The TEOGIC study project: a comprehensive characterization of early onset gastrointestinal cancer in the Northern area of Spain.

BACKGROUND: Gastrointestinal cancers represent one of the most prevalent diseases worldwide. Strikingly, the incidence of Early Onset Gastrointestinal Cancer (EOGIC) has been rising during the last decades and changes in lifestyle and environmental exposure seem to play a role. EOGIC has been defined as a different entity compared to on-average gastrointestinal cancer, with distinct clinical and molecular characteristics. Inherent to the particularities of younger age, there is an unmet need for a tailored approach for the management of these patients. The TEOGIC proposes a comprehensive study to characterize EOGIC patients in the northern of Spain. METHODS: Patients with histologically confirmed new diagnosis of colorectal, gastroesophageal and pancreatic adenocarcinoma will be considered for two cohorts: EOGIC (≤ 50 years old) and non-EOGIC (60-75 years old), with a ratio of 1:2. Two hundred and forty patients will be recruited in 4 Public Hospitals from northern Spain. After receiving unified informed consent, demographic and clinical data of the patients will be collected in a REDCap database. Lifestyle related data will be obtained in questionnaires assessing diet, physical activity and the general quality of life of the patients before diagnosis. Biological samples prior to any onco-specific treatment will be obtained for the analyses of circulating inflammatory proteins, gut microbiota, and the proteome of the tumor microenvironment. Histologic characteristics and routine biomarkers will be also collected. Thereafter, data will be integrated and analyzed to assess tumor specific, pan-tumor and sex-associated differential characteristics of EOGIC. DISCUSSION: The underlying risk factors and differential characteristics of EOGIC remain poorly studied, particularly in our geographical area. Although limited by the exploratory nature and the small sample size estimated to be recruited, TEOGIC represents the first attempt to comprehensively characterize these young patients, and thus attend to their special needs. Findings derived from this study could contribute to raise awareness and preventive behaviors in the population. In parallel, molecular studies could lead to the identification of potential novel non-invasive biomarkers and therapeutic targets that would help in the development of the tailored clinical management of these patients, focusing on screening programs for early diagnosis and precision medicine.

[Management of gastrointestinal stromal tumors]. / Prise en charge des tumeurs stromales gastro-intestinales.

MANAGEMENT OF GASTROINTESTINAL STROMAL TUMORS. Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma subtype. More than 80% of GIST are characterized by activating mutations in KIT or PDGFRA genes, but rare molecular subtypes exist. Localized GIST can be cured by surgery. Adjuvant treatment with imatinib is the gold standard in high-risk GIST presenting mutations sensitive to this tyrosine kinase inhibitor. The development of tyrosine kinase inhibitors targeting KIT and PDGFRA has revolutionized the prognosis of metastatic GIST, by increasing the median overall survival: from less than 18 months to more than 70 months within 20 years. Similary to other histological subtypes, the diagnostic and therapeutic management of GIST must be referred to sarcoma reference centers.

PRISE EN CHARGE DES TUMEURS STROMALES GASTRO-INTESTINALES. Les tumeurs stromales gastro-intestinales (GIST) représentent le sous-type de sarcomes le plus fréquent. Plus de 80 % des GIST sont caractérisées par des mutations activatrices des gènes KIT ou PDGFRA, mais des soustypes moléculaires plus rares existent. Au stade localisé, les GIST sont des maladies curables par exérèse chirurgicale. Le traitement adjuvant par imatinib est un standard thérapeutique dans les GIST associées à un haut risque de récidive et présentant des mutations sensibles au traitement. Au stade métastatique, le développement des inhibiteurs de tyrosine kinase ciblant KIT et PDGFRA a bouleversé la prise en charge et le pronostic des patients, en augmentant la survie globale : de moins de dix-huit mois il y a une vingtaine d'années à plus de soixante-dix mois aujourd'hui. Comme pour les autres sous-types histologiques, la prise en charge diagnostique et thérapeutique des GIST doit être réalisée dans des centres experts pour la prise en charge des sarcomes.

Discontinuation of imatinib in patients with oligometastatic gastrointestinal stromal tumour who are in complete radiological remission: a prospective multicentre phase II study.

