Purpose: It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method. Materials and Methods: DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed. Results: Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues. Conclusion This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Purpose: It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method. Materials and Methods: DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed. Results: Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues. Conclusion This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Purpose: It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method. Materials and Methods: DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed. Results: Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues. Conclusion This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

Tumor microenvironment is intrinsically hypoxic with abundant hypoxia-inducible factors-1α (HIF-1α), a primary regulator of the cellular response to hypoxia and various stresses imposed on the tumor cells. HIF-1α increases radioresistance and chemoresistance by reducing DNA damage, increasing repair of DNA damage, enhancing glycolysis that increases antioxidant capacity of tumors cells, and promoting angiogenesis. In addition, HIF-1α markedly enhances drug efflux, leading to multidrug resistance. Radiotherapy and certain chemotherapy drugs evoke profound anti-tumor immunity by inducing immunologic cell death that release tumor-associated antigens together with numerous pro-immunological factors, leading to priming of cytotoxic CD8+ T cells and enhancing the cytotoxicity of macrophages and natural killer cells. Radiotherapy and chemotherapy of tumors significantly increase HIF-1α activity in tumor cells. Unfortunately, HIF-1α effectively promotes various immune suppressive pathways including secretion of immune suppressive cytokines, activation of myeloid-derived suppressor cells, activation of regulatory T cells, inhibition of T cells priming and activity, and upregulation of immune checkpoints. Consequently, the anti-tumor immunity elevated by radiotherapy and chemotherapy is counterbalanced or masked by the potent immune suppression promoted by HIF-1α. Effective inhibition of HIF-1α may significantly increase the efficacy of radiotherapy and chemotherapy by increasing radiosensitivity and chemosensitivity of tumor cells and also by upregulating anti-tumor immunity.

Objective: Classification guides the surgical approach and predicts prognosis. However, existing classifications of spinal schwannomas often result in a high ‘unclassified’ rate. Here, we aim to develop a new comprehensive classification for spinal schwannomas based on their presumed origin. We compared the new classification with the existing classifications regarding the rate of ‘unclassified’. Finally, we assessed the surgical strategies, outcomes, and complications according to each type of the new classification. Methods: A new classification with 9 types was created by analyzing the anatomy of spinal nerves and the origin of significant tumor portions and cystic components in preoperative magnetic resonance images. A total of 482 patients with spinal schwannomas were analyzed to compare our new classification with the existing classifications. We defined ‘unclassified’ as the inability to classify a patient with spinal schwannoma using the classification criteria. Surgical approaches and outcomes were also aligned with our new classification. Results: Our classification uniquely reported no ‘unclassified’ cases, indicating full applicability. Also, the classification has demonstrated usefulness in predicting the surgical outcome with the approach planned. Gross total removal rates reached 88.0% overall, with type 1 and type 2 tumors at 95.3% and 96.0% respectively. The approach varied with tumor type, with laminectomy predominantly used for types 1, 2, and 9, and facetectomy with posterior fixation used for type 3 tumors. Conclusion The new classification for spinal schwannomas based on presumed origin is applicable to all spinal schwannomas. It could help plan a surgical approach and predict its outcome, compared with existing classifications.

Purpose: Conventional gonadal shields are manufactured in standardized sizes and shapes and do not conform to individual testicular contours, causing discomfort. We developed a novel patientspecific gonadal shield using thermoplastic sheets and tested its feasibility through dosimetric evaluations. Methods: During the computed tomography simulation, custom lead shields were fabricated using thermoplastic sheets that were molded to the testicular shape of the patient. The shielding efficacy was evaluated using optically stimulated luminescent dosimeters (OSLDs) for point dose measurements. Results: The thermoplastic sheet was molded to fit closely to the skin with a minimal air gap of approximately 8.4 cm³, providing comfort to the patient during treatment. The patient-specific shield effectively reduced the surface dose from 28 cGy to less than 15 cGy. By combining the OSLDs located in the same row and calculating the mean dose value, a shielding effect was achieved with a maximum dose reduction of 56.1%. Conclusions Customized gonadal shields were successfully created using thermoplastic sheets to minimize patient discomfort during application. However, further improvements in lead shield fabrication are needed to ensure full conformity.

Purpose: This study investigated the dose perturbation according to the size of the sensitive volume in the dosimeter in small-field dosimetry. Methods: The dose profiles with different field sizes were measured using three different dosimeters: the CC13, Razor ion chamber, and Edge solid-state detector. Both the open and wedged beams with different field sizes were employed in the measurement. The profiles were measured in a water phantom at maximum dose depths of 5, 10, and 20 cm. The penumbra and width of the open-beam profiles were compared according to the types of the dosimeters and beam. The dose fall-off between the peak and 20% dose was evaluated for the wedged beam profiles. Results: In the open-beam measurement, the fall-off of the profile was steeper with the Edge detector, which has the smallest sensitive volume. Meanwhile, the dose in the out-of-field region was the smallest with the Edge detector. The widths of the penumbra were 6.10, 4.47, and 4.03 mm for the profile of the 3×3 cm 2 field measured by the CC13 chamber, Razor chamber, and Edge detector, respectively. The width of the profile was not changed even if different dosimeters were used in the measurement. The wedged beam profiles showed more clear peaks at the field edge when a smaller dosimeter was used. Conclusions The results demonstrate the necessity of dosimeters with a small sensitive volume for measuring a small-field beam or a steep dose gradient.

Purpose: This study evaluated various methods for determining the half-value layer (HVL) of kilovoltage (kV) beams produced by the Varian TrueBeam STx on-board imager. By comparing these methods with the standard ionization chamber approach, the study aimed to identify practical solutions for HVL determination and dosimetric characterization of kV beams, particularly in resource-limited settings. Methods: HVLs for kV beams (40–140 kVp) were measured using an Exradin A12 ionization chamber and a Piranha MULTI meter. The ionization chamber measurements adhered to American Association of Physicists in Medicine Task Group 61 guidelines and served as the reference standard. Additionally, HVL values were calculated using two model-based approaches: SpekPy (a Python-based tool) and Monte Carlo (MC) simulations using Geant4 and GATE. The results from these methods were compared to assess consistency and reliability. Results: Deviations across all methods were generally below 4%. At 40 kV, the most significant discrepancies were attributed to lower signal levels from the ionization chamber. The consistency between the model-based methods and experimental measurements demonstrates the reliability of these alternative approaches for HVL determination. Conclusions Although the ionization chamber remains the gold standard, the Piranha MULTI meter and model-based methods, i.e., SpekPy and MC simulations, have shown promise as viable alternatives, especially in resource-constrained settings. These in silico approaches also offer advantages in convenience and accuracy, supporting their potential for broader future applications.