High control rate in patients with chondrosarcoma of the skull base after carbon ion therapy: first report of long-term results.

BACKGROUND: The current study was performed to evaluate the safety and effectiveness of irradiation with carbon ions using raster scanning as well as prognostic factors in patients with skull base chondrosarcomas. METHODS: Between 1998 and 2008, 79 patients with chondrosarcoma of the skull base were treated using carbon ions in raster scanning. The applied median total dose was 60 gray equivalent (GyE) at 3 GyE per fraction. Local control and overall survival (OS) were evaluated using the Kaplan-Meier method. Long-term toxicity was quantitatively assessed using questionnaires. RESULTS: The median follow-up after irradiation was 91 months (range, 3 months-175 months). Within the follow-up, 10 patients developed local disease recurrence. The 3-year, 5-year, and 10-year local control rates were 95.9%, 88%, and 88%, respectively; the corresponding OS rates were 96.1%, 96.1%, and 78.9%, respectively. With a median follow-up of 110 months after first diagnosis, the corresponding 3-year, 5-year, and 10-year OS rates were 97.5%, 97.5%, and 91.5%, respectively. Age ≤ 45 years and boost volume ≤ 55 mL were associated with significantly better local control rates. We observed a clinically relevant improvement in cranial nerve deficits 7 to 10 years after treatment (range, 45.5%-53.3%) compared with the baseline (73.4%). During follow-up, none of the patients in the current study developed a secondary malignancy. CONCLUSIONS: Carbon ion therapy is a safe and effective treatment in patients with chondrosarcoma of the skull base. For further evaluation, a prospective randomized phase 3 trial comparing protons versus carbon ions has been recruiting patients with low-grade and intermediate-grade chondrosarcoma of the skull base since 2009.

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. Evaluation of disease response is carried out according to the Response Evaluation Criteria in Solid Tumors (RECIST); toxicity is assessed using NCI CTC v 3.0. RESULTS: Twenty-nine patients were recruited from 07/2010 to 04/2011, all patients have at least completed first follow-up. Sixteen patients were treated in the R2-group, 13 in the R1-group. All treatments were completed as planned and well tolerated, mucositis CTC grade III was 25% (R2) and 15.4% (R1), no dysphagia CTC grade III was observed, no feeding tubes were necessary. Side-effects rapidly resolved, only 4 patients (13.8%) reported xerostomia grade II at first follow-up. Overall response rate (complete and partial response) according to RECIST in the R2-group is 68.8% at 6-8 weeks post treatment, all patients within this group showed radiological signs of treatment response. CONCLUSION: No unexpected toxicity was observed, mucositis rates and other side effects do not differ between patients with visible residual tumor and macroscopically completely resected tumors. Initial treatment response is promising though longer follow-up is needed to assess local control. TRIAL REGISTRATION: Clinical trial identifier NCT 01154270.

Combined treatment of nonsmall cell lung cancer NSCLC stage III with intensity-modulated RT radiotherapy and cetuximab: the NEAR trial.

BACKGROUND: The aim of this study was to evaluate efficacy and toxicity of radioimmunotherapy with intensity-modulated radiation (IMRT) and cetuximab in stage III nonsmall cell lung cancer (NSCLC). METHODS: NEAR was a prospective, monocentric phase II trial including patients unfit for chemoradiation regimen; treatment consisted of IMRT and weekly cetuximab followed by a 13-week maintenance period. Primary endpoints were toxicity and feasibility; secondary endpoints were remission rates at completion of the planned treatment according to Response Evaluation Criteria In Solid Tumor (RECIST), local/distant progression-free survival, and overall survival. RESULTS: Thirty patients (median age, 71 years) were treated within the protocol. Overall response rate was 63% (partial remission: 19 of 30) patients. Median locoregional, distant, overall progression-free survival was 20.5, 10.9, and 8.5 months. Median overall survival was 19.5 months, with an estimated 1- and 2-year survival of 66.7% and 34.9% respectively. Stage (IIIA vs IIIB) and histologic subtype did not have a significant impact on survival rates in our patients. Treatment was tolerated well with only mild toxicity (°3 pneumonitis: 3.3%, any °3 acute toxicity: 36.7%). CONCLUSIONS: Combined radioimmunotherapy with cetuximab was safe and feasible, especially in elderly patients with multiple comorbidities. A more intensified regimen warranted investigation.

Reirradiation of multiple brain metastases with helical tomotherapy. A multifocal simultaneous integrated boost for eight or more lesions.