INTRODUCTION: Metastatic gastrointestinal stromal tumour (GIST) is considered incurable, and life-long treatment with tyrosine kinase inhibitors is recommended. We investigated whether selected patients with metastatic GIST may remain in durable remission despite imatinib discontinuation. PATIENTS: In this 1-group, prospective, multicentre phase II trial selected patients with oligometastatic (≤3 metastases) GIST discontinued imatinib treatment. Eligible patients had been treated with imatinib >5 years without progression and had no radiologically detectable metastases after metastasectomy, radiofrequency ablation (RFA) or complete response to imatinib. The primary endpoint was progression-free survival (PFS) 3-years after stopping imatinib. Overall survival (OS) and quality of life (QoL) were secondary endpoints. RESULTS: The trial closed prematurely due to slow accrual. Between January 5, 2017, and June 5, 2019, 13 patients were enrolled, of whom 12 discontinued imatinib. The median follow-up time was 55 months (range, 36 to 69) after study entry. Five (42%) of the 12 eligible patients remained progression free, and seven (58%) progressed with a median time to progression 10 months. Median PFS was 23 months and the estimated 3-year PFS 41%. Six of the seven patients who progressed restarted imatinib, and all six responded. Three-year OS was 100%, and all patients were alive at the time of the study analysis. QoL measured 5 and 11 months after discontinuation of imatinib demonstrated improvement compared to the baseline. INTERPRETATION: A substantial proportion of selected patients with oligometastatic GIST treated with imatinib and metastasis surgery/RFA may remain disease-free for ≥3 years with improved QoL after stopping of imatinib.

Immune checkpoint inhibitor therapy in locally advanced MSI GI malignancies.

Locally advanced gastrointestinal (GI) malignancies have conventionally been treated in a multimodal fashion that combines (neo)adjuvant chemotherapy with or without radiation and definitive surgical resection. Clinical data have demonstrated the reduced responsiveness of GI malignancies with microsatellite instability (MSI) to both adjuvant and neoadjuvant systemic chemotherapy when compared with microsatellite stable (MSS) disease. The elevated tumor mutational burden associated with MSI tumors of all types sensitizes these tumors to the effects of immune checkpoint blockade in the metastatic setting, which led to tumor-agnostic approval of immune checkpoint inhibitors in this context. The recent demonstration of greater sensitivity and high pathologic complete response rates to neoadjuvant immunotherapy in locally advanced GI malignancies may ultimately establish a novel treatment paradigm and herald potential nonoperative management of this distinct subgroup of GI malignancies. This article provides an overview of immune checkpoint inhibitor therapy in locally advanced MSI GI malignancies. It also covers the clinical significance of MSI status across the GI cancer spectrum, the available data demonstrating differential responses of MSI and MSS disease to conventional chemotherapy, and the biological rationale for novel strategies utilizing immunotherapy in the neoadjuvant, adjuvant, and nonoperative settings.

Willingness to Pay for a Quality-Adjusted Life Year among Gastrointestinal Cancer Patients at a Tertiary Hospital of Vietnam, 2022.

BACKGROUND: Gastrointestinal (GI) cancer burden in Asia is increasing, and Vietnam is no exception. Assessing the affordability of achieving a quality-adjusted life year (QALY) in gastrointestinal cancer patients Vietnam, as well as identifying predictors of willingness to pay (WTP) per QALY, is crucial to decision-making around medical intervention prioritization and performing medical technology assessments for these cancers. OBJECTIVES: Our study aimed to estimate WTP/QALY gained and associated factors among patients diagnosed with GI cancer at a tertiary hospital in Hue, Vietnam. METHODS: A cross-sectional descriptive study, using contingent valuation methodology was conducted among 231 patients at tertiary hospital in 2022. A double limited dichotomous choice and the EQ-5D-5L were utilised to estimate WTP and QALY, respectively. Quantile regression was applied to determine predictors of WTP/QALY. RESULTS: The mean and median maximum WTP/QALY gained among GI patients was $15,165.6 (42,239.6) and $4,365.6 (IQR: 1,586.5-14,552.0), respectively, which was equal to 3.68 times the 2022 gross domestic product (GDP) per capita in Vietnam.  Additionally, cancer severity was found to have a significant impact  on WTP per QALY gained, with a higher amount identified among patients with earlier stages of GI cancer. Furthermore, living in an urban dwelling and patients' treatment modalities were significantly associated with WTP/QALY. CONCLUSION: Evidence from our study can be used to inform how decision-makers in Vietnam to determine the cost-effectiveness of GI cancer interventions.

