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.

Most patients with a newly diagnosed desmoid tumor should begin with multidisciplinary evaluation and active surveillance rather than immediate intervention, provided that symptoms are limited and further growth is unlikely to create irreversible morbidity. Treatment should be initiated when pain, functional limitation, sustained progression, or threatened critical structures make continued observation unacceptable. Percutaneous cryoablation is generally favored because the ice ball can be monitored directly, treatment can be personalized/tailored with the synergistic benefit of multiple probes, and the procedure can be repeated or staged when a complete margin would be unsafe. Complete ablation should be targeted when the entire tumor can be covered without jeopardizing skin, nerves, bowel, or other vulnerable structures; deliberate subtotal ablation is appropriate when the principal goal is pain relief or functional improvement and a safe circumferential margin is not achievable. Hydrodissection, skin warming, neural protection, and conservative treatment near critical anatomy are essential. Magnetic resonance-guided focused ultrasound is an attractive incisionless alternative for tumors with a favorable acoustic window. Microwave or radiofrequency ablation should be reserved for carefully selected lesions and experienced operators; electrochemotherapy and chemical ablation remain investigational with some promising early evidence. Embolization can be useful for hypervascular tumors that are poorly suited to direct percutaneous treatment. Local and systemic therapy should not be viewed as mutually exclusive: systemic treatment is often preferable for diffuse, intra-abdominal, or anatomically hazardous disease, while ablation can address a dominant symptomatic focus, residual viable tumor, or focal progression. Further study into the benefits and sequencing of combining local therapy with systemic or targeted options will be helpful in the multi-disciplinary evaluation of this complex patient cohort.

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.

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.

Mercaptopurine (6-MP) is a cornerstone drug for acute lymphoblastic leukemia (ALL) maintenance therapy. As a prodrug and purine analog, 6-MP is converted into the active cytotoxic product through a series of metabolic processes in the body. Its cytotoxic effects are mediated by the overactivation of deoxyribonucleic acid (DNA) mismatch repair mechanisms. The metabolism of 6-MP is influenced by multiple enzymes, and genetic polymorphisms encoding these enzymes affect drug tolerance and adverse reactions. Owing to significant individual variability, therapeutic drug monitoring (TDM) during 6-MP therapy has gained increasing attention, although no consensus has yet been established. Therefore, optimizing 6-MP maintenance regimens to mitigate adverse reactions and increase efficacy during this phase is critically important. Currently viable strategies include thiopurine enhanced ALL therapy (TEAM) and combination therapy with allopurinol. Finally, the issue of 6-MP resistance is attracting attention. Identifying methods for early detection of acquired resistance and developing corresponding strategies is important for improving the prognosis of ALL patients.

Well-differentiated liposarcoma (WDLPS) is a low-grade malignancy characterized by an indolent clinical course and a strong tendency for local recurrence. Unlike other sarcoma subtypes, pure WDLPS has a very low metastatic potential. However, in the course of the disease, dedifferentiation may occur and is associated with a substantially higher risk of metastases and mortality. Surgery remains the cornerstone of treatment for both primary and recurrent abdominal WDLPS, when a complete resection is possible. The role of systemic therapy in WDLPS is less clearly defined. Conventional cytotoxic chemotherapy generally has limited activity in pure WDLPS, and most clinical trials have included both WDLPS with dedifferentiated liposarcoma (DDLPS) or other liposarcoma subtypes, making the data for pure WDLPS difficult to interpret. Therefore, in clinical practice, we consider systemic treatment for patients with unresectable, symptomatic disease and in cases of repeated recurrences in which further local treatment is not possible. For selected patients with indolent and asymptomatic disease, active surveillance remains an appropriate strategy. The recent development of treatments directed against molecular alterations in WDLPS, namely CDK4 and MDM2 amplifications, have opened up a new era in the systemic treatment of this disease. Among these, anti-CDK4 agent palbociclib has shown the most mature clinical evidence to date, including recent results of overall survival data. MDM2 inhibition and combinations targeting both CDK4 and MDM2 represent promising areas which are currently under investigation. Due to the rarity of WDLPS and the lack of evidence from prospective studies, enrollment in clinical trials should be prioritized whenever possible.

