[show abstract][hide abstract] ABSTRACT: Characterization of combination effects of chemotherapy drugs with carbon ions in comparison to photons in vitro.
The human colon adenocarcinoma cell line WiDr was tested for combinations with camptothecin, cisplatin, gemcitabine and paclitaxel. In addition three other human tumour cell lines (A549: lung, LN-229: glioblastoma, PANC-1: pancreas) were tested for the combination with camptothecin. Cells were irradiated with photon doses of 2, 4, 6 and 8 Gy or carbon ion doses of 0.5, 1, 2 and 3 Gy. Cell survival was assessed using the clonogenic growth assay. Treatment dependent changes in cell cycle distribution (up to 12 hours post-treatment) were measured by FACS analysis after propidium-iodide staining. Apoptosis was monitored for up to 36 hours post-treatment by Nicoletti-assay (with qualitative verification using DAPI staining).
All cell lines exhibited the well-known increase of killing efficacy per unit dose of carbon ion exposure, with relative biological efficiencies at 10% survival (RBE10) ranging from 2.3 to 3.7 for the different cell lines. In combination with chemotherapy additive toxicity was the prevailing effect. Only in combination with gemcitabine or cisplatin (WiDr) or camptothecin (all cell lines) the photon sensitivity was slightly enhanced, whereas purely independent toxicities were found with the carbon ion irradiation, in all cases. Radiation-induced cell cycle changes displayed the generally observed dose-dependent G2-arrest with little effect on S-phase fraction for all cell lines for photons and for carbon ions. Only paclitaxel showed a significant induction of apoptosis in WiDr cell line but independent of the used radiation quality.
Combined effects of different chemotherapeutics with photons or with carbon ions do neither display qualitative nor substantial quantitative differences. Small radiosensitizing effects, when observed with photons are decreased with carbon ions. The data support the idea that a radiochemotherapy with common drugs and carbon ion irradiation might be as feasible as respective photon-based protocols. The present data serve as an important radiobiological basis for further combination experiments, as well as clinical studies on combination treatments.
[show abstract][hide abstract] ABSTRACT: Patients with malignant melanoma may develop brain metastases during the course of the disease, requiring radiotherapeutic treatment. In patients with 1--3 brain metastases, radiosurgery has been established as a treatment option besides surgery. For patients with 4 or more brain metastases, whole brain radiotherapy is considered the standard treatment. In certain patients with brain metastases, radiation treatment using whole brain helical Tomotherapy with integrated boost and hippocampal-sparing may improve prognosis of these patients.
The present prospective, randomized two-armed trial aims to exploratory investigate the treatment response to conventional whole brain radiotherapy applying 30 Gy in 10 fractions versus whole brain helical Tomotherapy applying 30 Gy in 10 fractions with an integrated boost of 50 Gy to the brain metastases as well as hippocampal-sparing in patients with brain metastases from malignant melanoma. The main inclusion criteria include magnetic resonance imaging confirmed brain metastases from a histopathologically confirmed malignant melanoma in patients with a minimum age of 18 years. The main exclusion criteria include a previous radiotherapy of the brain and not having recovered from acute high-grade toxicities of prior therapies. The primary endpoint is treatment-related toxicity. Secondary endpoints include imaging response, local and loco-regional progression-free survival, overall survival and quality of life.Trial registration: www.drks.de Trial ID: DRKS00005127.
[show abstract][hide abstract] ABSTRACT: For palliative care of spinal bone metastases, stability assessment is of crucial importance. Pathological fractures, instability-related patient immobility and the extent of bone metastasis have been reported to affect patient outcome and these parameters have therefore been used for treatment stratification. We report on stability-dependent fracture and survival rates in over 300 non-small cell lung cancer (NSCLC) patients.
Data from 303 patients with 868 osteolytic metastases treated with radiotherapy (RT) between 2000 and 2012 were evaluated retrospectively.
