Post-Irradiation Recovery of B14-150 Fibrosarcoma Cells after Combined Irradiation with Low and High Linear Energy Transfer.

The use of radiation with low and high linear energy transfer (LET) in the same treatment regimen is promising in terms of increasing the efficiency and reducing the severity of radiation complications. Here we studied combined effect of protons (LET≈3 keV/µm) and heavy recoils (HR) induced by 14.5 MeV neutrons (LET≈290 keV/µm) on B14-150 fibrosarcoma cells. Comparison of the 4 irradiation schemes with different high-LET/low-LET dose ratios and the irradiation sequences revealed higher effectiveness of the combined action in the HR→protons sequence and with increasing HR dose contribution to 40% of the total dose. The observed effects were due to differences in the recovery of damages induced in cells by radiations with low and high LET.

Intracellular delivery and passive tumor targeting of a self-assembled nanogel containing carborane clusters for boron neutron capture therapy.

Boron neutron capture therapy, based on the release of thermal neutron irradiation from boron, is a targeted radiation therapy for cancer. Targeted and sufficient accumulation of boron in tumor cells to achieve cytotoxic efficacy and reduce off-target effects remains a challenge. Carborane has been investigated for use as a delivery agent in boron neutron capture therapy because of its high boron content and chemical stability; however, it is cytotoxic, making safe delivery difficult. The aim of this study was to investigate the potential of carborane-bearing pullulan nanogels to safely and effectively deliver boron to tumor cells in vitro and in vivo and, consequently, assess their potential as a boron neutron capture therapeutic. Murine fibrosarcoma cells (CMS5a) were used for in vitro investigations of nanogel cytotoxicity, cell uptake. A mouse fibrosarcoma xenograft model was used to investigate the bio-distribution of nanogels after intravenous administration. The nanogels produced no apparent cytotoxicity and underwent cell uptake in CMS5a cells after a 24 h incubation at up to 2000 µg/mL and 400 µg/mL, respectively. The internalized nanogels were localized around the nuclear membrane. The nanogels were administered intravenously to mice bearing fibrosarcoma xenografts. Nanogel tumor localization likely occurred through the enhanced permeation and retention effect. The nanogels successfully reduced the cytotoxicity of carborane, were internalized into tumor cells, acted as a dual-delivery therapeutic and accumulated in tumors in vivo. Consequently, they demonstrate significant potential as a boron neutron capture therapeutic.

Successful treatment of a rare case of ameloblastic fibrosarcoma with radiation therapy.

Sarcomas are rare diseases of the head and neck region, representing around 1% of all malignancies. Amongst them, ameloblastic fibrosarcoma (AFS) is of even greater rarity, with less than 100 cases reported in the literature. Consequently, no standard treatment or guidelines have been made available. Surgery is often performed as primary therapy, but may be limited due to anatomical or functional reasons. We present a case of AFS successfully treated by postoperative radiation therapy. A detailed case study is provided, followed by a review of the English-language literature focusing on the role of radiation therapy.

Electron Paramagnetic Resonance pO2 Image Tumor Oxygen-Guided Radiation Therapy Optimization.

Modern standards for radiation treatment do not take into account tumor oxygenation for radiation treatment planning. Strong correlation between tumor oxygenation and radiation treatment success suggests that oxygen-guided radiation therapy (OGRT) may be a promising enhancement of cancer radiation treatment. We have developed an OGRT protocol for rodents. Electron paramagnetic resonance (EPR) imaging is used for recording oxygen maps with high spatial resolution and excellent accuracy better than 1 torr. Radiation is delivered with an animal intensity modulated radiation therapy (IMRT) XRAD225Cx micro-CT/ therapy system. The radiation plan is delivered in two steps. First, a uniform 15% tumor control dose (TCD15) is delivered to the whole tumor. In the second step, an additional booster dose amounting to the difference between TCD98 and TCD15 is delivered to radio-resistant, hypoxic tumor regions. Delivery of the booster dose is performed using a multiport conformal beam protocol. For radiation beam shaping we used individual radiation blocks 3D-printed from tungsten infused ABS polymer. Calculation of beam geometry and the production of blocks is performed next to the EPR imager, immediately after oxygen imaging. Preliminary results demonstrate the sub-millimeter precision of the radiation delivery and high dose accuracy. The efficacy of the radiation treatment is currently being tested on syngeneic FSa fibrosarcoma tumors grown in the legs of C3H mice.