Influence of reminiscence therapy on mental health and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer.

Reminiscence therapy (RT) attenuates psychological disorders in cancer patients. This study aimed to evaluate the effect of RT on anxiety, depression, spiritual well-being, and quality of life in elderly patients with unresectable, metastatic gastrointestinal cancer. A total of 222 elderly patients with unresectable, metastatic gastrointestinal cancer were randomized into RT group (RT plus usual care, n=112) or control group (usual care, n=110) with a 6-month intervention. Hospital Anxiety and Depression Scale for Anxiety (HADS-A) and Depression (HADS-D), Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp), and Quality of Life Questionnaire-Core 30 (QLQ-C30) were evaluated at month (M)0, M1, M3, and M6. Concerning the primary outcome, HADS-A score at M6 decreased in the RT group compared to the control group (P=0.005). As to secondary outcomes, the RT group showed decreased HADS-A scores at M3, anxiety rate at M3, HADS-D scores at M3 and M6, depression rate at M6, as well as greater FACIT-Sp scores at M1, M3, and M6 vs the control group (all P<0.050). Additionally, QLQ-C30 global health score was elevated at M1 (P=0.046) and M6 (P=0.005), functions score was greater at M6 (P=0.038), and symptoms score was lower at M3 (P=0.019) in the RT group than in the control group. Subgroup analysis revealed that the addition of RT was more effective for patients with anxiety or depression at baseline. In summary, RT alleviated anxiety and depression, and improved the spiritual well-being and quality of life within 6 months in elderly patients with unresectable, metastatic gastrointestinal cancer.

ChatGPT's Gastrointestinal Tumor Board Tango: A limping dance partner?

OBJECTIVES: This study aimed to assess the consistency and replicability of treatment recommendations provided by ChatGPT 3.5 compared to gastrointestinal tumor cases presented at multidisciplinary tumor boards (MTBs). It also aimed to distinguish between general and case-specific responses and investigated the precision of ChatGPT's recommendations in replicating exact treatment plans, particularly regarding chemotherapy regimens and follow-up protocols. MATERIAL AND METHODS: A retrospective study was carried out on 115 cases of gastrointestinal malignancies, selected from 448 patients reviewed in MTB meetings. A senior resident fed patient data into ChatGPT 3.5 to produce treatment recommendations, which were then evaluated against the tumor board's decisions by senior oncology fellows. RESULTS: Among the examined cases, ChatGPT 3.5 provided general information about the malignancy without considering individual patient characteristics in 19% of cases. However, only in 81% of cases, ChatGPT generated responses that were specific to the individual clinical scenarios. In the subset of case-specific responses, 83% of recommendations exhibited overall treatment strategy concordance between ChatGPT and MTB. However, the exact treatment concordance dropped to 65%, notably lower in recommending specific chemotherapy regimens. Cases recommended for surgery showed the highest concordance rates, while those involving chemotherapy recommendations faced challenges in precision. CONCLUSIONS: ChatGPT 3.5 demonstrates potential in aligning conceptual approaches to treatment strategies with MTB guidelines. However, it falls short in accurately duplicating specific treatment plans, especially concerning chemotherapy regimens and follow-up procedures. Ethical concerns and challenges in achieving exact replication necessitate prudence when considering ChatGPT 3.5 for direct clinical decision-making in MTBs.

Immunotherapy in the neoadjuvant treatment of gastrointestinal tumors: is the time ripe?

