Preventing Complications from High-Dose Rate Brachytherapy when Treating Mobile Tongue Cancer via the Application of a Modular Lead-Lined Spacer

<div><p>Purpose</p><p>To point out the advantages and drawbacks of high-dose rate brachytherapy in the treatment of mobile tongue cancer and indicate the clinical importance of modular lead-lined spacers when applying this technique to patients.</p><p>Methods</p><p>First, all basic steps to construct the modular spacer are shown. Second, we simulate and evaluate the dose rate reduction for a wide range of spacer configurations.</p><p>Results</p><p>With increasing distance to the source absorbed doses dropped considerably. Significantly more shielding was obtained when lead was added to the spacer and this effect was most pronounced on shorter (i.e. more clinically relevant) distances to the source.</p><p>Conclusions</p><p>The modular spacer represents an important addition to the planning and treatment stages of mobile tongue cancer using HDR-ISBT.</p></div

Percentage doses for various spacer types (Pb in mm) and distances (in mm) split out by plane and simulation type (Monte-Carlo vs. TG-43).

<p>Percentage doses for various spacer types (Pb in mm) and distances (in mm) split out by plane and simulation type (Monte-Carlo vs. TG-43).</p

Modular spacer during 3D-CT planning without lead-shield (i.e. eliciting no artifacts).

<p>Modular spacer during 3D-CT planning without lead-shield (i.e. eliciting no artifacts).</p

The modular spacer: inserting and holding the lead shield.

<p>The modular spacer: inserting and holding the lead shield.</p

Construction steps of a modular spacer containing shielding material.

<p>Construction steps of a modular spacer containing shielding material.</p

Radiation enhanced the local and distant anti-tumor efficacy in dual immune checkpoint blockade therapy in osteosarcoma

<div><p>Radiation therapy has been long utilized as localized cancer treatment. Recent studies have also demonstrated that it has a distant effect by the enhanced immunity, but it rarely occurs. The purpose of this study was to investigate whether X-ray irradiation combined with anti-PD-L1 and anti-CTLA-4 antibodies (P1C4) provides a higher probability of this distant effect as well as enhanced local antitumor efficacy for osteosarcoma. LM8 mouse osteosarcoma cells were inoculated into both legs of C3H mice assigned to one of four groups, namely no treatment (No Tx), P1C4, X-ray irradiation (RAD) to the leg of one side, and combination (COMB) groups. Survival and treatment-related immune molecular changes were analyzed. Administration of P1C4 produced a tumor growth delay on day 30 in 18% of the mice. In contrast, combination therapy produced the strongest tumor growth inhibition not only at the irradiated tumor but also at unirradiated tumor in 67% of the mice. Accordingly, lung metastasis in the COMB group was strongly reduced by 98%, with a significant survival benefit. Unirradiated tumor in mice in the COMB group significantly recruited CD8 + tumor-infiltrating lymphocytes with a moderate reduction of Treg, producing a significant increase in the CD8/Treg ratio. These results suggest that radiation enhances the efficacy of P1C4 treatment against distant metastasis as well as local control in osteosarcoma. Our data suggest that radiation therapy combined with dual checkpoint blockade may be a promising therapeutic option for osteosarcoma.</p></div

Effect of P1C4 and/or X-ray irradiation on overall survival by groups of the P1C4 (N = 6), RAD (N = 6), and COMB (N = 7).

<p>P-values were determined by the log-rank test with the adjustment by Holm method. Abbreviations: P1C4: Anti-PD-L1 and anti-CTLA-4 antibodies; COMB: Anti-PD-L1 and anti-CTLA-4 antibodies with X-ray irradiation; and RAD: X-ray irradiation.</p

Characteristics of intra-fraction prostate motion for 1929 timestamps.

<p>Two-dimensional scatter plots in the (A) axial, (B) sagittal, and (C) coronal planes, and histograms in the (D) right-left, (E) anterior-posterior, and (F) inferior-superior directions. The width of bins was 0.5 mm.</p

Changes in the tumor-infiltrated lymphocytes after treatment.

<p>(a) Representative plots of one animal per group for CD8 expression 20 days after tumor inoculation. (b) Representative plots of one animal per group for Treg expression 20 days after tumor inoculation. (c) Quantitative data of the proportion of CD8+ TILs. (d) Quantitative data of the proportion of FoxP3 + cells in CD4 + TILs. (e) Quantitative data of CD8 to Treg ratio. For CD8 analysis, the number of mice was 7, 11, 9, and 5 in the No Tx, P1C4, COMB, and RAD groups, respectively. Some of these mice were analyzed for Treg expression and CD8 to Treg ratio (No Tx; N = 5, P1C4; N = 5, COMB; N = 3, RAD; N = 4). P-values were determined by the Student t-test with Bonferroni correction; *, P<0.05, **, P<0.01. Bars show the median value. Abbreviations: No Tx: No treatment; P1C4: Anti-PD-L1 and anti-CTLA-4 antibodies; COMB: Anti-PD-L1 and anti-CTLA-4 antibodies with X-ray irradiation; and RAD: X-ray irradiation.</p

Effect of P1C4 and/or X-ray irradiation on tumor volume change in irradiated and unirradiated tumors.

<p>(a) Tumor volume change each day was normalized to volume on day 9 in the No Tx (N = 13), P1C4 (N = 11), X-ray irradiation (N = 9), and combination groups (N = 12). (b) Quantitative analysis of tumor volume change at day 21 and day 30. P-values were determined by Turkey’s honestly significant difference test. All data including the outlier were included in the statistical analysis. *, P<0.05. **, P<0.01. (c) Proportion of mice with partial response or complete response. The numbers in the pie chart indicate the number of mice. On day 30,2of 11 mice (18%) in the P1C4 alone group experienced a partial response whereas 8 of 12 mice (67%) in the combined therapy group had a partial response in the unirradiated tumor. On day 39, only 1 of 11 mice (9%) in the P1C4 group experienced complete response whereas 5 of 12 mice (42%) did so in the COMB group. <i>P</i>-values were determined by the Fisher’s exact test for comparison of the partial and complete response, and progressive disease between the P1C4 and COMB groups. Abbreviations: No Tx: No treatment; P1C4: Anti-PD-L1 and anti-CTLA-4 antibodies; COMB: Anti-PD-L1 and anti-CTLA-4 antibodies with X-ray irradiation; RAD: X-ray irradiation; IR-leg: Irradiated leg; UnIR-leg: Unirradiated leg, Vd: Volume on each day, Vint: Volume on the day of the initial treatment, CR: Complete response, PR: Partial response, and PD: Progressive disease.</p