In NSCLC patients with bone metastases only, the retrospective 6- and 12-month overall survival (OS) rates were 76.7 and 47.2 %, respectively. In patients with additional non-bone distant metastases, these values were 60.0 and 34.0 %, respectively. Survival rates were significantly lower in patients with multiple bone metastases and in those suffering pathological fractures (p = 0.017). No significant impact of histological type, location of spinal lesions or treatment regime was detected. Furthermore, stability assessment revealed no influence of vertebral column stability on patient outcome (p = 0.739).
Our analysis demonstrated a correlation between the pathological fractures of bone lesions, the number of bone metastases, additional distant metastases and survival. The results offer a rationale for future prospective investigations.
Strahlentherapie und Onkologie 09/2013; · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy as well as radiotherapy. In many cases, surgical resection is not possible, and therefore treatment alternatives have to be performed. Chemoradiation has been established as a convincing treatment alternative for locally advanced pancreatic cancer. Carbon ions offer physical and biological characteristics. 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 increased relative biological effectiveness (RBE), which can be calculated between 1.16 and 2.46 depending on the pancreatic cancer cell line as well as the endpoint analyzed. Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with pancreatic cancer.Methods and design: The present PHOENIX-01 trial evaluates carbon ion radiotherapy using the active rasterscanning technique in patients with advanced pancreatic cancer in combination with weekly gemcitabine and adjuvant gemcitabine. Primary endpoint is toxicity, secondary endpoints are overall survival, progression-free survival and response.
The physical and biological properties of the carbon ion beam promise to improve the therapeutic ratio in patients with pancreatic cancer: Due to the inverted dose profile dose deposition in the entry channel of the beam leads to sparing of normal tissue; the Bragg peak can be directed into the defined target volume, and the sharp dose fall-off thereafter again spares normal tissue behind the target volume. The higher RBE of carbon ions, which has been shown also for pancreatic cancer cell lines in the preclinical setting, is likely to contribute to an increase in local control, and perhaps in OS. Early data from Japanese centers have shown promising results. In conclusion, this is the first trial to evaluate actively delivered carbon ion beams in patients with locally advanced pancreatic cancer within a dose-escalation strategy.Trial registration: NCT01795274.
BMC Cancer 09/2013; 13(1):419. · 3.33 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent developments and innovations in modern radiation oncology enable radiation oncologists to deliver a biologically, physically and technically stratified individualized treatment. In urological oncology, radiotherapy can be offered as a valid treatment alternative for a number of tumors, such as prostate cancer or urothelial cancer/bladder cancer.
By improving the precision of radiotherapy, significant improvement in tumor control can be achieved, coupled with a reduction of the risk of treatment-related side effects. Techniques such as high precision radiotherapy and combinations of radiation and modern imaging, such as image-guided radiotherapy (IGRT) and adaptive radiotherapy (ART), make daily individually tailored treatment possible.
In the future the biological characteristics of tumors and of normal tissue as well as molecular markers can be used for treatment stratification.
Der Urologe 09/2013; 52(9):1276-82. · 0.46 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
In radiation oncology recurrence analysis is an important part in the evaluation process and clinical quality assurance of treatment concepts. With the example of 9 patients with locally advanced pancreatic cancer we developed and validated interactive analysis tools to support the evaluation workflow.
After an automatic registration of the radiation planning CTs with the follow-up images, the recurrence volumes are segmented manually. Based on these volumes the DVH (dose volume histogram) statistic is calculated, followed by the determination of the dose applied to the region of recurrence and the distance between the boost and recurrence volume. We calculated the percentage of the recurrence volume within the 80%-isodose volume and compared it to the location of the recurrence within the boost volume, boost + 1 cm, boost + 1.5 cm and boost + 2 cm volumes.
Recurrence analysis of 9 patients demonstrated that all recurrences except one occurred within the defined GTV/boost volume; one recurrence developed beyond the field border/outfield. With the defined distance volumes in relation to the recurrences, we could show that 7 recurrent lesions were within the 2 cm radius of the primary tumor. Two large recurrences extended beyond the 2 cm, however, this might be due to very rapid growth and/or late detection of the tumor progression.
