Editorial

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3 pages, 192 KiB

Open AccessEditorial

Young-Onset Cancers—Early Steps in the Right Direction

by Savio George Barreto and Irit Ben-Aharon

Cancers 2023, 15(9), 2599; https://doi.org/10.3390/cancers15092599 - 04 May 2023

Cited by 1 | Viewed by 1123

Abstract

The global incidence of young-onset (YO) cancer is on the rise [...] Full article

(This article belongs to the Special Issue Young-Onset GI Cancer)

Research

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10 pages, 248 KiB

Open AccessArticle

Variation in Treatment Patterns of Patients with Early-Onset Gastric Cancer

by Michael LaPelusa, Chan Shen, Erin A. Gillaspie, Christopher Cann, Eric Lambright, A. Bapsi Chakravarthy, Michael K. Gibson and Cathy Eng

Cancers 2022, 14(15), 3633; https://doi.org/10.3390/cancers14153633 - 26 Jul 2022

Cited by 4 | Viewed by 1740

Abstract

Background: Early-onset gastric cancer (EOGC), or gastric cancer in patients younger than 45 years old, is poorly understood and relatively uncommon. Similar to other gastrointestinal malignancies, the incidence of EOGC is rising in Western countries. It is unclear which populations experience a disproportionate [...] Read more.

Background: Early-onset gastric cancer (EOGC), or gastric cancer in patients younger than 45 years old, is poorly understood and relatively uncommon. Similar to other gastrointestinal malignancies, the incidence of EOGC is rising in Western countries. It is unclear which populations experience a disproportionate burden of EOGC and what factors influence how patients with EOGC are treated. Methods: We conducted a retrospective, population-based study of patients diagnosed with gastric cancer from 2004 to 2018 using the National Cancer Database (NCDB). In addition to identifying unique demographic characteristics of patients with EOGC, we evaluated (using multivariable logistic regression controlling for year of diagnoses, primary site, and stage) how gender/sex, race/ethnicity, treatment facility type, payor status, and location of residence influenced the receipt of surgery, chemotherapy, and radiation. Results: Compared to patients 45–70 and >70 years of age with gastric cancer, patients with EOGC were more likely to be female, Asian/Pacific Islander (PI), African American (AA), Hispanic, uninsured, and present with stage IV disease. On multivariable analysis, several differences among subsets of patients with EOGC were identified. Female patients with EOGC were less likely to receive surgery and chemotherapy than male patients with EOGC. Asian/Pacific Islander patients with EOGC were more likely to receive chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. African American patients were more likely to receive chemotherapy than Caucasian patients with EOGC. Hispanic patients were more likely to receive surgery and chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. Patients with EOGC treated at community cancer centers were more likely to receive surgery and less likely to receive chemotherapy than patients with EOGC treated at academic centers. Uninsured patients with EOGC were more likely to receive surgery and less likely to receive chemotherapy than privately insured patients with EOGC. Patients with EOGC living in locations not adjacent to metropolitan areas were less likely to receive surgery compared to patients with EOGC who resided in metropolitan areas, Conclusions: Patients with EOGC are a demographically distinct population. Treatment of these patients varies significantly based on several demographic factors. Additional analysis is needed to elucidate why particular groups are more affected by EOGC and how treatment decisions are made for, and by, these patients. Full article

(This article belongs to the Special Issue Young-Onset GI Cancer)

14 pages, 1052 KiB

Open AccessArticle

Young-Onset Gastrointestinal Adenocarcinoma Incidence and Survival Trends in the Northern Territory, Australia, with Emphasis on Indigenous Peoples

by Mia Shepherdson, Shalem Leemaqz, Gurmeet Singh, Courtney Ryder, Shahid Ullah, Karla Canuto, Joanne P. Young, Timothy J. Price, Ross A. McKinnon, Stephen J. Pandol, Claire T. Roberts and Savio George Barreto

Cancers 2022, 14(12), 2870; https://doi.org/10.3390/cancers14122870 - 10 Jun 2022

Cited by 1 | Viewed by 2243

Abstract

Background and Aims: A concerning rise in incidence of young-onset cancers globally led to the examination of trends in incidence and survival of gastrointestinal (GI) adenocarcinomas in the Northern Territory (NT), Australia, over a 28-year period, with a special emphasis on Indigenous peoples. [...] Read more.