Use of an electronic brachytherapy surface applicator to treat an epiglottal fibrosarcoma in a dog.

Presented is the case of an epiglottal fibrosarcoma in a dog. The location of the mass resulted in challenges in the delivery of adequate dose to the tumor, and herein we describe the treatment using an electronic brachytherapy source. The treatment consisted of four Gy fractions, twice daily for a total of 10 fractions (40 Gy total). Visual reevaluation two weeks after treatment supported adequate spatial dose delivery, and the patient was reportedly improved six weeks after treatment. We demonstrate that plesiotherapy using an electronic brachytherapy device is feasible and may be useful in the treatment of carefully selected veterinary tumors.

Evaluation of (188)Re-labeled NGR-VEGI protein for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts.

Vascular endothelial growth inhibitor (VEGI) is an anti-angiogenic protein, which includes three isoforms: VEGI-174, VEGI-192, and VEGI-251. The NGR (asparagine-glycine-arginine)-containing peptides can specifically bind to CD13 (Aminopeptidase N) receptor which is overexpressed in angiogenic blood vessels and tumor cells. In this study, a novel NGR-VEGI fusion protein was prepared and labeled with (188)Re for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts. Single photon emission computerized tomography (SPECT) imaging results revealed that (188)Re-NGR-VEGI exhibits good tumor-to-background contrast in CD13-positive HT-1080 tumor xenografts. The CD13 specificity of (188)Re-NGR-VEGI was further verified by significant reduction of tumor uptake in HT-1080 tumor xenografts with co-injection of the non-radiolabeled NGR-VEGI protein. The biodistribution results demonstrated good tumor-to-muscle ratio (4.98 ± 0.25) of (188)Re-NGR-VEGI at 24 h, which is consistent with the results from SPECT imaging. For radiotherapy, 18.5 MBq of (188)Re-NGR-VEGI showed excellent tumor inhibition effect in HT-1080 tumor xenografts with no observable toxicity, which was confirmed by the tumor size change and hematoxylin and eosin (H&E) staining of major mouse organs. In conclusion, these data demonstrated that (188)Re-NGR-VEGI has the potential as a theranostic agent for CD13-targeted tumor imaging and therapy.

Impact of infiltrative growth on the outcome of patients with undifferentiated pleomorphic sarcoma and myxofibrosarcoma.

BACKGROUND AND OBJECTIVES: Infiltrative growth, frequently observed in undifferentiated pleomorphic sarcoma (UPS) and myxofibrosarcoma (MFS), is often associated with a positive surgical margin as well as a local failure. The purpose of our study was to determine whether the radiographic growth patterns were associated with the outcomes of patients with UPS and MFS. METHODS: We reviewed 89 patients diagnosed with UPS or MFS and underwent initial surgery at our institute between 1994 and 2011. Growth patterns were assessed radiographically on preoperative MRI. Clinicopathological factors were collected and uni- and multivariate analyses were performed for survival. RESULTS: Infiltrative growth was observed in 21 patients (24%), which correlated with superficial tumors and positive surgical margin. Infiltrative growth correlated with poor disease-specific and distant failure-free survivals relative to non-infiltrative growth. Multivariate analysis confirmed that these factors remained as significant factors. Patients with non-infiltrative tumors resected inadequately exhibited slightly more favorable local control with postoperative radiotherapy, although no clinical benefit was seen for those with infiltrative tumors. CONCLUSIONS: Infiltrative growth was an adverse prognostic factor for not only local control, but also disease-specific and metastasis-free survival in patients with UPS and MFS. Radiotherapy could not salvage inadequately resected infiltrative tumors.

