often assumed to indicate complete absence of disease. We hypothesize that a significant number of patients may have residual esophageal cancer despite complete metabolic response (CMR).

A prospective database was reviewed for esophageal cancer patients receiving induction therapy followed by esophagectomy on whom both preinduction and postinduction positron emission tomography scans were obtained. Patients with a postinduction SUV of 0 (or "no uptake") were categorized as complete metabolic responders. Survival was calculated by the Kaplan-Meier statistic.

Among 120 patients, 32 (27%) had postinduction CMR after chemotherapy (21 of 81, 26%) or chemoradiation (11 of 39, 28%). At surgery, 19 patients (59%) with CMR had residual disease, including 12 (38%) with nodal metastases. Even among patients with a negative postinduction biopsy, 4 of 10 (40%) had residual disease. Final pathologic stages of patients with CMR were yp0 (complete pathologic response) in 13 (41%), ypI in 4 (12%), ypII in 9 (28%), and ypIII in 6 (19%). Three-year survival was 83% in the CMR group versus 41% in the remainder of the cohort (p = 0.02).

A CMR on postinduction positron emission tomography scan predicts but should not be assumed to be synonymous with complete pathologic response in esophageal cancer patients. The presence of residual disease should be strongly considered despite CMR and negative biopsy in patients receiving induction therapy.

To determine factors associated with symptomatic cardiac toxicity in patients with esophageal cancer treated with chemoradiotherapy.

We retrospectively evaluated 102 patients treated with chemoradiotherapy for locally advanced esophageal cancer. Our primary endpoint was symptomatic cardiac toxicity. Radiation dosimetry, patient demographic factors, and myocardial changes seen on (18)F-FDG PET were correlated with subsequent cardiac toxicity. Cardiac toxicity measured by RTOG and CTCAE v3.0 criteria was identified by chart review.

During the follow up period, 12 patients were identified with treatment related cardiac toxicity, 6 of which were symptomatic. The mean heart V20 (79.7% vs. 67.2%, p=0.05), V30 (75.8% vs. 61.9%, p=0.04), and V40 (69.2% vs. 53.8%, p=0.03) were significantly higher in patients with symptomatic cardiac toxicity than those without. We found the threshold for symptomatic cardiac toxicity to be a V20, V30 and V40 above 70%, 65% and 60%, respectively. There was no correlation between change myocardial SUV on PET and cardiac toxicity, however, a greater proportion of women suffered symptomatic cardiac toxicity compared to men (p=0.005).

A correlation did not exist between percent change in myocardial SUV and cardiac toxicity. Patients with symptomatic cardiac toxicity received significantly greater mean V20, 30 and 40 values to the heart compared to asymptomatic patients. These data need validation in a larger independent data set.

Reports have suggested that a reduction in tumour 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) examination during or after neoadjuvant chemotherapy may predict pathological response in oesophageal cancer. Our aim was to determine whether metabolic response predicts pathological response to a standardised neoadjuvant chemotherapy regimen within a prospective clinical trial.

Consecutive patients staged with potentially curable oesophageal cancer who underwent treatment within a non-randomised clinical trial were included. A standardised chemotherapy regimen (two cycles of oxaliplatin and 5-fluorouracil) was used. PET/CT was performed before chemotherapy and repeated 24-28 days after the start of cycle 2.

Forty-eight subjects were included: mean age 65 years; 37 male. Using the median percentage reduction in SUV(max) (42%) to define metabolic response, pathological response was seen in 71% of metabolic responders (17/24) compared with 33% of non-responders (8/24; P = 0.009, sensitivity 68%, specificity 70%). Pathological response was seen in 81% of subjects with a complete metabolic response (13/16) compared with 38% of those with a less than complete response (12/32; P = 0.0042, sensitivity 52%, specificity 87%). There was no significant histology-based effect.

There was a significant association between metabolic response and pathological response; however, accuracy in predicting pathological response was relatively low.