Background and Aims: A concerning rise in incidence of young-onset cancers globally led to the examination of trends in incidence and survival of gastrointestinal (GI) adenocarcinomas in the Northern Territory (NT), Australia, over a 28-year period, with a special emphasis on Indigenous peoples. Methods: This cross-sectional analysis of a prospective longitudinal database, NT Cancer Registry (1990–2017), includes all reported cases of GI (oesophagus, gastric, small intestinal, pancreas, colon, and rectum) adenocarcinomas. Poisson regression was used to estimate incidence ratio ratios, and survival was modelled using Cox proportional hazard models separately for people aged 18–50 years and >50 years. Results: A total of 1608 cases of GI adenocarcinoma were recorded during the time of the study. While the overall incidence in people 18–50 years remained unchanged over this time (p = 0.51), the rate in individuals aged >50 years decreased (IRR = 0.65 (95% CI 0.56–0.75; p < 0.0001)). Incidence rates were significantly less in females >50 years (IRR = 0.67 95% CI 0.59–0.75; p < 0.0001), and their survival was significantly better (HR = 0.84 (95%CI 0.72–0.98; p < 0.03)) compared to males. Overall survival across all GI subsites improved in both age cohorts, especially between 2010 and 2017 (HR = 0.45 (95%CI 0.29–0.72; p < 0.0007) and HR = 0.64 (95%CI 0.52–0.78; p < 0.0001), respectively) compared to 1990–1999, driven by an improvement in survival in colonic adenocarcinoma alone, as the survival remained unchanged in other GI subsites. The incidence was significantly lower in Indigenous patients compared to non-Indigenous patients, in both age cohorts (18–50 years IRR = 0.68 95% CI 0.51–0.91; p < 0.009 and >50 years IRR = 0.48 95% CI 0.40–0.57; p < 0.0001). However, Indigenous patients had worse survival rates (18–50 years HR = 2.06 95% CI 1.36–3.11; p < 0.0007 and >50 years HR = 1.66 95% CI 1.32–2.08; p < 0.0001). Conclusions: There is a trend towards an increased incidence of young-onset GI adenocarcinomas in the NT. Young Indigenous patients have lower incidence but worse survival across all GI subsites, highlighting significant health inequities in life expectancy. Targeted, culturally safe Indigenous community-focussed programs are needed for early detection and patient-centred management of GI adenocarcinomas. Full article

(This article belongs to the Special Issue Young-Onset GI Cancer)

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17 pages, 1597 KiB

Open AccessArticle

Intrinsic Cellular Susceptibility to Barrett’s Esophagus in Adults Born with Esophageal Atresia

by Chantal A. ten Kate, Annelies de Klein, Bianca M. de Graaf, Michail Doukas, Antti Koivusalo, Mikko P. Pakarinen, Robert van der Helm, Tom Brands, Hanneke IJsselstijn, Yolande van Bever, René M.H. Wijnen, Manon C.W. Spaander and Erwin Brosens

Cancers 2022, 14(3), 513; https://doi.org/10.3390/cancers14030513 - 20 Jan 2022

Cited by 3 | Viewed by 2547

Abstract

The prevalence of Barrett’s esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the [...] Read more.

The prevalence of Barrett’s esophagus (BE) in adults born with esophageal atresia (EA) is four times higher than in the general population and presents at a younger age (34 vs. 60 years). This is (partly) a consequence of chronic gastroesophageal reflux. Given the overlap between genes and pathways involved in foregut and BE development, we hypothesized that EA patients have an intrinsic predisposition to develop BE. Transcriptomes of Esophageal biopsies of EA patients with BE (n = 19, EA/BE); EA patients without BE (n = 44, EA-only) and BE patients without EA (n = 10, BE-only) were compared by RNA expression profiling. Subsequently, we simulated a reflux episode by exposing fibroblasts of 3 EA patients and 3 controls to acidic conditions. Transcriptome responses were compared to the differential expressed transcripts in the biopsies. Predisposing single nucleotide polymorphisms, associated with BE, were slightly increased in EA/BE versus BE-only patients. RNA expression profiling and pathway enrichment analysis revealed differences in retinoic acid metabolism and downstream signaling pathways and inflammatory, stress response and oncological processes. There was a similar effect on retinoic acid signaling and immune response in EA patients upon acid exposure. These results indicate that epithelial tissue homeostasis in EA patients is more prone to acidic disturbances. Full article

