Treatment of malignant sinonasal tumours with intensity-modulated radiotherapy (IMRT) and carbon ion boost (C12)

<p>Abstract</p> <p>Background</p> <p>Most patients with cancers of the nasal cavity or paranasal sinuses are candidates of radiation therapy either due incomplete resection or technical inoperability. Local control in this disease is dose dependent but technically challenging due to close proximity of critical organs and accompanying toxicity. Modern techniques such as IMRT improve toxicity rates while local control remains unchanged. Raster-scanned carbon ion therapy with highly conformal dose distributions may allow higher doses at comparable or reduced side-effects.</p> <p>Methods/design</p> <p>The IMRT-HIT-SNT trial is a prospective, mono-centric, phase II trial evaluating toxicity (primary endpoint: mucositis ≥ CTCAE°III) and efficacy (secondary endpoint: local control, disease-free and overall survival) in the combined treatment with IMRT and carbon ion boost in 30 patients with histologically proven (≥R1-resected or inoperable) adeno-/or squamous cell carcinoma of the nasal cavity or paransal sinuses. Patients receive 24 GyE carbon ions (8 fractions) and IMRT (50 Gy at 2.0 Gy/fraction).</p> <p>Discussion</p> <p>The primary objective of IMRT-HIT-SNT is to evaluate toxicity and feasibility of the proposed treatment in sinonasal malignancies.</p> <p>Trial Registration</p> <p>Clinical trial identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01220752">NCT 01220752</a></p

Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: The CLEOPATRA Trial

<p>Abstract</p> <p>Background</p> <p>Treatment standard for patients with primary glioblastoma (GBM) is combined radiochemotherapy with temozolomide (TMZ). Radiation is delivered up to a total dose of 60 Gy using photons. Using this treatment regimen, overall survival could be extended significantly however, median overall survival is still only about 15 months.</p> <p>Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.</p> <p>First Japanese Data on the evaluation of carbon ion radiation therapy showed promising results in a small and heterogeneous patient collective.</p> <p>Methods/Design</p> <p>In the current Phase II-CLEOPATRA-Study a carbon ion boost will be compared to a proton boost applied to the macroscopic tumor after surgery at primary diagnosis in patients with GBM applied after standard radiochemotherapy with TMZ up to 50 Gy. In the experimental arm, a carbon ion boost will be applied to the macroscopic tumor up to a total dose of 18 Gy E in 6 fractions at a single dose of 3 Gy E. In the standard arm, a proton boost will be applied up to a total dose 10 Gy E in 5 single fractions of 2 Gy E.</p> <p>Primary endpoint is overall survival, secondary objectives are progression-free survival, toxicity and safety.</p> <p>Discussion</p> <p>The Cleopatra Trial is the first study to evaluate the effect of carbon ion radiotherapy within multimodality treatment of primary glioblastoma in a randomized trial comparing this innovative treatment of the treatment standard, consisitng of photon radiotherapy in combination with temozolomide.</p> <p>Trial Registration</p> <p>ISRCTN37428883 and NCT01165671</p

Influence of food additives from fish milt roe and glycerin on productivity parameters of sturgeon fish

The effect of a new feed additive “GLINMOL” in the form of emulsion on productivity of sturgeons was studied. The aim of the research was to study the effect of newly developed feed additives based on fish milt roe and glycerin on sturgeon fish productivity. The experiment consisted of two parts; groups of fish of 3-4 and 4 maturity stages were formed. The first group (control) received complete mixed feed without additives, the second - 2.0% of glycerin of total feed weight; the third - feed additive “GLINMOL” at a dose of 2.0% of total feed weight. The largest gross increase of live weight for the entire rearing period was noted when “GLINMOL” feed additive was used - 11.9% (P<0.01) higher than the control parameter. Glycerin application in the second group also exceeded the control value of live weight increase by 8.1% (P<0.05). The final body length of sturgeons in the second experimental group was almost equal to the control. In the third group, this parameter significantly exceeded the control by 0.5% (P<0.05). The values of the fatness coefficient did not differ significantly among the groups and were in the range of 1.11-1.13

Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study

<p/> <p>Background</p> <p>Low and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours.</p> <p>Methods/Design</p> <p>The study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial.</p> <p>Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points.</p> <p>Discussion</p> <p>Up to now it was impossible to compare two different particle therapies, i.e. protons and carbon ions, directly at the same facility in connection with the treatment of low grade skull base chondrosarcomas.</p> <p>This trial is a phase III study to demonstrate that carbon ion radiotherapy (experimental treatment) is not relevantly inferior and at least as good as proton radiotherapy (standard treatment) with respect to 5 year LPFS in the treatment of chondrosarcomas. Additionally, we expect less toxicity in the carbon ion treatment arm.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: NCT01182753</p

Combined treatment of malignant salivary gland tumours with intensity-modulated radiation therapy (IMRT) and carbon ions: COSMIC

<p>Abstract</p> <p>Background</p> <p>Local control in malignant salivary gland tumours is dose dependent. High local control rates in adenoid cystic carcinomas could be achieved by highly conformal radiotherapy techniques and particle (neutron/carbon ion) therapy. Considering high doses are needed to achieve local control, all malignant salivary gland tumours probably profit from the use of particle therapy, which in case of carbon ion treatment, has been shown to be accompanied by only mild side-effects.</p> <p>Methods/design</p> <p>The COSMIC trial is a prospective, mono-centric, phase II trial evaluating toxicity (primary endpoint: mucositis ≥ CTCAE°3) and efficacy (secondary endpoint: local control, disease-free survival) in the combined treatment with IMRT and carbon ion boost in 54 patients with histologically proved (≥R1-resected, inoperable or Pn+) salivary gland malignancies. Patients receive 24 GyE carbon ions (8 fractions) and IMRT (50 Gy at 2.0 Gy/fraction).</p> <p>Discussion</p> <p>The primary objective of COSMIC is to evaluate toxicity and feasibility of the proposed treatment in all salivary gland malignancies.</p> <p>Trial Registration</p> <p>Clinical trial identifier NCT 01154270</p

Randomised trial of proton vs. carbon ion radiation therapy in patients with chordoma of the skull base, clinical phase III study HIT-1-Study

<p>Abstract</p> <p>Background</p> <p>Chordomas of the skull base are relative rare lesions of the bones. Surgical resection is the primary treatment standard, though complete resection is nearly impossible due to close proximity to critical and hence also dose limiting organs for radiation therapy. Level of recurrence after surgery alone is comparatively high, so adjuvant radiation therapy is very important for the improvement of local control rates. Proton therapy is the gold standard in the treatment of skull base chordomas. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors.</p> <p>Methods/design</p> <p>This clinical study is a prospective randomised phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie centre (HIT) and is a monocentric study.</p> <p>Patients with skull base chordoma will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume delineation will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV in carbon ion treatment (accelerated dose) will be 63 Gy E ± 5% and 72 Gy E ± 5% (standard dose) in proton therapy respectively. Local-progression free survival (LPFS) will be analysed as primary end point. Toxicity and overall survival are the secondary end points. Additional examined parameters are patterns of recurrence, prognostic factors and plan quality analysis.</p> <p>Discussion</p> <p>Up until now it was impossible to compare two different particle therapies, i.e. protons and carbon ions directly at the same facility.</p> <p>The aim of this study is to find out, whether the biological advantages of carbon ion therapy can also be clinically confirmed and translated into the better local control rates in the treatment of skull base chordomas.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: NCT01182779</p

Carbon ion therapy for ameloblastic carcinoma

Ameloblastic carcinomas are rare odontogenic tumors. Treatment usually consists of surgical resection and sometimes adjuvant radiation. We report the case of a 71 year-old male patient undergoing carbon ion therapy for extensive local relapse of ameloblastic carcinoma. Treatment outcome was favourable with a complete remission at 6 weeks post completion of radiotherapy while RT-treatment itself was tolerated well with only mild side effects. High dose radiation hence is a potential alternative for patients unfit or unwilling to undergo extensive surgery or in cases when only a subtotal resection is planned or the resection is mutilating