The main goal of using automatic analysis tools is to reduce time and effort conducting clinical analyses. We showed a first approach and use of a semi-automated workflow for recurrence analysis, which will be continuously optimized. In conclusion, despite the limitations of the automatic calculations we contributed to in-house optimization of subsequent study concepts based on an improved and validated target volume definition.
[show abstract][hide abstract] ABSTRACT: Hintergrund
In der Radioonkologie ist ein effizienter Umgang mit großen heterogenen Datenmengen, die sich auf verschiedene Informationssysteme in unterschiedlichen Dokumentationsformen verteilen, sowohl für eine optimale Behandlung als auch für wissenschaftliche Verwendungen sehr wichtig. Bis heute sind Analysen mit einem erheblichen zeitlichen Aufwand für die Auswertung verbunden. Am Beispiel der Therapieevaluation der Radiochemotherapie des Pankreaskarzinoms soll die Struktur und der Aufbau eines Auswertesystems in Kombination mit einem Dokumentationssystem mit automatisierter Auswertung dargestellt werden.
Material und Methoden
Für ein Patientenkollektiv von 783 Patienten wurde ein professionelles, datenbankbasiertes Dokumentationssystem für die Datensammlung und -zusammenführung genutzt. Strahlentherapeutische Parameter, diagnostische Bilddaten sowie Dosisverteilungen wurden in das webbasierte System integriert.
Für die Subgruppe von 36 neoadjuvant bestrahlten und an einem Rezidiv erkrankten Patienten wurde ein automatischer Analyseworkflow konzipiert und umgesetzt. Zuerst wird eine automatische Registrierung der Bestrahlungspläne mit den Nachsorgebildern berechnet. Danach erfolgt die manuelle Einzeichnung der Rezidivvolumina. Diese dienen als Grundlage für die Berechnung der DVH-(Dosis-Volumen-Histogramm-)Statistik sowie zur Bestimmung der auf die Rezidivregion applizierten Dosis. Alle Ergebnisse werden in die Datenbank zurückgeschrieben und dienen als Input statistischer Berechnungen.
Existierende Analysetools an ein Dokumentationssystem zu knüpfen, hat das Ziel, den Aufwand für klinische Studien zu reduzieren. Dies ist insbesondere für die Auswertung großer Patientenkollektive sinnvoll. Einige Analysetools sind bereits im Einsatz, jedoch bedarf es noch manueller Interaktion. Weitere Schritte zur Automatisierung des Analyseprozesses sind geplant. Schon jetzt zeichnen sich die Vorteile einer digitalen Datenführung und Auswertung ab. Durch die zentrale Speicherung sind Ergebnisse stets verwertbar. Deshalb ist beabsichtig, das Auswertesystem künftig generalisiert auch auf andere Tumorentitäten innerhalb der Strahlentherapie zu übertragen.
Strahlentherapie und Onkologie 08/2013; 188(12). · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background. To analyze relevant data on carbon ion radiotherapy for different tumor indications and to review current clinical trials. Material and methods. All published data on carbon ion radiotherapy were searched for with specific criteria in PUBMED. The terms for search were 'carbon ion and (radiotherapy OR radiation therapy) and (nirs OR chiba OR japan OR itep OR st. petersburg OR PSI OR dubna OR uppsala OR clatterbridge OR loma linda OR nice OR orsay OR itemba OR mpri OR himac OR triumf OR GSI OR HMI OR NCC OR ibmc OR pmrc OR MGH OR infn-lns OR shizuoka OR werc OR zibo OR md anderson OR fpti OR ncc ilsan OR boston OR heidelberg OR tsukuba) NOT in vitro NOT cell culture NOT review[Publication Type] Filters: Humans, English'. The search delivered 273 hits, of which only articles in English including 20 or more patients were included. Case reports were not considered. We subdivided into disease- and site-specific groups. Results and conclusion. To date, several studies have been performed, however, no randomized trials have been conducted. Therefore, carbon ion radiotherapy must be considered an experimental treatment, and randomized trials comparing modern photon as well as proton treatments are necessary.
[show abstract][hide abstract] ABSTRACT: To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods. In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results. Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neurocognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion. The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neurocognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications.