(This article belongs to the Special Issue Young-Onset GI Cancer)

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13 pages, 5394 KiB

Open AccessArticle

Gastrointestinal Adenocarcinoma Incidence and Survival Trends in South Australia, 1990–2017

by Dominique Schell, Shahid Ullah, Mark E. Brooke-Smith, Paul Hollington, Marina Yeow, Christos S. Karapetis, David I. Watson, Stephen J. Pandol, Claire T. Roberts and Savio G. Barreto

Cancers 2022, 14(2), 275; https://doi.org/10.3390/cancers14020275 - 06 Jan 2022

Cited by 8 | Viewed by 3513

Abstract

Background & Aims: Globally, there has been a concerning rise in the incidence of young-onset cancers. The aim of this study was to provide trends in the incidence and survival of gastrointestinal adenocarcinomas (oesophagus, stomach, pancreas, and colorectal) in South Australia over a [...] Read more.

Background & Aims: Globally, there has been a concerning rise in the incidence of young-onset cancers. The aim of this study was to provide trends in the incidence and survival of gastrointestinal adenocarcinomas (oesophagus, stomach, pancreas, and colorectal) in South Australia over a 27-year period. Methods: This is a cross-sectional analysis of a prospective longitudinal database including all cases of gastrointestinal adenocarcinomas prospectively reported to the South Australian (State) Cancer Registry from 1990 to 2017. Results: A total of 28,566 patients diagnosed with oesophageal, stomach, pancreatic, or colorectal adenocarcinoma between 1990 and 2017 were included in the study. While the overall incidence for gastrointestinal adenocarcinomas in individuals >50 years has decreased since 2000 (IRR of 0.97 (95% CI 0.94–1.00; p = 0.06)) compared to 1990–1999, the rate amongst individuals aged 18–50 has significantly increased (IRR 1.41 (95% CI 1.27–1.57; p < 0.001)) during the same reference time period. Although noted in both sexes, the rate of increase in incidence was significantly greater in males (11.5 to 19.7/100,000; p < 0.001). The overall survival from adenocarcinomas across all subsites improved in the >50-year cohort in the last decade (HR 0.89 (95% CI 0.86–0.93; p < 0.001)) compared to 1990–1999. In individuals aged 18–50 years, there has only been a significant improvement in survival for colorectal cancer (HR 0.82 (95% CI 0.68–0.99; p < 0.04)), but not the other subsites. A lower overall survival was noted for males in both age cohorts (18–50 years—HR 1.24 (95% CI 1.09–1.13; p < 0.01) and >50 years—HR 1.13 (95% CI 1.10–1.16; p < 0.001), respectively) compared to females. Conclusions: This study from South Australia demonstrates a significant increase in young-onset gastrointestinal adenocarcinomas over the last 28 years, with a greater increase in the male sex. The only significant improvement in survival in this cohort has been noted in colorectal cancer patients. Full article

(This article belongs to the Special Issue Young-Onset GI Cancer)

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11 pages, 1127 KiB

Open AccessArticle

Clinical, Molecular and Genetic Characteristics of Early Onset Gastric Cancer: Analysis of a Large Multicenter Study

by Anna Pocurull, Cristina Herrera-Pariente, Sabela Carballal, Joan Llach, Ariadna Sánchez, Laura Carot, Josep María Botargues, Miriam Cuatrecasas, Teresa Ocaña, Francesc Balaguer, Luis Bujanda and Leticia Moreira

Cancers 2021, 13(13), 3132; https://doi.org/10.3390/cancers13133132 - 23 Jun 2021

Cited by 11 | Viewed by 2667

Abstract

Gastric adenocarcinoma (GC) is a common tumor with high morbidity and mortality. Only 7% of patients with GC are diagnosed before age 50 (early onset gastric cancer (EOGC)), and their characteristics have been poorly described. We aimed to describe clinical, molecular, and genetic [...] Read more.