Immune checkpoint inhibitors (ICIs) revolutionized the management of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal (GI) cancers. Based on notable results observed in the metastatic setting, several clinical trials investigated ICIs as neoadjuvant treatment (NAT) for localized dMMR/MSI-H GI cancers, achieving striking results in terms of clinical and pathological responses and creating the opportunity to spare patients from neoadjuvant chemotherapy and/or radiotherapy and even surgical resection. Nevertheless, these impressive findings are mainly derived from small proof of concept phase II studies and there are still several open questions to address. Moreover, dMMR/MSI-H represents a limited subgroup accounting for less than 10% of GI cancers. Consequently, many efforts have been produced to investigate neoadjuvant ICIs also in mismatch repair-proficient/microsatellite stable (MSS) cancers, considering the potential synergistic effect in combining immune-targeted agents with standard therapies such as chemo and/or radiotherapy. However, results for combining ICIs to the standard of care in the unselected population are still unsatisfactory, without improvements in event-free survival in esophago-gastric adenocarcinoma for the addition of pembrolizumab to chemotherapy, and sometimes limited benefit in patients with locally advanced rectal cancer. Therefore, a major challenge will be to identify among the heterogenous spectrum of this disease, those patients that could take advantage of neoadjuvant immunotherapy and deliver the most effective treatment. In this review we discuss the rationale of NAT in GI malignancies, summarize the available evidence regarding the completed trials that evaluated this treatment strategy in both MSI-H and MSS tumors. Finally, we discuss ongoing studies and future perspectives to render neoadjuvant immunotherapy another arrow in the quiver for the treatment of locally advanced GI tumors.

State-of-the-art and upcoming trends in RAS-directed therapies in gastrointestinal malignancies.

PURPOSE OF REVIEW: Overall, the review underscores the evolving landscape of KRAS-targeted therapy and the potential for these approaches to improve outcomes for patients with gastrointestinal malignancies. It highlights the importance of ongoing research and clinical trials in advancing precision medicine strategies for KRAS-driven cancers. This review provides a comprehensive overview of the RAS signaling pathway and its significance in gastrointestinal malignancies. RECENT FINDINGS: The introduction of KRAS inhibitor represents a significant advancement in the treatment landscape for KRAS-mutant cancers. In this review, we discuss upcoming trends in KRAS-targeted therapy, including the development of mutant-specific direct KRAS inhibitors like MRTX1133 and pan-RAS inhibitors such as RMC-6236. It also explores indirect RAS inhibitors targeting upstream and downstream components of the RAS pathway. Additionally, the review examines other upcoming strategies like combination therapies, such as CDK4/6 and ERK MAPK inhibitors, as well as adoptive cell therapy and cancer vaccines targeting KRAS-mutant cancers. SUMMARY: Targeting RAS has become an important strategy in treating gastrointestinal cancer. These findings in this review underscore the importance of a multidisciplinary approach, integrating advances in molecular profiling, targeted therapy, immunotherapy, and clinical research to optimize treatment strategies for patients with KRAS-mutant gastrointestinal malignancies.

The long-term efficacy of imatinib with hepatic resection or other local treatment for gastrointestinal stromal tumours liver metastases: a retrospective cohort study.

BACKGROUND: The liver is the most common site of metastasis from gastrointestinal stromal tumors (GISTs). The authors aimed to evaluate imatinib (IM) combined with hepatic resection (HR) or other local treatments such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), compared to IM monotherapy in long-term survival benefits in patients suffering from GIST liver metastases. METHODS: Our research encompassed 238 patients diagnosed with liver metastases of GISTs from January 2002 to April 2022 at the First Affiliated Hospital of Sun Yat-Sen University. The oncological outcomes of concern included overall survival (OS), progression-free survival (PFS), and liver-specific PFS. RESULTS: Of all 238 patients, 126 were treated with IM alone (IM group), 81 with IM combined with HR (IM+HR group), and 31 with IM combined with RFA/TACE (IM+RFA/TACE group). The median follow-up time was 44.83 months. The median OS in the IM group was 132.60 months and was not reached in either the IM+HR group or the IM+RFA/TACE group. The 10-year OS rate in the IM+HR group was significantly superior to the IM group and the IM+RFA/TACE group (91.9% vs. 61.1% vs. 55.2%, respectively, P =0.015), and the liver-specific PFS ( P =0.642) and PFS ( P =0.369) in the three groups showed a beneficial trend in the combined treatment group. Multivariate analyses showed that age less than or equal to 60 years (HR 0.280, P< 0.001) and IM+HR (HR 0.361, P =0.047) were independently associated with better OS. Achieving no evidence of disease through surgical intervention was independently correlated with enhanced OS (HR 0.099, P =0.034), liver-specific PFS (HR 0.388, P =0.014), and PFS (HR 0.402, P =0.004). CONCLUSIONS: In patients with GIST liver metastases, IM combined with HR might improve OS in selected patients compared with IM alone and IM combined with RFA/TACE. Achieving no evidence of disease status with surgical treatment of patients results in significant prolonging of OS, liver-specific PFS, and PFS.

