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.

We present the clinical results of a phase 2 trial combining neoadjuvant docetaxel, cisplatin, 5 Flourouracil, and the PD-L1 inhibitor avelumab in locally advanced gastro-esophageal adenocarcinoma (GEA). Fifty-one patients receive neoadjuvant therapy with 50 proceeding to surgery. Grade 3-4 adverse events occur in 40%; complete/major pathological response is found in 7/50 (14%) and 9/50 (18%), with 2-year disease-free survival of 67.5%. There is no correlation between tumor regression and PD-L1 or mismatch repair (MMR) status. Multiplex immunohistochemistry and longitudinal single-cell transcriptomic profiling reveal alterations in certain innate immune cell populations, particularly noting an M2-tumor-associated macrophage (M2-TAM) proliferation in non-responding tumors. These findings describe the effective nature of this treatment regimen for GEA and reveal associated features of the inflammatory milieux associated with response to chemo-immunotherapy. The specific character of the inflammatory environment in non-responders may, in the future, help personalize treatment. This study was registered at ClinicalTrials.gov (NCT03288350).

Positron Emission Tomography/Computed Tomography (PET/CT) plays a critical role in managing gastrointestinal (GI) cancers within radiation oncology. It enhances tumor detection, staging, and lymph node involvement assessment, leading to better-targeted radiation treatment. PET/CT also aids in delineating tumor volumes to minimize geographic misses, enabling precise dose escalation to metabolically active regions. Despite its benefits, PET/CT has limitations such as false positives and dependency on complementary imaging. Emerging technologies offer real-time adjustments and personalized treatments, advancing precision medicine in GI radiation oncology. Further research is needed to refine PET/CT integration for improved treatment outcomes and cost-effectiveness.

Neoadjuvant chemotherapy is widely recognized as the established treatment for advanced gastric cancer. However, predicting its efficacy before surgery remains challenging.

The present study aimed to evaluate the effectiveness of 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) as a predictor of treatment response to the S-1+Oxaliplatin regimen (SOX).

Thirty patients who underwent gastrectomy following neoadjuvant SOX between January 2021 and July 2023 were included. Patients underwent FDG-PET pre- and postsurgery. The maximum standardized uptake value (SUVmax) from FDG-PET was examined in relation to histological tumor response and prognosis. SUVmax decreased significantly after chemotherapy in all patients (p < 0.001), especially in those with Grade 1a, 2, and 3 tumors (p < 0.05). SUV reduction increased stepwise with the histological response grade. Optimal cut-off values for the percentage decrease in SUVmax (ΔSUVmax) predictive of histologic efficacy were identified as 53% (area under curve 0.855, p = 0.0018) for Grade 1b or higher and 75% (area under curve 0.806, p = 0.0044) for Grade 2 or higher. Patients with ΔSUVmax > 50% had improved recurrence-free survival (p = 0.027).

FDG-PET may be useful as a predictor of treatment response in neoadjuvant SOX therapy for gastric cancer. The determination of the optimal ΔSUVmax value may enhance the precision of histological tumor response prediction.

Recent advancements in radiotherapy for esophageal cancer have significantly improved treatment outcomes and patient quality of life. Traditional radiotherapy techniques have been enhanced by the integration of advanced imaging and precision targeting technologies, such as intensity-modulated radiotherapy and proton therapy, which allow for more accurate tumor targeting while minimizing damage to surrounding healthy tissues. Additionally, combining radiotherapy with immunotherapy has shown promising results, leveraging the body's immune response to enhance the effectiveness of cancer treatment. Studies have also highlighted the benefits of neoadjuvant chemoradiation followed by surgical resection, which has been associated with improved overall survival rates compared to radiotherapy alone. These innovations are paving the way for more effective and personalized treatment strategies, offering new hope for patients with esophageal cancer.

To explore the influence of Epstein-Barr virus (EBV) DNA levels before and after induction chemotherapy (IC), tumor response to IC, and baseline factors on overall survival (OS) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). A nomogram was subsequently constructed to explore the individualized optimal cumulative cisplatin dose (CCD) in concurrent chemoradiotherapy (CCRT).

A total of 581 LA-NPC patients were included, randomly divided into training and validation cohorts in a 7:3 ratio. In the training cohort, a nomogram was subsequently established based on multivariate Cox regression analysis and then validated. Subsequently, patients were classified into different risk groups based on the nomogram, and the impact of different levels of CCD on survival outcomes was evaluated.

EBV DNA levels after IC, tumor response to IC, age, and LDH were independent prognostic factors of OS. Schoenfeld residual analysis indicated overall satisfaction of the proportional hazards assumption for the Cox regression model. The C-index of the nomogram was 0.758 (95% CI: 0.695-0.821) for the training cohort and 0.701 (95% CI: 0.589-0.813) for the validation cohort. Calibration curves demonstrated good correlation between the nomogram and actual survival outcomes. DCA confirmed the clinical utility enhancement of the nomogram over the TNM staging system. For OS, patients in the medium/high-risk group with a CCD > 200 mg/m² had better outcomes than those with CCD ≤ 200 mg/m², although the difference was not statistically significant (p = 0.097). No significant difference was observed in local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) across various levels of CCD in different risk subgroups (p > 0.05).