A novel APC gene mutation associated with a severe phenotype in a patient with Turcot syndrome.

Turcot syndrome is a rare inherited condition of colonic polyposis associated with central nervous system tumors. We report a patient with a novel adenomatous polyposis coli gene mutation leading to a severe phenotype including medulloblastoma, low-grade fibromyxoid sarcoma following cranial radiation, pilomatrixomas, colonic adenomas, and abdominal desmoid tumor following colectomy, all of which were successfully treated. Multiple tumors may be seen in patients with Turcot syndrome but the occurrence of sarcomas is rare. This case highlights the importance of close follow-up for patients with Turcot syndrome and the importance of a broad differential diagnosis in evaluating a condition in which multiple tumors are frequently seen.

Is Perioperative Radiotherapy Effective in Preventing Local Recurrence in Myxofibrosarcoma?

Background: Myxofibrosarcoma (MFS) is a rare type of soft tissue sarcoma that is locally aggressive and has a high risk of recurrence. The effectiveness of perioperative radiotherapy (RT) in preventing local recurrence (LR) of MFS remains uncertain. This retrospective study aimed to evaluate the impact of perioperative radiotherapy on local recurrence in patients with MFS. Methods: A total of 75 patients diagnosed with MFS and treated at a single institution were included in the study. Patient data, including demographics, tumor characteristics, and treatment variables, were collected from electronic medical records. The primary endpoint was the occurrence of local recurrence. Results: Among the patients, 25/75 (33.3%) received radiation therapy, while 50/75 (66.7%) did not. Local recurrence in the radiated group was 28% (7/25) compared to 36% (18/50) in the non-irradiated group (p = 0.20). The LR rate trended higher in patients who received RT postoperatively (adjuvant) (6/12, 50%) than preoperatively (neoadjuvant) (1/13, 7.6%) (p = 0.124). Of the 54 patients with negative margins, the local recurrence rate was lower in the radiated group (1/12, 8.33) than the non-irradiated group (9/36, 25%) (p = 0.034). A subgroup analysis based on tumor grade did not reveal any significant differences in recurrence rates between the radiated and non-irradiated groups. Furthermore, there was no significant difference in recurrence rates between the irradiated and non-irradiated groups at the one-year (p = 0.32), two-year (p = 0.24), and five-year (p = 0.32) follow-up marks. Conclusion: Although radiotherapy demonstrated a trend toward reduction in recurrence rates in patients with MFS in this study, the observed difference did not reach statistical significance. Neoadjuvant radiation appears to be more effective than adjuvant radiation. However, there was a significant reduction in recurrence in patients with negative margins who received radiation demonstrating that effective surgical resection continues to be the most important intervention in patients with myxofibrosarcoma. Level of Evidence: III.

Phase 2 study of preoperative image-guided intensity-modulated radiation therapy to reduce wound and combined modality morbidities in lower extremity soft tissue sarcoma.

BACKGROUND: This study sought to determine if preoperative image-guided intensity-modulated radiotherapy (IG-IMRT) can reduce morbidity, including wound complications, by minimizing dose to uninvolved tissues in adults with lower extremity soft tissue sarcoma. METHODS: The primary endpoint was the development of an acute wound complication (WC). IG-IMRT was used to conform volumes to avoid normal tissues (skin flaps for wound closure, bone, or other uninvolved soft tissues). From July 2005 to June 2009, 70 adults were enrolled; 59 were evaluable for the primary endpoint. Median tumor size was 9.5 cm; 55 tumors (93%) were high-grade and 58 (98%) were deep to fascia. RESULTS: Eighteen (30.5%) patients developed WCs. This was not statistically significantly different from the result of the National Cancer Institute of Canada SR2 trial (P = .2); however, primary closure technique was possible more often (55 of 59 patients [93.2%] versus 50 of 70 patients [71.4%]; P = .002), and secondary operations for WCs were somewhat reduced (6 of 18 patients [33%] versus 13 of 30 patients [43%]; P = .55). Moderate edema, skin, subcutaneous, and joint toxicity was present in 6 (11.1%), 1 (1.9%), 5 (9.3%), and 3 (5.6%) patients, respectively, but there were no bone fractures. Four local recurrences (6.8%, none near the flaps) occurred with median follow-up of 49 months. CONCLUSIONS: The 30.5% incidence of WCs was numerically lower than the 43% risk derived from the National Cancer Institute of Canada SR2 trial, but did not reach statistical significance. Preoperative IG-IMRT significantly diminished the need for tissue transfer. RT chronic morbidities and the need for subsequent secondary operations for WCs were lowered, although not significantly, whereas good limb function was maintained.

