Purpose: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with ¹⁸FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. Methods: a one-armed two-stage Simon’s design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0–G2 (vs. G3–G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the β = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0–G2 acute HT to further proceed with the trial. We employed ¹⁸FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. Results: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0–G2 events, way above the threshold set by the trial design. Conclusion: ¹⁸FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

One of the main problems during in the treatment of anal cancer with chemotherapy and radiation is the occurrence of Hematologic Toxicity (HT). In particular, during radiotherapy it is crucial to spare Bone Marrow (BM), since the radiation dose received by BM in pelvic bones predicts the onset of HT. In this direction, the most popular strategies are based on the identification of the hematopoietically active BM (actBM), that is the part of BM in charge of blood cells generation, using MRI, SPECT or PET, but no approached have been proposed based on CT. In this study we compare four different classifiers in recognizing actBM from CT images using 36 radiomic features. We used Genetic Algorithms (GAs) to simultaneously optimize the feature subsets and the classifier parameters, separately for three pelvic subregions: iliac bone marrow (IBM), lower pelvis bone marrow (LPBM), and lumbosacral bone marrow (LSBM). The obtained classifiers were applied to CT sequences of a cohort of 25 patients affected by carcinoma of the anal canal. Classifiers results were compared with the actBM identified from 18FDG-PET (reference standard, RS). It emerged that the performances of the 4 classifiers are similar and they are satisfactory for IBM and LSBM subregions (Dice > 0.7) whereas they are poor for LPBM (Dice < 0.5).

Background: Actinic keratoses are common keratinocytic precursor lesions arising within chronically ultraviolet-damaged skin and are associated with an increased risk of progression to cutaneous squamous cell carcinoma. The concept of field cancerization has shifted therapeutic strategies from the treatment of isolated visible lesions toward broader field-directed approaches targeting both clinical and subclinical disease. Methods: This narrative review summarizes the rationale, mechanisms of action, efficacy profile, tolerability, and practical limitations of currently available field-directed therapies for actinic keratosis, including 5-fluorouracil, imiquimod, diclofenac, photodynamic therapy, and tirbanibulin. Based on their distinct biological targets, we propose a mechanism-based framework for sequential treatment strategies. Results: Available therapies act through partially non-overlapping mechanisms, including cytotoxic activity, immune activation, cyclooxygenase-2 inhibition, photodynamic oxidative damage, and tubulin/Src pathway inhibition. These complementary effects provide a biological rationale for sequential regimens aimed at addressing the heterogeneity of field cancerization. However, direct clinical evidence supporting specific treatment sequences remains limited, and proposed regimens should be interpreted as hypothesis-generating rather than as validated therapeutic protocols. Conclusions: Mechanism-based sequential field therapy may represent a rational strategy to optimize long-term control of actinic keratosis and field cancerization. Prospective comparative studies are needed to define optimal sequences, treatment intervals, patient selection criteria, and clinically meaningful endpoints, including sustained field clearance, recurrence reduction, tolerability, adherence, and prevention of progression to invasive cutaneous squamous cell carcinoma.

Background: Circulating extracellular vesicle (EV)-associated particle profiles may differ between patients with melanoma and those with benign lesions. Methods: Preoperative citrated whole blood from 77 patients with clinically suspicious lesions was assessed by direct fluorescence-based flow cytometry; histopathology identified 20 CMM cases (12 primary and 8 metastatic) and 57 benign-lesion controls. Results: The reported total particle concentration was higher in CMM than controls (3299.86 ± 456.61 vs. 2873.40 ± 427.74 events/µL). CD45+, PD-L1+, and CD45+/PD-L1+ populations were also increased. CD45+/VISTA+ particles were higher in the reduced subset of 9 CMM cases and 48 controls. Conclusions: These exploratory observations require analytical validation and independent clinical confirmation before diagnostic or prognostic utility can be established.

Dear Editor, The occurrence of multiple primary neoplasms in a single patient is rare but well documented, and the incidental discovery of a previously undiagnosed thyroid carcinoma during lymph node dissection for another primary malignancy presents a unique diagnostic challenge.