The nomogram based on EBV DNA levels after IC, tumor response, LDH, and age effectively predicts OS in LA-NPC patients, aids in risk stratification, and may guide treatment decisions.

Neoadjuvant immunochemotherapy (NICT) has shown promising therapeutic benefits in patients with locally advanced gastric cancer (LAGC). Our study aimed to predict the pathological response to NICT in LAGC before surgery by correlating the metabolic parameters of baseline and post-treatment 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) of the primary lesion with the pathological response following radical surgery.

Thirty-six LAGC patients who received three cycles of NICT (combination of sintilimab and CapeOx), followed by radical surgery, were included in this study. Both baseline 18F-FDG PET/CT (bPET) and post-treatment 18F-FDG PET/CT (pPET) were conducted, the metabolic parameters derived from the PET/CT scans, including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on bPET and pPET (bSUVmax and pSUVmax, bMTV and pMTV, bTLG and pTLG), as well as their reductions post-treatment (ΔSUVmax, ΔMTV, and ΔTLG), were assessed for their correlation with treatment efficacy and tumor regression grade (TRG) following NICT.

Out of the 36 patients, 13 patients had a good response (GR), which included 5 cases with TRG 0 and 8 cases with TRG 1. Conversely, 23 patients exhibited a poor response (PR), with 20 patients having TRG 2 and 3 patients having TRG 3. Univariate analysis revealed that pMTV and pTLG in the GR group were significantly lower compared to the PR group (all p < 0.05). The identified cutoff values of pMTV and pTLG were 1.68 cm³ (area under the cure (AUC) = 0.683) and 4.71 cm³ (AUC = 0.683) for the GR and PR groups, respectively. On receiver operating characteristic (ROC) curve analyses, these values corresponded to sensitivity, specificity, and accuracy of 68.8%, 80.0%, and 73.1%, respectively, with no statistically significant differences between them after the DeLong test and McNemar test (all p > 0.05). Furthermore, bSUVmax, bMTV, bTLG, ΔSUVmax, ΔMTV, and ΔTLG in the TRG 0 group were significantly higher than those in the TRG 1 group (all p < 0.05). Upon performing ROC curve analyses for the TRG 0 group, the thresholds for bSUVmax, bMTV, bTLG, ΔSUVmax, ΔMTV, and ΔTLG were determined to be 7.8 (AUC = 0.916), 36.76 (AUC = 0.768), 105.55 (AUC = 0.819), 4.82 (AUC = 0.923), 22.64 (AUC = 0.807), and 104.7 (AUC = 0.845), with no statistically significant differences between them after the DeLong test (all p > 0.05). These thresholds demonstrated high sensitivity (80% for bMTV and 100% for others), specificity (83.9%, 71.0%, 67.7%, 83.9%, 61.3%, and 71.0%), and accuracy (86.1%, 66.7%, 72.2%, 86.1%, 66.7%, and 75.0%) in predicting TRG 0 after NICT, with no statistically significant differences between them after the McNemar test (all p > 0.05).

Imaging biomarkers from the combination of baseline and post-treatment 18F-FDG PET/CT showed potential in predicting pathological response to NICT in LAGC patients before surgery.

This single-center, single-arm, phase II trial (ChiCTR2100050057) investigated the ability of 18F-labeled fibroblast activation protein inhibitor ([18F]AlF-NOTA-FAPI-04, denoted as 18F-FAPI) PET/CT to predict the response to neoadjuvant camrelizumab plus chemotherapy (nCC) in locally advanced esophageal squamous cell carcinoma (LA-ESCC). Methods: This study included 32 newly diagnosed LA-ESCC participants who underwent 18F-FAPI PET/CT at baseline, of whom 23 also underwent scanning after 2 cycles of nCC. The participants underwent surgery after 2 cycles of nCC. Recorded PET parameters included maximum, peak, and mean SUVs and tumor-to-background ratios (TBRs), metabolic tumor volume, and total lesion FAP expression. PET parameters were compared between patient groups with good and poor pathologic responses, and the predictive performance for treatment response was analyzed. Results: The good and poor response groups each included 16 participants (16/32, 50.0%). On 18F-FAPI PET/CT, the posttreatment SUVs were significantly lower in good responders than in poor responders, whereas the changes in SUVs with treatment were significantly higher (all P < 0.05). SUVmax (area under the curve [AUC], 0.87; P = 0.0026), SUVpeak (AUC, 0.89; P = 0.0017), SUVmean (AUC, 0.88; P = 0.0021), TBRmax (AUC, 0.86; P = 0.0031), and TBRmean (AUC, 0.88; P = 0.0021) after nCC were significant predictors of pathologic response to nCC, with sensitivities of 63.64%-81.82% and specificities of 83.33%-100%. Changes in SUVmax (AUC, 0.81; P = 0.0116), SUVpeak (AUC, 0.82; P = 0.0097), SUVmean (AUC, 0.81; P = 0.0116), and TBRmean (AUC, 0.74; P = 0.0489) also were significant predictors of the pathologic response to nCC, with sensitivities and specificities in similar ranges. Conclusion: 18F-FAPI PET/CT parameters after treatment and their changes from baseline can predict the pathologic response to nCC in LA-ESCC participants.

