[Show abstract][Hide abstract] ABSTRACT: Background
The standard trimodal treatment concept in locally advanced and non-metastasized non-small-cell superior sulcus tumors consists of a preoperative chemoradiation followed by surgical resection. High linear energy transfer (LET) radiation as, for example, C12 heavy-ion beam therapy theoretically offers biological advantages compared to high energy x-ray therapy as, for example, higher biological efficiency.
In the present prospective, single-armed, open pilot study performed at the Heidelberg Ion-Beam Therapy Center (HIT) in Heidelberg, the radiation treatment within the standard trimodal concept will be exchanged against C12 heavy-ion beam treatment and apply 39GyE in 13 single fractions in combination with a chemotherapy consisting of cisplatin and vinorelbine (local standard). The primary endpoint is feasibility and safety measured by the incidence of NCI-CTCAE grade 3/4 toxicity and/or discontinuation due to any reason. Secondary endpoint is the degree of regression in the histological specimen. The main inclusion criteria are histologically confirmed non-small-cell superior sulcus tumor, nodal disease stage ≤ N2, Karnofsky performance score ≥70%, patient age between 18 and 75 years as well as written informed consent. The main exclusion criteria include medical contraindications against elements of the trimodal treatment concept, PET confirmed nodal disease stage N3, stage IV disease, prior thoracic irradiation and decompensated diseases of the lung, cardio-vascular system, metabolism, hematopoietic and coagulation system and renal function. Furthermore, patients with implanted active medical devices without certification for ion-beam therapy are not allowed to take part in the study. Trial registration number: DRKS00006323 (www.drks.de).
BMC Cancer 12/2015; 15(1). DOI:10.1186/s12885-015-1163-7 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST).
We retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts).
Median follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays).
Carbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial.
[Show abstract][Hide abstract] ABSTRACT: A prospective study to assess toxicity and survival outcomes after intensity-modulated whole-abdominal irradiation (IM-WAI) following surgery and adjuvant intravenous carboplatin/taxane chemotherapy in advanced FIGO stage III ovarian cancer.
Between 2006 and 2009, 16 patients with optimally resected FIGO stage III ovarian cancer, who had received six cycles of adjuvant carboplatin/taxane chemotherapy were treated with consolidation IM-WAI. Radiotherapy was delivered to a total dose of 30 Gy in 1.5-Gy fractions, using step-and-shoot (n = 3) or helical tomotherapy (n = 13). The first 10 patients were treated within a phase I trial; the following patients received the same treatment modality. The target volume included the entire peritoneal cavity, the diaphragm, the liver capsule, and the pelvic and para-aortic node regions. Organs at risk were kidneys, liver, heart, and bone marrow.
Median follow-up was 44 months (range 19.2-67.2 months). No grade 4 toxicities occurred during IM-WAI. Common Toxicity Criteria for Adverse Events (CTCAE) grade 3 toxicities were: diarrhea (25 %), leucopenia (19 %), nausea/vomiting (6 %), and thrombocytopenia (6 %). No toxicity-related treatment break was necessary. Small bowel obstruction occurred in a total of 6 patients: in 3 cases (19 %) due to postsurgical adhesions and in 3 cases due to local tumor recurrence (19 %). Median recurrence-free survival (RFS) was 27.6 months (95 % confidence interval, CI = 24-44 months) and median overall survival (OS) was 42.1 months (95 %CI = 17-68 months). The peritoneal cavity was the most frequent site of initial failure.
Consolidation IM-WAI following surgery and adjuvant chemotherapy is feasible and can be performed with manageable acute and late toxicity. The favorable RFS outcome is promising and justifies further clinical trials.
Strahlentherapie und Onkologie 03/2015; 191(7). DOI:10.1007/s00066-015-0830-6 · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this work was to evaluate the results of high-dose radiation treatment using carbon ion therapy, alone or combined with intensity-modulated radiation treatment (IMRT), in patients with sacral chordoma.
Between 2009 and 2012, 56 patients with sacral chordoma were treated in our center. The tumor was located above S3 in 33 patients and in S3 or below in 23 patients. In all, 41 patients received radiation therapy for the primary tumor, while 15 patients were treated for the recurrent tumor. Toxicity was measured using NCI CTCAE v.4.03. Local control (LC) and overall survival (OS) were evaluated with the Kaplan-Meier method.
A total of 23 patients were irradiated with carbon ions in combination with photon IMRT, while 33 received carbon ion therapy only. Forty-three patients had a macroscopic tumor at treatment start with a median tumor size (GTV) of 244 ml (range 5-1188 ml). The median total dose was 66 Gy (range 60-74 Gy; RBE). After a median follow-up time of 25 months, the 2- and 3-year local control probability was 76 % and 53 %, respectively. The overall survival rate was 100 %. Treatment for primary tumor and male patients resulted in significant better local control. No higher toxicity occurred within the follow-up time.
