The Phase 1/2 ACCEPT Trial: Concurrent Cetuximab and Intensity Modulated Radiation Therapy with Carbon Ion Boost for Adenoid Cystic Carcinoma of the Head and Neck.

Purpose: The adenoid cystic carcinoma (ACC), Erbitux, and Particle Therapy (ACCEPT) phase 1/2 trial (NCT01192087) evaluated a combined-modality approach (concurrent cetuximab and intensity modulated radiation therapy with carbon ion boost) for newly diagnosed nonmetastatic head and neck ACC.

Methods And Materials: Twenty-three patients with ACC were enrolled between June 2012 and June 2017 after initial diagnosis or postoperatively. All received a 400 mg/m cetuximab loading dose a week before radiation therapy, followed by weekly 250 mg/m doses starting on the first day of radiation therapy.

Persistence of radiation-induced aberrations in patients after radiotherapy with C-ions and IMRT.

Background And Purpose: Chromosomal aberrations in peripheral blood lymphocytes are a biomarker for radiation exposure and are associated with an increased risk for malignancies. To determine the long-term cytogenetic effect of radiotherapy, we analyzed the persistence of different aberration types up to 2.5 years after the treatment.

COSMIC: A Regimen of Intensity Modulated Radiation Therapy Plus Dose-Escalated, Raster-Scanned Carbon Ion Boost for Malignant Salivary Gland Tumors: Results of the Prospective Phase 2 Trial.

Purpose: To investigate the effect of intensity modulated radiation therapy (IMRT) and dose-escalated carbon ion (C12) therapy in adenoid cystic carcinoma (ACC) and other malignant salivary gland tumors (MSGTs) of the head and neck.

Patients And Methods: COSMIC (combined treatment of malignant salivary gland tumors with intensity modulated radiation therapy and carbon ions) is a prospective phase 2 trial of 24 Gy(RBE) C12 followed by 50 Gy IMRT in patients with pathologically confirmed MSGT. The primary endpoint is mucositis Common Terminology Criteria grade 3; the secondary endpoints are locoregional control (LC), progression-free survival (PFS), overall survival (OS), and toxicity.

High-LET radiotherapy for adenoid cystic carcinoma of the head and neck: 15 years' experience with raster-scanned carbon ion therapy.

Purpose: Locoregional control (LC) in malignant salivary gland tumors is dose-dependent, initial results with particle therapy were promising. We report our experience with raster-scanned, intensity-controlled carbon ion therapy (C12) and IMRT in 309 patients with pathologically confirmed adenoid cystic carcinoma (ACC) of the head and neck.

Patients And Methods: Treatment records of patients treated with C12 between 08/1998 and 05/2013 were evaluated regarding tumor stage, treatment, toxicity (CTCAE v3), LC, progression-free survival (PFS) and overall survival (OS).

Combined intensity-modulated radiotherapy plus raster-scanned carbon ion boost for advanced adenoid cystic carcinoma of the head and neck results in superior locoregional control and overall survival.

Background: Local control in patients with adenoid cystic carcinoma (ACC) of the head and neck remains a challenge because of the relative radioresistance of these tumors. This prospective carbon ion pilot project was designed to evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost (C12 therapy). The authors present the first analysis of long-term outcomes of raster-scanned C12 therapy compared with modern photon techniques.

Re-irradiation of adenoid cystic carcinoma: analysis and evaluation of outcome in 52 consecutive patients treated with raster-scanned carbon ion therapy.

Background: Treatment of local relapse in adenoid cystic carcinoma (ACC) following prior radiation remains a challenge: without the possibility of surgical salvage patients face the choice between palliative chemotherapy and re-irradiation. Chemotherapy yields response rates around 30% and application of tumouricidal doses is difficult due to proximity of critical structures. Carbon ion therapy (C12) is a promising method to minimize side-effects and maximize re-treatment dose in this indication.

Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma: interim analysis.

Background: To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123).

Methods: Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50 Gy to PTV and 50-56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12 Gy).

Chromosome inversions in lymphocytes of prostate cancer patients treated with X-rays and carbon ions.

Background And Purpose: To investigate the cytogenetic damage of the intrachange type in peripheral blood lymphocytes of patients treated for prostate cancer with different radiation qualities.

Material And Methods: Prostate cancer patients were enrolled in a clinical trial based at the Heidelberg University Hospital and at the GSI Helmholtz Centre for Heavy Ion Research in 2006. Patients were treated either with intensity-modulated radiation therapy (IMRT) alone or with a carbon-ion boost followed by IMRT.

Age-dependent effect of static magnetic field on brain tissue hydration.

Age-dependent effect of Static Magnetic Field (SMF) on rats in a condition of active and inactive Na(+)/K(+) pump was studied for comparison of brain tissues hydration state changes and magnetic sensitivity. Influence of 15 min 0, 2 Tesla (T) SMF on brain tissue hydration of three aged groups of male albino rats was studied. Tyrode's physiological solution and 10(-4) M ouabain was used for intraperitoneal injections.

The impact of background radiation, illumination and temperature on EMF-induced changes of aqua medium properties.

The effects of extremely low frequency electromagnetic field (ELF EMF) on physicochemical properties of physiological solution at different environmental media were studied. The existence of frequency "windows" at 4 and 8 Hz frequencies of ELF EMF having effects on heat fusion period, hydrogen peroxide (H2O2) formation and oxygen (O2) content of water solution and different dependency on temperature, background radiation and illumination was shown. Obtained data allow us to suggest that EMF-induced effect on water physicochemical properties depends on abovementioned environmental factors.

A clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma.

Background: Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted.

IMRT and carbon ion boost for malignant salivary gland tumors: interim analysis of the COSMIC trial.

Background: The COSMIC trial is designed to evaluate toxicity in dose-escalated treatment with intensity-modulated radiotherapy (IMRT) and carbon ion boost for malignant salivary gland tumors (MSGT) of the head and neck including patients with inoperable/ incompletely resected MSGTs (R2-group) and completely resected tumors plus involved margins or perineural spread (R1-group).

Methods: COSMIC is a prospective phase II trial of IMRT (25 × 2 Gy) and carbon ion boost (8 × 3 GyE). Primary endpoint is mucositis CTC°III, secondary endpoints are local control, progression-free survival, and toxicity.

Radiochemoimmunotherapy with intensity-modulated concomitant boost: interim analysis of the REACH trial.

Purpose: To evaluate efficacy and toxicity clinical in the intensified treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) with the combination of chemotherapy, the EGFR antibody cetuximab, and intensity-modulated radiation therapy (IMRT) in a concomitant boost concept.

Methods: REACH is a prospective, bi-centric phase II trial of carboplatin/5-FU and cetuximab weekly combined with IMRT. Primary endpoint is locoregional control, secondary endpoints include acute radiation effects and adverse events.

Cell bathing medium as a target for non thermal effect of millimeter waves.

Non thermal (NT) effect of direct radiation 4 Hz-modulated 90-160 GHz of Millimeter Waves (MMW) and preliminary MMW-treated physiological solution (PS) influence were studied on snail isolated neuron, rat's brain tissue hydration and skin penetration. It was shown that the 4 Hz-modulated low intensity 90-160 GHz MMW direct radiation and MMW-treated PS leads to on single neuron shrinkage, skin and brain tissue dehydration. On the basis of obtained data it was suggested that the cell bathing aqua medium serve as a target through which the NT effect of MMW on cell hydration is realized.

Raster-scanned carbon ion therapy for malignant salivary gland tumors: acute toxicity and initial treatment response.

Background And Purpose: To investigate toxicity and efficacy in high-risk malignant salivary gland tumors (MSGT) of the head and neck. Local control in R2-resected adenoid cystic carcinoma was already improved with a combination of IMRT and carbon ion boost at only mild side-effects, hence this treatment was also offered to patients with MSGT and microscopic residual disease (R1) or perineural spread (Pn+).

Methods: From November 2009, all patients with MSGT treated with carbon ion therapy were evaluated.

Acute toxicity of combined photon IMRT and carbon ion boost for intermediate-risk prostate cancer - acute toxicity of 12C for PC.

Background: Carbon ion ((12)C) therapy in the treatment of prostate cancer (PC) might result in an improved outcome as compared to low linear energy transfer irradiation techniques. In this study, we present the first interim report of acute side effects of the first intermediate-risk PC patients treated at the GSI (Gesellschaft für Schwerionenforschung) and the University of Heidelberg in an ongoing clinical phase I/II trial using combined photon intensity modulated radiation therapy (IMRT) and (12)C carbon ion boost.

Material And Methods: Fourteen patients (planned accrual: 31 pts) have been treated within this trial so far.

Re-irradiation with scanned charged particle beams in recurrent tumours of the head and neck: acute toxicity and feasibility.

Background: Treatment of surgically unresectable recurrence in the head and neck region remains a therapeutic problem with the only curative option being a second course of radiation with a tumouricidal dose. We report initial toxicity and efficacy of charged particle therapy in this situation.

Methods: Treatment-related side-effects of patients treated with charged particle beams for recurrent tumours of the head and neck were prospectively collected and patient data was retrospectively analysed with regard to toxicity and efficacy of the treatment according to CTCAE v.

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

Background: 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.

Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity.

Purpose: To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects.

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

Background: 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.

Assessment of early toxicity and response in patients treated with proton and carbon ion therapy at the Heidelberg ion therapy center using the raster scanning technique.

Unlabelled: PUROPOSE: To asses early toxicity and response in 118 patients treated with scanned ion beams to validate the safety of intensity-controlled raster scanning at the Heidelberg Ion Therapy Center.

Patients And Methods: Between November 2009 and June 2010, we treated 118 patients with proton and carbon ion radiotherapy (RT) using active beam delivery. The main indications included skull base chordomas and chondrosarcomas, salivary gland tumors, and gliomas.

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.

Carbon ion radiotherapy performed as re-irradiation using active beam delivery in patients with tumors of the brain, skull base and sacral region.

Introduction: To asses carbon ion radiation therapy (RT) performed as re-irradiation in 28 patients with recurrent tumors.

Materials And Methods: Twenty-eight patients were treated with carbon ion RT as re-irradiation for recurrent chordoma and chondrosarcoma of the skull base (n=16 and n=2), one chordoma and one chondrosarcoma of the os sacrum, high-risk meningioma (n=3), adenoid-cystic carcinoma (n=4) as well as one SCCHN. All patients were treated using active raster scanning, and treatment planning was performed on CT- and MRI-basis.

Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease.

Purpose: To investigate treatment outcome in patients suffering from sacral chordoma after intensity modulated radiotherapy (IMRT) for primary versus recurrent disease.

Material/methods: We report on 34 patients with histologically proven sacral chordoma. Seventeen patients were treated at time of initial diagnosis with post-operative IMRT (n=13) or with IMRT alone (n=4).

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

Background: 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.