[show abstract][hide abstract] ABSTRACT: The objective of this retrospective analysis is to systematically assess osseous lesions on the basis of a validated scoring system in terms of stability and fractures prior to and following radiotherapy in 338 lung cancer patients with bone metastases in the vertebral column.
The stability of 338 patients with 981 osteolytic metastases in the thoracic and lumbar spine was evaluated retrospectively on the basis of the Taneichi-Score between January 2000 and January 2012.
64% (215 patients) were classified stable prior to radiotherapy. Of the stable osseous metastases, none were rated unstable in the further course (p < 0.001, McNemar test). Of the 123 patients in whom the metastases were classified unstable prior to radiotherapy, 21 patients (17%) were classified stable after three months, and 30 patients (24%) stable after six months. A pathological fracture was diagnosed in 62 patients (18%) prior to radiotherapy. Regarding cases of osteolytic metastases of the vertebral bodies in which no fractures could be detected prior to the start of therapy, fractures occurred in 2% of all patients (n = 7) within six months following radiotherapy.
Our analysis demonstrated that pathological fractures following radiotherapy occur in the very minority of vertebral lesions for patients with a favorable outcome. The use of a systematic radiological scoring system to classify osteolytic metastases of the vertebral column has shown to be feasible in daily routine. Prospective clinical trials are warranted in order to analyse, to what extent patients with osseous metastases can be mobilized by physiotherapy for strengthening the paravertebral muscles before radiotherapy effects can be measured by means of radiological recalcification.
[show abstract][hide abstract] ABSTRACT: Modern radiotherapy (RT) techniques such as stereotactic RT, intensity-modulated RT, or particle irradiation allow local dose escalation with simultaneous sparing of critical organs. Several trials are currently investigating their benefit in glioma reirradiation and boost irradiation. Target volume definition is of critical importance especially when steep dose gradient techniques are employed. In this manuscript we investigate the impact of O-(2-(F-18)fluoroethyl)-l-tyrosine-positron emission tomography/computer tomography (FET-PET/CT) on target volume definition in low and high grade glioma patients undergoing either first or re-irradiation with particles.
We investigated volumetric size and uniformity of magnetic resonance imaging (MRI)- vs. FET-PET/CT-derived gross tumor volumes (GTVs) and planning target volumes (PTVs) of 41 glioma patients. Clinical cases are presented to demonstrate potential benefits of integrating FET-PET/CT-planning into daily routine.
Integrating FET-uptake into the delineation of GTVs yields larger volumes. Combined modality-derived PTVs are significantly enlarged in high grade glioma patients and in case of primary RT. The congruence of MRI and FET signals for the identification of glioma GTVs is poor with mean uniformity indices of 0.39. MRI-based PTVs miss 17% of FET-PET/CT-based GTVs. Non significant alterations were detected in low grade glioma patients and in those undergoing reirradiation.
Target volume definition for malignant gliomas during initial RT may yield significantly differing results depending upon the imaging modality, which the contouring process is based upon. The integration of both MRI and FET-PET/CT may help to improve GTV coverage by avoiding larger incongruences between physical and biological imaging techniques. In low grade gliomas and in cases of reirradiation, more studies are needed in order to investigate a potential benefit of FET-PET/CT for planning of RT.
Radiotherapy and Oncology 08/2013; · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: To compare retrospectively outcome after photon radiotherapy alone, radiochemotherapy with temozolomide (TMZ), and carbon ion radiotherapy in patients with high-grade gliomas and to generate a hypothetical outcome curve for C12 and TMZ.
Patients treated within a Phase I/II Trial with a carbon ion boost were compared retrospectively with randomly chosen patients treated with photons or photons in combination with TMZ in a retrospective analysis. Per treatment group, 16 patients with anaplastic astocytoma (AA), and 32 patients with glioblastoma (GBM) were included. Treatment outcome with focus on progression-free survival (PFS) and overall survival (OS) was analyzed.