BACKGROUND AND PURPOSE: : Recurrent brain metastases or new brain lesions after whole-brain radiotherapy represent a therapeutic challenge. While several treatment methods for single or few lesions have been described, options for multiple lesions are limited. This case report is intended to show an approach of whole-brain reirradiation with a simultaneous multifocal integrated boost using helical tomotherapy. Technique, feasibility, and acute side effects are presented. PATIENTS AND METHODS: : Two patients with multiple relapsed brain metastases (eight and eleven lesions) were reirradiated after previous whole-brain radiotherapy (total dose of 40 Gy 18 months before). Whole-brain reirradiation was performed using helical tomotherapy with a total dose of 15 Gy (single dose 1.5 Gy) and a multifocal simultaneous integrated boost with a total dose of 30 Gy (single dose 3 Gy) to the brain lesions. The boost planning target volume was delineated around the lesions visible on MRI plus a 2-mm margin. Follow-up of these patients was 6 and 12 months. RESULTS: : Radiation plans with excellent conformity and homogeneity were obtained. High dose exposure to normal brain tissue was kept minimal. Mean radiation time was 13 min. The only acute side effect observed was a mild headache over 2 days at the end of treatment. So far, no further side effects and no signs of recurrence have been observed. CONCLUSION: : Helical tomotherapy offers new treatment options for the reirradiation of multiple brain metastases. The number of cases treated with the described protocol is very limited but it is considered a promising option for patients that have responded well to the initial radiotherapy and are in a good performance status.

Comparison of arc-modulated cone beam therapy and helical tomotherapy for three different types of cancer.

PURPOSE: Arc-modulated cone beam therapy (AMCBT) is a fast treatment technique deliverable in a single rotation with a conventional C-arm shaped linac. In this planning study, the authors assess the dosimetric properties of single-arc therapy in comparison to helical tomotherapy for three different tumor types. METHODS: Treatment plans for three patients with prostate carcinoma, three patients with anal cancer, and three patients with head and neck cancer were optimized for helical tomotherapy and AMCBT. The dosimetric comparison of the two techniques is based on physical quantities derived from dose-volume histograms. RESULTS: For prostate cancer, the quality of dose distributions calculated for AMCBT was of equal quality as that generated for tomotherapy with the additional benefits of a faster delivery and a lower integral dose. For highly complex geometries, the plan quality achievable with helical tomotherapy could not be achieved with arc-modulated cone beam therapy. CONCLUSIONS: Rotation therapy with a conventional linac in a single arc is capable to deliver a high and homogeneous dose to the target and spare organs at risk. Advantages of this technique are a fast treatment time and a lower integral dose in comparison to helical tomotherapy. For highly complex cases, e.g., with several target regions, the dose shaping capabilities of AMCBT are inferior to those of tomotherapy. However, treatment plans for AMCBT were also clinically acceptable.

Evaluating target coverage and normal tissue sparing in the adjuvant radiotherapy of malignant pleural mesothelioma: helical tomotherapy compared with step-and-shoot IMRT.

PURPOSE: To evaluate the potential of helical tomotherapy in the adjuvant treatment of malignant pleural mesothelioma and compare target homogeneity, conformity and normal tissue dose with step-and-shoot intensity-modulated radiotherapy. METHODS AND MATERIALS: Ten patients with malignant pleural mesothelioma who had undergone neoadjuvant chemotherapy with cisplatin and permetrexed followed by extrapleural pneumonectomy (EPP) were treated in our department with 54 Gy to the hemithorax delivered by step-and-shoot IMRT. A planning comparison was performed by creating radiation plans for helical tomotherapy. The different plans were compared by analysing target homogeneity using the homogeneity indices HI(max) and HI(min) and target conformity by using the conformity index CI(95). To assess target coverage and normal tissue sparing TV(90), TV(95) and mean and maximum doses were compared. RESULTS: Both modalities achieved excellent dose distributions while sparing organs at risk. Target coverage and homogeneity could be increased significantly with helical tomotherapy compared with step-and-shoot IMRT. Mean dose to the contralateral lung could be lowered beyond 5 Gy. CONCLUSIONS: Our planning study showed that helical tomotherapy is an excellent option for the adjuvant intensity-modulated radiotherapy of MPM. It is capable of improving target coverage and homogeneity.

Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine.

PURPOSE: The aim of this study was to compare changes in salivary gland function after intensity-modulated radiotherapy (IMRT) and conventional radiotherapy (RT), with or without Amifostine, for tumors of the head-and-neck region using quantitative salivary gland scintigraphy (QSGS). METHODS AND MATERIALS: A total of 75 patients received pre- and post-therapeutic QSGS to quantify the salivary gland function. In all, 251 salivary glands were independently evaluated. Changes in the maximum uptake (DeltaU) and relative excretion rate (DeltaF) both pre- and post-RT were determined to characterize radiation-induced changes in the salivary gland function. In addition, dose-response curves were calculated. RESULTS: In all groups, maximum uptake and relative excretion rate were reduced after RT (DeltaU

Carbon Ion irradiation in the treatment of grossly incomplete or unresectable malignant peripheral nerve sheaths tumors: acute toxicity and preliminary outcome.

