Abscopal effect in maxillary sinus cancer: Insights from two case reports and a literature review.

BACKGROUND: The abscopal effect is a rare phenomenon in which localized radiation therapy triggers tumor reduction in nontargeted areas. Although this phenomenon has been observed in various cancer types, it remains infrequent and not fully understood. CASE: Two patients with maxillary sinus cancer with distant metastases were treated with radiotherapy after immune checkpoint inhibitor (ICI) therapy. The patients demonstrated abscopal effects following ICI therapy and radiotherapy, showing shrinkage in metastatic areas not directly targeted by radiation. CONCLUSION: This report was reviewed to examine the synergistic effects of ICI and radiotherapy and to identify optimal strategies to enhance the abscopal effect in clinical practice. It has also touched on various ongoing debates and clinical trials aimed at understanding and exploiting this effect to improve cancer treatment. The exact mechanisms and optimal treatment protocols remain areas for future research.

Differentiation Capacity of Porcine Skeletal Muscle-Derived Stem Cells as Intermediate Species between Mice and Humans.

Large animal experiments are important for preclinical studies of regenerative stem cell transplantation therapy. Therefore, we investigated the differentiation capacity of pig skeletal muscle-derived stem cells (Sk-MSCs) as an intermediate model between mice and humans for nerve muscle regenerative therapy. Enzymatically extracted cells were obtained from green-fluorescence transgenic micro-mini pigs (GFP-Tg MMP) and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN) fractions. The ability to differentiate into skeletal muscle, peripheral nerve, and vascular cell lineages was examined via in vitro cell culture and in vivo cell transplantation into the damaged tibialis anterior muscle and sciatic nerves of nude mice and rats. Protein and mRNA levels were analyzed using RT-PCR, immunohistochemistry, and immunoelectron microscopy. The myogenic potential, which was tested by Pax7 and MyoD expression and the formation of muscle fibers, was higher in Sk-DN cells than in Sk-34 cells but remained weak in the latter. In contrast, the capacity to differentiate into peripheral nerve and vascular cell lineages was significantly stronger in Sk-34 cells. In particular, Sk-DN cells did not engraft to the damaged nerve, whereas Sk-34 cells showed active engraftment and differentiation into perineurial/endoneurial cells, endothelial cells, and vascular smooth muscle cells, similar to the human case, as previously reported. Therefore, we concluded that Sk-34 and Sk-DN cells in pigs are closer to those in humans than to those in mice.

Local control correlates with overall survival in radiotherapy for early-stage non-small cell lung cancer: A systematic review.

PURPOSE: Local control (LC) is an important outcome of local cancer therapy, besides overall survival (OS). We conducted a comprehensive literature search to investigate whether a high LC rate contributes to good OS in radiotherapy for early-stage non-small cell lung cancer (ES-NSCLC). MATERIALS AND METHODS: Studies in patients receiving radiotherapy for peripheral ES-NSCLC, mainly staged as T1-2N0M0 were included for a systematic review. Relevant information was collected including, dose fractionation, T stage, median age, 3-year LC, cancer-specific survival (CSS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and OS. Correlations between outcomes and clinical variables were evaluated. RESULTS: After screening, 101 data points from 87 studies including 13,435 patients were selected for the quantitative synthesis. Univariate meta-regression analysis revealed that the coefficients between the 3-year LC and 3-year DFS, DMFS, CSS, and OS were 0.753 (95% confidence interval (CI): 0.307-1.199; p < 0.001), 0.360 (95% CI: 0.128-0.593; p = 0.002), 0.766 (95% CI: 0.489-1.044; p < 0.001), and 0.574 (95% CI: 0.275-0.822; p < 0.001), respectively. Multivariate analysis revealed that the 3-year LC (coefficient, 0.561; 95% CI: 0.254-0.830; p < 0.001) and T1 proportion (coefficient, 0.207; 95% CI: 0.030-0.385; p = 0.012) were significantly associated with the 3-year OS and CSS (coefficient for 3-year LC, 0.720; 95% CI: 0.468-0.972; p < 0.001 and T1 proportion, 0.002; 95% CI: 0.000-0.003; p = 0.012). Toxicities ≥ grade 3 were low (3.4%). CONCLUSIONS: Three-year LC was correlated with three-year OS in patients receiving radiotherapy for ES-NSCLC. A 5% increase in 3-year LC is expected to improve the 3-year CSS and OS rates by 3.8% and 2.8%, respectively.