This study aimed to comprehensively explore the different metabolic connectivity topological changes in MTLE and NTLE, as well as their association with surgical outcomes.

This study enrolled a cohort of patients with intractable MTLE and NTLE. Each individual's metabolic connectome, as determined by Kullback-Leibler divergence similarity estimation for the [18F]FDG PET image, was employed to conduct a comprehensive analysis of the cerebral metabolic network. Alterations in network connectivity were assessed by extracting and evaluating the strength of edge and weighted connectivity. By utilizing these two connectivity strength metrics with the cerebellum, we explored the network properties of connectivity and its association with prognosis in surgical patients.

Both MTLE and NTLE patients exhibited substantial alterations in the connectivity of the metabolic network at the edge and nodal levels (p < 0.01, FDR corrected). The key disparity between MTLE and NTLE was observed in the cerebellum. In MTLE, there was a predominance of increased connectivity strength in the cerebellum. Whereas, a decrease in cerebellar connectivity was identified in NTLE. It was found that in MTLE, higher edge connectivity and weighted connectivity strength in the contralateral cerebellar hemisphere correlated with improved surgical outcomes. Conversely, in NTLE, a higher edge metabolic connectivity strength in the ipsilateral cerebellar hemisphere suggested a worse surgical prognosis.

The cerebellum exhibits distinct topological characteristics in the metabolic networks between MTLE and NTLE. The hyper- or hypo-metabolic connectivity in the cerebellum may be a prognostic biomarker of surgical prognosis, which might aid in therapeutic decision-making for TLE individuals.

Despite our increased understanding of the biological and molecular aspects of gastro-oesophageal tumourigenesis, the identification of prognostic or predictive factors remains challenging. Patients with resectable gastric and oesophageal adenocarcinoma are often treated similarly after surgical resection, regardless of their tumour biology, clinical characteristics, and histological treatment response. Substantial progress has been made in the past 5 years in managing patients with gastric or oesophageal adenocarcinoma, including the use of immune checkpoint inhibitors and new targeted therapies, leading to substantial improvements in clinical outcomes. These advancements have primarily been established in advanced and metastatic disease, while the management framework for local and locoregional disease is just beginning to shift. We provide an overview of existing data on biomarkers and tumour-related and host-related factors that are relevant to stratify patients into low-risk and high-risk recurrence groups, both before and after surgery, paving the way for more personalised treatment approaches.

While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC.

We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival.

The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors.

Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

The prognostic value of tumor regression scores (TRS) in patients with esophageal adenocarcinoma (EAC) who underwent neoadjuvant chemoradiation remains unclear. We sought to investigate the prognostic value of pathologic and metabolic treatment response among EAC patients undergoing neoadjuvant chemoradiation.

Patients who underwent esophagectomy for EAC after neoadjuvant CROSS protocol between 2016 and 2020 were evaluated. TRS was grouped according to the modified Ryan score; metabolic response, according to the PERCIST criteria. Variables from endoscopic ultrasound, endoscopic biopsies, and positron emission tomography (primary and regional lymph node standardized uptake values [SUVs]) were collected.

The study population comprised 277 patients. A TRS of 0 (complete response) was identified in 66 patients (23.8%). Seventy-eight patients (28.1%) had TRS 1 (partial response), 97 (35%) had TRS 2 (poor response), and 36 (13%) had TRS 3 (no response). On survival analysis for overall survival (OS), patients with TRS 0 had longer survival compared to those with TRS 1, 2, or 3 (P = .010, P < .001, and P = .005, respectively). On multivariable logistic regression, the presence of signet ring cell features on endoscopic biopsy (odds ratio [OR], 7.54; P = .012) and greater SUV uptake at regional lymph nodes (OR, 1.42; P = .007) were significantly associated with residual tumor at pathology (TRS 1, 2, or 3). On multivariate Cox regression for predictors of OS, higher SUVmax at the most metabolically active nodal station (hazard ratio [HR], 1.08; P = .005) was independently associated with decreased OS, whereas pathologic complete response (HR, 0.61; P = .021) was independently associated with higher OS.

Patients with pathologic complete response had prolonged OS, whereas no difference in survival was detected among other TRS categories. At initial staging, the presence of signet ring cells and greater SUV uptake at regional lymph nodes predicted residual disease at pathology and shorter OS, suggesting the need for new treatment strategies for these patients.

Esophageal cancer is the seventh most common malignancy worldwide, with over 470 000 new cases diagnosed each year. Two distinct histological subtypes predominate, and should be considered biologically separate disease entities.1 These subtypes are esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Outcomes remain poor regardless of subtype, with most patients presenting with late stage disease.2 Novel strategies to improve early detection of the respective precursor lesions, squamous dysplasia, and Barrett's esophagus offer the potential to improve outcomes. The introduction of a limited number of biologic agents, as well as immune checkpoint inhibitors, is resulting in improvements in the systemic treatment of locally advanced and metastatic esophageal cancer. These developments, coupled with improvements in minimally invasive surgical and endoscopic treatment approaches, as well as adaptive and precision radiotherapy technologies, offer the potential to improve outcomes still further. This review summarizes the latest advances in the diagnosis and management of esophageal cancer, and the developments in understanding of the biology of this disease.