High-dose photon/carbon ion beam radiation therapy is safe and, especially for primary sacral chordomas, highly effective. A randomized trial is required to evaluate the role of primary definitive hypofractionated particle therapy compared with surgery with or without adjuvant radiotherapy.
Strahlentherapie und Onkologie 03/2015; 191(7). DOI:10.1007/s00066-015-0825-3 · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hintergrund und Fragestellung: Publikationen zur Low-Dose-Radiotherapie (LDRT) von indolenten Lymphomen konnten über hohe Ansprechraten berichten [1, 2, 3]. In dieser prospektiven, randomisierten, multizentrischen Phase-III-Studie aus Großbritannien wurde die Effektivität einer LDRT (2-mal 2 Gy) mit der Standardbestrahlung von 12-mal 2 Gy bei Patienten mit indolenten Lymphomen überprüft.Patienten und Methoden: Von April 2006 bis Juni 2011 wurden Patienten mit histologisch gesicherten follikulären oder Marginalzonenlymphomen der Stadien I-IV, die einen Monat zuvor keine weitere Therapie erhalten hatten, in die Studie eingeschlossen. Nach zentraler Randomisierung wurden 614 Bestrahlungsareale (299 mit 24 Gy; 315 mit 4 Gy) ausgewertet. Ziel war der Nachweis einer Nichtunterlegenheit der LDRT bezüglich lokaler Progressionsfreiheit nach zwei Jahren (primärer Endpunkt: Unterschied < 10 %; Hazard Ratio [HR] 1,37). Als sekundäre Endpunkte wurden das Gesamtüberleben, die Toxizität sowie die Leb ...
[Show abstract][Hide abstract] ABSTRACT: 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. We describe our initial results for re-irradiation in heavily pre-treated ACC patients.
Patients treated with carbon ion therapy between 04/2010 and 05/2013 (N=52pts, median age: 54 a) were retrospectively evaluated regarding toxicity (NCI CTC v.4), tumour response (RECIST) and control rates. 48pts (92.3%) received carbon ions only, 4pts received IMRT plus C12.
4pts were treated following R1-resection, 43pts for inoperable local relapse. Most common tumour sites were paranasal sinus (36.5%), parotid (19.2%), and base of skull (17.3%). Pts received a median dose of 51GyE C12/63Gy BED and cumulative dose of 128Gy BED [67-182Gy] after a median RT-interval of 61months. Median target volume was 93ml [9-618ml]. No higher-grade (>°II) acute reactions were observed, 7pts showed blood-brain-barrier changes (°I/II: 8pts; °III: 2pts), 1 pt corneal ulceration, xerophthalmia 7pts, °IV bleeding 1 pt, tissue necrosis 2pts, otherwise no significant late reactions. Objective response rate (CR/PR) was 56.6%. With a median follow-up of 14months [1-39months] local control and distant control at 1a are 70.3% and 72.6% respectively. Of the 18pts with local relapse, 13pts have recurred in-field, 1 pt at the field edge, 3pts out of field, and one in the dose gradient.
Despite high applied doses, C12 re-irradiation shows moderate side-effects, response rates even in these heavily pre-treated patients are encouraging and present a good alternative to palliative chemotherapy. Though most local recurrences occur within the high-dose area, further dose escalation should be viewed with caution.
Radiotherapy and Oncology 01/2015; 60(2). DOI:10.1016/j.radonc.2015.01.002 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate HPV-DNA and p16INK4a (p16) expression as prognostic markers for outcome in patients with anal cancer.Methods
From January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry.ResultsMedian follow-up was 48.6 months (range 2.8–169.1 months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p = 0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p < 0.001] and improved local control [81.0% vs. 55.9%, p = 0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p = 0.015] and PFS [p = 0.002] for cHPPAC.Conclusion
The combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.