Median OS for patients with GBM was 9months with RT, 14months with RCHT group, and 18months in the C12 group. There was no significant difference between the C12 and the RCHT group. For patients with AA, median OS was 13months for RT, 39months for RCHT, and 35months after C12. The difference from RCHT to C12 was not significant. Median PFS for patients with GBM was 5months in the RT group, 6months in the RCHT group, and 8months in the C12 group. There was a significant difference between the RCHT group and the C12 group. For AA, median PFS was 15months with RT, 6months with RCHT, and 34 with C12. Comparing subgroups, C12 was significantly different from RCHT. Based on the significant OS increase from RT to RCHT, and from RT to C12, we projected the potential increase in outcome when combined C12 and TMZ would have been applied. A generated hypothetical curve based on the abovementioned outcome as well as preclinical examinations suggests there might be a benefit from the addition of C12 in patients with high-grade gliomas.
This exploratory retrospective study suggests a potential benefit of carbon ions in patients with high-grade gliomas. This hypothesis is now being evaluated prospectively in GBM within the randomized CLEOPATRA clinical trial.
Radiotherapy and Oncology 08/2013; · 4.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
This study's primary objective was evaluation of the progression-free survival rate at 6 months (PFS-6) in patients with newly diagnosed glioblastoma without O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter hypermethylation postsurgically treated with enzastaurin before and concomitantly with radiation therapy, followed by enzastaurin maintenance therapy. PFS-6 of at least 55% was set to be relevant compared with the data of the EORTC 26981/22981 NCIC CE.3 trial.Methods
Adult patients with a life expectancy of at least 12 weeks who were newly diagnosed with a histologically proven supratentorial glioblastoma without MGMT promoter hypermethylation were eligible. Patients were treated with enzastaurin prior to, concomitantly with, and after standard partial brain radiotherapy. Here we report on a multicenter, open-label, uncontrolled phase II study of patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation treated with enzastaurin and radiation therapy within 4 study periods.ResultsPFS-6 was 53.6% (95% confidence interval [CI]: 39.8-65.6). The median overall survival was 15.0 months (95% CI: 11.9-17.9) for all patients, 3.9 months (95% CI: 0.8-9.0) for patients with biopsy, 15.4 months (95% CI: 10.1-17.9) for patients with partial resection, and 18.9 months (95% CI: 13.9-28.5) for patients with complete resection. The safety profile in this study was as expected from previous trials, and the therapy was well tolerated.ConclusionsPFS-6 missed the primary planned outcome of 55%. The secondary exploratory analysis according to resection status of the different subgroups of patients with biopsies, partial resection, and complete resection demonstrates the strong prognostic influence of resection on overall survival.
[show abstract][hide abstract] ABSTRACT: To evaluate outcome after intensity modulated radiotherapy (IMRT) compared to 3D conformal radiotherapy (3D-RT) as neoadjuvant treatment in patients with locally advanced pancreatic cancer (LAPC).
In total, 57 patients with LAPC were treated with IMRT and chemotherapy. A median total dose of 45 Gy to the PTV_baseplan and 54 Gy to the PTV_boost in single doses of 1.8 Gy for the PTV_baseplan and median single doses of 2.2 Gy in the PTV_boost were applied. Outcomes were evaluated and compared to a large cohort of patients treated with 3D-RT.
Overall treatment was well tolerated in all patients and IMRT could be completed without interruptions. Median overall survival was 11 months (range 5-37.5 months). Actuarial overall survival at 12 and 24 months was 36 % and 8 %, respectively. A significant impact on overall survival could only be observed for a decrease in CA 19-9 during treatment, patients with less pre-treatment CA 19-9 than the median, as well as weight loss during treatment. Local progression-free survival was 79 % after 6 months, 39 % after 12 months, and 13 % after 24 months. No factors significantly influencing local progression-free survival could be identified. There was no difference in overall and progression-free survival between 3D-RT and IMRT. Secondary resectability was similar in both groups (26 % vs. 28 %). Toxicity was comparable and consisted mainly of hematological toxicity due to chemotherapy.
IMRT leads to a comparable outcome compared to 3D-RT in patients with LAPC. In the future, the improved dose distribution, as well as advances in image-guided radiotherapy (IGRT) techniques, may improve the use of IMRT in local dose escalation strategies to potentially improve outcome.
