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Patients with advanced malignant melanoma (MM) often do not receive satisfactory treatment. The present study reports the case of a 51-year-old female patient with stage IV MM of unknown primary. After undergoing immune checkpoint inhibitor therapy, the patient received multiple doses of hypofractionated radiotherapy (HFRT) for the left inguinal lymph node and single-fraction high-dose-rate brachytherapy for the left and right lung metastases. After combination treatment, the patient experienced almost complete remission of the inguinal target area, significant relief of pain and discomfort and an improved quality of life. The time of lung radiotherapy lesion control was 8 months. Meanwhile, the observed lesions (observation lesions 1, 2, 3 and 5) adjacent to the target lesion received lower doses of scattering (0.9-1.8 Gy) and the time of control for these lung observation lesions was 9 months. In addition, restarting targeted therapy after cessation of other treatments due to myelosuppression resulted in a progression-free survival time of 6 months. Nevertheless, the patient developed new metastases in the brain and abdomen. The present case report demonstrates that high-dose radiotherapy combined with immunotherapy may be effective for local lesions and that multiple doses of HFRT may be superior to single-fraction high-dose-rate brachytherapy for certain patients. Low-dose scattering also shows improvement for local lesions. Furthermore, restarting targeted therapy may be effective in the presence of target sites. Thus, the present case report provides a possible therapeutic option for the treatment of advanced melanoma.

Purpose To implement and validate a beam current transformer as a passive monitoring device on a pulsed electron beam medical linear accelerator (LINAC) for ultra‐high dose rate (UHDR) irradiations in the operational range of at least 3 Gy to improve dosimetric procedures currently in use for FLASH radiotherapy (FLASH‐RT) studies. Methods Two beam current transformers (BCTs) were placed at the exit of a medical LINAC capable of UHDR irradiations. The BCTs were validated as monitoring devices by verifying beam parameters consistency between nominal values and measured values, determining the relationship between the charge measured and the absorbed dose, and checking the short‐ and long‐term stability of the charge‐absorbed dose ratio. Results The beam parameters measured by the BCTs coincide with the nominal values. The charge‐dose relationship was found to be linear and independent of pulse width and frequency. Short‐ and long‐term stabilities were measured to be within acceptable limits. Conclusions The BCTs were implemented and validated on a pulsed electron beam medical LINAC, thus improving current dosimetric procedures and allowing for a more complete analysis of beam characteristics. BCTs were shown to be a valid method for beam monitoring for UHDR (and therefore FLASH) experiments.

Background Vonoprazan and amoxicillin dual therapy has demonstrated favorable efficacy in the initial treatment of Helicobacter pylori (H. pylori) infection. This study aimed to evaluate the efficacy and safety of vonoprazan and high‐dose amoxicillin (VHA) dual therapy for H. pylori rescue treatment. Methods This was an open label, multicenter, non‐inferiority, and randomized controlled clinical trial conducted at four institutions in both central and northwestern China. A total of 688 H. pylori‐infected patients who had failed previous treatments were randomly assigned (1:1) to receive either VHA dual therapy or the tetracycline‐ and furazolidone‐based bismuth‐containing quadruple therapy (TFEB) for 14 days. Eradication rates, adverse event (AE) rates, and the patient compliance were compared between the two groups. Results The eradication rates in the VHA and TFEB groups were 73.8% and 76.2% (p = 0.481), respectively, by intention‐to‐treat (ITT) analysis; 81.9% and 85.6% (p = 0.215), respectively, by modified ITT (MITT) analysis; and 82.1% and 85.6% (p = 0.248), respectively, by per‐protocol (PP) analysis. VHA therapy remained non‐inferior to TFEB in ITT, MITT, and PP analyses. The overall AE incidence in the VHA group was significantly lower compared with that in the TFEB group (13.4% vs.. 28.5%, p < 0.001). Patients' compliance was similar between the two groups. A history of multiple prior eradication failures was an independent risk factor (2 failures: OR = 0.566, p = 0.032; ≥ 3 failures: OR = 0.335, p < 0.001) reducing the efficacy of H. pylori rescue therapy. Conclusion The 14‐day VHA dual therapy was non‐inferior to bismuth‐containing quadruple therapy, with a lower incidence of adverse events and good compliance, and may represent an effective alternative for H.pylori rescue treatment. Trial Registration This trial was registered at ClinicalTrials.gov (No. NCT06168084) Summary Summarise the established knowledge on this subject ◦ VHA dual therapy demonstrated significant efficacy in first‐line H. pylori treatment. ◦ BQT remains the recommended rescue regimen in most guidelines. ◦ BQT may pose challenges such as higher adverse events and potential secondary resistance risk in H. pylori. What are the significant and/or new findings of this study? ◦ VHA dual therapy was non‐inferior to BQT and may represent an effective alternative for H. pylori rescue treatment. ◦ A history of multiple prior eradication failures was an independent risk factor reducing the efficacy of H. pylori rescue therapy.