Factors Involved in the Choice Between Thoracic and Abdominal Deep Inspiration Breath Holds During Left Breast Cancer Radiotherapy.

PURPOSE: Deep inspiration breath hold (DIBH) is used with adjuvant radiation therapy after left breast cancer surgery to reduce radiation dose to the heart. In this study we determined whether thoracic DIBH (T-DIBH) or abdominal DIBH (A-DIBH) should be selected based on patient background. METHODS: Three-dimensional conformal radiation therapy plans were created under the same conditions using free breathing (FB), T-DIBH, and A-DIBH CT scans of patients who had previously undergone treatment at our hospital. RESULTS: A-DIBH decreased the left lung dose compared to FB. In comparing T-DIBH and A-DIBH, the heart maximum and left lung doses were significantly lower in A-DIBH. The differences in the heart mean dose (Dmean) between FB, and T-DIBH and A-DIBH were correlated with the cardiothoracic ratio, heart volume, and left lung volume. The difference in the heart Dmean and the left lung dose of T-DIBH and A-DIBH correlated with the forced vital capacity (FVC). CONCLUSIONS: A-DIBH is preferable over T-DIBH with respect to the heart and left lung doses; however, with respect to the heart Dmean, T-DIBH was more effective in reducing the dose in some cases, and the FVC was a relevant factor in this study.

Effect on Heart and Lung Doses Reduction of Abdominal and Thoracic Deep Inspiratory Breath-hold Assuming Involved-field Radiation Therapy in Patients with Simulated Esophageal Cancer.

PURPOSE: The purpose of this study was to evaluate the lung and heart doses in volumetric-modulated arc therapy (VMAT) using involved-field irradiation in patients with middle-to-lower thoracic esophageal cancer during free breathing (FB), abdominal deep inspiratory breath-hold (A-DIBH), and thoracic DIBH (T-DIBH) images. METHODS: Computed tomography images of A-DIBH, T-DIBH, and FB from 25 patients with breast cancer were used to simulate patients with esophageal cancer. The irradiation field was set at an involved-field, and target and risk organs were outlined according to uniform criteria. VMAT optimization was performed, and lung and heart doses were evaluated. RESULTS: A-DIBH had a lower lung V20 Gy than FB and a lower lung V40 Gy, V30 Gy, V20 Gy than T-DIBH. The heart all dose indices were lower in T-DIBH than FB, and the heart V10 Gy was lower in A-DIBH than FB. However, the heart Dmean was comparable with A-DIBH and T-DIBH. CONCLUSIONS: A-DIBH had significant dose advantages for lungs compared to FB and T-DIBH, and the heart Dmean was comparable to T-DIBH. Therefore, when performing DIBH, A-DIBH is suggested for radiotherapy in patients with middle-to-lower thoracic esophageal cancer, excluding irradiation of the prophylactic area.

Dose and organ displacement comparisons with breast conservative radiotherapy using abdominal and thoracic deep-inspiration breath-holds: A comparative dosimetric study.

