A Nomogram to Predict Distant Metastases After Multimodality Therapy for Patients With Localized Esophageal Cancer

Sudo, Kazuki; Wang, Xuemei; Xiao, Lianchun; Wadhwa, Roopma; Shiozaki, Hironori; Elimova, Elena; Rice, David C.; Lee, Jeffrey H.; Weston, Brian; Bhutani, Manoop S.; Hiremath, Adarsh; Charalampakis, Nikolaos; Komaki, Ritsuko; Blum, Mariela A.; Swisher, Stephen G.; Maru, Dipen M.; Skinner, Heath D.; Garris, Jeana L.; Rogers, Jane E.; Hofstetter, Wayne L.; Ajani, Jaffer A.

doi:10.6004/jnccn.2016.0020

Cited by 11 publications

(15 citation statements)

References 14 publications

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“…The proposed risk score - based on well-recognized prognostic factors [ 3 , 20 , 21 , 24 , 25 , 30 ] - has reasonable predictive value and may guide clinical decision making. The data indicate that patients with low scores have limited risk of interval metastases, and that in these patients a restaging 18 F-FDG PET/CT may be safely omitted without subjecting the patient to the risks of further diagnostic tests.…”

Section: Discussionmentioning

confidence: 99%

“…Categories were based on previously published cut-off points or estimated by receiver operating characteristic (ROC) curve analysis while maximizing sensitivity and specificity. Clinical factors available before initiation of treatment that have previously been identified as prognostic factors in oesophageal cancer included gender [ 19 ], age (dichotomized into <65 and ≥ 65) [ 20 ], Histology (adenocarcinoma versus squamous cell carcinoma [ 3 , 20 ], histologic differentiation grade (good/moderate versus poor) [ 20 , 21 ], signet ring cell adenocarcinoma [ 22 , 23 ], EUS-based tumor length (dichotomized into <4.0 cm and ≥ 4.0 cm) [ 24 , 25 ], nontraversability by EUS [ 15 , 24 ], tumor location (upper/middle versus distal or gastro-oesophageal junction) [ 18 ], clinical T-status (T1b-2 versus T3–4) [ 19 , 20 ], clinical N status (N0 versus N1–3) [ 20 , 21 ], maximum lymph node diameter measured on axial CT image (<1.0 cm versus ≥1 cm) [ 26 , 27 ], and 18 F-FDG avid nodes at baseline PET [ 15 ]. The maximum standardized uptake value (SUV max ) of the primary tumor was dichotomized into <9.6 and ≥ 9.6 based on ROC curve analysis.…”

Section: Methodsmentioning

confidence: 99%

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Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT

Goense

Ruurda

Carter

et al. 2018

Eur J Nucl Med Mol Imaging

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ObjectiveDuring neoadjuvant chemoradiotherapy for oesophageal cancer, or in the interval prior to surgery, some patients develop systemic metastasis. This study aimed to evaluate the diagnostic performance of 18F-FDG PET/CT for the detection of interval metastasis and to identify predictors of interval metastases in a large cohort of oesophageal cancer patients.MethodsIn total, 783 consecutive patients with potentially resectable oesophageal cancer who underwent chemoradiotherapy and pre- and post-treatment 18F-FDG PET/CT between 2006 and 2015 were analyzed from a prospectively maintained database. Diagnostic accuracy measures were calculated on a per-patient basis using histological verification or clinical follow-up as a reference standard. Multivariable logistic regression analysis was performed to determine pre-treatment predictors of interval metastasis. A prediction score was developed to predict the probability of interval metastasis.ResultsOf 783 patients that underwent 18F-FDG PET/CT restaging, 65 (8.3%) were found to have interval metastasis and 44 (5.6%) were deemed to have false positive lesions. The resulting sensitivity and specificity was 74.7% (95% CI: 64.3–83.4%) and 93.7% (95% CI: 91.6–95.4%), respectively. Multivariable analysis revealed that tumor length, cN status, squamous cell tumor histology, and baseline SUVmax were associated with interval metastasis. Based on these criteria, a prediction score was developed with an optimism adjusted C-index of 0.67 that demonstrated accurate calibration.Conclusions18F-FDG PET/CT restaging detects distant interval metastases in 8.3% of patients after chemoradiotherapy for oesophageal cancer. The provided prediction score may stratify risk of developing interval metastasis, and could be used to prioritize additional restaging modalities for patients most likely to benefit.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT

Goense

Ruurda

Carter

et al. 2018

Eur J Nucl Med Mol Imaging

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“… 27 , 28 Another option would be to avoid chemoradiation due to its considerable morbidity and directly move to esophagectomy. 29 However, risk stratified treatment pathways in this setting that are most beneficial for patients have yet to be investigated.…”