([18F])fluorodeoxyglycose-Positron Emission Tomography/Computer Tomography (([18F])FDG-PET/CT) is commonly used in staging of locally advanced esophageal cancer. Its predictive value for response to neoadjuvant therapy and survival after multimodality therapy is controversial.

Sixty-six consecutive patients with locally advanced adenocarcinoma of the esophagus or esophagogastric junction underwent surgery after neoadjuvant chemotherapy. Staging was done prospectively with ([18F])FDG-PET/CT, before and after completion of neoadjuvant therapy. Pre- and post-therapy maximal standardized uptake values for the primary tumor (SUV1 and SUV2) were determined, and their relative change (SUV∆%) calculated. Percentage change in SUV1 was compared with histopathologic response (HPR, complete or subtotal histologic remission), disease-free- (DFS) and overall survival (OS).

Resection with negative margins was achieved in 60 patients. HPR rate was 14 of 66 (21.2%). Median follow-up was 16 months (range 4-72). For all patients, OS probability at three years was 59% and DFS 50%. In receiver operating characteristics (ROC) analysis, HPR was optimally predicted by a > 67% change in baseline maximal SUV (sensitivity 79% and specificity 75%). In univariate survival analysis (Cox regression proportional hazards), HPR associated with improved DFS (HR 0.208, p = 0.033) but not OS (HR 0.030, p = 0.101), SUV % > 67% associated with improved OS (HR 0.249, p = 0.027) and DFS (HR 0.383, p = 0.040). In a multivariate model (adjusted by age, sex, and ASA score), neither HPR nor SUV∆% > 67% was predictive of improved OS and DFS. However, SUV∆% as a continuous variable was an independent predictor of OS (HR 0.966, p < 0.0001) or DFS (HR 0.973, p < 0.0001).

Our results support previous results showing that ([18F])FDG-PET/CT can distinguish a group of patients with worse prognosis after neoadjuvant chemotherapy in adenocarcinoma of the esophagus or esophagogastric junction. This information could offer a new independent preoperative marker of prognosis.

Neoadjuvant therapy for the treatment of oesophageal cancer was introduced in an effort to improve prognosis. Response assessment is crucial for the treatment of patients with oesophageal cancer. Currently, ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) seems to be the best available tool to assess neoadjuvant therapy response in patients with oesophageal cancer. The purpose of this study was to assess the diagnostic value of ¹⁸F-FDG PET for the evaluation of neoadjuvant therapy responses in patients with oesophageal cancer using a meta-analysis. A unified procedure and evaluation standard for ¹⁸F-FDG PET in the assessment of neoadjuvant therapy response should be established.

All published English-language studies pertaining to the assessment of neoadjuvant therapy response in patients with oesophageal cancer using ¹⁸F-FDG PET in the MEDLINE and EMBASE databases were collected. The methodological quality of the included studies was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies quality assessment tool. Pooled sensitivity, specificity, diagnostic odds ratios and summary receiver operating characteristic curves were obtained using statistical software.

Thirteen studies included in the meta-analysis fulfilled the inclusion criteria of the Quality Assessment of Diagnostic Accuracy Studies quality assessment tool. The pooled sensitivity, specificity and diagnostic odds ratios for F-¹⁸FDG PET in the evaluation of neoadjuvant therapy response in patients with oesophageal cancer were 70.3% [95% confidence interval (CI): 64.4-75.8], 70.1% (95% CI: 65.1-74.8) and 9.389 (95% CI: 3.482-25.319), respectively. The area under the curve and the Q value for the summary receiver operating characteristic curve were 0.8244 and 0.7575, respectively.

¹⁸F-FDG PET has some value in the assessment of neoadjuvant therapy response in patients with oesophageal cancer. A 50% reduction in standardized uptake value between pretherapy and posttherapy positron emission tomography scans performed in the first 2 weeks after the initiation of neoadjuvant therapy is the optimal condition for predicting a response to neoadjuvant therapy in patients with oesophageal cancer.