[Palliative Care in patients with gastrointestinal cancer]. / Palliativmedizin in der gastrointestinalen Onkologie.

Comprehensive Cancer Care stands for a concept of broad care providing substantial benefits to cancer patients. Beside prevention of cancer as first pillar and curative therapy as second pillar, comprehensive care also encompasses palliative care representing a third pillar providing service for incurable cancer patients burdened with physical symptoms and psychological, social and spiritual needs. This article describes the integration of palliative medicine into comprehensive cancer care for patients with gastrointestinal cancer.

[Immunotherapy for gastrointestinal cancer]. / Immuntherapie bei gastrointestinalen Tumoren.

Cancers of gastrointestinal tract make up the largest group of solid tumour diseases in Germany. The prognosis at diagnosis is often critical. Drug therapies reduce the risk of relapse after resection and can halt the progression of metastatic disease. Immunotherapies contribute increasingly to the treatment of gastrointestinal tumours. Monoclonal antibodies (mAB) against surface receptors from the epidermal growth factor receptor family (EGFR, Her2) are well established. The effect is partly based on the interruption of the oncogenic downstream signalling cascades and partly on immune effector mechanisms such as antibody-dependent cellular cytotoxicity. In clinical practice mAB directed against programmed cell death protein 1 (PD-1), its ligand (PD-L1) and cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) - so-called immune checkpoint inhibitors - play an increasing role and change the natural history of some subgroups of gastrointestinal cancers, especially those with deficient DNA mismatch repair which leads to genomic microsatellite instability.

[Regarding the selection of individualized therapy after neoadjuvant therapy for gastrointestinal tumors].

Gastrointestinal tumors have been widely concerned because of increasing morbidity and mortality. In the process of exploring the therapeutic patterns of gastrointestinal tumors, patients treated with neoadjuvant therapies have good effect of tumor regression and favorable prognosis. Thus, neoadjuvant therapy strategies are recommended by major guidelines of gastrointestinal tumors in the world. Meanwhile, they have a great impact on the traditional methods of surgery, the influence mainly involves the reduction of the surgical margin and the scope of lymph node dissection in gastric cancer, while involves performing organ preservation and watch & wait in selective patients with colorectal cancer. These effects and changes were based on effective control of local recurrence by neoadjuvant therapies, and the advantages of neoadjuvant therapy in terms of tumor regression and survival supported by many studies. It is also based on the patient's desire for organ preservation and non-surgical treatment. Meanwhile, application of neoadjuvant therapy strategies increase surgical difficulty and postoperative complications, but the overall impact on patient prognosis is weak. Therefore, the selection of an appropriate treatment model after neoadjuvant therapy requires an effective overall post-treatment evaluation. In particular, it is necessary to pay attention to the evaluation of imaging, endoscopy, etc., while effectively performing monitoring and follow-up, and finally establishing an appropriate salvage treatment. This article will review the status and problems of individualized treatment after neoadjuvant therapy of gastrointestinal tumor.

Associations between health-related quality of life and subsequent need for specialized palliative care and hospital utilization in patients with gastrointestinal cancer-a prospective single-center cohort study.