Hypofractionated radiotherapy is an attractive approach for minimizing patient burden and treatment cost. Technological advancements in external beam radiotherapy (EBRT) delivery and image guidance have resulted in improved targeting and conformality of the absorbed dose to the disease and a reduction in dose to healthy tissue. These advances in EBRT have led to an increasing adoption and interest in hypofractionation. Furthermore, for many treatment sites, proton beam therapy (PBT) provides an improved absorbed dose distribution compared to X-ray (photon) EBRT. In the past 10 years there has been a notable increase in reported clinical data involving hypofractionation with PBT, reflecting the interest in this treatment approach. This review will discuss the reported clinical data and radiobiology of hypofractionated PBT. Over 50 published manuscripts reporting clinical results involving hypofractionation and PBT were included in this review, ~90% of which were published since 2010. The most common treatment regions reported were prostate, lung and liver, making over 70% of the reported results. Many of the reported clinical data indicate that hypofractionated PBT can be well tolerated, however future clinical trials are still needed to determine the optimal fractionation regime.

Purpose Radiotherapy delivered at ultra‐high‐dose‐rates (≥40 Gy/s), that is, FLASH, has the potential to effectively widen the therapeutic window and considerably improve the care of cancer patients. The underlying mechanism of the FLASH effect is not well understood, and commercial systems capable of delivering such dose rates are scarce. The purpose of this study was to perform the initial acceptance and commissioning tests of an electron FLASH research product for preclinical studies. Methods A linear accelerator (Clinac 23EX) was modified to include a non‐clinical FLASH research extension (the Clinac‐FLEX system) by Varian, a Siemens Healthineers company (Palo Alto, CA) capable of delivering a 16 MeV electron beam with FLASH and conventional dose rates. The acceptance, commissioning, and dosimetric characterization of the FLEX system was performed using radiochromic film, optically stimulated luminescent dosimeters, and a plane‐parallel ionization chamber. A radiation survey was conducted for which the shielding of the pre‐existing vault was deemed sufficient. Results The Clinac‐FLEX system is capable of delivering a 16 MeV electron FLASH beam of approximately 1 Gy/pulse at isocenter and reached a maximum dose rate >3.8 Gy/pulse near the upper accessory mount on the linac gantry. The percent depth dose curves of the 16 MeV FLASH and conventional modes for the 10 × 10 cm2 applicator agreed within 0.5 mm at a range of 50% of the maximum dose. Their respective profiles agreed well in terms of flatness but deviated for field sizes >10 × 10 cm2. The output stability of the FLASH system exhibited a dose deviation of <1%. Preliminary cell studies showed that the FLASH dose rate (180 Gy/s) had much less impact on the cell morphology of 76N breast normal cells compared to the non‐FLASH dose rate (18 Gy/s), which induced large‐size cells. Conclusion Our studies characterized the non‐clinical Clinac‐FLEX system as a viable solution to conduct FLASH research that could substantially increase access to ultra‐high‐dose‐rate capabilities for scientists.