Radiation therapy is an effective treatment modality in the management of patients with esophageal cancer regardless of tumor location (proximal, middle, or distal esophagus) or histology (squamous cell vs adenocarcinoma). The addition of neoadjuvant CRT to surgery in patients who are surgical candidates has consistently shown a benefit in terms of locoregional recurrence, pathologic downstaging, and overall survival. For patients who are not surgical candidates, CRT has a role as definitive treatment.

Recent developments in hybrid SPECT/CT systems and the use of cadmium-zinc-telluride (CZT) detectors have improved the diagnostic accuracy of bone scintigraphy. These advancements have paved the way for novel quantitative approaches to accurate and reproducible treatment monitoring of bone metastases. PET/CT imaging using [18F]F-FDG and [18F]F-NaF have shown promising clinical utility in bone metastases assessment and monitoring response to therapy and prediction of treatment response in a broad range of malignancies. Additionally, specific tumor-targeting tracers like [99mTc]Tc-PSMA, [68Ga]Ga-PSMA, or [11C]C- or [18F]F-Choline revealed high diagnostic performance for early assessment and prognostication of bone metastases, particularly in prostate cancer. PET/MRI appears highly accurate imaging modality, but has associated limitations notably, limited availability, more complex logistics and high installation costs. Advances in artificial intelligence (Al) seem to improve the accuracy of imaging modalities and provide an assistant role in the evaluation of treatment response of bone metastases.

Standard curative-intent chemoradiotherapy for human papillomavirus (HPV)-related oropharyngeal carcinoma results in significant toxicity. Since hypoxic tumors are radioresistant, we posited that the aerobic state of a tumor could identify patients eligible for de-escalation of chemoradiotherapy while maintaining treatment efficacy.

We enrolled patients with HPV-related oropharyngeal carcinoma to receive de-escalated definitive chemoradiotherapy in a phase II study (ClinicalTrials.gov identifier: NCT03323463). Patients first underwent surgical removal of disease at their primary site, but not of gross disease in the neck. A baseline 18F-fluoromisonidazole positron emission tomography scan was used to measure tumor hypoxia and was repeated 1-2 weeks intratreatment. Patients with nonhypoxic tumors received 30 Gy (3 weeks) with chemotherapy, whereas those with hypoxic tumors received standard chemoradiotherapy to 70 Gy (7 weeks). The primary objective was achieving a 2-year locoregional control (LRC) of 95% with a 7% noninferiority margin.

One hundred fifty-eight patients with T0-2/N1-N2c were enrolled, of which 152 patients were eligible for analyses. Of these, 128 patients met criteria for 30 Gy and 24 patients received 70 Gy. The 2-year LRC was 94.7% (95% CI, 89.8 to 97.7), meeting our primary objective. With a median follow-up time of 38.3 (range, 22.1-58.4) months, the 2-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 100%, respectively, for the 30-Gy cohort. The 70-Gy cohort had similar 2-year PFS and OS rates at 96% and 96%, respectively. Acute grade 3-4 adverse events were more common in 70 Gy versus 30 Gy (58.3% v 32%; P = .02). Late grade 3-4 adverse events only occurred in the 70-Gy cohort, in which 4.5% complained of late dysphagia.

Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

Outcomes for patients with esophageal cancer have improved over the last decade with the implementation of multimodality therapy. There are currently no comprehensive guidelines addressing multidisciplinary management of esophageal cancer that have incorporated the input of surgeons, radiation oncologists, and medical oncologists. To address the need for multidisciplinary input in the management of esophageal cancer and to meet current best practices for clinical practice guidelines, the current guidelines were created as a collaboration between The Society of Thoracic Surgeons (STS), American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology (ASCO). Physician representatives chose 8 key clinical questions pertinent to the care of patients with locally advanced, resectable thoracic esophageal cancer (excluding cervical location). A comprehensive literature review was performed identifying 227 articles that met the inclusion criteria covering the use of induction chemotherapy, chemotherapy vs chemoradiotherapy before surgery, optimal radiation dose, the value of esophagectomy, timing of esophagectomy, the approach and extent of lymphadenectomy, the use of minimally invasive esophagectomy, and the value of adjuvant therapy after resection. The relevant data were reviewed and voted on by the panel with 80% of the authors, with 75% agreement on class and level of evidence. These data were then complied into the guidelines document.

This document is a summary of the French intergroup guidelines regarding the management of esophageal cancer (EC) published in July 2022, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org).

This collaborative work was conducted under the auspices of several French medical and surgical societies involved in the management of EC. Recommendations were graded in three categories (A, B and C), according to the level of evidence found in the literature until April 2022.

EC diagnosis and staging evaluation are mainly based on patient's general condition assessment, endoscopy plus biopsies, TAP CT-scan and 18F FDG-PET. Surgery alone is recommended for early-stage EC, while locally advanced disease (N+ and/or T3-4) is treated with perioperative chemotherapy (FLOT) or preoperative chemoradiation (CROSS regimen) followed by immunotherapy for adenocarcinoma. Preoperative chemoradiation (CROSS regimen) followed by immunotherapy or definitive chemoradiation with the possibility of organ preservation are the two options for squamous cell carcinoma. Salvage surgery is recommended for incomplete response or recurrence after definitive chemoradiation and should be performed in an expert center. Treatment for metastatic disease is based on systemic therapy including chemotherapy, immunotherapy or combined targeted therapy according to biomarkers testing such as HER2 status, MMR status and PD-L1 expression.