BACKGROUND: To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST). METHODS: 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). RESULTS: 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). CONCLUSION: 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.

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. We describe our initial results for re-irradiation in heavily pre-treated ACC patients. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Stereotactic single-dose radiotherapy of stage I non-small-cell lung cancer (NSCLC).

PURPOSE: The treatment of early-stage lung cancers is a primary domain of thoracic surgery, leading to persuasive results. In patients with medical contraindications, radiotherapy is an alternative, although with considerably worse outcome. Radiotherapy is associated with the risk of severe acute side effects and a permanent decrease of lung function. By the introduction of an extracranial stereotactic treatment technique, the amount of normal tissue in the high-dose region can be reduced, allowing the performance of single-dose treatment with high, biologically effective doses. METHODS AND MATERIALS: Between October 1998 and May 2001, 10 patients with histologically confirmed Stage I non-small-cell lung cancer were treated with stereotactic single-dose radiotherapy. A self-developed stereotactic frame was used for patient positioning and navigation. Total doses applied ranged from 19 to 26 Gy. After treatment, regular CT-based follow-up was performed. RESULTS: During a median follow-up period of 14.9 months, the tumors in 8 of 10 patients were locally controlled. The actuarial overall survival was 80% and 64%, respectively, 12 and 24 months after therapy. Actuarial local recurrence-free survival reached 88.9% and 71.1%, respectively. Therapy-related perifocal normal-tissue reaction occurred in 70% of all treated patients, although no major clinical symptoms were seen. In 5 patients, systemic metastases were found during follow-up; 1 patient developed suspect mediastinal lymph nodes. CONCLUSION: Stereotactic single-fraction radiotherapy is a feasible, safe, and effective procedure for the treatment of Stage I non-small-cell lung cancer. It promises high local control with a reduced overall treatment time. However, further investigation in a larger patient collective with extended follow-up is necessary.

Fractionated stereotactic radiotherapy for craniopharyngiomas.

PURPOSE: To investigate outcome and toxicity after fractionated stereotactic radiation therapy (FSRT) in patients with craniopharyngiomas. METHODS AND MATERIALS: Twenty-six patients with craniopharyngiomas were treated with FSRT between May 1989 and February 2001. Median age was 33.5 years (range: 5-57 years). Nine patients received FSRT after surgery as primary treatment, and 17 patients were irradiated for recurrent tumor or progressive growth after initial surgery. Median target dose was 52.2 Gy (range: 50.0-57.6 Gy) with conventional fractionation. Follow-up included MRI and neurologic, ophthalmologic, and endocrinologic examinations. RESULTS: The median follow-up was 43 months (range: 7-143 months). The actuarial local control rate and actuarial overall survival rates were 100% and 100%, respectively, at 5 years and 100% and 83%, respectively, at 10 years. Four patients showed complete response, 14 patients showed partial response, and 8 patients remained stable. In 5 patients, vision improved after radiation therapy. Acute toxicity was mild. One patient required cyst drainage 3 months after radiotherapy. Late toxicity after radiotherapy included impairment of hormone function in 3 out of 18 patients at risk. We did not observe any vision impairment, radionecrosis, or secondary malignancies. CONCLUSIONS: FSRT is effective and safe in the treatment of cystic craniopharyngiomas. Toxicity is extremely low using this conformal technique.

Assessment of focal liver reaction by multiphasic CT after stereotactic single-dose radiotherapy of liver tumors.