Although theoretical studies have shown that the mixture strategy, which uses multiple toxins simultaneously, can effectively delay the evolution of insecticide resistance, whether it is the optimal management strategy under different insect life histories and insecticide types remains unknown. To test the robustness of this management strategy over different life histories, we developed a series of simulation models that cover almost all the diploid insect types and have the same basic structure describing pest population dynamics and resistance evolution with discrete time steps. For each of two insecticidal toxins, independent one‐locus two‐allele autosomal inheritance of resistance was assumed. The simulations demonstrated the optimality of the mixture strategy either when insecticide efficacy was incomplete or when some part of the population disperses between patches before mating. The rotation strategy, which uses one insecticide on one pest generation and a different one on the next, did not differ from sequential usage in the time to resistance, except when dominance was low. It was the optimal strategy when insecticide efficacy was high and premating selection and dispersal occur.

Background TG‐43 formalism assumes homogeneous water media, potentially overlooking anatomical heterogeneities that affect dose accuracy. AcurosBV, a model‐based dose calculation algorithm, accounts for tissue and material heterogeneities. This study evaluates their dosimetric differences in high‐dose‐rate (HDR) brachytherapy using Harrison‐Anderson‐Mick (H.A.M.) applicators. Purpose To compare dose‐volume histogram (DVH) metrics calculated using TG‐43 formalism and AcurosBV in patients treated with HDR brachytherapy using H.A.M. applicators for superficial lesions in the head and neck regions. Methods Twenty patients (17 nasal, 3 non‐nasal) received HDR brachytherapy with H.A.M. applicators to a total dose of 40 Gy in eight fractions. Original plans calculated with TG‐43 formalism were retrospectively re‐calculated using AcurosBV (Eclipse v16.1), incorporating Hounsfield unit‐based heterogeneity corrections with dose‐to‐medium reporting. Planning target volumes (PTVs) were contoured by radiation oncologists; organs at risk (OARs) including brain, eyes, lens, optical nerve and skin were auto‐segmented using AutoContour (Radformation Inc., NY). DVH metrics (mean dose, D90%, V100%, V150%, V200%, D0.1cc, D0.2cc, D1cc and D2cc) were compared. The isodose distributions from both algorithms were also evaluated slice by slice. Statistical significance was assessed using a paired Student's t‐test (p < 0.05). Results AcurosBV consistently reported lower DVH value in PTV than TG‐43. The average PTV mean dose was 48.65 ± 1.22 Gy (AcurosBV) versus 50.78 ± 1.40 Gy (TG‐43), with significant difference in V100 (−6.43 ± 0.95%, p < 0.003). OAR dose differences were modest (∼1.5%) except for the skin, which showed larger reductions (∼4–5% in D0.1cc–D2cc, p < 10−8). Visual inspection revealed less conformal isodose distributions in AcurosBV plans due to air cavities and tissue inhomogeneities. Conclusion AcurosBV yielded lower and anatomically informed dose estimates compared with TG‐43 in HDR brachytherapy using H.A.M. applicators. These results support clinical adoption of model‐based algorithms but warrant caution, as dosimetric differences and prior TG‐43 experience may affect existing dose constraints and clinical outcomes.