Radiotherapy and Oncology 11/2014; 113(3). DOI:10.1016/j.radonc.2014.11.013 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND
The current study was conducted to evaluate the long-term results of irradiation with carbon ions in a raster scanning technique in patients with skull base chordomas. METHODS
Between 1998 and 2008, a total of 155 patients (76 men and 79 women) with a median age of 48 years (range, 15 years-85 years) were irradiated with carbon ions using a raster scan technique. The irradiation was performed at the Society for Heavy Ion Research in Darmstadt, Germany. The median total dose was 60 gray (relative biological effectiveness) at 3 gray (relative biological effectiveness) per fraction. The median boost planning target volume was 70 mL (range, 2 mL-294 mL). Local control (LC) and overall survival (OS) were evaluated using the Kaplan-Meier method, whereas long-term toxicity was evaluated via questionnaires. RESULTSThe median follow-up was 72 months (range, 12 months-165 months). All patients had residual macroscopic tumors at the initiation of radiotherapy. The authors observed 55 local recurrences during follow-up, as well as systemic disease progression in 4 patients. The resulting 3-year, 5-year, and 10-year LC rates were 82%, 72%, and 54%, respectively, whereas the 3-year, 5-year, and 10-year OS rates were 95%, 85%, and 75%, respectively. Age <48 years and a boost volume >75 mL were associated with a significantly improved LC and OS. Primary treatment resulted in a significantly better OS probability. No higher late toxicity could be detected after carbon ion treatment. CONCLUSIONS
Carbon ion therapy appears to be a safe and effective treatment for patients with skull base chordoma, resulting in high LC and OS rates. Cancer 2014;120:3410-3417. (c) 2014 American Cancer Society.
Cancer 11/2014; 120(21). DOI:10.1002/cncr.28877 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Protons and carbon ions currently are the most used charged-particle therapies in the cancer treatment of humans. This review summarizes the physical and biological differences and their impact on clinical use. Furthermore, published data in the treatment of several tumor entities and the use of protons and carbon ions are collected and discussed.
The Cancer Journal 11/2014; 20(6):433-9. DOI:10.1097/PPO.0000000000000078 · 4.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In radiotherapy, in vivo measurement of dose distribution within patients' lymphocytes can be performed by detecting gamma-H2AX foci in lymphocyte nuclei. This method can help in determining the whole-body dose. Options for risk estimations for toxicities in normal tissue and for the incidence of secondary malignancy are still under debate. In this investigation, helical tomotherapy (TOMO) is compared with step-and-shoot IMRT (SSIMRT) of the prostate gland by measuring the dose distribution within patients' lymphocytes. In this prospective study, blood was taken from 20 patients before and 10 min after their first irradiation fraction for each technique. The isolated leukocytes were fixed 2 h after radiation. DNA double-stranded breaks in lymphocyte nuclei were stained immunocytochemically using anti-gamma-H2AX antibodies. Gamma-H2AX foci distribution in lymphocytes was determined for each patient. Using a calibration line, dose distributions in patients' lymphocytes were determined by studying the gamma-H2AX foci distribution, and these data were used to generate a cumulative dose-lymphocyte histogram (DLH). Measured in vivo (DLH), significantly fewer lymphocytes indicated low-dose exposure (<40% of the applied dose) during TOMO compared with SSIMRT. The dose exposure range, between 45 and 100%, was equal with both radiation techniques. The mean number of gamma-H2AX foci per lymphocyte was significantly lower in the TOMO group compared with the SSIMRT group. In radiotherapy of the prostate gland, TOMO generates a smaller fraction of patients' lymphocytes with low-dose exposure relative to the whole body compared with SSIMRT. Differences in the constructional buildup of the different linear accelerator systems, e.g. the flattening filter, may be the cause thereof. The influence of these methods on the incidence of secondary malignancy should be investigated in further studies.
Journal of Radiation Research 10/2014; 56(2). DOI:10.1093/jrr/rru096 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose
Hypofractionated radiation therapy as primary treatment for prostate cancer is currently being investigated in large phase 3 trials. However, there are few data on postoperative hypofractionation. The Radiation therapy for the Prostate Bed With or Without the Pelvic Lymph Nodes (PRIAMOS 1) trial was initiated as a prospective phase 2 trial to assess treatment safety and toxicity of a hypofractionated intensity modulated radiation therapy (IMRT) of the prostate bed.
Methods and Materials
From February to September 2012, 40 patients with indications for adjuvant or salvage radiation therapy were enrolled. One patient dropped out before treatment. Patients received 54 Gy in 18 fractions to the prostate bed with IMRT and daily image guidance. Gastrointestinal (GI) and genitourinary (GU) toxicities (according to National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0) were recorded weekly during treatment and 10 weeks after radiation therapy.
Overall acute toxicity was favorable, with no recorded adverse events grade ≥3. Acute GI toxicity rates were 56.4% (grade 1) and 17.9% (grade 2). Acute GU toxicity was recorded in 35.9% of patients (maximum grade 1). Urinary stress incontinence was not influenced by radiation therapy. The incidence of grade 1 urinary urge incontinence increased from 2.6% before to 23.1% 10 weeks after therapy, but grade 2 urge incontinence remained unchanged.
Postoperative hypofractionated IMRT of the prostate bed is tolerated well, with no severe acute side effects.