These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice and are subject to ongoing optimization. Each individual case should be discussed by a multidisciplinary team.

The surgical procedure for esophagogastric junction (EGJ) adenocarcinoma usually depends on the location of its epicenter or proximal margin, but accurate evaluation of these positions is often difficult. The usefulness of positron emission tomography-computed tomography (PET-CT) for this purpose is unknown.

Between June 2005 and February 2015, we enrolled 30 patients with cT2-4 EGJ adenocarcinoma (Siewert type I/II) who underwent surgical resection. We ascertained the sensitivity and specificity of preoperative PET-CT for identifying the primary tumor and regional lymph node metastasis, and compared PET-CT and pathological findings in terms of the distance from the EGJ to the tumor epicenter or proximal tumor margin.

PET-CT detected the primary tumor with a sensitivity of 97% (29/30), and detected lymph node metastasis with a sensitivity and specificity of 22% (4/18) and 100% (8/8), respectively. No significant association was observed between the maximal standardized uptake value and histological type, tumor size, or pT status. Regarding the accuracy of evaluating tumor location, the median differences between PET-CT and pathological measurements were .6 cm for the tumor epicenter and .5 cm for the proximal margin from the EGJ. PET-CT and pathological findings showed agreement regarding Siewert classification type (I or II) and lengths of esophageal involvement exceeding 4 cm or 2 cm in 77% (10/13), 85% (11/13), and 85% (11/13) of cases, respectively.

PET-CT had high sensitivity for primary EGJ adenocarcinoma. It may effectively locate the tumor epicenter and proximal margin and thus help clinicians determine the optimal surgical procedure.

To investigate the utility of serum soluble mesothelin-related peptide (SMRP) and tumor mesothelin expression in the management of esophageal adenocarcinoma (ADC).

Clinical management of esophageal ADC is limited by a lack of accurate evaluation of tumor burden, treatment response, and disease recurrence. Our retrospective data showed that tumor mesothelin and its serum correlate, SMRP, are overexpressed and associated with poor outcomes in patients with esophageal ADC.

Serum SMRP and tumoral mesothelin expression from 101 patients with locally advanced esophageal ADC were analyzed before induction chemoradiation (pretreatment) and at the time of resection (posttreatment), as a biomarker for treatment response, disease recurrence, and overall survival (OS).

Pre and posttreatment serum SMRP was ≥1 nM in 49% and 53%, and pre and post-treatment tumor mesothelin expression was >25% in 35% and 46% of patients, respectively. Pretreatment serum SMRP was not significantly associated with tumor stage ( P = 0.9), treatment response (radiologic response, P = 0.4; pathologic response, P = 0.7), or recurrence ( P =0.229). Pretreatment tumor mesothelin expression was associated with OS (hazard ratio: 2.08; 95% CI: 1.14-3.79; P = 0.017) but had no statistically significant association with recurrence ( P = 0.9). Three-year OS of patients with pretreatment tumor mesothelin expression of ≤25% was 78% (95% CI: 68%-89%), compared with 49% (95% CI: 35%-70%) among those with >25%.

Pretreatment tumor mesothelin expression is prognostic of OS for patients with locally advanced esophageal ADC, whereas serum SMRP is not a reliable biomarker for monitoring treatment response or recurrence.

Better predictive markers are needed to deliver individualized care for patients with primary esophagogastric cancer. This exploratory study aimed to assess whether pre-treatment imaging parameters from dynamic contrast-enhanced MRI and 18F-fluorodeoxyglucose (18F-FDG) PET/CT are associated with response to neoadjuvant therapy or outcome.

Following ethical approval and informed consent, prospective participants underwent dynamic contrast-enhanced MRI and 18F-FDG PET/CT prior to neoadjuvant chemotherapy/chemoradiotherapy ± surgery. Vascular dynamic contrast-enhanced MRI and metabolic 18F-FDG PET parameters were compared by tumor characteristics using Mann Whitney U test and with pathological response (Mandard tumor regression grade), recurrence-free and overall survival using logistic regression modelling, adjusting for predefined clinical variables.

39 of 47 recruited participants (30 males; median age 65 years, IQR: 54, 72 years) were included in the final analysis. The tumor vascular-metabolic ratio was higher in patients remaining node positive following neoadjuvant therapy (median tumor peak enhancement/SUVmax ratio: 0.052 vs. 0.023, p = 0.02). In multivariable analysis adjusted for age, gender, pre-treatment tumor and nodal stage, peak enhancement (highest gadolinium concentration value prior to contrast washout) was associated with pathological tumor regression grade. The odds of response decreased by 5% for each 0.01 unit increase (OR 0.95; 95% CI: 0.90, 1.00, p = 0.04). No 18F-FDG PET/CT parameters were predictive of pathological tumor response. No relationships between pre-treatment imaging and survival were identified.