Melanoma is the most aggressive form of skin cancer and remains a leading cause of skin cancer-related mortality. The therapeutic landscape of melanoma has been revolutionized by the advent of immune checkpoint inhibitors (ICIs), resulting in significant improvements in patient survival. Nevertheless, treatment-related toxicities, resistance mechanisms, and disease progression remain major barriers to durable clinical benefit, highlighting an ongoing unmet medical need. Tumor-infiltrating lymphocyte (TIL) therapy has emerged as a clinically active immunotherapeutic strategy for melanoma, particularly in patients with advanced or refractory disease. Continuous advances in biological understanding, manufacturing technologies, and clinical development have further strengthened its therapeutic potential. This review summarizes the biological basis of TIL therapy and outlines the manufacturing process from tumor procurement to lymphodepletion, TIL infusion, and interleukin-2 support. We then review current clinical evidence for conventional TIL products, including lifileucel, TM001, LM103, HS-IT101, and GC101, highlighting their efficacy and safety profiles. Emerging combination strategies integrating immune checkpoint inhibitors, targeted therapies, and oncolytic adenoviruses are also reviewed. In addition, advances in genetically engineered TILs, such as OBX-115, KSQ-001EX, and IOV-4001, are reviewed. Moreover, this review covers recent advances for improving therapeutic outcomes, including safety optimization, product optimization, next-generation engineered TILs, and predictive biomarkers. Challenges and future directions of TIL therapy in melanoma are also discussed. Overall, TIL therapy constitutes a rapidly evolving and clinically potent treatment modality for melanoma.

Esophageal cancer remains one of the most lethal malignancies worldwide, with particularly poor outcomes following disease progression after first-line chemoimmunotherapy. Antibody-drug conjugates (ADCs) have emerged as a transformative therapeutic class that combines the targeting precision of monoclonal antibodies with potent cytotoxic payloads, enabling selective tumor cell killing while minimizing off-target toxicity. In the management of advanced esophageal cancer, I advocate for the integration of ADCs as a therapeutic option following progression on first-line chemoimmunotherapy. For patients with human epidermal growth factor receptor 2 (HER2)-positive gastroesophageal junction adenocarcinoma, trastuzumab deruxtecan is my preferred choice based on its superior overall survival benefit and robust bystander killing effect, which also confers activity in HER2-low tumors. For HER2-negative gastroesophageal adenocarcinoma, trophoblast cell-surface antigen 2 represents a promising target given its high prevalence of moderate to strong expression in nearly 80% of cases, and sacituzumab tirumotecan is currently under phase III investigation in this setting. In esophageal squamous cell carcinoma, I recommend biomarker-guided selection among ADCs targeting B7-H3, given its overexpression in over 90% of cases. For Nectin-4-expressing tumors, enfortumab vedotin may be considered as a later-line alternative despite modest activity. Notably, the bispecific ADC targeting both epidermal growth factor receptor and human epidermal growth factor receptor 3, BL-B01D1, has demonstrated compelling efficacy in immunotherapy-refractory esophageal squamous cell carcinoma, and I consider it a breakthrough option in this subtype. For claudin-18.2-positive gastroesophageal junction adenocarcinoma, several ADCs including CMG901, IBI343, and tecotabart vedotin represent promising later-line choices. I emphasize that patient selection should be guided by validated predictive biomarkers, and treatment decisions must account for distinctive toxicity profiles, particularly interstitial lung disease with trastuzumab deruxtecan. Finally, I strongly support advancing ADCs into earlier lines of therapy and perioperative settings through well-designed clinical trials to further improve long-term outcomes in this aggressive malignancy.

Lung cancer remains the leading cause of cancer-related mortality. The 5-year survival rate for advanced non-small cell lung cancer (NSCLC) is only 20%-30%, highlighting an urgent need for more effective therapeutic strategies. Immune checkpoint inhibitors and anti-angiogenic agents are now widely used in clinical practice and have significantly prolonged patient survival. However, their efficacy and safety remain constrained by multiple reasons. This review systematically outlines the synergistic mechanisms and recent advances of combined anti-PD-1/PD-L1 and anti-angiogenic therapy. It also evaluates the clinical value of novel bispecific antibodies in NSCLC, with a specific focus on their potential advantages in patients with comorbidities. By systematically synthesizing preclinical and clinical data from 2020 to 2026, this article analyzes the mechanistic roles of the combination strategy. The clinical efficacy and safety profile are comprehensively assessed. Current evidence demonstrates that combining anti-PD-1/PD-L1 agents with anti-angiogenic therapy synergistically remodels the tumor immune microenvironment. This approach enhances T cell infiltration and function and effectively overcomes monotherapy resistance. Clinical studies have confirmed that this regimen extends median overall survival (mOS) by 4.8 months. Bispecific antibodies developed on this foundation optimize pharmacokinetic matching and improve safety profiles. These single-agent therapies show promising clinical potential for managing NSCLC with chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF). In conclusion, combined therapy has become a pivotal direction in NSCLC systemic treatment. Future research should prioritize optimizing treatment regimens, refining real-world safety assessments, and expanding clinical application in patients with complex comorbidities to address current unmet therapeutic needs.