PURPOSE: To characterize and quantitatively assess focal radiation reactions in the liver after stereotactic single-dose radiotherapy for liver malignancies. METHODS AND MATERIALS: A total of 131 multiphasic CT scans were performed in 36 patients before and after stereotactic radiotherapy for liver tumors. The examination protocol included a nonenhanced scan and contrast-enhanced scans at different times after contrast injection. The volume of the reaction was determined in each scan and the threshold dose calculated using the dose-volume histogram of the treatment plan. RESULTS: Every patient showed a focal radiation reaction on at least one follow-up examination. In 74% of the posttherapeutic scans, a sharply demarcated hypodense area surrounded the treated tumor in the nonenhanced scans. The reaction occurred at a median of 1.8 months (range 1.2-4.6) after radiotherapy. The median threshold dose was 13.7 Gy (range 8.9-19.2). The threshold dose strongly correlated with the time of detection after therapy (r = 0.7). Radiologically, three reaction types were found on the enhanced scans: type 1, portal-venous phase: hypodense and late phase: isodense; type 2, portal-venous phase: hypodense and late phase: hyperdense; and type 3, portal-venous phase: isodense/hyperdense and late phase: hyperdense. Type 1 or 2 reactions were observed significantly earlier than type 3 (p <0.05). The median threshold dose for type 1 or 2 reactions was significantly lower than for type 3 (p <0.05). The reaction volume decreased with longer follow-up (2-4 months: median 40% of initial volume). The reaction types shifted with follow-up: 58% were of type 1 at the initial manifestation and 58% were of type 3 at the next examination thereafter. CONCLUSION: A focal radiation reaction occurs after stereotactic single-dose therapy in the liver. The volume of the reaction decreases and changes its radiologic appearance during follow-up. This reaction has to be differentiated from recurrent tumor.

PET and SPECT for detection of tumor progression in irradiated low-grade astrocytoma: a receiver-operating-characteristic analysis.

UNLABELLED: Differentiation between tumor progression and radiation necrosis is one of the most difficult tasks in oncologic neuroradiology. Functional imaging of tumor metabolism can help with this task, but the choice of tracer is still controversial. This prospective study following up irradiated low-grade astrocytoma (LGA) was, to our knowledge, the first receiver-operating-characteristic (ROC) analysis that intraindividually evaluated the diagnostic performance of the SPECT tracers 3-[(123)I]iodo-alpha-methyl-L-tyrosine (IMT) and (99m)Tc(I)-hexakis(2-methoxyisobutylisonitrile) (MIBI) and the PET tracer (18)F-FDG. METHODS: We examined 17 patients, initially with histologically proven LGA and treated by stereotactic radiotherapy, who presented with new gadolinium-diethylenetriaminepentaacetic acid-enhancing lesions (n = 26) on MRI. At that time, MRI could not differentiate between progressive tumor and nonprogressive tumor. This MRI examination was closely followed by (18)F-FDG PET and by (99m)Tc-MIBI and (123)I-IMT SPECT. Lesions were classified as progressive tumor (n = 17) or nonprogressive tumor (n = 9) on the basis of prospective follow-up (through clinical examination, MRI, and proton MR spectroscopy) for 26.6 +/- 6.6 mo after PET or SPECT. RESULTS: (123)I-IMT yielded the best ROC characteristics and was the most accurate for classification, with an area under the ROC curve (A(z)) of 0.991. The A(z) of (18)F-FDG (0.947) was not significantly lower than that of (123)I-IMT. The difference in the A(z) of (99m)Tc-MIBI (0.713) from the A(z) of the other tracers used in our study was highly significant (P

Single-dose radiosurgical treatment for hepatic metastases--therapeutic outcome of 138 treated lesions from a single institution.

BACKGROUND: Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. PATIENTS AND METHODS: From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31-89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. RESULTS: Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. CONCLUSION: This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics.

A multi-institutional clinical trial of rectal dose reduction via injected polyethylene-glycol hydrogel during intensity modulated radiation therapy for prostate cancer: analysis of dosimetric outcomes.

PURPOSE: To characterize the effect of a prostate-rectum spacer on dose to rectum during external beam radiation therapy for prostate cancer and to assess for factors correlated with rectal dose reduction. METHODS AND MATERIALS: Fifty-two patients at 4 institutions were enrolled into a prospective pilot clinical trial. Patients underwent baseline scans and then were injected with perirectal spacing hydrogel and rescanned. Intensity modulated radiation therapy plans were created on both scans for comparison. The objectives were to establish rates of creation of ≥ 7.5 mm of prostate-rectal separation, and decrease in rectal V70 of ≥ 25%. Multiple regression analysis was performed to evaluate the associations between preinjection and postinjection changes in rectal V70 and changes in plan conformity, rectal volume, bladder volume, bladder V70, planning target volume (PTV), and postinjection midgland separation, gel volume, gel thickness, length of PTV/gel contact, and gel left-to-right symmetry. RESULTS: Hydrogel resulted in ≥7.5-mm prostate-rectal separation in 95.8% of patients; 95.7% had decreased rectal V70 of ≥ 25%, with a mean reduction of 8.0 Gy. There were no significant differences in preinjection and postinjection prostate, PTV, rectal, and bladder volumes. Plan conformities were significantly different before versus after injection (P=.02); plans with worse conformity indexes after injection compared with before injection (n=13) still had improvements in rectal V70. In multiple regression analysis, greater postinjection reduction in V70 was associated with decreased relative postinjection plan conformity (P=.01). Reductions in V70 did not significantly vary by institution, despite significant interinstitutional variations in plan conformity. There were no significant relationships between reduction in V70 and the other characteristics analyzed. CONCLUSIONS: Injection of hydrogel into the prostate-rectal interface resulted in dose reductions to rectum for >90% of patients treated. Rectal sparing was statistically significant across a range of 10 to 75 Gy and was demonstrated within the presence of significant interinstitutional variability in plan conformity, target definitions, and injection results.