Restaging of patients with locally advanced non-small-cell lung cancer (NSCLC) is of paramount importance, since only patients with down-staging after induction therapy will benefit from surgery. In this study, we assessed the aetiology of new (18)fluoro-2-deoxy-d-glucose (FDG)-positive focal abnormalities on restaging positron emission tomography/computed tomography (PET/CT) in patients with a good response after induction chemotherapy in the primary tumour and lymph nodes.

Between 2004 and 2008, 31 patients with histological proven stage III NSCLC had a PET/CT prior and after induction chemotherapy. Their medical charts were retrospectively reviewed.

Restaging PET/CT revealed a new FDG-positive lesion in 6 of 31 (20%) patients. The initial clinical stage of the disease was IIIA N2 in four and IIIB T4 in two patients. The maximal standard uptake value in the primary tumour (P = 0.043) and in the initially involved mediastinal nodes (P = 0.068) decreased after induction treatment in all patients. The new PET/CT findings were located in an ipsilateral cervical lymph node in two patients, a contralateral mediastinal in one patient and an ipsilateral mammary internal lymph node in one patient. Two other patients had a lesion on the contralateral lung. Malignant lymph node infiltrations were excluded following fine-needle puncture, intraoperative biopsy or follow-up PET/CT. Contralateral pulmonary lesions were diagnosed as benign following mini thoracotomy and pulmonary wedge resection.

New solitary FDG-positive lesions on restaging PET/CT after induction chemotherapy for NSCLC are not rare in good responders to chemotherapy. In our experience, all these lesions were not associated with malignancy.

Patients with ESCC (squamous cell carcinoma of the esophagus) are most commonly diagnosed with locally advanced tumor stages. Early metastatic disease and late diagnosis are common reasons responsible for this tumor's poor clinical outcome. The prognosis of esophageal cancer is very poor because patients usually do not have symptoms in early disease stages. Squamous cell carcinoma of the esophagus frequently complicates patients with multiple co-morbidities and these patients often require interdisciplinary diagnosis and treatment procedures. At present time, neoadjuvant radiation therapy and chemotherapy followed by surgery are regarded as the international standard of care. Meta-analyses have confirmed that this approach provides the patient with better local tumor control and an increased overall survival rate. It is recommended that patients with positive tumor response to neoadjuvant therapy and who are poor surgical candidates should consider definitive radiochemotherapy without surgery as a treatment option. In future, EGFR antibodies may also be administered to patients during therapy to improve the current treatment effectiveness. Positron-emission tomography proves to be an early response-imaging tool used to evaluate the effect of the neoadjuvant therapy and could be used as a predictive factor for the survival rate in ESCC. The percentage proportions of residual tumor cells in the histopathological analyses represent a gold standard for evaluating the response rate to radiochemotherapy. In the future, early response evaluation and molecular biological tests could be important diagnostic tools in influencing the treatment decisions of ESCC patients.

We aimed to study whether positron emission tomography/computed tomography (PET/CT) findings are associated with lymph node staging, as outlined by the 7th edition American Joint Committee on Cancer (AJCC) TNM staging system in patients with esophageal squamous cell carcinoma (ESCC).

A series of 76 ESCC patients undergoing esophagectomy were included in this study. The relation between PET/CT findings [maximum standardized uptake value (SUVmax)] and pathologic lymph node status (N stage) was studied.

The SUVmax of extra-tumor uptake, but not that of the main tumor, was significantly associated with the N classification. N2/N3 disease was observed in 61.1% of patients with an SUVmax for extra-tumor uptake of >4.9, whereas only 17.2% of patients with an SUVmax of extra-tumor uptake of <4.9 were classified as N2/N3 The number of PET abnormalities (NPAs) was also significantly associated with the N classification. Patients with three or more NPAs had a 65% chance of being classified as N2/N3, whereas patients with one or two NPAs had less than a 20% chance of being classified as N2/N3.