Deep-inspiration breath-hold (DIBH) reduces the radiation dose to the heart and lungs during breast radiotherapy in cancer. However, there is not enough discussion about suitable breathing methods for DIBH. Therefore, we investigated the radiation doses and organ and body surface displacement in abdominal DIBH (A-DIBH) and thoracic DIBH (T-DIBH). Free-breathing, A-DIBH, and T-DIBH computed tomography images of 100 patients were used. After contouring the targets, heart, and lungs, radiotherapy plans were created. We investigated the heart and lung doses, the associations between the heart and left lung displacements, and the thorax and abdominal surface displacements. No significant differences were observed in the target dose indices. However, the heart and lung doses were significantly lower in A-DIBH than in T-DIBH for all the indices; the mean heart and lung doses were 1.69 and 3.48 Gy, and 1.91 and 3.55 Gy in A-DIBH and T-DIBH, respectively. The inferior displacement of the heart and the left lung was more significant in A-DIBH. Therefore, inferior expansion of the heart and lungs may be responsible for the respective dose reductions. The abdominal surface displaced more than the thoracic surface in both A-DIBH and T-DIBH, and thoracic surface displacement was greater in T-DIBH than in A-DIBH. Moreover, A-DIBH can be identified because abdominal surface displacement was greater in A-DIBH than in T-DIBH. In conclusion, A-DIBH and T-DIBH could be distinguished by comparing the abdominal and thoracic surfaces of A-DIBH and T-DIBH, thereby ensuring the implementation of A-DIBH and reducing the heart and lung doses.

Examination of the dose distribution of volumetric modulated arc radiotherapy using a high-definition multi-leaf collimator for breast cancer patients with irradiated regional lymph nodes.

Background: A high-definition multi-leaf collimator (HD-MLC) with 5- and 10-mm fine MLCs is useful for radiotherapy. However, it is difficult to irradiate the mammary gland and supraclavicular region using a HD-MLC because of the narrow field of volumetric modulated arc radiotherapy (VMAT). Therefore, we aimed to evaluate the dose distribution of the VMAT dose using a HD-MLC in 15 patients with left breast cancer undergoing postoperative irradiation of breast and regional lymph nodes, including the internal mammary node. Materials and methods: The following four plans were generated: three-arc VMAT using HD-MLC (HD-VMAT), two tangential arcs and one-arc VMAT using HD-MLC (tHD-VMAT), three-dimensional conformal radiotherapy (3DCRT) using HD-MLC, and two-arc VMAT using the Millennium 120-leaf MLC (M-VMAT). We assessed the doses to the target volume and organs at risk. Results: The target dose distributions were higher for HD-VMAT than 3DCRT. There were no significant differences in the heart mean dose (Dmean) or lung volume receiving 20 Gy (V20 Gy) between HD-VMAT and 3DCRT. The heart Dmean and lung V20 Gy of tHD-VMAT were higher than those of HD-VMAT, and the heart Dmean of M-VMAT was higher than that of HD-VMAT. However, the target doses of tHD-VMAT, M-VMAT, and HD-VMAT were equivalent. Conclusions: In cases of the mammary gland and regional lymph node irradiation, including the internal mammary node in patients with left breast cancer, HD-VMAT was not inferior to M-VMAT and provided a better dose distribution to the target volume and organs at risk compared with 3DCRT and tHD-VMAT.

Quantitative Evaluation of the Reduced Capacity of Skeletal Muscle Hypertrophy after Total Body Irradiation in Relation to Stem/Progenitor Cells.

The effects of total body irradiation (TBI) to the capacity of skeletal muscle hypertrophy were quantified using the compensatory muscle hypertrophy model. We additionally assessed the responses of stem and/or progenitor cells in the muscles. A single TBI of 9.0, 5.0 and 2.5 Gy was delivered to C57BL/6 mice. Bone marrow stromal cells were obtained from GFP-Tg mice, and were injected into the tail vein of the recipient mice (1 × 106 cells/mouse), for bone marrow transplantation (BMT). Five weeks after TBI, the mean GFP-chimerism in the blood was 96 ± 0.8% in the 9 Gy, 83 ± 3.9% in the 5 Gy, and 8.4 ± 3.4% in the 2.5 Gy groups. This implied that the impact of 2.5 Gy is quite low and unavailable as the BMT treatment. Six weeks after the TBI/BMT procedure, muscle hypertrophy was induced in the right plantaris muscle by surgical ablation (SA) of the synergist muscles (gastrocnemius and soleus), and the contralateral left side was preserved as a control. The muscle hypertrophy capacity significantly decreased by 95% in the 9 Gy, 48% in the 5 Gy, and 36% in the 2.5 Gy groups. Furthermore, stem/progenitor cells in the muscle were enzymatically isolated and fractionated into non-sorted bulk cells, CD45-/34-/29+ (Sk-DN), and CD45-/34+ (Sk-34) cells, and myogenic capacity was confirmed by the presence of Pax7+ and MyoD+ cells in culture. Myogenic capacity also declined significantly in the Bulk and Sk-DN cell groups in all three TBI conditions, possibly implying that skeletal muscles are more susceptible to TBI than bone marrow. However, interstitial Sk-34 cells were insusceptible to TBI, retaining their myogenic/proliferative capacity.