The efficiency of upfront consolidation with high‐dose chemotherapy/autologous stem‐cell transplantation (HDCT/ASCT) for newly diagnosed high‐risk diffuse large B‐cell lymphoma (DLBCL) may be influenced by induction chemotherapy. To select better induction chemotherapy regimens for HDCT/ASCT, a randomized phase II study was conducted in high‐risk DLBCL patients having an age‐adjusted International Prognostic Index (aaIPI) score of 2 or 3. As induction chemotherapy, 6 cycles of R‐CHOP‐14 (arm A) or 3 cycles of R‐CHOP‐14 followed by 3 cycles of CHASER (arm B) were planned, and patients who responded proceeded to HDCT with LEED and ASCT. The primary endpoint was 2‐y progression‐free survival (PFS), and the main secondary endpoints included overall survival, overall response rate, and adverse events (AEs). In total, 71 patients were enrolled. With a median follow‐up of 40.3 mo, 2‐y PFS in arms A and B were 68.6% (95% confidence interval [CI], 50.5%‐81.2%) and 66.7% (95% CI: 48.8%‐79.5%), respectively. Overall survival at 2 y in arms A and B was 74.3% (95% CI: 56.4%‐85.7%) and 83.3% (95% CI: 66.6%‐92.1%). Overall response rates were 82.9% in arm A and 69.4% in arm B. During induction chemotherapy, 45.7% and 75.0% of patients in arms A and B, respectively, had grade ≥ 3 non‐hematologic toxicities. One patient in arm A and 6 in arm B discontinued induction chemotherapy due to AEs. In conclusion, R‐CHOP‐14 showed higher 2‐y PFS and less toxicity compared with R‐CHOP‐14/CHASER in patients with high‐risk DLBCL, suggesting the former to be a more promising induction regimen for further investigations (UMIN‐CTR, UMIN000003823). The efficiency of upfront consolidation with high‐dose chemotherapy/autologous stem‐cell transplantation (HDCT/ASCT) for newly diagnosed high‐risk diffuse large B‐cell lymphoma (DLBCL) may be influenced by induction chemotherapy. To select better induction chemotherapy regimens for HDCT/ASCT, a randomized phase II study was conducted in patients with high‐risk DLBCL who had an age‐adjusted International Prognostic Index (aaIPI) score of 2 or 3. R‐CHOP‐14 showed higher 2‐y PFS and less toxicity compared with R‐CHOP‐14/CHASER in patients with high‐risk DLBCL, suggesting the former to be a more promising induction regimen for further investigations.

(1) Background: The Exradin W2 is a commercially available scintillator detector designed for reference and relative dosimetry in small fields. In this work, we investigated the performance of the W2 scintillator in a 10 MV flattening-filter-free photon beam and compared it to the performance of ion chambers designed for small field measurements. (2) Methods: We measured beam profiles and percent depth dose curves with each detector and investigated the linearity of each system based on dose per pulse (DPP) and pulse repetition frequency. (3) Results: We found excellent agreement between the W2 scintillator and the ion chambers for beam profiles and percent depth dose curves. Our results also showed that the two-voltage method of calculating the ion recombination correction factor was sufficient to correct for the ion recombination effect of ion chambers, even at the highest DPP. (4) Conclusions: These findings show that the W2 scintillator shows excellent agreement with ion chambers in high DPP conditions.

Background The FLASH effect, induced by ultra‐high dose rate (UHDR) irradiations, offers the potential to spare normal tissue while effectively treating tumors. It is important to achieve precise and accurate dose delivery and to establish reliable detector systems, particularly for clinical trials needed to help the clinical transfer of FLASH‐Radiotherapy (FLASH‐RT). However, the use of monitoring chambers with UHDR beams is presently limited, leading to the reliance on passive dosimetry and machine stability. Purpose This study aimed to investigate the energy and output stability of a UHDR Mobetron (IntraOp, USA) and to compare it with its conventional dose rate (CDR) mode. Furthermore, we assessed the dosimetric accuracy of a human clinical protocol for FLASH‐RT. Methods Over a 26‐month duration, we assessed the short‐ and long‐term stability of the output and energy of the Mobetron system. Daily checks were conducted for 9 MeV CDR and UHDR. In parallel, the IMPulse clinical trial involving patients with skin metastases from melanoma was initiated. Prescription doses ranging from 22 to 28 Gy were administered. Pre‐, post‐, and in vivo dosimetry using alanine and thermoluminescent dosimeters (TLDs) was performed and compared to the prescription doses. Results Short‐term output fluctuations remained below 0.6 % and 1 % for 9 MeV CDR and UHDR, respectively. Long‐term output fluctuations were within 2 % and the long‐term energy fluctuations were below 2 mm (R50) for both modes. The delivered doses of the IMPulse trial showed deviations below 4 % compared to prescription doses for all patients. Conclusions The Mobetron system demonstrated favorable short‐ and long‐term stability. There was a good agreement between the prescribed and the measured dose for the clinical IMPulse trial. The stability of this UHDR machine allows us to effectively conduct human clinical protocols as well as preclinical experiments, even in the absence of a real‐time monitoring system.