The SUVmax of extra-tumor uptake and the NPAs were significantly associated with the N classification outlined by the 7th edition of the AJCC TNM staging system. PET/CT does help identify patients with advanced lymph node metastasis (N2/N3 stage) instead of simply indicating nodal involvement.

No consensus exists on the optimal treatment strategy for clinical T2-T3N0M0 esophageal cancer. This study was conducted to determine rates of nodal positivity (N+) and to evaluate results of treatment strategies in this cohort.

Surgically treated patients with cT2-T3N0M0 esophageal cancer were reviewed. Adequacy of lymph node dissection was assessed by guidelines applied to clinical stage. Survival was determined by Kaplan-Meier analysis. Univariate and multivariate analyses were done for predictors of N+ and survival.

We identified 102 patients, 51 cT2N0 and 51 cT3N0, 39 (38%) of whom had induction therapy. Despite being clinically node negative, 61 patients (60%) had nodal metastases. Applied to cT classification, adequate nodal dissection was achieved in 64 patients (63%). Transthoracic esophagectomy was more likely than transhiatal esophagectomy to achieve adequate nodal dissection (69% versus 31%, p=0.005). Adequate nodal dissection was more likely to document pN+ disease in both the surgery alone group (70% versus 50%, p=0.13) and induction therapy group (71% versus 33%, p=0.02). Five-year overall survival was 44% with surgery alone and 55% with induction therapy. On multivariate analysis, pN+ was the strongest predictor of overall survival (relative risk 2.73, confidence interval: 1.29 to 5.78).

Most cT2-T3N0M0 patients have pN+ disease. Despite induction therapy, more than 50% have persistent nodal disease. Transthoracic esophagectomy is more likely to detect pN+ disease and more likely to meet criteria of adequate nodal dissection than is transhiatal esophagectomy. Therefore, the majority of patients with cT2-T3N0M0 should be considered for neoadjuvant protocols and should be treated by transthoracic resection whenever possible.

(18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been used extensively to explore whether FDG Uptake can be used to provide prognostic information for esophageal cancer patients. The aim of the present review is to evaluate the literature available to date concerning the potential prognostic value of FDG uptake in esophageal cancer patients, in terms of absolute pretreatment values and of decrease in FDG uptake during or after neoadjuvant therapy.

A computer-aided search of the English language literature concerning esophageal cancer and standardized uptake values was performed. This search focused on clinical studies evaluating the prognostic value of FDG uptake as an absolute value or the decrease in FDG uptake and using overall mortality and/or disease-related mortality as an end point.

In total, 31 studies met the predefined criteria. Two main groups were identified based on the tested prognostic parameter: (1) FDG uptake and (2) decrease in FDG uptake. Most studies showed that pretreatment FDG uptake and postneoadjuvant treatment FDG uptake, as absolute values, are predictors for survival in univariate analysis. Moreover, early decrease in FDG uptake during neoadjuvant therapy is predictive for response and survival in most studies described. However, late decrease in FDG uptake after completion of neoadjuvant therapy was predictive for pathological response and survival in only 2 of 6 studies.

Measuring decrease in FDG uptake early during neoadjuvant therapy is most appealing, moreover because the observed range of values expressed as relative decrease to discriminate responding from nonresponding patients is very small. At present inter-institutional comparison of results is difficult because several different normalization factors for FDG uptake are in use. Therefore, more research focusing on standardization of protocols and inter-institutional differences should be performed, before a PET-guided algorithm can be universally advocated.

Esophageal cancer ranks among the ten most common malignancies in the world and is a frequent cause of cancer-related death. Almost all therapeutic modalities for esophageal cancer are associated with considerable mortality and morbidity. Consequently, there has been growing concern regarding effective management of esophageal cancer. Imaging plays an important role in the initial selection of patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) is playing an increasing role in the management of esophageal cancer. The role of FDG-PET in diagnosis, preoperative staging, monitoring of response to neoadjuvant therapy, and detection of disease recurrence is evaluated in this chapter.

