Sustained activation of the FGF1-MEK-ERK pathway inhibits proliferation, invasion and migration and enhances radiosensitivity in mouse angiosarcoma cells.

Angiosarcoma is a rare refractory soft-tissue tumor with a poor prognosis and is treated by radiotherapy. The fibroblast growth factor 1 (FGF1) mutant, with enhanced thermostability due to several substituted amino acids, inhibits angiosarcoma cell metastasis, yet the mechanism of action is unclear. This study aims to clarify the FGF1 mutant mechanism of action using ISOS-1 mouse angiosarcoma cells. The wild-type FGF1 or FGF1 mutant was added to ISOS-1 cells and cultured, evaluating cell numbers over time. The invasive and migratory capacity of ISOS-1 cells was assessed by transwell analysis. ISOS-1 cell radiosensitivity was assessed by colony formation assay after X-ray irradiation. To examine whether mitogen-activated protein kinase (MEK) inhibitor counteracts the FGF1 mutant effects, a combination of MEK inhibitor and FGF1 mutant was added to ISOS-1 cells and cultured. The FGF1 mutant was observed to inhibit ISOS-1 cell proliferation, invasion and migration by sustained FGF1 signaling activation. A MEK inhibitor suppressed the FGF1 mutant-induced inhibition of proliferation, invasion and migration of ISOS-1 cells. Furthermore, the FGF1 mutant enhanced radiosensitivity of ISOS-1 cells, but MEK inhibition suppressed the increased radiosensitivity. In addition, we found that the FGF1 mutant strongly inhibits actin polymerization, suggesting that actin cytoskeletal dynamics are closely related to ISOS-1 cell radiosensitivity. Overall, this study demonstrated that in ISOS-1 cells, the FGF1 mutant inhibits proliferation, invasion and migration while enhancing radiosensitivity through sustained activation of the MEK-mediated signaling pathway.

Neoadjuvant Reirradiation for Radiation Therapy-Associated Angiosarcoma of the Breast.

PURPOSE: Radiation-associated angiosarcoma of the breast (RAASB) is a rare side effect after breast radiation and has been associated with poor outcomes. At this time, there is no consensus regarding management of RAASB, and the role of reirradiation remains controversial. We present our modern institutional outcomes in managing RAASB with incorporation of neoadjuvant hyperfractionated reirradiation. METHODS AND MATERIALS: Patients identified were treated between 2016 and 2020 with inclusion of any histologically proven RAASB without metastatic disease at diagnosis, while excluding those with a history of radiation therapy outside of the breast/chest wall or other sarcoma histologies. Major wound complications were defined as requiring wound care and/or wound vacuum or return to the operating room for wound repair at any time after surgery. RESULTS: Eight patients were identified, and the median follow-up was 34 months. Median time to RAASB development was 8 years from initial radiation therapy. With respect to RAASB management, all underwent surgery and neoadjuvant reirradiation therapy, and all but 1 patient received taxol-based chemotherapy. At last follow-up, 7 patients remained free of disease, and 1 patient died with distant disease. With respect to acute toxicity after reirradiation, all patients developed at least acute grade 2 toxicities. Five of the 8 patients developed a major wound complication. CONCLUSIONS: Our institutional analysis suggests excellent local control and survival outcomes for RAASB treated with neoadjuvant hyperfractionated reirradiation, surgery, and taxol-based chemotherapy. However, major wound complications represent a major challenge with this approach. Future studies should consider how best to improve the therapeutic ratio while maintaining high rates of local control and survival.

Clinical outcomes of scalp or face angiosarcoma treatment with intensity-modulated radiotherapy: a multicenter study.