Section: Discussionmentioning

confidence: 99%

“…These findings are in concordance with previous reports on risk factors for oncologic outcomes (i.e., RFS and OS) after esophagectomy. 10 , 19 – 21 , 29 By stratifying patients using cutoff values from the proposed nomogram, it was possible to separate patients in low-risk and high-risk groups for 1-year disease recurrence with distinct OS outcomes. For patients with a low-risk profile, the prognosis after trimodality therapy was substantially better compared with patients treated with bimodality therapy.…”

Section: Discussionmentioning

confidence: 99%

Preoperative Nomogram to Risk Stratify Patients for the Benefit of Trimodality Therapy in Esophageal Adenocarcinoma

Goense

Rossum

et al. 2018

Ann Surg Oncol

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PurposeTo develop a nomogram that estimates 1-year recurrence-free survival (RFS) after trimodality therapy for esophageal adenocarcinoma and to assess the overall survival (OS) benefit of esophagectomy after chemoradiotherapy (CRT) on the basis of 1-year recurrence risk.MethodsIn total, 568 consecutive patients with potentially resectable esophageal adenocarcinoma who underwent CRT were included for analysis, including 373 patients who underwent esophagectomy after CRT (trimodality therapy), and 195 who did not undergo surgery (bimodality therapy). A nomogram for 1-year RFS was created using a Cox regression model. The upper tertile of the nomogram score was used to stratify patients in low-risk and high-risk groups for 1-year recurrence. The 5-year OS was compared between trimodality and bimodality therapy in low-risk and high-risk patients after propensity score matching, respectively.ResultsMedian follow-up for the entire cohort was 62 months. The 5-year OS in the trimodality and bimodality treatment groups was 56.3% (95% confidence interval [CI] 47.9–64.7) and 36.9% (95% CI 31.4–42.4), respectively. The final nomogram for the prediction of 1-year RFS included male gender, poor histologic grade, signet ring cell adenocarcinoma, cN1, cN2-3, and baseline SUVmax, with accurate calibration and reasonable discrimination (C-statistic: 0.66). Trimodality therapy was associated with improved 5-year OS in low-risk patients (p = 0.003), whereas it showed no significant survival benefit in high-risk patients (p = 0.302).ConclusionsThe proposed nomogram estimates early recurrence risk. The addition of surgery to CRT provides a clear OS benefit in low-risk patients. The OS benefit of surgery in high-risk patients is less pronounced.Electronic supplementary materialThe online version of this article (10.1245/s10434-018-6435-4) contains supplementary material, which is available to authorized users.

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“…This can only be done by understanding the molecular biology in depth rather than exercising empiricism. Other attempts to prognosticate based on initial SUV, 82 prediction of pathCR by clinical variables, 83 biomarkers, 84 and timing, risk and frequency of the development of metastases 85, 86 have been challenging and will need a lot of work to refine. Currently we do not recommend the use of PET to direct therapy changes.…”

Section: Esophageal and Gastroesophageal Junction Cancersmentioning

confidence: 99%

Potentially Curable Cancers of the Esophagus and Stomach

Elimova

Kaya

Harada

et al. 2016

Mayo Clinic Proceedings

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Gastric and gastroesophageal adenocarcinomas continue to be a significant health burden globally and collectively represent the third leading cause of cancer death. When metastatic, most patients succumb to their cancer because of a limited number of modestly effective regimens available today. The progress against these cancers has been slow compared to many other solid tumors despite many attempts. In depth molecular profiling is also not completed. Even when these cancers are localized, they impose significant challenges for the patient, relatives, and treating team alike. Localized gastric or gastroesophageal cancer is best managed by a multidisciplinary approach. This review will focus on the management of localized cancers by reviewing the current literature and explaining certain principles that help guide therapy of these patients. The future, however, will afford a number of opportunities including exploitation of the Cancer Genome Atlas (TCGA) generated initial data to identify novel targets and drugs, harnessing the prowess of the immune system, and finally, customizing therapy for each patient. Localized gastric or gastroesophageal cancer is best managed by a multidisciplinary approach and involves multimodality therapy of locally advanced disease and team work. The exploitation of the Cancer Genome Atlas (TCGA) generated initial data to identify novel targets and drugs, harnessing the prowess of the immune system, and finally, customizing therapy for each patient.

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A Nomogram to Predict Distant Metastases After Multimodality Therapy for Patients With Localized Esophageal Cancer

Abstract: Our nomogram identified patients with LEC who developed DM with a high probability. The model needs to be refined (tumor and blood biomarkers) and validated. This type of model will allow implementation of novel strategies in patients with LEC.

Cited by 11 publications

References 14 publications

Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT

Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using 18F-FDG PET/CT

Preoperative Nomogram to Risk Stratify Patients for the Benefit of Trimodality Therapy in Esophageal Adenocarcinoma

Potentially Curable Cancers of the Esophagus and Stomach

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