BACKGROUND: We lack knowledge of which factors are associated with the risk of developing complex palliative care needs. The aim of this study was to investigate the associations between patient-reported health-related quality of life and subsequent referral to specialized palliative care (SPC) and hospital utilization. METHODS: This was a prospective single-center cohort study. Data on patient-reported outcomes were collected through the European Organization of Research and Treatment of Cancer Questionnaire-Core-15-Palliative Care (EORTC QLQ-C15-PAL) at the time of diagnosis. Covariates and hospital utilization outcomes were collected from medical records. Adjusted logistic and Poisson regression were applied in the analyses. Participants were newly diagnosed with incurable gastrointestinal cancer and affiliated with a palliative care case management intervention established in a gastroenterology department. RESULTS: Out of 397 patients with incurable gastrointestinal cancer, 170 were included in the study. Patients newly diagnosed with incurable gastrointestinal cancer experienced a substantial burden of symptoms. Pain was significantly associated with subsequent referral to SPC (OR 1.015; 95% CI 1.001-1.029). Patients with lower education levels (OR 0.210; 95% CI 0.056-0.778) and a Charlson Comorbidity Index score of 2 or more (OR 0.173; 95% CI 0.041-0.733) were less likely to be referred to SPC. Pain (IRR 1.011; 95% CI 1.005-1.018), constipation (IRR 1.009; 95% CI 1.004-1.015), and impaired overall quality of life (IRR 0.991; 95% CI 0.983-0.999) were significantly associated with increased risk of hospital admissions. CONCLUSION: The study indicates a need for interventions in hospital departments to identify and manage the substantial symptom burden experienced by patients, provide palliative care, and ensure timely referral to SPC.

Potential therapeutic targets in myeloid cell therapy for overcoming chemoresistance and immune suppression in gastrointestinal tumors.

In the tumor microenvironment (TME), myeloid cells play a pivotal role. Myeloid-derived immunosuppressive cells, including tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), are central components in shaping the immunosuppressive milieu of the tumor. Within the TME, a majority of TAMs assume an M2 phenotype, characterized by their pro-tumoral activity. These cells promote tumor cell growth, angiogenesis, invasion, and migration. In contrast, M1 macrophages, under appropriate activation conditions, exhibit cytotoxic capabilities against cancer cells. However, an excessive M1 response may lead to pro-tumoral inflammation. As a result, myeloid cells have emerged as crucial targets in cancer therapy. This review concentrates on gastrointestinal tumors, detailing methods for targeting macrophages to enhance tumor radiotherapy and immunotherapy sensitivity. We specifically delve into monocytes and tumor-associated macrophages' various functions, establishing an immunosuppressive microenvironment, promoting tumorigenic inflammation, and fostering neovascularization and stromal remodeling. Additionally, we examine combination therapeutic strategies.

Response Evaluation Criteria in Gastrointestinal and Abdominal Cancers: Which to Use and How to Measure.

As the management of gastrointestinal malignancy has evolved, tumor response assessment has expanded from size-based assessments to those that include tumor enhancement, in addition to functional data such as those derived from PET and diffusion-weighted imaging. Accurate interpretation of tumor response therefore requires knowledge of imaging modalities used in gastrointestinal malignancy, anticancer therapies, and tumor biology. Targeted therapies such as immunotherapy pose additional considerations due to unique imaging response patterns and drug toxicity; as a consequence, immunotherapy response criteria have been developed. Some gastrointestinal malignancies require assessment with tumor-specific criteria when assessing response, often to guide clinical management (such as watchful waiting in rectal cancer or suitability for surgery in pancreatic cancer). Moreover, anatomic measurements can underestimate therapeutic response when applied to molecular-targeted therapies or locoregional therapies in hypervascular malignancies such as hepatocellular carcinoma. In these cases, responding tumors may exhibit morphologic changes including cystic degeneration, necrosis, and hemorrhage, often without significant reduction in size. Awareness of pitfalls when interpreting gastrointestinal tumor response is required to correctly interpret response assessment imaging and guide appropriate oncologic management. Data-driven image analyses such as radiomics have been investigated in a variety of gastrointestinal tumors, such as identifying those more likely to respond to therapy or recur, with the aim of delivering precision medicine. Multimedia-enhanced radiology reports can facilitate communication of gastrointestinal tumor response by automatically embedding response categories, key data, and representative images. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

[Gastrointestinal stromal tumors : Where do we stand?] / Gastrointestinale Stromatumoren : Wo stehen wir?

For more than 20 years gastrointestinal stromal tumors (GIST) have been a paradigm for a targeted treatment with tyrosine kinase inhibitors. A fundamental prerequisite for a neoadjuvant or adjuvant treatment of localized GIST or an additive treatment of metastatic GIST is the molecular typing of tumors, ideally at the initial diagnosis. In addition, the possibility of a hereditary or syndromic predisposition must be considered because this results in consequences for the treatment and a different follow-up strategy.