AGA Clinical Practice Update on Screening and Surveillance in Individuals at Increased Risk for Gastric Cancer in the United States: Expert Review.
Gastric cancer (GC) is a leading cause of preventable cancer and mortality in certain US populations. The most impactful way to reduce GC mortality is via primary prevention, namely Helicobacter pylori eradication, and secondary prevention, namely endoscopic screening and surveillance of precancerous conditions, such as gastric intestinal metaplasia (GIM). An emerging body of evidence supports the possible impact of these strategies on GC incidence and mortality in identifiable high-risk populations in the United States. Accordingly, the primary objective of this American Gastroenterological Association (AGA) Clinical Practice Update (CPU) Expert Review is to provide best practice advice for primary and secondary prevention of GC in the context of current clinical practice and evidence in the United States.
This CPU Expert Review was commissioned and approved by the AGA Institute CPU Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer review by the CPU Committee and external peer review through standard procedures of Gastroenterology. These best practice advice statements were drawn from a review of the published literature and expert opinion. Because systematic reviews were not performed, these best practice advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: There are identifiable high-risk groups in the United States who should be considered for GC screening. These include first-generation immigrants from high-incidence GC regions and possibly other non-White racial and ethnic groups, those with a family history of GC in a first-degree relative, and individuals with certain hereditary gastrointestinal polyposis or hereditary cancer syndromes. BEST PRACTICE ADVICE 2: Endoscopy is the best test for screening or surveillance in individuals at increased risk for GC. Endoscopy enables direct visualization to endoscopically stage the mucosa and identify areas concerning for neoplasia, as well as enables biopsies for further histologic examination and mucosal staging. Both endoscopic and histologic staging are key for risk stratification and determining whether ongoing surveillance is indicated and at what interval. BEST PRACTICE ADVICE 3: High-quality upper endoscopy for the detection of premalignant and malignant gastric lesions should include the use of a high-definition white-light endoscopy system with image enhancement, gastric mucosal cleansing, and insufflation to achieve optimal mucosal visualization, in addition to adequate visual inspection time, photodocumentation, and use of a systematic biopsy protocol for mucosal staging when appropriate. BEST PRACTICE ADVICE 4: H pylori eradication is essential and serves as an adjunct to endoscopic screening and surveillance for primary and secondary prevention of GC. Opportunistic screening for H pylori infection should be considered in individuals deemed to be at increased risk for GC (refer to Best Practice Advice 1). Screening for H pylori infection in adult household members of individuals who test positive for H pylori (so-called "familial-based testing") should also be considered. BEST PRACTICE ADVICE 5: In individuals with suspected gastric atrophy with or without intestinal metaplasia, gastric biopsies should be obtained according to a systematic protocol (eg, updated Sydney System) to enable histologic confirmation and staging. A minimum of 5 total biopsies should be obtained, with samples from the antrum/incisura and corpus placed in separately labeled jars (eg, jar 1, "antrum/incisura" and jar 2, "corpus"). Any suspicious areas should be described and biopsied separately. BEST PRACTICE ADVICE 6: GIM and dysplasia are endoscopically detectable. However, these findings often go undiagnosed when endoscopists are unfamiliar with the characteristic visual features; accordingly, there is an unmet need for improved training, especially in the United States. Artificial intelligence tools appear promising for the detection of early gastric neoplasia in the adequately visualized stomach, but data are too preliminary to recommend routine use. BEST PRACTICE ADVICE 7: Endoscopists should work with their local pathologists to achieve consensus for consistent documentation of histologic risk-stratification parameters when atrophic gastritis with or without metaplasia is diagnosed. At a minimum, the presence or absence of H pylori infection, severity of atrophy and/or metaplasia, and histologic subtyping of GIM, if applicable, should be documented to inform clinical decision making. BEST PRACTICE ADVICE 8: If the index screening endoscopy performed in an individual at increased risk for GC (refer to Best Practice Advice 1) does not identify atrophy, GIM, or neoplasia, then the decision to continue screening should be based on that individual's risk factors and preferences. If the individual has a family history of GC or multiple risk factors for GC, then ongoing screening should be considered. The optimal screening intervals in such scenarios are not well defined. BEST PRACTICE ADVICE 9: Endoscopists should ensure that all individuals with confirmed gastric atrophy with or without GIM undergo risk stratification. Individuals with severe atrophic gastritis and/or multifocal or incomplete GIM are likely to benefit from endoscopic surveillance, particularly if they have other risk factors for GC (eg, family history). Endoscopic surveillance should be considered every 3 years; however, intervals are not well defined and shorter intervals may be advisable in those with multiple risk factors, such as severe GIM that is anatomically extensive. BEST PRACTICE ADVICE 10: Indefinite and low-grade dysplasia can be difficult to reproducibly identify by endoscopy and accurately diagnose on histopathology. Accordingly, all dysplasia should be confirmed by an experienced gastrointestinal pathologist, and clinicians should refer patients with visible or nonvisible dysplasia to an endoscopist or center with expertise in the diagnosis and management of gastric neoplasia. Individuals with indefinite or low-grade dysplasia who are infected with H pylori should be treated and have eradication confirmed, followed by repeat endoscopy and biopsies by an experienced endoscopist, as visual and histologic discernment may improve once inflammation subsides. BEST PRACTICE ADVICE 11: Individuals with suspected high-grade dysplasia or early GC should undergo endoscopic submucosal dissection with the goal of en bloc, R0 resection to enable accurate pathologic staging with curative intent. Eradication of active H pylori infection is essential, but should not delay endoscopic intervention. Endoscopic submucosal dissection should be performed at a center with endoscopic and pathologic expertise. BEST PRACTICE ADVICE 12: Individuals with a history of successfully resected gastric dysplasia or cancer require ongoing endoscopic surveillance. Suggested surveillance intervals exist, but additional data are required to refine surveillance recommendations, particularly in the United States. BEST PRACTICE ADVICE 13: Type I gastric carcinoids in individuals with atrophic gastritis are typically indolent, especially if <1 cm. Endoscopists may consider resecting gastric carcinoids <1 cm and should endoscopically resect lesions measuring 1-2 cm. Individuals with type I gastric carcinoids >2 cm should undergo cross-sectional imaging and be referred for surgical resection, given the risk of metastasis. Individuals with type I gastric carcinoids should undergo surveillance, but the intervals are not well defined. BEST PRACTICE ADVICE 14: In general, only individuals who are fit for endoscopic or potentially surgical treatment should be screened for GC and continued surveillance of premalignant gastric conditions. If a person is no longer fit for endoscopic or surgical treatment, then screening and surveillance should be stopped. BEST PRACTICE ADVICE 15: To achieve health equity, a personalized approach should be taken to assess an individual's risk for GC to determine whether screening and surveillance should be pursued. In conjunction, modifiable risk factors for GC should be distinctly addressed, as most of these risk factors disproportionately impact people at high risk for GC and represent health care disparities.
Shah SC
，Wang AY
，Wallace MB
，Hwang JH
... -
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Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.
Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided.
(1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS?
Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses.
Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS.
Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments.
Level III, diagnostic study.
Lee CC
，Chen CW
，Yen HK
，Lin YP
，Lai CY
，Wang JL
，Groot OQ
，Janssen SJ
，Schwab JH
，Hsu FM
，Lin WH
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ResearchGate
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钛学术
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