International journal of radiation oncology, biology, physics 09/2014; 90(4). DOI:10.1016/j.ijrobp.2014.07.015 · 4.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a practical guideline for safe and effective stereotactic body radiotherapy (SBRT) of liver tumors.
METHODS: The literature on the clinical evidence of SBRT for both primary liver tumors and liver metastases was reviewed and analyzed focusing on both physical requirements and special biological characteristics.
RESULTS: Recommendations were developed for patient selection, imaging, planning, treatment delivery, motion management, dose reporting, and follow-up. Radiation dose constraints to critical organs at risk are provided.
CONCLUSION: SBRT is a well-established treatment option for primary and secondary liver tumors associated with low morbidity.
Strahlentherapie und Onkologie 08/2014; 190(10). DOI:10.1007/s00066-014-0714-1 · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OriginalbeitragTjessem KH, Johansen S, Malinen E et al (2013) Long-term cardiac mortality after hypofractionated radiation therapy in breast cancer. Int J Radiat Oncol Biol Phys 87:337–343Ziel der ArbeitWährend der letzten Jahre gewinnt die hypofraktionierte Radiotherapie beim Mammakarzinom zunehmend an Bedeutung. Tjessem und Kollegen aus Norwegen führten daher eine retrospektive Analyse der kardial bedingten Letalität innerhalb von 20 Jahren nach lokoregionaler Bestrahlung bei Patientinnen mit Mammakarzinom in Bezug auf den Grad der Hypofraktionierung und weiterer Behandlungsvariablen durch.Patienten und MethodeDie Fall-Kontroll-Studie umfasste 1566 norwegische Mammakarzinompatientinnen aus den Jahren 1975 bis 1991. Zwei hypofraktionierte Bestrahlungsregime kamen zum Einsatz: entweder 4,3 Gy 2-mal/Woche bis zu einer Gesamtdosis von 43,0 Gy (n = 1107) oder 2,5 Gy 4-mal/Woche bis zu einer Gesamtdosis von 50,0 Gy (n = 459). Um die kardiale Dosis retrospektiv abschätzen zu können, wurden ...
Strahlentherapie und Onkologie 08/2014; 190(8):774-775. DOI:10.1007/s00066-014-0684-3 · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Scalp angiosarcoma represents a therapeutic challenge to all disciplines. This case report demonstrates the potential usefulness of helical tomotherapy (HT) as a new radiotherapeutic treatment option. A 71-year-old woman presented with a superficial angiosarcoma of the scalp, forehead, and left pre- and postauricular areas, with several nodular ulcerating and bleeding lesions. Irradiation of the gross tumor was performed with a total dose of 70 Gy in 2-Gy fractions and of the left cervical lymph nodes with 56 Gy in 1.6-Gy fractions. Good target coverage was achieved without compromising organs at risk, notably the brain. Treatment was very fast (661 seconds per fraction) and was administered with minimal acute toxicity (National Cancer Institute Common Toxicity Criteria: grade 2 erythema and grade 2 dysphagia). During treatment, tumor nodules dissolved into hyperkeratosis. We conclude that with HT, irradiation of the scalp and cervical lymph nodes can be conducted with minimal acute toxicity and without junction problems.
[Show abstract][Hide abstract] ABSTRACT: Background
Concurrent chemotherapy and radiation therapy is the preferred standard of care for patients with anal cancer. Several studies have suggested a benefit of intensity-modulated radiation therapy (IMRT) compared with 3D-conformal radiation (3D-CRT) regarding acute toxicity. This study evaluates outcome and toxicity of patients undergoing IMRT/Tomotherapy or 3D-CRT at our institution.
A cohort of 105 anal cancer patients was treated with chemoradiation or radiation alone (16.2%) between January 2000 and December 2011. 37 patients received 3D-CRT while 68 patients were treated with IMRT. Follow-up exams were performed every 3 to 6 months for a minimum of 3 years and then annually.
Median follow-up was 41.4 months (2.8 – 158.4). Overall survival (OS), Progression-free survival (PFS) and local control (LC) at 3 years was 70.3%, 66.5%, 78.3% in the 3D-CRT group and 82.9%, 66.5%, 75.3% in the IMRT group without statistically significant difference. 3-year Colostomy-free survival (CFS) was 85.7% in the IMRT/Tomotherapy group and 91.8% in the 3D-CRT group (p = 0.48). No grade 4 toxicity was found in both groups. Severe (G2/3) acute skin toxicity (94.6% vs. 63.2%; p < 0.001) and acute gastrointestinal toxicity rate (67.6% vs. 47.1%; p = 0.03) was significantly higher with 3D-CRT compared to IMRT/Tomotherapy.
The use of IMRT can reduce acute severe side effects of the skin and gastrointestinal tract but did not demonstrate improved results regarding OS, PFS, LC and CFS.