Current response guidelines for the treatment of solid tumours are based on CT criteria. Over the last decades new techniques have emerged to evaluate cancer therapy. FDG-PET scanning is a more functional imaging technique, which can measure differences in metabolic activity. Although it has a low specificity, studies show that it can outperform classical CT scanning criteria. Especially in lung, breast and oesophageal cancer it can predict response earlier in the neo-adjuvant setting. This could reduce the use of ineffective cancer therapies, reducing costs and patient toxicity, and direct patients sooner towards effective therapy. The main problem with FDG-PET remains the difficulty in defining thresholds for response, as there is clearly a lack in large prospective randomized studies validating the use of FDG-PET in response guidelines.We give an overview of data on response prediction in solid tumours by the application of PET.

To systematically review the accuracy of fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) in the prediction of tumor response to neoadjuvant therapy in patients with esophageal cancer.

The MEDLINE and EMBASE databases were systematically searched for relevant studies. Methodologic quality of the included studies was assessed. Sensitivities and specificities of (18)F FDG PET in individual studies were calculated and underwent meta-analysis with a random effects model. A summary receiver operating characteristic curve (sROC) was constructed with the Moses-Shapiro-Littenberg method. A chi(2) test was performed to test for heterogeneity (defined as P < .10). Potential sources for heterogeneity were explored by assessing whether certain covariates significantly (P < .05) influenced the relative diagnostic odds ratio.

Twenty reports, comprising a total of 849 patients with esophageal cancer, were included. Overall, the studies were of moderate methodologic quality. Sensitivity and specificity of (18)F FDG PET ranged from 33% to 100% and from 30% to 100%, respectively, with pooled estimates of 67% (95% confidence interval: 62%, 72%) and 68% (95% confidence interval: 64%, 73%), respectively. The area under the sROC curve was 0.7815. There was significant heterogeneity in both the sensitivity and specificity of the included studies (P < .0001). Spearman rho between the logit of sensitivity and the logit of 1-specificity was 0.086 (P = .719), which suggested that there was no threshold effect. Studies performed outside of the United States and studies of higher methodologic quality yielded significantly higher overall accuracy.

On the basis of current evidence, (18)F FDG PET should not yet be used in routine clinical practice to guide neoadjuvant therapy decisions in patients with esophageal cancer.

http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09091324/-/DC1.

For assessing response to neoadjuvant therapy in patients with esophageal cancer, both endoscopic ultrasonography (EUS) and fluorodeoxyglucose positron emission tomography (FDG-PET) are commonly used, and despite few controlled trials, it is not known if one imaging modality is superior to the other. Also, relative diagnostic accuracy of early (during the course of neoadjuvant therapy) and FDG-PET after completion of neoadjuvant therapy has not been reviewed. The aim of this study was to perform a systematic review of published information to compare diagnostic accuracy of EUS and FDG-PET in this setting. A search of the MEDLINE, EMBASE, and Cochrane databases was performed along with a manual search of cross-references of eligible articles. Data on the accuracy of the imaging modalities were compared by constructing summary receiver-operating characteristic curves. Seven studies with EUS and 15 with FDG-PET were included in the final analysis (N= 966). The sensitivity of EUS and FDG-PET ranged from 20 to 100% and 42 to 100%, respectively. The specificity ranged from 36 to 100% and 27 to 100%, respectively. The areas under the curve were 0.86 (95% confidence interval [CI]: 0.77-0.96) for EUS and 0.80 (95% CI: 0.72-0.89) for FDG PET (P= 0.37). The maximum joint sensitivity and specificity (Q* index) values for EUS and FDG-PET were 0.79 (95% CI: 0.70-0.88) and 0.74 (95% CI: 0.66-0.81), respectively (P= 0.38). There was no difference in accuracy between early FDG-PET and FDG-PET after completion of neoadjuvant therapy. EUS and FDG-PET have similar overall diagnostic accuracy for assessment of response to neoadjuvant therapy in patients with esophageal cancer.