Combined modality therapy, including radiotherapy (RT), is a common treatment for scalp or face angiosarcoma. Although intensity-modulated radiotherapy (IMRT) can deliver homogeneous doses to the scalp or face, clinical data are limited. This multicenter study aimed to evaluate scalp or face angiosarcoma treated with definitive or post-operative IMRT. We retrospectively analyzed data from patients who received IMRT for scalp or face angiosarcoma at three institutions between January 2015 and March 2020. Local control (LC) rate, overall survival (OS), progression-free survival (PFS), recurrence patterns and toxicity were evaluated. Fifteen patients underwent IMRT during the study period. Definitive RT was performed on 10 patients and post-operative RT was performed on 5 patients. The 1-year LC rate was 85.7% (95% confidence interval [CI], 53.9-96.2%). The 1-year OS and PFS rates were 66.7% (95% CI, 37.5-84.6%) and 53.3% (95% CI, 26.3%-74.4%), respectively. Univariate analysis revealed that a clinical target volume over 500 cm3 was associated with poor LC. Distant metastasis was the most common recurrence pattern. All patients experienced Grade 2 or 3 radiation dermatitis, and five patients experienced grade ≥ 3 skin ulceration. One patient who underwent maintenance therapy with pazopanib developed Grade 5 skin ulceration. Fisher's exact test showed that post-operative RT was significantly associated with an increased risk of skin ulceration of grade ≥ 3. These results demonstrate that IMRT is a feasible and effective treatment for scalp or face angiosarcoma, although skin ulceration of grade ≥ 3 is a common adverse event in patients who receive post-operative RT.

High-dose planned adaptive helical tomotherapy for cutaneous angiosarcoma of the scalp.

PURPOSE: The purpose of this study was to investigate the feasibility and effectiveness of high-dose planned adaptive intensity-modulated radiation therapy (IMRT) with helical tomotherapy (HT) for cutaneous angiosarcoma (cAS) of the scalp. METHODS: This retrospective cross-sectional included a total of 12 consecutive patients with cAS of the scalp who underwent high-dose planned adaptive IMRT with HT. Prescribed doses were 72.5-74 Gy in 35-37 fractions for the gross tumor volume plus a 1-2 mm margin (PTV1), 58-60 Gy in 29-30 fractions for the clinical target volume plus a 2-3 mm margin (PTV2), and 46 Gy in 23 fractions for the clinical target volume plus a 5-15 mm margin (PTV3) over periods of 7.5, 6 and 4.5 weeks, respectively. RESULTS: The estimated 1­year and 2­year overall survival rate were 65.6% and 27.3%, respectively, and the local progression-free survival at 2 years was 74.1%. All local recurrences were either in or marginal to the PTV2 or PTV3. No local recurrence was observed in the PTV1. All patients tolerated the treatment without grade 3 or higher adverse events during the radiotherapy period. No late adverse events were observed during the follow-up period. CONCLUSION: Planned adaptive high-dose IMRT with HT has the potential to improve local control rate without increasing adverse events.

Dosimetric Comparison of Helical Tomotherapy and HyperArc Treatment Plans for Angiosarcoma of the Scalp.

BACKGROUND/AIM: Angiosarcoma of the scalp (AS) is a rare tumor that has often been treated by total scalp irradiation (TSI). TSI has technical and dosimetric challenges. This study aimed to compare the dosimetric performance of helical tomotherapy (HT) plans with that of HyperArc (HA) plans for TSI in AS. PATIENTS AND METHODS: A planning study was conducted for 11 patients with AS (70 Gy/35 fr). HT and HA planning was performed using TomoHDA and TrueBeam Edge systems, respectively. The performance of three different plans were compared: HT, HA, and HA with half-field beams (HF-HA). The dose distribution and dosimetric parameters for each plan were evaluated. RESULTS: All constraint parameters for the target and organs at risk (OARs) met the goals within acceptable limits for the three techniques. The HA and HF-HA plans provided significantly lower mean brain dose (12.46±2.48 Gy and 8.02±1.48 Gy) than did the HT plan (17.59±3.47 Gy). The doses receiving 0.1 cc of the volume for brainstem and chiasm were significantly lower in the HA and HF-HA plans than those in the HT plan. The HA and HF-HA plans provided a shorter beam-on time (155±3 s and 181±14 s) than did the HT plan (962±221 s). CONCLUSION: The HA plan provided significantly better OARs sparing than the HT plan for TSI in AS and had an advantage to using half-field beams.

