Cancers

Background: Rare cancers combine low incidence with high biological heterogeneity and multi-institutional care trajectories. These features make single-center learning structurally incomplete and render pathway fragmentation a dominant driver of preventable harm, variability, and waste. In this context, care quality is best understood as a property of pathway integrity across routing, diagnostics (imaging/biopsy planning), multidisciplinary intent-setting, definitive treatment, and surveillance—rather than as a department-level attribute. Objective: To define a pragmatic, transferable operating blueprint for a rare-cancer Learning Health System (LHS) that turns routine care into continuous, auditable learning under explicit governance, while maintaining claims discipline and protecting measurement validity. Approach: We synthesize an implementation-oriented operating model using the Swiss Sarcoma Network (SSN) as an exemplar. The blueprint couples clinical governance (Integrated Practice Unit logic, hub-and-spoke routing, auditable multidisciplinary team decision systems) with an interoperable real-world-time data backbone designed for benchmarking, pathway mapping, and feedback. The operating logic is expressed as a closed-loop control cycle: capture → harmonize → benchmark → learn → implement → re-measure, with explicit owners, minimum requirements, and failure modes. Results/Blueprint: (i) The model specifies a minimal set of data primitives—time-stamped and traceable decision points covering baseline and tumor characteristics, pathway timing, treatment exposure, outcomes and complications, and feasible longitudinal PROMs and PREMs; (ii) a VBHC-ready, multi-domain measurement backbone spanning outcomes, harms, timeliness, function, process fidelity, and resource stewardship; and (iii) two non-negotiable validity guardrails: explicit applicability (“N/A”) rules and mandatory case-mix/complexity stratification. Implementation is treated as a governed step with defined workflow levers, fidelity criteria, balancing measures, and escalation thresholds to prevent “dashboard medicine” and surrogate-driven optimization. Conclusions: This perspective contributes an operating model—not a platform or single intervention—that enables credible improvement science and establishes prerequisites for downstream causal learning and minimum viable digital twins. By distinguishing enabling infrastructure from the governed clinical system as the primary intervention, the blueprint supports scalable, learnable excellence in rare-cancer care while protecting against gaming, inequity, and inference drift. Distinct from generic LHS or VBHC frameworks, this blueprint specifies validity gates required for rare-cancer benchmarking—explicit applicability (“N/A”) rules, denominator integrity/capture completeness disclosure, anti-gaming safeguards, and escalation governance. These elements are critical in rare cancers because small denominators, high heterogeneity, and multi-institutional pathways otherwise make benchmarking prone to artifacts and unsafe inferences.

Background: Numerous studies have demonstrated the impact of post-transplant immunosuppressive therapy on cancer development, particularly in the skin. Despite the growing number of observations, there is still a lack of comprehensive analyses assessing the influence of specific immunosuppressive regimens on the development of melanoma in kidney transplant recipients. The aim of this study was to describe the incidence and temporal patterns of cutaneous melanoma (CM) among kidney transplant recipients in Poland between 2010 and 2022, with particular focus on recipients treated with calcineurin inhibitor (CNI)-based immunosuppression, including cyclosporine (CsA) and tacrolimus (TAC). Methods: This nationwide, descriptive analysis was conducted using comprehensive national administrative data obtained from the Polish National Health Fund (PNHF) and the Polish National Cancer Registry (PNCR). The study assessed the incidence of cutaneous melanoma and temporal trends over the study period. Results: Melanoma skin cancer occurred in 27 cases observed in a population of 12,205 kidney transplant recipients over 13 years of follow-up, corresponding to a final cumulative incidence of 0.23% (95% CI: 0.15–0.34). Calcineurin inhibitor (CNI)-based regimens in kidney transplant recipients were associated with significantly lower risk profiles over 10 years, with only nine cases observed in a cohort of 7107 patients, culminating in a cumulative incidence of 0.13% (95% CI: 0.06–0.24). The stratified analysis of CM incidence under CNI-based immunosuppressive regimens by calcineurin inhibitor type revealed a modest cumulative risk in the TAC subgroup, reaching 0.14% (95% CI: 0.06–0.26) by year 10, with all nine observed cases occurring exclusively in this group, while the CsA subgroup reported zero events throughout the follow-up period. Risk differences progressively increased to 0.14% (95% CI: −0.20 to 0.26) by year 10, but they were not statistically significant in any year (p ≥ 0.230). Conclusions: Although all melanoma cases occurred in the TAC subgroup, the data do not allow us to conclude that TAC confers a higher risk than CsA. This lack of significance likely reflects both the rarity of events and the limited statistical power to detect small differences between TAC and CsA. These results highlight the need for careful dermatologic monitoring in all kidney transplant recipients, while the choice of calcineurin inhibitor should be individualized based on patient-specific factors.

Background: Dendritic and histiocytic cell sarcoma (DHCS) and clear cell sarcoma (CCS) are ultra-rare soft-tissue sarcomas characterized by diagnostic ambiguity, limited treatment guidelines, and poor outcomes. Their rarity has restricted the development of evidence-based management strategies, leaving clinical decisions reliant on small case series and institutional experience. DHCS typically presents without a unifying molecular driver and is often misclassified without comprehensive immunophenotyping. CCS is defined by EWSR1-ATF1/CREB1 fusions but exhibits low responsiveness to conventional chemotherapy. There remains a clear need to clarify natural history, therapeutic responses, and molecular characteristics in both. Methods: We conducted a retrospective cohort study of adult patients with histologically confirmed DHCS or CCS seen at The Ohio State University Comprehensive Cancer Center between 2010 and 2022. Demographics, treatment modalities, clinical outcomes, and molecular profiles were extracted and analyzed descriptively. Time to progression (TTP) and progression rates by treatment modality were recorded. A structured literature review was conducted to provide context for the findings. Results: Outcomes are descriptive and cohort-specific, reflecting institutional experience rather than generalizable estimates. Total of 10 patients with DHCS and 5 with CCS were evaluable. Most DHCS patients presented with metastatic disease. Among DHCS patients who received systemic therapies, five of eight (62.5%) experienced progression during or shortly after treatment. Among CCS patients who received systemic therapies, three of four (75%) progressed during or shortly after treatment. Overall mortality occurred in 4 of 10 DHCS patients (40%) and 3 of 5 CCS patients (60%). TP53 mutations were identified in four of seven next-generation sequencing (NGS)-tested DHCS cases, and PD-L1 positivity was detected in five of seven tested DHCS cases and one of five tested CCS cases. Conclusions: Despite multimodal treatment, this referral-based cohort of patients with ultra-rare DHCS and CCS showed high rates of progression and mortality. Our findings underscore the urgent need for multi-institutional collaboration and biomarker-driven clinical trials to guide management of these ultra-rare sarcoma subtypes.