Comparing the toxicity and disease control rate of radiotherapy for prostate cancer between salvage settings after high-intensity focused ultrasound therapy and initial settings.

The purpose of this retrospective study was to compare the toxicity and disease control rate of radiotherapy for prostate cancer in salvage settings after high-intensity focused ultrasound (HIFU) therapy (HIFU cohort) with those in radical settings (non-HIFU cohort). From 2012 to 2020, 215 patients were identified for this study and 17 were treated in the salvage settings after HIFU. The median follow-up time was 34.5 months (range: 7-102 months, inter-quartile range [IQR]: 16-64 months). Genitourinary (GU) and gastrointestinal (GI) adverse events were evaluated in acute and late periods with Common Terminology Criteria for Adverse Events version 5, and the rates of biochemical-clinical failure free survival (BCFS) and overall survival (OS) were estimated. The cumulative incidence of late GU Grade 2 or greater toxicity after five years was significantly different between the non-HIFU and HIFU cohorts with rates of 7.3% and 26.2%, respectively (P = 0.03). Regarding GI Grade 2 or greater toxicity, there was no significant difference between the two cohorts. The 5y-BCFS was 84.2% in the non-HIFU cohort and 69.5% in the HIFU cohort with no significant difference (P = 0.10) and the 5y-OS was 95.9% and 92.3%, respectively (P = 0.47). We concluded that the possibility of increased late GU Grade 2 or greater should be considered when applying salvage radiotherapy for local recurrence after HIFU.

Peripheral Nerve Regeneration Using a Cytokine Cocktail Secreted by Skeletal Muscle-Derived Stem Cells in a Mouse Model.

Severe peripheral nerve injury, which does not promise natural healing, inevitably requires clinical treatment. Here, we demonstrated the facilitation effect of peripheral nerve regeneration using a cytokine cocktail secreted by skeletal muscle-derived stem cells (Sk-MSCs). Mouse sciatic nerve was transected with a 6 mm gap and bridged collagen tube, and the culture supernatant of Sk-MSCs with 20% adult mouse serum (AMS)/Iscove's modified Dulbecco's medium (IMDM) was administered into the tube immediately after the operation, followed by an injection once a week for six weeks through the skin to the surrounding tube of the cytokine (CT) group. Similarly, 20% AMS/IMDM without cytokines was administered to the non-cytokine control (NT) group. Tension recovery in the plantar flexor muscles via electrical stimulation at the upper portion of the damaged nerve site, as well as the numerical recovery of axons and myelinated fibers at the damaged site, were evaluated as an index of nerve regeneration. Specific cytokines secreted by Sk-MSCs were compared with damaged sciatic nerve-derived cytokines. Six weeks after operation, significantly higher tension output and numerical recovery of the axon and myelinated fibers were consistently observed in the CT group, showing that the present cytokine cocktail may be a useful nerve regeneration acceleration agent. We also determined 17 candidate factors, which are likely included in the cocktail.

Dosimetric study of whole-brain irradiation with high-energy photon beams for dose reduction to the scalp.