Outcomes after definitive treatment for cutaneous angiosarcomas of the face and scalp: Reevaluating the role of surgery and radiation therapy.

INTRODUCTION: We investigated outcomes and prognostic factors for patients treated for cutaneous angiosarcoma (CA). METHODS: We conducted a retrospective review of patients treated for CA of the face and scalp from 1962 to 2019. All received definitive treatment with surgery, radiation (RT), or a combination (S-XRT). The Kaplan-Meier method was used to estimate outcomes. Multivariable analyses were conducted using the Cox proportional hazards model. RESULTS: For the 143 patients evaluated median follow-up was 33 months. Five-year LC was 51% and worse in patients with tumors >5 cm, multifocal tumors, those treated pre-2000, and with single modality therapy (SMT). These remained associated with worse LC on multivariable analysis. The 5-year disease-specific survival (DSS) for the cohort was 56%. Tumor size >5 cm, non-scalp primary site, treatment pre-2000, and SMT were associated with worse DSS. CONCLUSION: Large or multifocal tumors are negative prognostic factors in patients with head and neck CA. S-XRT improved outcomes.

Treatment of radiation-associated angiosarcoma.

PURPOSE OF REVIEW: Radiation-associated angiosarcoma is a cutaneous aggressive tumor that is very rare and it represents a specific entity poorly studied in literature. It requires new therapeutic opportunity. RECENT FINDINGS: The complete surgical resection with negative margins is the mainstay treatment of localized treatment, even though it is difficult to reach in case of diffuse cutaneous infiltration. Adjuvant re-irradiation may improve local control with no benefit demonstrated on survival. Many systemic treatments can be efficient not only in metastatic setting but also in neoadjuvant setting in case of diffuse presentation. These treatments have never been compared to each other; the most efficient regimen remains to be determined, and a high heterogeneity of treatment is observed, even between sarcoma reference centers. SUMMARY: Immune therapy represents the most promising treatment under development. At the time of building clinical trial to assess the efficacy of immune therapy, the lack of randomized studies prevents the identification of a strong and consensual reference arm treatment. Given the rarity of the disease, only international collaborative clinical trials may have a chance to include enough patients to draw any conclusion and so will have to counteract the heterogeneity of management.

Clinical significance of local control of primary tumour in definitive radiotherapy for scalp angiosarcomas.

INTRODUCTION: Scalp angiosarcoma is a rare and aggressive cancer. Definitive radiotherapy is a treatment option for localised scalp angiosarcoma patients. Although definitive surgical resection reportedly prolongs overall survival (OS), whether initial local treatment effect affects OS when definitive radiotherapy is administered is unclear. Therefore, this study analysed whether local recurrence within 6 months of irradiation correlates with OS and cancer-specific survival (CSS). Furthermore, how local control affects patients' quality of life was investigated. MATERIALS AND METHODS: Thirty-one localised scalp angiosarcoma patients who had received definitive radiotherapy at our institution between October 2010 and July 2021 were analysed retrospectively. The most commonly used dose fractionation was 70 Gy in 35 fractions (83.9%). Local recurrence within 6 months of radiotherapy and other clinical factors were examined in univariate and subsequent multivariate analyses for correlation with OS and CSS. RESULTS: The median follow-up period was 16 months (range, 6-45 months). Local recurrence was detected in 16 patients (51.6%), 12 of whom had recurrence within 6 months. In multivariate analyses, the presence of local recurrence within 6 months of radiotherapy was significantly associated with OS and CSS (p = 0.003, 0.0001, respectively). Ten of the 16 patients with local recurrence had severe symptoms such as bleeding, pain, difficulty opening the eye and malodour. CONCLUSIONS: The initial local treatment effect was significantly associated with OS and CSS after definitive radiotherapy. Furthermore, local recurrence after radiotherapy resulted in a variety of symptoms, including bleeding and pain, which reduced the patient's quality of life.