Non-randomized therapy trial to determine the safety and efficacy of heavy ion radiotherapy in patients with non-resectable osteosarcoma

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. For effective treatment, local control of the tumor is absolutely critical, because the chances of long term survival are <10% and might effectively approach zero if a complete surgical resection of the tumor is not possible. Up to date there is no curative treatment protocol for patients with non-resectable osteosarcomas, who are excluded from current osteosarcoma trials, e.g. <it>EURAMOS1</it>. Local photon radiotherapy has previously been used in small series and in an uncontrolled, highly individualized fashion, which, however, documented that high dose radiotherapy can, in principle, be used to achieve local control. Generally the radiation dose that is necessary for a curative approach can hardly be achieved with conventional photon radiotherapy in patients with non-resectable tumors that are usually located near radiosensitive critical organs such as the brain, the spine or the pelvis. In these cases particle Radiotherapy (proton therapy (PT)/heavy ion therapy (HIT) may offer a promising new alternative. Moreover, compared with photons, heavy ion beams provide a higher physical selectivity because of their finite depth coverage in tissue. They achieve a higher relative biological effectiveness. Phase I/II dose escalation studies of HIT in adults with non-resectable bone and soft tissue sarcomas have already shown favorable results.</p> <p>Methods/Design</p> <p>This is a monocenter, single-arm study for patients ≥ 6 years of age with non-resectable osteosarcoma. Desired target dose is 60-66 Cobalt Gray Equivalent (Gy E) with 45 Gy PT (proton therapy) and a carbon ion boost of 15-21 GyE. Weekly fractionation of 5-6 × 3 Gy E is used. PT/HIT will be administered exclusively at the Ion Radiotherapy Center in Heidelberg. Furthermore, FDG-PET imaging characteristics of non-resectable osteosarcoma before and after PT/HIT will be investigated prospectively. Systemic disease before and after PT/HIT is targeted by standard chemotherapy protocols and is not part of this trial.</p> <p>Discussion</p> <p>The primary objectives of this trial are the determination of feasibility and toxicity of HIT. Secondary objectives are tumor response, disease free survival and overall survival. The aim is to improve outcome for patients with non-resectable osteosarcoma.</p> <p>Trail Registration</p> <p>Registration number (ClinicalTrials.gov): NCT01005043</p

Combined treatment of adenoid cystic carcinoma with cetuximab and IMRT plus C12 heavy ion boost: ACCEPT [ACC, Erbitux® and particle therapy]

<p>Abstract</p> <p>Background</p> <p>Local control in adjuvant/definitive RT of adenoid cystic carcinoma (ACC) is largely dose-dependent leading to the establishment of particle therapy in this indication. However, even modern techniques leave space for improvement of local control by intensification of local treatment. Radiation sensitization by exploitation of high EGFR-expression in ACC with the EGFR receptor antibody cetuximab seems promising.</p> <p>Methods/design</p> <p>The ACCEPT trial is a prospective, mono-centric, phase I/II trial evaluating toxicity (primary endpoint: acute and late effects) and efficacy (secondary endpoint: local control, distant control, disease-free survival, overall survival) of the combined treatment with IMRT/carbon ion boost and weekly cetuximab in 49 patients with histologically proven (≥R1-resected, inoperable or Pn+) ACC. Patients receive 18 GyE carbon ions (6 fractions) and 54 Gy IMRT (2.0 Gy/fraction) in combination with weekly cetuximab throughout radiotherapy.</p> <p>Discussion</p> <p>The primary objective of ACCEPT is to evaluate toxicity and feasibility of cetuximab and particle therapy in adenoid cystic carcinoma.</p> <p>Trial Registration</p> <p>Clinical Trial Identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01192087">NCT 01192087</a></p> <p>EudraCT number: 2010 - 022425 - 15</p