Gastric adenocarcinoma (GC) is a common tumor with high morbidity and mortality. Only 7% of patients with GC are diagnosed before age 50 (early onset gastric cancer (EOGC)), and their characteristics have been poorly described. We aimed to describe clinical, molecular, and genetic characteristics of EOGC. A total of 309 patients with EOGC were retrospectively studied in four Spanish centers. Personal information, family history, and tumor information were registered. Germinal genetic analysis was performed in patients who met current criteria of a hereditary syndrome at the time of diagnosis. The median age at diagnosis was 44 years. The majority (73.3%) of tumors were diffuse, and 78.3% were diagnosed in an advanced stage. Familial aggregation of GC was present in 18/117 (15.4%) cases, and 5/117 (4.3%) met criteria for familial GC. MMR-IHC was performed in 126/309 (40.7%) tumors: 4/126 (3.1%) had loss of expression in MLH1/PMS2, without an associated germline mutation. Sixteen germline genetic analyses were performed, detecting a pathogenic variant in four (25%) cases: one in BRCA2, one in TP53, and two in CDH1. Most EOGC are diffuse and diagnosed in an advanced stage. In these patients, DNA MMR system deficiency is uncommon. Although familial aggregation was observed in only 15% of cases, a germline mutation was found in 25% of patients tested with clinical criteria. This demonstrates that EOGC has a marked genetic heterogeneity, reinforcing the importance of an accurate genetic counseling and enhancing the emerging use of multigene panels. Full article

(This article belongs to the Special Issue Young-Onset GI Cancer)

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Review

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20 pages, 879 KiB

Open AccessReview

Pediatric Neuroendocrine Neoplasms: Rare Malignancies with Incredible Variability

by Jennifer T. Castle, Brittany E. Levy and Aman Chauhan

Cancers 2022, 14(20), 5049; https://doi.org/10.3390/cancers14205049 - 15 Oct 2022

Cited by 1 | Viewed by 4221

Abstract

Neuroendocrine neoplasms (NENs) encompass a variety of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) which can arise anywhere in the body. While relatively rare in the pediatric population, the incidence of NENs has increased in the past few decades. These neoplasms can be [...] Read more.

Neuroendocrine neoplasms (NENs) encompass a variety of neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs) which can arise anywhere in the body. While relatively rare in the pediatric population, the incidence of NENs has increased in the past few decades. These neoplasms can be devastating if not diagnosed and treated early, however, symptoms are variable and can be indolent for many years. There is a reported median of 10 years from the appearance of the first symptoms to time of diagnosis. Considering some of these neoplasms have a mortality rate as high as 90%, it is crucial healthcare providers are aware of NENs and remain vigilant. With better provider education and easily accessible resources for information about these neoplasms, awareness can be improved leading to earlier disease recognition and diagnosis. This manuscript aims to provide an overview of both the most common NENs as well as the rarer NENs with high lethality in the pediatric population. This review provides up to date evidence and recommendations, encompassing recent changes in classification and advances in treatment modalities, including recently completed and ongoing clinical trials. Full article

(This article belongs to the Special Issue Young-Onset GI Cancer)

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22 pages, 908 KiB

Open AccessReview

Treatment of Gastrointestinal Stromal Tumors (GISTs): A Focus on Younger Patients

by Monika Dudzisz-Śledź, Anna Klimczak, Elżbieta Bylina and Piotr Rutkowski

Cancers 2022, 14(12), 2831; https://doi.org/10.3390/cancers14122831 - 08 Jun 2022

Cited by 5 | Viewed by 2347

Abstract

Gastrointestinal stromal tumors (GISTs) originate from Cajal’s cells and are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs in young adults, i.e., patients before the age of 40, are rare and differ from those in older patients and GISTs in children [...] Read more.

Gastrointestinal stromal tumors (GISTs) originate from Cajal’s cells and are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs in young adults, i.e., patients before the age of 40, are rare and differ from those in older patients and GISTs in children in terms of the molecular and clinical features, including the location and type of mutations. They often harbor other molecular abnormalities than KIT and PDGFRA mutations (wild-type GISTs). The general principles of therapeutic management in young patients are the same as in the elderly. Considering some differences in molecular abnormalities, molecular testing should be the standard procedure to allow appropriate systemic therapy if needed. The optimal treatment strategy should be established by a multidisciplinary team experienced in sarcoma treatment. The impact of treatment on the quality of life and daily activities, including the impact on work, pregnancy, and fertility, in this patient population should be especially taken into consideration. Full article

(This article belongs to the Special Issue Young-Onset GI Cancer)

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