Definitive Radiotherapy Using Electron Beam and Intensity-modulated Radiotherapy for Unresectable Angiosarcoma of the Scalp.

BACKGROUND/AIM: Radiotherapy for angiosarcoma of the scalp has not been standardised yet. Hence, we aimed to retrospectively analyse the outcomes of patients treated with electron beam therapy or intensity-modulated radiation therapy (IMRT) for unresectable angiosarcoma of the scalp. PATIENTS AND METHODS: Data from patients treated with chemoradiotherapy or radiotherapy alone for unresectable angiosarcoma of the scalp between March 2009 and March 2021 were evaluated. Survival and local control rates were analysed using the Kaplan-Meier method, and the log-rank test was used to compare groups. Adverse events were analysed using the Common Terminology Criteria for Adverse Events ver. 5.0. RESULTS: Sixteen patients were eligible for the study. Eight patients were treated with electron beam therapy and eight patients with IMRT. The median follow-up period was 18.0 months. The median radiation dose was 57 Gy in 19 fractions in the electron beam therapy group and 70 Gy in 35 fractions in the IMRT group. In the IMRT group, acute non-haematologic toxicity was observed in two patients with grade 3 dermatitis. The one-year overall survival rate, progression-free survival rate, and local control rate in the electron beam therapy group were 80.8%, 56.3%, and 77.4%, respectively, and the corresponding values in the IMRT group were 100%, 75%, and 100%, respectively. One-year local control was significantly better in the IMRT group compared to that in the electron beam therapy group (p=0.016). CONCLUSION: IMRT for angiosarcoma of the scalp may improve local control rates compared to electron beam therapy, but long-term follow-up studies are required to validate this finding.

MYC-Nonamplified Secondary Lymphatic-Type Angiosarcoma With Prominent Lymphocytic Infiltrate Following Radiation Therapy for Myxoid Liposarcoma.

ABSTRACT: Cutaneous angiosarcomas (AS) are uncommon and morphologically heterogeneous. Recently, a distinctive lymphatic-type AS with prominent lymphocytic infiltrate has been observed. Although conventional AS typically bear poor prognosis, lymphatic-type AS with prominent lymphocytic infiltrate and pseudolymphomatous AS show prolonged survival with rare extracutaneous spread. We describe a unique case of AS in a 55-year-old woman who received surgical resection and radiation therapy for her prior myxoid liposarcoma. She developed a suspected recurrence 15 years later. Microscopically, the lesion showed an infiltration of the reticular dermis by irregular interanastamosing vascular spaces lined by atypical endothelial cells with nuclear "hobnailing" and hyperchromasia. A prominent intratumoral and peritumoral lymphocytic infiltrate obscuring the tumor cells was also present. The tumor cells were diffusely positive for endothelial cell markers, including D2-40. Notably, there was no evidence of MYC gene amplification by FISH. Additional NGS-based molecular analysis demonstrated no significant genetic mutations. The patient is alive with a history of two local recurrences, but no evidence of metastasis. We present this case to raise awareness of MYC-nonamplified secondary lymphatic-type AS with prominent lymphocytic infiltrate (pseudolymphomatous AS) and to discuss its differential diagnosis.

Prognostic factor analysis of definitive radiotherapy using intensity-modulated radiation therapy and volumetric modulated arc therapy with boluses for scalp angiosarcomas.