Radiosensitizing effect of intratumoral interleukin-12 gene electrotransfer in murine sarcoma.

BACKGROUND: Interleukin-12 (IL-12) based radiosensitization is an effective way of tumor treatment. Local cytokine production, without systemic shedding, might provide clinical benefit in radiation treatment of sarcomas. Therefore, the aim was to stimulate intratumoral IL-12 production by gene electrotransfer of plasmid coding for mouse IL-12 (mIL-12) into the tumors, in order to explore its radiosensitizing effect after single or multiple intratumoral gene electrotransfer. METHODS: Solid SA-1 fibrosarcoma tumors, on the back of A/J mice, were treated intratumorally by mIL-12 gene electrotransfer and 24 h later irradiated with a single dose. Treatment effectiveness was measured by tumor growth delay and local tumor control assay (TCD(50) assay). With respect to therapeutic index, skin reaction in the radiation field was scored. The tumor and serum concentrations of cytokines mIL-12 and mouse interferon γ (mIFNγ) were measured. Besides single, also multiple intratumoral mIL-12 gene electrotransfer before and after tumor irradiation was evaluated. RESULTS: Single intratumoral mIL-12 gene electrotransfer resulted in increased intratumoral but not serum mIL-12 and mIFNγ concentrations, and had good antitumor (7.1% tumor cures) and radiosensitizing effect (21.4% tumor cures). Combined treatment resulted in the radiation dose-modifying factor of 2.16. Multiple mIL-12 gene electrotransfer had an even more pronounced antitumor (50% tumor cures) and radiosensitizing (86.7% tumor cures) effect. CONCLUSIONS: Single or multiple intratumoral mIL-12 gene electrotransfer resulted in increased intratumoral mIL-12 and mIFNγ cytokine level, and may provide an efficient treatment modality for soft tissue sarcoma as single or adjuvant therapy to tumor irradiation.

[Sclerosing epithelioid fibrosarcoma of the paravertebral column. Case report and literature review]. / Fibrosarcoma epitelioide esclerosante a nivel paraespinal. Caso clínico y revisión de la literatura.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare variant of low-grade fibrosarcoma, with specific histological and immunohistochemical features and a poor prognosis. We report a case of SEF of the paravertebral column in a 49-year old male who presented a paraspinal mass with extension into the L4-L5 neural foramen and invasion of the L5 nerve root. Histology of the tumourectomy specimen and its immunohistochemical study led to the diagnosis of SEF. This case was particularly unusual due to its paravertebral column location and, despite its low grade, illustrates the malignant potential of SEF.

Ultrasound-stimulated microbubbles enhanced vascular disruption in fractionated radiotherapy-treated tumours via ASMase activation.