OBJECTIVE: To evaluate the efficiency of high-energy photons for mitigating alopecia due to whole-brain irradiation (WBRT). METHODS: Planning CT data from 10 patients who received WBRT were collected. We prepared 4 WBRT plans that used 6 or 15 MV photon beams, with or without use of a field-in-field (FiF) technique, and compared outcomes using a treatment planning system. The primary outcome was dose parameters to the scalp, including the mean dose, maximum dose, and dose received to 50% scalp(D50%). Secondary outcomes were minimum dose to the brain surface. RESULTS: Using FiF, the mean doses were 24.4-26.0 and 22.4-24.1 Gy, and the maximum doses were 30.5-32.1 and 28.5-30.8 Gy for 6 and 15 MV photon beams, respectively. Without FiF, the mean doses were 24.6-26.9 and 22.6-24.5 Gy, and the maximum doses were 30.8-34.6 and 28.6-32.4 Gy for 6 and 15 MV photon beams. The 15 MV plan resulted in a lower scalp dose for each dose parameter (p < 0.001). Using FiF, the minimum doses to the brain surface for the 6 and 15 MV plans were 28.9 ± 0.440 and 29.0 ± 0.557 Gy, respectively (p = 0.70). Without FiF, the minimum doses to the brain surface for the 6 and 15 MV plans were 28.9 ± 0.456 and 29.0 ± 0.529, respectively (p = 0.66). CONCLUSION: Compared with the 6 MV plan, the 15 MV plan achieved a lower scalp dose without impairing the brain surface dose. ADVANCES IN KNOWLEDGE: High-energy photon WBRT may mitigate alopecia of patients who receiving WBRT.

Cutaneous Metastases from Testicular Diffuse Large B-cell Malignant Lymphoma and Bowen Disease: 18F-FDG PET-CT Findings.

Here, we report the case of cutaneous metastases from testicular diffuse large B-cell malignant lymphoma (DLBCL) concurrent with Bowen disease evaluated with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT). A 60-year-old male underwent orchiectomy to remove his left testicle because of DLBCL. Multiple skin lesions appeared 1 month postoperatively. Furthermore, an intractable erythematous plaque localized to the right lower leg was present from 2 years before the operation. 18F-FDG PET-CT images revealed multiple skin lesions with marked FDG uptakes in the face, neck, and thigh of this patient, as well as a lower leg lesion with minimal FDG uptake. Biopsy of both lesions revealed cutaneous metastases from DLBCL and Bowen disease (BD) of the lower leg lesion. 18F-FDG PET-CT images following chemotherapy and resection of BD demonstrated no FDG uptake.

Dosimetric evaluation of the feasibility of stereotactic body radiotherapy for primary lung cancer with lobe-specific selective elective nodal irradiation.

More than 10% of all patients treated with stereotactic body radiotherapy (SBRT) for primary lung cancer develop regional lymph node recurrence. We evaluated the dosimetric feasibility of SBRT with lobe-specific selective elective nodal irradiation (ENI) on dose-volume histograms. A total of 21 patients were treated with SBRT for Stage I primary lung cancer between January 2010 and June 2012 at our institution. The extents of lobe-specific selective ENI fields were determined with reference to prior surgical reports. The ENI fields included lymph node stations (LNS) 3 + 4 + 11 for the right upper lobe tumors, LNS 7 + 11 for the right middle or lower lobe tumors, LNS 5 + 11 for the left upper lobe tumors, and LNS 7 + 11 for the left lower lobe tumors. A composite plan was generated by combining the ENI plan and the SBRT plan and recalculating for biologically equivalent doses of 2 Gy per fraction, using a linear quadratic model. The V20 of the lung, D(1cm3) of the spinal cord, D(1cm3) and D(10cm3) of the esophagus and D(10cm3) of the tracheobronchial wall were evaluated. Of the 21 patients, nine patients (43%) could not fulfill the dose constraints. In all these patients, the distance between the planning target volume (PTV) of ENI (PTVeni) and the PTV of SBRT (PTVsrt) was ≤2.0 cm. Of the three patients who developed regional metastasis, two patients had isolated lymph node failure, and the lymph node metastasis was included within the ENI field. When the distance between the PTVeni and PTVsrt is >2.0 cm, SBRT with selective ENI may therefore dosimetrically feasible.