The management of locally advanced rectal cancer is increasingly moving beyond a uniform cytotoxic framework toward biomarker-informed multimodal treatment. Short-course radiotherapy (SCRT) is an established and convenient radiotherapy option and may also provide an immunomodulatory context for immune checkpoint blockade. Preclinical evidence suggests that hypofractionated radiotherapy can promote immunogenic cell death and modulate the tumor immune microenvironment; however, whether the fractionation schedule of SCRT provides a clinically meaningful immunological advantage over long-course chemoradiotherapy remains uncertain. Early randomized studies of SCRT-based chemoimmunotherapy in predominantly proficient mismatch repair/microsatellite-stable (pMMR/MSS) populations have reported encouraging improvements in pathological or overall complete response rates compared with their respective control regimens. Nevertheless, differences in comparator arms, chemotherapy exposure, immunotherapy schedules, endpoint definitions, and follow-up duration preclude firm conclusions regarding the optimal radiotherapy backbone or long-term survival benefit. These findings support further prospective evaluation of SCRT-based combinations and response-adapted non-operative management in appropriately selected patients. Longitudinal circulating tumor DNA, multi-omics profiling, MR-guided adaptive radiotherapy, and computational models such as “digital twins” may contribute to improved patient selection and surveillance, but their clinical utility requires prospective validation.
Retroperitoneal sarcomas are a group of rare malignancies comprised of several histological types, each carrying a unique risk of local recurrence and metastatic potential. In primary disease, surgery remains the mainstay of treatment and is the best opportunity for cure. In recurrent disease, treatment algorithms are less well defined. Surgery, radiation, systemic therapy, and in select cases, observation can be considered for management of recurrent disease. Histologic type drives a significant portion of clinical decision-making but incorporating all relevant clinicopathological data is important. To guide selection and timing of treatment, patients should undergo risk stratification. Nomograms and risk calculators are available to facilitate this. Experience and clinical judgement remain paramount. In the future, deeper molecular and radiologic characterization may further optimize decision-making in these challenging cases.
Soft tissue sarcomas represent a diverse set of malignancies with equally diverse behavior, ranging from relatively indolent low-grade tumors to aggressive high-grade tumors with high metastatic potential. Initial diagnosis hinges on tissue biopsy for determining histologic subtype and grade, while conventional imaging plays critical roles in defining local tumor size and extent, staging, treatment response, and disease surveillance. However, conventional semantic interpretation of imaging studies overlooks much of the complex imaging data embedded in routine clinical studies. Radiomics encompasses the identification of novel disease biomarkers extracted from highly quantitative characterizations of tumor structure and heterogeneity and has shown promise in providing a deeper understanding of soft tissue sarcomas. Given the increasing usage of imaging in soft tissue sarcomas, particularly usage of MRI, it behooves both clinicians and radiologists to further the depth of understanding that may be gleaned from radiomics. These insights, although primarily experimental, represent a rapidly evolving landscape in soft tissue sarcoma diagnosis and management where radiomics will be increasingly integrated into clinical practice. The present work focuses on the latest updates with regards to the application of radiomics to the diagnosis, prediction of treatment response, assessment of treatment response, and prognosis of soft tissue sarcomas and how they may affect sarcoma management.
Perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) has established a new curative-intent standard for resectable gastric and gastroesophageal junction adenocarcinoma. Recurrence after this regimen creates a clinically distinct, pre-exposed metastatic state for which no prospective sequencing standard exists. Because direct post-D-FLOT evidence is absent, treatment decisions should distinguish exposure-analogous evidence from extrapolation from conventional metastatic trials. In practice, we first determine whether recurrence after perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is potentially amenable to local treatment and, if systemic therapy is required, document the recurrence phase, the dates of the last FLOT and durvalumab doses, prior radiographic and pathological response, residual neuropathy, immune-related adverse events, organ function, performance status, and disease tempo. We then obtain recurrent-tumor tissue when feasible and reassess human epidermal growth factor receptor 2 (HER2), claudin 18.2 (CLDN18.2), and microsatellite instability/mismatch repair status; programmed death-ligand 1 results are interpreted in the context of assay differences and prior durvalumab exposure. If HER2 is positive and no prior HER2-directed therapy was given, we prioritize a HER2-directed strategy. If CLDN18.2 is positive and HER2 negative, zolbetuximab-based therapy is reasonable when oxaliplatin re-use is clinically defensible, but very early relapse or persistent neuropathy should favor an alternative strategy or a clinical trial. Microsatellite instability-high or mismatch repair-deficient disease remains immunologically compelling, although checkpoint-inhibitor re-use after durvalumab is not established. In biomarker-negative disease recurring during treatment or within about 6 months, we favor a non-cross-resistant approach, using ramucirumab- or irinotecan-based therapy according to prior taxane exposure, neuropathy, and regional availability. With a longer treatment-free interval and recovered toxicity, selective fluoropyrimidine/platinum reintroduction becomes more reasonable. We avoid routine checkpoint-inhibitor rechallenge solely because programmed death-ligand 1 is positive. For trial eligibility and line-of-therapy nomenclature, we count recurrence within 12 months of the last administered perioperative systemic dose (chemotherapy or durvalumab, whichever was later) as one prior systemic line, while recognizing that this is a pragmatic classification rather than a validated biologic cutoff.