In our view, molecular classification should guide, but not independently determine, treatment for endometrial cancer. The four major molecular subtypes-POLE-mutated (POLEmut), mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H), p53-abnormal/copy-number-high (p53abn/CNH), and no specific molecular profile/copy-number-low (NSMP/CNL)-should be interpreted together with histological type, tumor grade, stage, myometrial invasion, lymphovascular space invasion, comorbidities, fertility goals, treatment accessibility, and patient preferences. For advanced or recurrent dMMR/MSI-H disease, we favor immune checkpoint inhibition because this subtype has the clearest predictive evidence, with immunotherapy increasingly incorporated into first-line treatment. For tumors harboring a confirmed pathogenic POLE exonuclease-domain mutation, we support careful consideration of adjuvant treatment de-escalation, while avoiding de-escalation based on non-pathogenic variants, variants of uncertain significance, or molecular classification alone in advanced-stage disease. We regard p53abn/CNH tumors as a high-risk phenotype requiring appropriately intensive multimodality treatment; human epidermal growth factor receptor 2-targeted therapy, DNA damage response-directed strategies, WEE1 G2 checkpoint kinase inhibition, and antibody-drug conjugates should be considered according to tumor biomarkers, treatment setting, and evidence strength. NSMP/CNL should not be managed as a uniform residual category. Secondary stratification using estrogen receptor/progesterone receptor status, L1 cell adhesion molecule expression, catenin beta 1 alterations, and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway alterations may identify hormone-sensitive, high-risk, and potentially targetable subgroups. In fertility-sparing management, molecular findings may refine counseling and surveillance but should not replace established eligibility criteria. At recurrence or progression, repeat biopsy and biomarker reassessment should be considered when clinically feasible and likely to alter treatment.

Microscopically positive surgical margins (R1) complicate 15-30% of soft tissue sarcoma (STS) resections and independently worsen local recurrence and overall survival, yet no randomised trial has targeted the R1 population; we recommend risk-adapted management directed by a multidisciplinary team at a specialist sarcoma centre. Decision-making should integrate histological subtype, tumour grade, anatomical site, margin context, and individualised prognostic risk estimated by validated nomograms such as Sarculator and PERSARC. Planned positive margins on critical anatomical structures, most often encountered in retroperitoneal sarcoma, do not mandate re-excision, as local recurrence rates approximate those of R0 resection, and management should proceed directly to histotype-tailored adjuvant radiotherapy where indicated. Inadvertent positive margins after unplanned or non-specialist excision carry a substantially higher local recurrence risk and warrant re-excision whenever secondary R0 is achievable without prohibitive morbidity, followed by adjuvant radiotherapy in high-grade or deep tumours. When further surgery is not feasible, adjuvant radiotherapy alone remains the standard adjunct and substantially reduces local recurrence in extremity STS. Adjuvant anthracycline-ifosfamide chemotherapy should be considered in patients identified as high-risk by validated nomograms, in whom R1 status is the strongest predictor of survival benefit. Active surveillance with structured imaging follow-up is a reasonable option for small, low-grade R1 tumours at sites of prohibitive re-excision morbidity. Referral to a specialist sarcoma centre before any initial intervention remains the single most impactful measure to reduce R1 incidence and optimise oncological outcomes and should be regarded as the overarching standard of care.

Pancreatic cancer represents a malignant tumor of the digestive system with an inferior clinical prognosis, primarily attributable to the challenges in early diagnosis that preclude surgery-based treatment for most patients. Furthermore, the high postoperative recurrence rate significantly limits long-term survival in surgical candidates. Among patients experiencing recurrence after pancreatic cancer resection, local recurrence emerges as one of the most prevalent patterns. Early detection remains equally critical for recurrent cases, as selected patients undergoing potentially curative therapy for localized recurrence demonstrate that they can still extend post-recurrence survival. This comprehensive review synthesizes current evidence regarding the pathogenesis, risk determinants, diagnostic approaches, therapeutic interventions, and preventive measures for local recurrence following pancreatic cancer surgery. Emphasis is placed on analyzing the potential etiopathogenetic mechanisms and risk determinants for postoperative local recurrence, including tumor biology characteristics, tumor microenvironment interactions, and clinicopathological influences, providing foundations for preventive strategies. Emerging diagnostic modalities, particularly advanced imaging, and histopathological techniques, enhance early detection of locoregional recurrence. The review further examines evolving treatment paradigms encompassing precision radiotherapy, targeted systemic therapies, and innovative immunotherapeutic approaches for recurrent disease management. By integrating multidisciplinary perspectives, this work aims to inform optimized preventive approaches, surveillance and diagnostic protocols, and advance personalized management strategies for postoperative local recurrence in patients with pancreatic cancer.