Pre-treatment esophagogastric tumor vascular and metabolic parameters may provide additional information in assessing response to neoadjuvant therapy.

Background: Neoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal adenocarcinoma. Induction chemotherapy with a tailored approach to chemoradiation based on metabolic response to therapy on PET was explored as an alternative strategy in the CALGB 80803 trial. We sought to describe real-world institutional experience implementing this approach outside of a clinical trial. Methods: Patients who were treated with induction fluorouracil-leucovorin-oxaliplatin (FOLFOX) or fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) with tailored chemoradiation based on PET response and subsequent esophagectomy were identified from a prospectively maintained database. Primary outcomes were pathologic complete response (pCR) and overall survival (OS) following completion of all therapy. Results: There were 35 patients who completed induction chemotherapy, chemoradiation, and esophagectomy. Thirty-three completed restaging PET following induction chemotherapy with metabolic response seen in 76% (n = 25/33). The pCR rate was 31% (n = 11/35) and the ypN0 rate was 71% (n = 25/35). Among the patients who demonstrated metabolic response to induction FOLFOX/FLOT and subsequently continued fluorouracil-based chemoradiation, the pCR rate was 39% (n = 9/23). The rate of pathologically negative lymph nodes in this group was high (n = 19/23, 83%) with 100% R0 resection rate (n = 23/23). With the median follow-up of 43 months, the median OS was not reached for this group and was significantly longer than the OS for the remainder of the cohort (p = 0.027, p = 0.046 adjusted for clinical stage). Conclusions: Induction FOLFOX/FLOT chemotherapy with evaluation of sensitivity via metabolic response and tailored chemoradiation seems to lead to high pCR and ypN0 rates in high-risk patients with adenocarcinoma of the esophagus and GE junction. This approach in clinical practice seems to recapitulate encouraging results in clinical trials.

Quantifying treatment response to gastroesophageal junction (GEJ) adenocarcinomas is crucial to provide an optimal therapeutic strategy. Routinely taken tissue samples provide an opportunity to enhance existing positron emission tomography-computed tomography (PET/CT)-based therapy response evaluation. Our objective was to investigate if deep learning (DL) algorithms are capable of predicting the therapy response of patients with GEJ adenocarcinoma to neoadjuvant chemotherapy on the basis of histologic tissue samples.

This diagnostic study recruited 67 patients with I-III GEJ adenocarcinoma from the multicentric nonrandomized MEMORI trial including three German university hospitals TUM (University Hospital Rechts der Isar, Munich), LMU (Hospital of the Ludwig-Maximilians-University, Munich), and UME (University Hospital Essen, Essen). All patients underwent baseline PET/CT scans and esophageal biopsy before and 14-21 days after treatment initiation. Treatment response was defined as a ≥35% decrease in SUVmax from baseline. Several DL algorithms were developed to predict PET/CT-based responders and nonresponders to neoadjuvant chemotherapy using digitized histopathologic whole slide images (WSIs).

The resulting models were trained on TUM (n = 25 pretherapy, n = 47 on-therapy) patients and evaluated on our internal validation cohort from LMU and UME (n = 17 pretherapy, n = 15 on-therapy). Compared with multiple architectures, the best pretherapy network achieves an area under the receiver operating characteristic curve (AUROC) of 0.81 (95% CI, 0.61 to 1.00), an area under the precision-recall curve (AUPRC) of 0.82 (95% CI, 0.61 to 1.00), a balanced accuracy of 0.78 (95% CI, 0.60 to 0.94), and a Matthews correlation coefficient (MCC) of 0.55 (95% CI, 0.18 to 0.88). The best on-therapy network achieves an AUROC of 0.84 (95% CI, 0.64 to 1.00), an AUPRC of 0.82 (95% CI, 0.56 to 1.00), a balanced accuracy of 0.80 (95% CI, 0.65 to 1.00), and a MCC of 0.71 (95% CI, 0.38 to 1.00).

Our results show that DL algorithms can predict treatment response to neoadjuvant chemotherapy using WSI with high accuracy even before therapy initiation, suggesting the presence of predictive morphologic tissue biomarkers.

Gastric cancer is among the top five causes of cancer-related death worldwide. Preoperative chemotherapy has been established as an option in patients with locally advanced gastric cancer. However, chemotherapy yields variable results, owing to the cellular and molecular heterogeneity of this disease. Identifying patients who did or did not respond to preoperative therapy can allow clinicians to alter treatment modalities and provide important information related to prognostication. A pathologic response to preoperative therapies, called the Tumor Response Grade (TRG), has been evaluated to quantify treatment response. Multiple systems for TRG have been established. However, the literature has demonstrated inconsistent results for TRG systems and prognosis, possibly due to variability in interpretation of tumor response between systems and interobserver variability. Radiographic responses to preoperative therapies using RECIST 1.1 criteria and endoscopically assessed tumor response have demonstrated association with survival; however, their use in gastric cancer remains challenging given the inability to accurately and consistently identify and measure the tumor, especially in the setting of neoadjuvant therapy, where treatment-related changes can obscure the gastric wall layers. While the response to preoperative therapies with positron emission tomography (PET) has shown promising results in esophageal and esophagogastric junction (EGJ) malignancies, its role in gastric cancer is still under investigation. This review is focused on summarizing the available literature related to evaluating TRG in gastric cancer, as well as providing a brief overview of the use of radiographic and endoscopic methods to assess response to preoperative therapies. Lastly, we outline future directions regarding the use of a universal TRG system to guide care and assist with prognosis.