18F-FDG PET yields physiologic information that allows for identifying cancer based on altered tissue metabolism. The aim of this study was to prospectively validate the predictive value of positron emission tomography (PET) in squamous cell carcinoma (SCC) of the esophagus treated by pre-operative chemotherapy followed by esophagectomy.

Prospective efficacy and toxicity study of patients enrolled between January 1999 and September 2003.

Twenty-one patients with SCC of the esophagus who were potentially resectable underwent 18F-FDG PET imaging before the first cycle of neoadjuvant chemotherapy and at least 14 days after the third cycle. A patient was classified as a metabolic responder when the metabolic activity of the primary tumor as measured by the maximum standardized uptake values had decreased by 50% or more at the time of the second 18F-FDG PET.

The median age of the study cohort was 60 years with a range of 39-70 years; 12 patients were males and 9 were females. 18F-FDG PET had increased activity in the primary tumor in all patients. Metabolic response occurred in 14/21 patients (66%), while 7/21 (33%) patients did not show a metabolic response. Metabolic responders had a high clinical response rate (92%), a median progression free survival (PFS) of 16.4 months and a median overall survival (OS) of 35.3 months. In contrast, prognosis was poor for metabolic non-responders with a clinical response rate of 42% (P=.025), a median PFS of 7.13 months (P=.032) and median OS of 12 months (P=.038).

Our results demonstrate that changes in tumor metabolic activity after neoadjuvant chemotherapy predicts PFS and OS in esophageal SCC patients.

Positron emission tomography (PET) and PET/computed tomography (CT) with the glucose analog (18)F-fluorodeoxyglucose (FDG) are increasingly used to assess response to therapy in patients, and there is converging evidence that changes in glucose utilization during therapy can be used to predict clinical outcome. Today, integrated PET/CT systems have mainly replaced stand-alone PET devices, providing the opportunity to integrate morphologic information and functional information. However, the use of PET/CT systems also gives rise to methodological challenges for the quantitative analysis of PET scans for treatment monitoring. Recently published single-center studies demonstrate that FDG-PET and FDG-PET/CT have been successfully used for monitoring of tumor response to cytotoxic therapy in a variety of tumor entities. The potential early identification of nonresponding tumors provides an opportunity to alter treatment regimens according to the individual chemosensitivity of the tumor tissue. In this article, we review the methodological background to monitoring of cancer treatment with PET/CT, the diagnostic and prognostic performance of PET/CT for predicting tumor response with the glucose analog FDG in various tumor entities, and the clinical potential of new imaging probes. In addition, the future direction of research and clinical applications is discussed.

Despite substantial improvements in the diagnosis and treatment of many gastrointestinal cancers, particularly colorectal cancer, numerous patients are only diagnosed in advanced stages of disease, which can preclude curative treatment. Screening and early diagnosis of high-risk individuals might be the most promising approach to improve prognosis; however, molecular biomarkers for early diagnosis of most gastrointestinal cancers are not yet available. The prognosis of patients with advanced gastrointestinal cancers has improved through the development of multimodal treatments and the introduction of targeted therapies. Nonetheless, not all patients benefit equally from these treatment approaches, and toxicity can be substantial. The ability to predict whether a patient will respond to therapy early in their treatment for gastrointestinal cancer may be of particular value to stratify and individualize patient treatment strategies. Despite improvement in the understanding of cancer pathogenesis and progression at the molecular level, the molecular changes that underlie treatment response and/or drug resistance are still largely unknown. PET is the first technique to show promise in prediction of response to therapy, and has resulted in promising advancements, particularly in esophageal and gastric cancers. Tissue-based and blood-based molecular biomarkers are still subject to validation. Prediction of response to treatment could ultimately lead to an overall improvement in prognosis.

