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Background Gaucher disease (GD) is caused by reduced lysosomal enzyme β-glucocerebrosidase activity. Heterogeneous genotypes and phenotypes have been observed within GD types and across ethnicities. Enzyme replacement therapy is generally recommended for patients with type 1 GD, the least severe form of GD. In Japan, velaglucerase alfa has a broad indication covering type 1, 2 or 3 GD.  Methods All patients with type 1, 2, or 3 GD administered velaglucerase alfa 60 U/kg every 2 weeks via intravenous infusion after its launch date in Japan in 2014, were enrolled in a non-interventional, observational post-marketing surveillance (PMS). Individual patient data were reported via case report forms (CRFs). Key safety endpoints investigated included the incidence of infusion-related reactions (IRRs), the safety of velaglucerase alfa in patients with types 2 and 3 GD, from patients under one year of age to elderly patients (≥ 65 years of age). Long-term efficacy was also assessed.  Results In total, 53 patients with GD were registered. CRFs were available for 41 (77.4%) patients at the 6-year interim analysis. Fourteen adverse drug reactions (ADRs) were reported in seven patients. All reported ADRs occurred in patients with type 2 GD. ADRs were reported by 63.6% (7/11) of patients with type 2 GD. Ten ADRs were reported in five patients aged < 4 years. No elderly patients experienced any ADR during the surveillance period. Five ADRs occurring in three (10.0%) patients were classified as IRRs, with one case of vomiting (moderate severity) resulting in treatment discontinuation. Ten serious adverse events were reported in five (16.7%) patients. Three fatal events were considered to be unrelated to treatment with velaglucerase alfa. Platelet counts increased after the administration of velaglucerase alfa and were generally maintained within the normal range over the administration period. Among eleven patients tested for neutralizing anti-velaglucerase alfa antibodies, two (18.2%) were assessed as positive results.  Conclusion PMS data from patients with types 1–3 GD in Japan indicate that long-term treatment with velaglucerase alfa was well-tolerated and associated with increased platelet counts, which is consistent with observations made in studies outside of Japan. Trial registration: NCT03625882 registered July 2014.

We have performed superselective intra-arterial cisplatin infusion with concomitant radiotherapy (RADPLAT) for patients with maxillary sinus cancer. The promising treatment outcomes of this non-surgical treatment were reported in past studies. However, few clinical studies have been conducted to evaluate the outcome of salvage surgery following RADPLAT. The purpose of this study was to analyze the treatment outcomes of salvage surgery for patients with recurrent maxillary sinus cancer after RADPLAT. MethodsWe assessed 45 patients who had recurrence following RADPLAT between 1999 and 2017, and conducted a retrospective analysis. We excluded patients who did not complete RADPLAT. Patients were not considered to have completed RADPLAT if they underwent intra-arterial cisplatin less than three times or received a total radiation dose of less than 60 Gy. The primary endpoint was overall survival. The median follow-up period for surviving patients after recurrence was 5.1 years. ResultsTwenty-five of the 45 (56%) patients underwent salvage surgery. The 5-year overall survival rate was 68% in patients who underwent salvage surgery, while all patients who did not undergo salvage surgery died during the observation period.Fifteen of 24 (63%) patients with local recurrence underwent salvage surgery. Eight patients did not undergo salvage surgery because of unresectable disease; five out of the eight patients had unresectable posterior extension. All nine patients with nodal recurrence underwent neck dissection. ConclusionTreatment outcomes of salvage surgery following RADPLAT were favorable enough for it to be generally recommended. To reduce unresectable recurrence, the posterior section should be eradicated by RADPLAT.

Background Online adaptation during intensity‐modulated proton therapy (IMPT) can minimize the effect of inter‐fractional anatomical changes, but remains challenging because of the complex workflow. One approach for fast and automated online IMPT adaptation is dose restoration, which restores the initial dose distribution on the updated anatomy. However, this method may fail in cases where tumor deformation or position changes occur. Purpose To develop a fast and robust IMPT online adaptation method named “deformed dose restoration (DDR)” that can adjust for inter‐fractional tumor deformation and position changes. Methods The DDR method comprises two steps: (1) calculation of the deformed dose distribution, and (2) restoration of the deformed dose distribution. First, the deformable image registration (DIR) between the initial clinical target volume (CTV) and the new CTV were performed to calculate the vector field. To ensure robustness for setup and range uncertainty and the ability to restore the deformed dose distribution, an expanded CTV‐based registration to maintain the dose gradient outside the CTV was developed. The deformed dose distribution was obtained by applying the vector field to the initial dose distribution. Then, the voxel‐by‐voxel dose difference optimization was performed to calculate beam parameters that restore the deformed dose distribution on the updated anatomy. The optimization function was the sum of total dose differences and dose differences of each field to restore the initial dose overlap of each field. This method only requires target contouring, which eliminates the need for organs at risk (OARs) contouring. Six clinical cases wherein the tumor deformation and/or position changed on repeated CTs were selected. DDR feasibility was evaluated by comparing the results with those from three other strategies, namely, not adapted (continuing the initial plan), adapted by previous dose restoration, and fully optimized. Results In all cases, continuing the initial plan was largely distorted on the repeated CTs and the dose‐volume histogram (DVH) metrics for the target were reduced due to the tumor deformation or position changes. On the other hand, DDR improved DVH metrics for the target to the same level as the initial dose distribution. Dose increase was seen for some OARs because tumor growth had reduced the relative distance between CTVs and OARs. Robustness evaluation for setup and range uncertainty (3 mm/3.5%) showed that deviation in DVH‐bandwidth for CTV D95% from the initial plan was 0.4% ± 0.5% (Mean ± S.D.) for DDR. The calculation time was 8.1 ± 6.4 min. Conclusions An online adaptation algorithm was developed that improved the treatment quality for inter‐fractional anatomical changes and retained robustness for intra‐fractional setup and range uncertainty. The main advantage of this method is that it only requires target contouring alone and saves the time for OARs contouring. The fast and robust adaptation method for tumor deformation and position changes described h...