The utility of early metabolic response assessment to guide selection of the systemic component of definitive chemoradiotherapy (dCRT) for oesophageal cancer is uncertain.

In this multi-centre, randomised, open-label, phase II substudy of the radiotherapy dose-escalation SCOPE2 trial we evaluated the role of ¹⁸F-Fluorodeoxyglucose positron emission tomography (PET) at day 14 of cycle 1 of three-weekly induction cis/cap (cisplatin (60 mg/m²)/capecitabine (625 mg/m² days 1-21)) in patients with oesophageal squamous cell carcinoma (OSCC) or adenocarcinoma (OAC). Non-responders, who had a less than 35% reduction in maximum standardised uptake value (SUV_max) from pre-treatment baseline, were randomly assigned to continue cis/cap or switch to car/pac (carboplatin AUC 5/paclitaxel 175 mg/m²) for a further induction cycle, then concurrently with radiotherapy over 25 fractions. Responders continued cis/cap for the duration of treatment. All patients (including responders) were randomised to standard (50Gy) or high (60Gy) dose radiation as part of the main study. Primary endpoint for the substudy was treatment failure-free survival (TFFS) at week 24. The trial was registered with International Standard Randomized Controlled Trial Number 97125464 and ClinicalTrials.govNCT02741856.

This substudy was closed on 1st August 2021 by the Independent Data Monitoring Committee on the grounds of futility and possible harm. To this point from 22nd November 2016, 103 patients from 16 UK centres had participated in the PET-CT substudy; 63 (61.2%; 52/83 OSCC, 11/20 OAC) of whom were non-responders. Of these, 31 were randomised to car/pac and 32 to remain on cis/cap. All patients were followed up until at least 24 weeks, at which point in OSCC both TFFS (25/27 (92.6%) vs 17/25 (68%); p = 0.028) and overall survival (42.5 vs. 20.4 months, adjusted HR 0.36; p = 0.018) favoured cis/cap over car/pac. There was a trend towards worse survival in OSCC + OAC cis/cap responders (33.6 months; 95%CI 23.1-nr) vs. non-responders (42.5 (95%CI 27.0-nr) months; HR = 1.43; 95%CI 0.67-3.08; p = 0.35).

In OSCC, early metabolic response assessment is not prognostic for TFFS or overall survival and should not be used to personalise systemic therapy in patients receiving dCRT.

Cancer Research UK.

Esophageal cancer is the eighth most common cancer worldwide and is the sixth most common cause of cancer-related mortality. The paradigm has shifted to include a multimodality approach with surgery, chemotherapy, targeted therapy (including immunotherapy), and radiation therapy. Advances in radiotherapy through techniques such as intensity modulated radiotherapy and proton beam therapy have allowed for the more dose homogeneity and improved organ sparing. In addition, recent studies of targeted therapies and predictive approaches in patients with locally advanced disease provide clinicians with new approaches to modify multimodality treatment to improve clinical outcomes.

Esophageal adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, is uncommon in the United States, but is associated with a rising incidence in young adults, and has a traditionally poor prognosis. Despite the incremental benefits that have been made with multimodality approaches to locally advanced disease, most patients will go on to develop metastatic disease, and long-term outcomes remain suboptimal. Over the last decade, PET-CT has emerged as a key tool in the management of this disease, with several prospective and retrospective studies evaluating its role in this disease. Herein, we review the key data pertaining to the use of PET-CT in the management of locally advanced esophageal and GEJ adenocarcinoma, with a focus on staging, prognostication, PET-CT adapted therapy in the neoadjuvant setting, and surveillance.

The care of patients with oesophageal cancer or of individuals who have an elevated risk of oesophageal cancer has changed dramatically. The epidemiology of squamous cell and adenocarcinoma of the oesophagus has diverged over the past several decades, with a marked increase in incidence only for oesophageal adenocarcinoma. Only in the past decade, however, have molecular features that distinguish these two forms of the disease been identified. This advance has the potential to improve screening for oesophageal cancers through the development of novel minimally invasive diagnostic technologies predicated on cancer-specific genomic or epigenetic alterations. Surgical techniques have also evolved towards less invasive approaches associated with less morbidity, without compromising oncological outcomes. With improvements in multidisciplinary care, advances in radiotherapy and new tools to detect minimal residual disease, certain patients may no longer even require surgical tumour resection. However, perhaps the most anticipated advance in the treatment of patients with oesophageal cancer is the advent of immune-checkpoint inhibitors, which harness and enhance the host immune response against cancer. In this Review, we discuss all these advances in the management of oesophageal cancer, representing only the beginning of a transformation in our quest to improve patient outcomes.

To evaluate the prognostic role of [¹⁸F]FDG PET/CT metabolic parameters in gastric cancer (GC) and gastroesophageal adenocarcinoma (GEJAC) patients receiving neoadjuvant chemotherapy.