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 side effects were scored according to CTCAE v.4.03. Tumor response was assessed according to RECIST where applicable. RESULTS: 103 patients were treated from 11/2009 to 03/2011, median follow-up is 6 months. 60 pts received treatment following R2 resections or as definitive radiation, 43 patients received adjuvant radiation for R1 and/or Pn+. 16 patients received carbon ion treatment for re-irradiation. Median total dose was 73.2 GyE (23.9 GyE carbon ions + 49,9 Gy IMRT) for primary treatment and 44.9 GyE carbon ions for re-irradiation. All treatments were completed as planned and generally well tolerated with no > CTC°III toxicity. Rates of CTC°III toxicity (mucositis and dysphagia) were 8.7% with side-effects almost completely resolved at first follow-up.47 patients showed good treatment responses (CR/PR) according to RECIST. CONCLUSION: Acute toxicity remains low in IMRT with carbon ion boost also in R1-resected patients and patients undergoing re-irradiation. R2-resected patients showed high rates of treatment response, though follow-up is too short to assess long-term disease control.

Intensity-modulated whole abdominal radiotherapy after surgery and carboplatin/taxane chemotherapy for advanced ovarian cancer: phase I study.

PURPOSE: To assess the feasibility and toxicity of consolidative intensity-modulated whole abdominal radiotherapy (WAR) after surgery and chemotherapy in high-risk patients with advanced ovarian cancer. METHODS AND MATERIALS: Ten patients with optimally debulked ovarian cancer International Federation of Gynecology and Obstetrics Stage IIIc were treated in a Phase I study with intensity-modulated WAR up to a total dose of 30 Gy in 1.5-Gy fractions as consolidation therapy after adjuvant carboplatin/taxane chemotherapy. Treatment was delivered using intensity-modulated radiotherapy in a step-and-shoot technique (n = 3) or a helical tomotherapy technique (n = 7). The planning target volume included the entire peritoneal cavity and the pelvic and para-aortal node regions. Organs at risk were kidneys, liver, heart, vertebral bodies, and pelvic bones. RESULTS: Intensity-modulated WAR resulted in an excellent coverage of the planning target volume and an effective sparing of the organs at risk. The treatment was well tolerated, and no severe Grade 4 acute side effects occurred. Common Toxicity Criteria Grade III toxicities were as follows: diarrhea (n = 1), thrombocytopenia (n = 1), and leukopenia (n = 3). Radiotherapy could be completed by all the patients without any toxicity-related interruption. Median follow-up was 23 months, and 4 patients had tumor recurrence (intraperitoneal progression, n = 3; hepatic metastasis, n = 1). Small bowel obstruction caused by adhesions occurred in 3 patients. CONCLUSIONS: The results of this Phase I study showed for the first time, to our knowledge, the clinical feasibility of intensity-modulated whole abdominal radiotherapy, which could offer a new therapeutic option for consolidation treatment of advanced ovarian carcinoma after adjuvant chemotherapy in selected subgroups of patients. We initiated a Phase II study to further evaluate the toxicity of this intensive multimodal treatment.

Absence of tissue reaction after focal high-dose irradiation of rabbit liver.

BACKGROUND: A focal reaction of the liver is radiologically seen after stereotactic high dose radiotherapy of liver tumors. The histological counterpart of this reaction should be clarified using an animal model. MATERIALS AND METHODS: Six New Zealand white rabbits were positioned on a special stereotactic set-up. Parts of the liver (1.5-8 ml) were irradiated with either 20-24 Gy/80% (n = 3) or 36 Gy/80% (n = 3). The animals were followed by CT examination up to 2 years after radiotherapy. Finally, the animals were sacrificed and the liver macroscopically and microscopically inspected. RESULTS: No focal reaction could be observed in any liver at any time by CT examination. The liver macroscopically and microscopically showed no changes 6 months or 2 years after radiotherapy. CONCLUSION: Up to a single dose of 36 Gy/80%, rabbits seem to show no focal tissue reaction after high dose radiation therapy of small parts of the liver.