Recent studies have indicated that radiotherapy affects tumour vasculature as well as tumour cells. The use of ultrasound-stimulated microbubbles (USMB) can potentially enhance the effects of radiotherapy through the activation of the acid sphingomyelinase [ASMase or sphingomyelin phosphodiesterase 1 (SMPD1)]-ceramide pathway. ASMase knockout (ASMase-/-) and wild-type (WT) mice bearing fibrosarcoma (MCA/129 tumour line) were treated with 10 Gy or 20 Gy in five fractions alongside or independently of USMB treatments. The results indicated that tumour responses to fractionated radiotherapy (fXRT) were enhanced when fXRT was coupled with USMB as part of the treatment regimen. Sphingosine-1-phosphate (S1P)-treated mice and ASMase-/- mice demonstrated radioresistance against fXRT alone, whereas only ASMase-/- mice showed radioresistance against fXRT treatment alone and when combined with USMB. Results indicated that in WT and S1P-treated cohorts, the use of USMB with fXRT enhanced the tumour response compared to use of USMB or fXRT alone. Although in WT and S1P-treated cohorts, there was enhanced vascular disruption, ASMase-/- cohorts demonstrated no significant vascular disruption, indicating the importance of ASMase in facilitating vascular changes in response to fXRT and USMB treatment.

Radiolabeled iodohypericin as tumor necrosis avid tracer: diagnostic and therapeutic potential.

It is estimated that 30-80% of solid tumor mass represents necrotic tissue that consists out of a significant number of dead and dying cells. The fact that these necrotic zones are restricted to dysplastic and malignant tissue and are rarely present in normal tissue makes necrosis an interesting target both for cancer diagnosis and therapy. In this study, the avidity of hypericin, [(123) I]iodohypericin and [(131) I]iodohypericin to tumor necrosis was explored for both diagnosis and therapy of experimental malignancies. The intratumoral distribution in RIF-1 tumors was investigated by means of fluorescence microscopy (hypericin) and autoradiography ([(123) I]iodohypericin). Results show high uptake of the tracers in necrosis at 24 hr, lasting for up to 72 hr p.i. Ratios of activity of [(123) I]iodohypericin in necrotic tissue over viable tumor reached up to 19.63 ± 4.66, correlating with 9.20% ID/g in necrosis. Nude mice bearing RIF-1 tumors that received three injections of 300 µCi over a 3-week treatment period showed stabilization in tumor growth for 5 days, as measured by caliper and micro-positron emission tomography using [(18) F]fluorodeoxyglucose. Based on these results, we suggest the potentials of radiolabeled hypericin (1) in diagnostic aspects including prognosis or staging assessment of bulky necrotic cancers, monitoring of treatments and therapeutic follow-up; and (2) in cancer treatment based on tumor necrosis. In conclusion, we showed that hypericin radiolabeled with iodine is a necrosis avid tracer that can be used both as a tumor diagnostic and therapeutic.

In vivo sensitized and in vitro activated B cells mediate tumor regression in cancer adoptive immunotherapy.

Adoptive cellular immunotherapy utilizing tumor-reactive T cells has proven to be a promising strategy for cancer treatment. However, we hypothesize that successful treatment strategies will have to appropriately stimulate not only cellular immunity, but also humoral immunity. We previously reported that B cells in tumor-draining lymph nodes (TDLNs) may function as APCs. In this study, we identified TDLN B cells as effector cells in an adoptive immunotherapy model. In vivo primed and in vitro activated TDLN B cells alone mediated effective (p < 0.05) tumor regression after adoptive transfer into two histologically distinct murine pulmonary metastatic tumor models. Prior lymphodepletion of the host with either chemotherapy or whole-body irradiation augmented the therapeutic efficacy of the adoptively transferred TDLN B cells in the treatment of s.c. tumors as well as metastatic pulmonary tumors. Furthermore, B cell plus T cell transfers resulted in substantially more efficient antitumor responses than B cells or T cells alone (p < 0.05). Activated TDLN B cells conferred strong humoral responses to tumor. This was evident by the production of IgM, IgG, and IgG2b, which bound specifically to tumor cells and led to specific tumor cell lysis in the presence of complement. Collectively, these data indicate that in vivo primed and in vitro activated B cells can be employed as effector cells for cancer therapy. The synergistic antitumor efficacy of cotransferred activated B effector cells and T effector cells represents a novel approach for cancer adoptive immunotherapy.