The effort to improve outcomes in esophageal cancer has included attempts at improving staging and patient selection. 2-Deoxy-2-[(18)F]fluoro-Dglucose positron emission tomography (FDG-PET) has been extensively studied in this context and has been widely accepted as a staging tool. Its role in restaging or assessing therapeutic response is investigational and promising. Laparoscopy has also been studied as a means for improving staging, but its role may be limited in the era of PET. This article discusses the literature assessing these modalities, particularly with regard to the practical management of the patient in the clinic.

The aim of this review is to consolidate our knowledge on an important and rapidly expanding area of expertise. Numerous methods for predicting response (in terms of pathological response and survival) to neoadjuvant therapy (chemotherapy/chemo-radiotherapy) in oesophageal and junctional cancers have been proposed. This review concerns itself only with the use of positron emission tomography for such a purpose. At present there are no standardised criteria amongst PET trials as to what determines a response according to PET, what is the optimal time to perform PET in relation to the timing of neoadjuvant therapy, and what is the ideal method of quantifying PET tracer uptake.

An electronic search was performed of PubMed, Ovid and Embase websites to identify studies, in the English language, using the search terms: PET; oesophageal; oesophago-gastric; survival; cancer; response; chemotherapy and chemo-radiotherapy. The reference lists were searched manually to identify further relevant studies.

Twenty-two studies were identified, all using (18)FDG as the tracer, using PET to predict response in terms of pathological response and survival following neoadjuvant therapy (chemotherapy/chemo-radiotherapy). PET had a varying degree of success in predicting both pathological response and survival outcomes, with only one study using PET to influence management decisions.

PET seems a promising technique, but large-scale conclusions are hindered by small study numbers, lack of criteria as to what constitutes a response and markedly differing PET imaging times. A large randomised trial concerning a homogeneous group of patients and tumours is required before PET might be used to influence management.

This article reviews developments in the treatment of locally advanced esophageal cancer with surgery and chemoradiation published in 2007.

Overall long-term survival is the same for patients after transhiatal or transthoracic esophagectomy. The pathology report of the resected specimen should contain information on lymph node status, such as size, location and lymph node ratio. If surgery is performed in patients with advanced esophageal cancer, there is small survival advantage if combined with neoadjuvant therapy, that is chemoradiation. Prognostic factors are a good performance status, a major response to chemoradiation and an early metabolic response with fluorine-18 fluorodeoxyglucose PET. Definitive chemoradiation may have similar results as combination treatment including surgery in selected patients with esophageal squamous cell cancer. Salvage surgery should be considered if definitive chemoradiation fails, provided that an R0 resection can be performed. Nutritional status is a prognostic factor in patients undergoing treatment of esophageal cancer.

In 2007, refinements of the nodal status in the tumor, node, metastasis system were proposed. Chemoradiation followed by surgery is increasingly being used in patients with advanced esophageal cancer. Evidence suggests that definitive chemoradiation could be a reliable treatment option in selected patients with esophageal squamous cell cancer.

Upper gastrointestinal tumors involving the esophagus and the stomach are a serious public health problem worldwide. The West has seen a dramatic increase in the incidence of gastroesophageal cancers in the past 2 decades. Although Barrett esophagus has been well characterized, the exact pathway to developing frank malignancy remains undefined. Current treatments for locoregional disease include surgery, chemotherapy, radiation therapy, or some combination thereof. Clinical trials are currently investigating biologic agents that target signaling pathways in carcinogenesis. Whether this research translates into an improved therapeutic index remains to be seen. This review provides a comprehensive update to physicians and residents who contribute to the care of these patients. Studies in the English language were identified searching PubMed (January 1, 1980, through February 29, 2008) using the terms esophagus, gastric, carcinoma, adenocarcinoma, squamous cell, radiation, chemotherapy, surgery, esophagectomy, and targeted therapy.