In this retrospective study, 31 patients with biopsy-proven GC or GEJAC were included between August 2016 and March 2020. [¹⁸F]FDG PET/CT was performed before the neoadjuvant chemotherapy. Primary tumours' semi-quantitative metabolic parameters were extracted. All patients received a perioperative FLOT regimen thereafter. Post-chemotherapy [¹⁸F]FDG PET/CT was performed in most patients (17/31). All patients underwent surgical resection. Histopathology response to treatment and progression-free survival (PFS) were evaluated. Two-sided p-values < 0.05 were considered statistically significant.

Thirty-one patients (mean age = 62 ± 8), including 21 GC and 10 GEJAC patients, were evaluated. 20/31(65%) patients were histopathology responders to neoadjuvant chemotherapy, including twelve complete and eight partial responders. During the median follow-up of 42.0 months, nine patients experienced recurrence. The median PFS was 60(95% CI:32.9-87.1) months. Pre-neoadjuvant chemotherapy SULpeak was significantly correlated with pathological response to treatment (p-value = 0.03;odds ratio = 16.75). In survival analysis, SUVmax (p-value = 0.01;hazard ratio[HR] = 1.55), SUVmean (p-value = 0.04;HR = 2.73), SULpeak (p-value < 0.001;HR = 1.91) and SULmean (p-value = 0.04;HR = 4.22) in the post-neoadjuvant chemotherapy pre-operative [¹⁸F]FDG PET/CT showed significant correlation with PFS. Additionally, aspects of staging were significantly correlated with PFS (p-value = 0.01;HR = 2.21).

Pre-neoadjuvant chemotherapy [¹⁸F]FDG PET/CT parameters, especially SULpeak, could predict the pathological response to treatment in GC and GEJAC patients. Additionally, in survival analysis, post-chemotherapy metabolic parameters significantly correlated with PFS. Thus, performing [¹⁸F]FDG PET/CT before chemotherapy may help to identify patients at risk for inadequate response to perioperative FLOT and, after chemotherapy, may predict clinical outcomes.

2-deoxy-2[¹⁸F]Fluoro-D-glucose (FDG) PET-CT has an emerging role in assessing response to neoadjuvant therapy in oesophageal cancer. This study evaluated FDG PET-CT in predicting pathological tumour response (pTR), pathological nodal response (pNR) and survival.

Cohort study of 75 patients with oesophageal or oesophago-gastric junction (GOJ) adenocarcinoma treated with neoadjuvant chemotherapy then surgery at Guy's and St Thomas' NHS Foundation Trust, London (2017-2020). Standardised uptake value (SUV) metrics on pre- and post-treatment FDG PET-CT in the primary tumour (mTR) and loco-regional lymph nodes (mNR) were derived. Optimum SUV_max thresholds for predicting pathological response were identified using receiver operating characteristic analysis. Predictive accuracy was compared to PERCIST (30% SUV_max reduction) and MUNICON (35%) criteria. Survival was assessed using Cox regression.

Optimum tumour SUV_max decrease for predicting pTR was 51.2%. A 50% cut-off predicted pTR with 73.5% sensitivity, 69.2% specificity and greater accuracy than PERCIST or MUNICON (area under the curve [AUC] 0.714, PERCIST 0.631, MUNICON 0.659). Using a 30% SUV_max threshold, mNR predicted pNR with high sensitivity but low specificity (AUC 0.749, sensitivity 92.6%, specificity 57.1%, p = 0.010). pTR, mTR, pNR and mNR were independent predictive factors for survival (pTR hazard ratio [HR] 0.10 95% confidence interval [CI] 0.03-0.34; mTR HR 0.17 95% CI 0.06-0.48; pNR HR 0.17 95% CI 0.06-0.54; mNR HR 0.13 95% CI 0.02-0.66).

Metabolic tumour and nodal response predicted pTR and pNR, respectively, in patients with oesophageal or GOJ adenocarcinoma. However, currently utilised response criteria may not be optimal. pTR, mTR, pNR and mNR were independent predictors of survival.

• FDG PET-CT has an emerging role in evaluating response to neoadjuvant therapy in patients with oesophageal cancer. • Prospective cohort study demonstrated that metabolic response in the primary tumour and lymph nodes was predictive of pathological response in a cohort of patients with adenocarcinoma of the oesophagus or oesophago-gastric junction treated with neoadjuvant chemotherapy followed by surgical resection. • Patients who demonstrated a response to neoadjuvant chemotherapy in the primary tumour or lymph nodes on FDG PET-CT demonstrated better survival and reduced rates of tumour recurrence.

To compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC.

nCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy.

We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression.

In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group.

Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.

Neoadjuvant strategies with multimodal therapy including chemotherapy and radiation are the standard of care in locally advanced esophageal cancer. The role of immunotherapy in the perioperative management of esophageal cancer is expanding, and adjuvant nivolumab for patients with residual disease following trimodality therapy has been shown to improve disease-free survival. Applications of checkpoint blockade and positron emission tomography (PET)-directed therapy in the neoadjuvant setting are under investigation in several clinical trials. We review the perioperative management of locally advanced esophageal cancer and recent evidence exploring the role of immune checkpoint inhibitors and PET in guiding neoadjuvant management.