Modulation of tumor hypoxia by topical formulations with vasodilators for enhancing therapy.

Tumor hypoxia is a well known therapeutic problem which contributes to radioresistance and aggressive tumor characteristics. Lack of techniques for repeated measurements of tumor oxygenation (pO(2), partial pressure of oxygen) has restricted the optimization of hypoxia modifying methods and their efficacious application with radiotherapy. We have investigated a non-invasive method to enhance tissue pO(2) of peripheral tumors using topical application of formulations with BN (Benzyl Nicotinate), a vasodilator, and have used EPR (Electron Paramagnetic Resonance) oximetry to follow its effect on tumor oxygenation.We incorporated 2.5% BN in both hydrogel and microemulsions and investigated the effects on pO(2) of subcutaneous RIF-1 (Radiation Induced Fibrosarcoma) tumors in C3H mice. The experiments were repeated for five consecutive days. The topical application of BN in hydrogel led to a significant increase from a pre-treatment pO(2) of 9.3 mmHg to 11 - 16 mmHg at 30 - 50 min on day 1. However, the magnitude and the time of significant increase in pO(2) decreased with repeated topical applications. The BN in a microemulsion resulted in a significant increase from a baseline pO(2) of 8.8 mmHg to 13 - 18 mmHg at 10 - 50 min on day 1. Experiments repeated on subsequent days showed a decline in the magnitude of pO(2) increase on repeated applications. No significant change in tumor pO(2) was observed in experiments with formulations without BN (vehicle only).EPR oximetry was successfully used to follow the temporal changes in tumor pO(2) during repeated applications for five consecutive days. This approach can be potentially used to enhance radiotherapeutic outcome by scheduling radiation doses when an increase in tumor pO(2) is observed after topical applications of BN formulations.

The importance of clear margins in myxofibrosarcoma: Improving local control by means of staged resection and reconstruction.

INTRODUCTION: Myxofibrosarcomas are associated with a locally infiltrative growth pattern, making a clear-margin resection margin challenging. This leads to high local recurrence rates. While immediate wound closure and adjuvant radiotherapy has been proposed to mitigate incomplete excisions, we present our experience treating myxofibrosarcomas with staged excisions until clear margins are obtained, prior to reconstruction. METHODS: All patients with myxofibrosarcomas treated with a curative intent at our centre between 2009 and 2019 were identified. Patient demographics, tumour characteristics, number of resections, method of reconstruction, adjuvant therapy, complications, local recurrence rates, length of hospital stay and overall survival were assessed. RESULTS: 97 consecutive eligible patients were identified. Forty-six (47%) had positive margins reported following a first resection. The median number of resections required to obtain clear margins was two and the median time from first excision to definitive wound closure was 15 days. Local recurrence rate for the whole cohort was 14%. Patients who had staged resection until clear margins were obtained had a significantly lower rate of local recurrence compared to those who had positive margins at time of reconstruction (p-value = 0.001). The estimated 5-year disease-specific survival for the whole cohort was 93%. DISCUSSION: Obtaining clear margins in myxofibrosarcoma via staged resections was associated with lower local recurrence rates for patients who had an initial resection with positive margins. The outcomes of performing staged resections are equivalent to patients for whom a clear margin were obtained in the first instance.

Small Animal IMRT Using 3D-Printed Compensators.