Dedifferentiated chondrosarcoma (DDCS) remains one of the most aggressive and therapeutically challenging primary bone malignancies. While surgery continues to represent the cornerstone of treatment for localized disease, outcomes remain poor due to high rates of local recurrence and metastatic progression. The role of adjuvant therapies remains less clear. Radiotherapy may be considered in selected patients with unresectable tumors, positive margins, or for symptom palliation, whereas conventional chemotherapy has demonstrated inconsistent and generally limited benefit despite the use of osteosarcoma-based regimens. Recent advances in molecular profiling have improved our understanding of DDCS biology and revealed potential therapeutic opportunities. Recurrent IDH1/2 mutations appear to contribute to tumor progression and dedifferentiation and may represent actionable therapeutic targets. In our practice, comprehensive molecular profiling should be considered whenever feasible, particularly in advanced disease. Emerging evidence suggests that immunotherapy can induce durable responses in a small subset of patients, while early studies combining immune checkpoint inhibitors with antiangiogenic tyrosine kinase inhibitors have demonstrated encouraging response rates that exceed those historically achieved with chemotherapy alone. Although these findings require prospective validation, they support a shift toward biomarker-driven and combination treatment strategies.

In our practice, the treatment of pelvic bone tumors should begin with a multidisciplinary sarcoma-board evaluation that integrates biopsy-proven histology, high-resolution CT/MRI/PET imaging, neurovascular and visceral involvement, Enneking zone, expected survival, and patient-specific functional goals. For potentially curable primary pelvic sarcomas, we consider negative-margin resection the non-negotiable oncologic priority. Limb-salvage internal hemipelvectomy is preferred when an R0 resection can be achieved while preserving limb viability and a meaningful postoperative function; external hemipelvectomy should be reserved for tumors with unreconstructable femoral or iliac vessel involvement, extensive sciatic or lumbosacral plexus invasion, uncontrolled infection, or recurrent disease in which safe margins cannot otherwise be obtained. Histology should drive sequencing: osteosarcoma and Ewing sarcoma generally require effective neoadjuvant systemic therapy before definitive local treatment, whereas conventional chondrosarcoma requires meticulous wide en bloc surgery because chemotherapy and conventional radiotherapy have limited curative value. Reconstruction should not be selected by technology alone. For non-weight-bearing or palliative defects, no reconstruction, flail hip, hip transposition, or standard metastatic acetabular procedures may offer the best time-adjusted quality of life. For long-term survivors with periacetabular, sacroiliac, or spinopelvic instability, we favor anatomy-restoring reconstruction using navigation-assisted resection and carefully planned biological, modular, or patient-specific 3D-printed implants, provided soft-tissue coverage and infection risk are acceptable. Emerging tools such as computer-assisted navigation, robotics, artificial intelligence-based segmentation, liquid biopsy, digital twins, and smart biomaterials should be used to reinforce classic oncologic principles rather than replace them. Their adoption should depend on validated margin benefit, durable functional gain, complication reduction, cost-effectiveness, and equitable access.

Trial participation is increasingly recognised as a crucial component of optimal cancer care, yet patients with advanced cancer receiving palliative care often face significant challenges in meeting the logistical demands of traditional clinical trials. Decentralised clinical trials (DCTs), including teletrials, which conduct study activities outside a central site - frequently in participant's homes or local communities - offer a promising model to overcome these barriers. By enabling remote participation, DCTs can overcome geographical and functional barriers, making trials more accessible to this often-frail population. However, there are important concerns that warrant careful consideration. DCTs may inadvertently fragment care, expose vulnerable patients to novel medications in an isolated setting, and exacerbate digital health inequities. In our experience these challenges can be mitigated through careful trial selection, as well as the implementation of rigorous screening and support systems to ensure both patient suitability and continuity of care. Key measures include close liaison with treating oncologists and palliative care teams, 24/7 clinical phone support, accessible IT assistance during working hours, and collaboration with local trial coordinators when available. This approach not only extends the geographical reach of clinical trial participation for patients with advanced cancer receiving palliative care, but also maintains trial rigour and patient safety.