Cutaneous angiosarcomas is a rare cancer with poor prognoses. The common radiotherapy techniques that have been reported so far are two pairs of lateral X-ray and electron fields. However, it is quite difficult to irradiate scalp angiosarcomas (SAs) homogeneously with this technique. In this study, safety, effectiveness, and risk factors were assessed for localized SAs ≥ 5 cm treated with intensity-modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with boluses. Sixty-eight angiosarcoma patients who had received radiotherapy in our institution between January 2007 and November 2020 were retrieved from our radiotherapy database. Of these patients, 27 localized SA patients were included in the retrospective analysis. The 2-year overall survival, local progression-free rate, and distant metastases-free survival were 41.8%, 48.4%, and 33.1%. All the patients experienced acute radiation dermatitis ≥ grade 2, with18 (66.7%) ≥ grade 3. No nodule lesion was a significant unfavorable predictive factor of acute radiation dermatitis ≥ grade 3. Tumor bleeding at the initiation of radiotherapy and tumor invasion to the face were significant predictive factors of overall survival, and tumor bleeding at the initiation of radiotherapy was also a significant predictive factor of local progression-free rate.

Radiation-associated angiosarcoma of the breast: An international multicenter analysis.

INTRODUCTION: Radiation-associated angiosarcoma (RAAS) is a rare and serious complication of breast irradiation. Due to the rarity of the condition, clinical experience is limited and publications on this topic include only retrospective studies or case reports. MATERIALS AND METHODS: All patients diagnosed with RAAS between January 2000 and December 2017 in twelve centers across the Czech Republic and Slovakia were evaluated. RESULTS: Data of 53 patients were analyzed. The median age at diagnosis was 72 (range 44-89) years. The median latency period between irradiation and diagnosis of RAAS was 78 (range 36-172) months. The median radiation dose was 57.6 (range 34-66) Gy. The whole breast radiation therapy with radiation boost to the tumor bed was the most common radiotherapy regimen. Total mastectomy due to RAAS was performed in 43 patients (81%), radical excision in 8 (15%); 2 patients were not surgically treated due to unresectable disease. Adjuvant chemotherapy followed surgical therapy of RAAS in 18 patients, 3 patients underwent adjuvant radiotherapy. The local recurrence rate of RAAS was 43% and the median time from surgery to the onset of recurrence was 7.5 months (range 3-66 months). The 3-year survival rate was 56%, the 5-year survival rate was only 33%. 46% of patients died during the follow-up period. CONCLUSION: The present data demonstrate that RAAS is a rare condition with high local recurrence rate (43%) and mortality (the 5-year survival rate was 33%.). Early diagnosis of RAAS based on biopsy is crucial for treatment with radical intent. Surgery with negative margins constitutes the most important part of the therapy; the role of adjuvant chemotherapy and radiotherapy is still unclear.

Inoperable scalp cutaneous angiosarcoma: Complete response after definitive external beam radiation therapy - brachytherapy association.

Effective treatments are scarce in non-operable scalp cutaneous angiosarcoma patients. Curative-intent definitive sequential IMRT and plesiobrachytherapy allowed complete response with limited side effect in two elder patients. This could represent a non-invasive therapeutic option for patients with locally advanced presentation.

Radiological progression of extremity soft tissue sarcoma following pre-operative radiotherapy predicts for poor survival.

OBJECTIVES: To determine if radiological response to pre-operative radiotherapy is related to oncologic outcome in patients with extremity soft tissue sarcomas (STSs). METHODS: 309 patients with extremity STS who underwent pre-operative radiation and wide resection were identified from a prospective database. Pre- and post-radiation MRI scans were retrospectively reviewed. Radiological response was defined by the modified Response Evaluation Criteria in Solid Tumours. Local recurrence-free, metastasis-free (MFS) and overall survival (OS) were compared across response groups. RESULTS: Tumour volume decreased in 106 patients (34.3%; PR - partial responders), remained stable in 97 (31.4%; SD - stable disease), increased in 106 (34.3%; PD - progressive disease). The PD group were older (p = 0.007), had more upper extremity (p = 0.03) and high-grade tumours (p < 0.001). 81% of myxoid liposarcomas showed substantial decrease in size. There was no difference in initial tumour diameter (p = 0.5), type of surgery (p = 0.5), margin status (p = 0.4), or complications (p = 0.8) between the three groups. There were 10 (3.2%) local recurrences with no differences between the three response groups (p = 0.06). 5-year MFS was 52.1% for the PD group vs 73.8 and 78.5% for the PR and SD groups, respectively (p < 0.001). OS was similar (p < 0.001). Following multivariable analysis, worse MFS and OS were associated with higher grade, larger tumour size at diagnosis and tumour growth following pre-operative radiation. Older age was also associated with worse OS. CONCLUSION: STS that enlarge according to Response Evaluation Criteria in Solid Tumour criteria following pre-operative radiotherapy identify a high risk group of patients with worse systemic outcomes but equivalent local control. ADVANCES IN KNOWLEDGE: Post-radiation therapy, STS enlargement may identify patients with potential for worse systemic outcomes but equivalent local control. Therefore, adjunct therapeutic approaches could be considered in these patients.