PURPOSE: Preclinical radiation replicating clinical intensity modulated radiation therapy (IMRT) techniques can provide data translatable to clinical practice. For this work, treatment plans were created for oxygen-guided dose-painting in small animals using inverse-planned IMRT. Spatially varying beam intensities were achieved using 3-dimensional (3D)-printed compensators. METHODS AND MATERIALS: Optimized beam fluence from arbitrary gantry angles was determined using a verified model of the XRAD225Cx treatment beam. Compensators were 3D-printed with varied thickness to provide desired attenuation using copper/polylactic-acid. Spatial resolution capabilities were investigated using printed test-patterns. Following American Association of Physicists in Medicine TG119, a 5-beam IMRT plan was created for a miniaturized (∼1/8th scale) C-shape target. Electron paramagnetic resonance imaging of murine tumor oxygenation guided simultaneous integrated boost (SIB) plans conformally treating tumor to a base dose (Rx1) with boost (Rx2) based on tumor oxygenation. The 3D-printed compensator intensity modulation accuracy and precision was evaluated by individually delivering each field to a phantom containing radiochromic film and subsequent per-field gamma analysis. The methodology was validated end-to-end with composite delivery (incorporating 3D-printed tungsten/polylactic-acid beam trimmers to reduce out-of-field leakage) of the oxygen-guided SIB plan to a phantom containing film and subsequent gamma analysis. RESULTS: Resolution test-patterns demonstrate practical printer resolution of ∼0.7 mm, corresponding to 1.0 mm bixels at the isocenter. The miniaturized C-shape plan provides planning target volume coverage (V95% = 95%) with organ sparing (organs at risk Dmax < 50%). The SIB plan to hypoxic tumor demonstrates the utility of this approach (hypoxic tumor V95%,Rx2 = 91.6%, normoxic tumor V95%,Rx1 = 95.7%, normal tissue V100%,Rx1 = 7.1%). The more challenging SIB plan to boost the normoxic tumor rim achieved normoxic tumor V95%,Rx2 = 90.9%, hypoxic tumor V95%,Rx1 = 62.7%, and normal tissue V100%,Rx2 = 5.3%. Average per-field gamma passing rates using 3%/1.0 mm, 3%/0.7 mm, and 3%/0.5 mm criteria were 98.8% ± 2.8%, 96.6% ± 4.1%, and 90.6% ± 5.9%, respectively. Composite delivery of the hypoxia boost plan and gamma analysis (3%/1 mm) gave passing results of 95.3% and 98.1% for the 2 measured orthogonal dose planes. CONCLUSIONS: This simple and cost-effective approach using 3D-printed compensators for small-animal IMRT provides a methodology enabling preclinical studies that can be readily translated into the clinic. The presented oxygen-guided dose-painting demonstrates that this methodology will facilitate studies driving much needed biologic personalization of radiation therapy for improvements in patient outcomes.

4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication.

Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.

Is there a role for chemotherapy and radiation in the treatment of patients with low-grade myofibroblastic sarcoma?

PURPOSE: Low-grade myofibroblastic sarcoma (LGMS) is a rare entity with a predilection for the head and neck. There are still no optimal treatment strategies for patients with LGMS. We retrospectively investigated the efficacies of chemotherapy and radiation treatment for patients with LGMS. METHODS/PATIENTS: We obtained data from the Surveillance, Epidemiology, and End Result (SEER) database for 96 patients diagnosed with LGMS between 2001 and 2015. We used Kaplan-Meier curves and log-rank tests to estimate overall survival (OS) and Cox proportional hazard regression to identify prognostic factors. RESULTS: The median age of the patients was 55.0 years. Twenty-two of the patients had LGMS in the head and neck region. Of the 96 patients, 86 (89.6%) received surgical treatment, 28 (29.2%) received radiation treatment, and 20 (10.4%) received chemotherapy. The mean OS was 125.2 [95% confidence interval (CI) 106.3-144.2] months. The 1, 3, 5, and 10-year OS rates were 88%, 77%, 70%, and 59%, respectively. Age greater than 60 years, positive nodal status, and no surgical treatment were independent prognostic factors for patients with LGMS, whereas chemotherapy and radiation treatment were not. CONCLUSIONS: Surgical resection is the most effective therapy for LGMS. Chemotherapy and radiation had limited effects on survival improvement for patients with LGMS. Therefore, chemotherapy and/or radiation therapy should not be routinely performed in LGMS, especially for those with negative margins after surgery.