German Cancer Research Center (DKFZ), Department of Translational Immunotherapy, German Cancer Research Center (DKFZ), Germany; Helmholtz-Institute for Translational Oncology Mainz (HI-TRON Mainz), Germany; Department of Medical Oncology and Internal Medicine VI, National Center for Tumor Diseases (NCT), Heidelberg, Germany; Institute for Immunology, University Hospital Heidelberg, University Heidelberg.
Department of Nuclear Medicine, University Hospital Heidelberg, Germany; Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), Heidelberg, Germany.
Semin Nucl Med. 2020 Sep;50(5):389-398. doi: 10.1053/j.semnuclmed.2020.06.003. Epub 2020 Jul 8.
New scientific insights in cancer biology and immunobiology have changed the clinical practice of medical oncology in recent years. The molecular stratification of solid tumors has led to improved clinical outcomes and is a key part in the diagnostic workup. Beyond mutational spectra (like Rat sarcoma [RAS] mutations or tumor mutational burden), the investigation of the immunological microenvironment has attracted more efforts. Especially as immunotherapies have changed the standard treatment for some solid tumors dramatically and have become an important part of routine oncology, also for gastrointestinal tumors. Still only a subgroup of patients benefits from immunotherapy in gastrointestinal tumors with prominent examples from colorectal, pancreatic or gastric cancer. Not only microsatellite instability as a marker for response to immunotherapy has shown its utility, there plenty of other approaches currently being investigated to better stratify and understand the microenvironment. But these insights have not translated into clinical utility. Reasons for this are limited technical capabilities for stratification and for coping with heterogeneity of tumor cells and the microenvironment as such. So the situation for gastrointestinal tumors has shown mainly progress for a subgroup of immunotherapy-receptive tumors (eg, microsatellite instability), but advances for the remaining majority have been in the area of stratification and combinatorial therapies, including approaches without chemotherapy. Molecular stratification (eg, B-Rapidly Accelerated Fibrosarcoma [BRAF] V600E mutation in colorectal cancer or NRG1 fusions in Kirsten-rat sarcoma (KRAS) Wild-Type Pancreatic Cancer) has clearly improved the possibilities for directed therapies, but there is a plethora of clinical situations where further developments are needed to improve patient care. Finding these areas and identifying the technical approach to unravel the complexities is the next decisive step. Here the recent advances are summarized and an outlook on possible diagnostic and treatment options in areas of unmet need is given with the context of new molecular imaging possibilities and cutting edge advances in nuclear medicine.
近年来，癌症生物学和免疫生物学的新科学见解改变了肿瘤医学的临床实践。实体瘤的分子分层导致了临床结果的改善，是诊断工作的关键部分。除了突变谱（如 Rat sarcoma [RAS] 突变或肿瘤突变负担）外，免疫微环境的研究也引起了更多的关注。特别是免疫疗法改变了一些实体肿瘤的标准治疗方法，已成为肿瘤学常规治疗的重要组成部分，也包括胃肠道肿瘤。在胃肠道肿瘤中，仍只有一部分患者受益于免疫治疗，其中结直肠癌、胰腺癌或胃癌就是突出的例子。不仅微卫星不稳定性作为免疫治疗反应的标志物已经显示出其效用，还有许多其他方法目前正在研究中，以更好地分层和了解微环境。但这些见解尚未转化为临床应用。其原因是分层和应对肿瘤细胞和微环境异质性的技术能力有限。因此，胃肠道肿瘤的情况主要是对免疫治疗敏感的肿瘤亚群（如微卫星不稳定性）取得了进展，但对于其余大多数肿瘤，进展主要在分层和联合治疗领域，包括无化疗的方法。分子分层（如结直肠癌中的 B-Rapidly Accelerated Fibrosarcoma [BRAF] V600E 突变或 Kirsten-rat sarcoma (KRAS) Wild-Type Pancreatic Cancer 中的 NRG1 融合）显然改善了靶向治疗的可能性，但在许多临床情况下，需要进一步发展以改善患者的护理。找到这些领域并确定解决复杂性的技术方法是下一步的决定性步骤。在此，总结了最近的进展，并根据新的分子成像可能性和核医学的前沿进展，概述了在未满足需求领域的可能诊断和治疗选择。