Neoadjuvant radiation for cutaneous and soft tissue angiosarcoma.

BACKGROUND AND OBJECTIVES: Neoadjuvant radiation (NRT) is frequently utilized in soft tissue sarcomas to increase local control. Its utility in cutaneous and soft tissue angiosarcoma remains poorly defined. METHODS: This retrospective cohort study was performed using the National Cancer Database (2004-2016) evaluating patients with clinically localized, surgically resected angiosarcomas. Factors associated with receipt of NRT in the overall cohort and margin positivity in treatment naïve patients were identified by univariate and multivariable logistic regression analyses. Survival was assessed using Kaplan-Meier analysis. RESULTS: Of 597 patients, 27 (4.5%) received NRT. Increasing age (odds ratio [OR] 0.95, p = 0.025), tumor size more than or equal to 5 cm (OR 3.16, p = 0.02), and extremity tumor location (OR 3.99, p = 0.04) were associated with receipt of NRT. All patients who received NRT achieved an R0 resection (p = 0.03) compared with 17.9% of patients without NRT. Factors associated with risk of margin positivity included tumor size more than or equal to 5 cm (OR 1.85, p = 0.01), and head/neck location (OR 2.24, p = 0.006). NRT was not significantly associated with improved survival (p = 0.21). CONCLUSIONS: NRT improves rates of R0 resection but is infrequently utilized in cutaneous and soft tissue angiosarcoma. Increased usage of NRT, particularly for patients with lesions more than or equal to 5 cm, or head and neck location, may help achieve complete resections.

A successful approach for angiosarcoma of the scalp using helical tomotherapy and customized surface mold brachytherapy: A case report.

RATIONALE: Angiosarcoma of the scalp (ASS) is a rare solid tumor with a high risk of local recurrence. Effective treatment strategies are not currently available for angiosarcoma of the scalp (ASS). The aim of this study was to report the utility of high-dose-rate brachytherapy (HDRBT) as a boost treatment for ASS following total scalp irradiation using helical tomotherapy (HT). This is the first report of successful treatment of ASS using HT and HDRBT. PATIENT CONCERNS: An 81-year-old woman presented with hemorrhagic nodular skin tumors of the scalp. The patient first noticed the scalp mass 3 months before consultation, which became significantly enlarged within a short period. The tumor was positioned mostly in the parietal area, although the skin color change was widely spread to the surrounding scalp. DIAGNOSIS: The patient underwent biopsy of the skin lesion at the right parietal region, which revealed the presence of angiosarcoma on pathological examination. There was neither regional lymphadenopathy nor distant metastases on PET/CT. INTERVENTIONS: Considering the patient's old age and poor performance status because of a history of cerebral infarction, we considered that she was eligible for definitive chemoradiotherapy of the scalp. We adopted an individual surface mold HDRBT boost of 18 Gy in three fractions following total scalp irradiation with 50 Gy in 25 fractions delivered using HT. Docetaxel (40 mg/m2) was administered every 4 weeks, concurrently with radiotherapy. OUTCOMES: Treatment tolerance was good, and severe toxicity has not been observed to date. At 18 months after radiotherapy, the patient does not have any evidence of recurrence. CONCLUSION: Customized surface mold HDRBT following total scalp irradiation using HT resulted in excellent disease control and minimal toxicity; thus, it may be a promising therapeutic option for ASS.

Efficacy of tangential irradiation with volumetric modulated arc therapy on scalp angiosarcoma using medical linac.

PURPOSE: To increase the superficial dose and reduce the brain dose for radiotherapy of scalp angiosarcoma, we propose a novel irradiation technique of tangential irradiation volumetric modulated arc therapy (TI-VMAT). METHODS: TI-VMAT and the conventional VMAT treatment plans for thirteen scalp angiosarcoma patients were created with a prescribed dose of 70 Gy. Each treatment was normalized to cover 95% of the planning target volume (PTV) with its prescribed dose. To realize TI-VMAT, an avoidance structure (AS) function was applied. AS was defined as a contour subtracted PTV by a certain space from the brain contour. TI-VMAT treatment plans for six different spaces between PTV and AS were developed and compared with the conventional VMAT treatment plan with respect to the following dosimetric parameters: homogeneity index (HI) and conformity index (CI) of the PTV, mean brain dose, and brain volume irradiated with 20% (V20% [cc]), 40% (V40% [cc]), 60% (V60% [cc]), 80% (V80% [cc]), and 100% (V100% [cc]) of the prescribed dose. RESULTS: HI and CI were comparable between TI-VMAT and the conventional VMAT, the mean brain dose for TI-VMAT with AS defined by a space of 2.0 cm and jaw tracking was 14.27 Gy, which was significantly lower than that for the conventional VMAT (21.20 Gy). In addition, dosimetric parameters such as V20% [cc] were significantly suppressed compared to those for high doses. CONCLUSION: Our proposed irradiation technique TI-VMAT shows the potential to reduce radiation doses in the brain with maintaining higher dose coverage on the PTV.

Dosimetric Comparison of Helical Tomotherapy, Volumetric-Modulated Arc Therapy, and Intensity-Modulated Proton Therapy for Angiosarcoma of the Scalp.

OBJECTIVE: We compared radiotherapy plans among helical tomotherapy (HT), volumetric-modulated arc therapy (VMAT), and intensity-modulated proton therapy (IMPT) for angiosarcoma of the scalp (AS). METHODS: We conducted a planning study for 19 patients with AS. The clinical target volume (CTV) 1 and CTV2 were defined as the gross tumor volume with a specific margin and total scalp, respectively. For HT and VMAT, the planning target volume (PTV) 1 and PTV2 were defined as CTV1 and CTV2 with 0.5-cm margins, respectively. For IMPT, robust optimization was used instead of a CTV-PTV margin (i.e. CTV robust). The targets of the HT and VMAT plans were the PTV, whereas the IMPT plans targeted the CTV robust. In total, 70 Gy and 56 Gy were prescribed as the D95% (i.e. dose to 95% volume) of PTV1 (or CTV1 robust) and PTV2 (or CTV2 robust), respectively, using the simultaneous integrated boost (SIB) technique. Other constraint goals were also defined for the target and organs at risk (OAR). RESULTS: All dose constraint parameters for the target and OAR met the goals within the acceptable ranges for the 3 techniques. The coverage of the targets replaced by D95% and D98% were almost equivalent among the 3 techniques. The homogeneity index of PTV1 or CTV1 robust was equivalent among the 3 techniques, whereas that of PTV2 or CTV2 robust was significantly higher in the IMPT plans than in the other plans. IMPT reduced the Dmean of the brain and hippocampus by 49% to 95%, and the Dmax of the spinal cord, brainstem, and optic pathway by 70% to 92% compared with the other techniques. CONCLUSION: The 3 techniques with SIB methods provided sufficient coverage and satisfactory homogeneity for the targets, but IMPT achieved the best OAR sparing.