Strahlentherapie und Onkologie 07/2013; · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cancer patients commonly suffer from weight loss since rapid tumor growth can cause catabolic metabolism and depletion of energy stores such as abdominal fat. In locally advanced pancreatic cancer this is even more pronounced due to abdominal pain, fatigue, nausea or malnutrition. In the present article, we quantify this frequently observed weight loss and assess its impact on outcome and survival.
Data on demographics, biometrics, toxicity and survival were collected for the last 100 patients treated with neoadjuvant chemoradiation for locally advanced pancreatic cancer at our department (45.0 Gy and boost up to 54.0 Gy plus concurrent and subsequent gemcitabine), and the subcutaneous fat area at the umbilicus level was measured by computer tomography before and after chemoradiation.
After chemoradiation, patients showed a highly statistically significant weight loss and reduction of the subcutaneous fat area. We could determine a very strong correlation of subcutaneous fat area to patient BMI. By categorizing patients according to their BMI based on the WHO classification as slender, normal, overweight and obese, we found improved but not statistically significant survival among obese patients. Accordingly, patients who showed less weight loss tended to survive longer.
In this study, patients with pancreatic cancer lost weight during chemoradiation and their subcutaneous fat diminished. Changes in subcutaneous fat area were highly correlated with patients' BMI. Moreover, obese patients and patients who lost less weight had an improved outcome after treatment. Although the extent of weight loss was not significantly correlated with survival, the observed trend warrants greater attention to nutritional status in the future.
Strahlentherapie und Onkologie 07/2013; · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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 methodsFrom 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 up to four lesions at once were irradiated simultaneously. Local progression-free (PFS) and overall survival (OS) from treatment day on were investigated using uni- and multivariable survival regression models.
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 multivariate analysis (p = 0.05). Multivariate 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.
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.
[show abstract][hide abstract] ABSTRACT: Purposes: First, to evaluate outcome, the benefit of concurrent chemotherapy and prognostic factors in a cohort of sixty-four high-grade glioma patients who underwent a second course of radiation therapy at progression. Second, to validate a new prognostic score for overall survival after reirradiation of progressive gliomas with an independent patient cohort.Patients and methods: All patients underwent fractionated reirradiation with a median physical dose of 36 Gy. Median planned target volume was 110.4 ml. Thirty-six patients received concurrent chemotherapy consisting in 24/36 cases (67%) of carboplatin and etoposide and in 12/36 cases (33%) of temozolomide. We used the Kaplan Meier method, log rank test and proportional hazards regression analysis for statistical assessment.
Median overall survival from the start of reirradiation was 7.7 +/- 0.7 months. Overall survival rates at 6 and 12 months were 60 +/- 6% and 24 +/- 6%, respectively. Despite relatively large target volumes we did not observe any major acute toxicity. Concurrent chemotherapy did not appear to improve outcome. In contrast, female gender, young age, WHO grade III histology, favorable Karnofsky performance score and complete resection of the tumor prior to reirradiation were identified as positive prognostic factors for overall survival. We finally validated a recent suggestion for a prognostic score with our independent but small patient cohort. Our preliminary findings suggest that its ability to discriminate between different prognostic groups is limited.
Outcome of our patients was comparable to previous studies. Even in case of large target volumes reirradiation seems to be feasible without observing major toxicity. The benefit of concurrent chemotherapy is still elusive. A reassessment of the prognostic score, tested in this study, using a larger patient cohort is needed.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The purpose of this study was to evaluate long-term outcome after radiation therapy (RT) for skull base or head-and-neck chemodectomas. METHODS: We treated 39 patients with chemodectomas with RT. Patients were treated with either single dose stereotactic radiosurgery, fractionated stereotactic radiotherapy, or intensity modulated radiotherapy (IMRT), depending on the size and anatomy of the lesion. At primary diagnosis, 16 patients were treated with surgical resection (41%), 4 with interventional embolization (10%), and 19 with primary RT (49%). Single doses of 18 Gy/80% isodose were applied. For fractionated treatments delivered as primary RT, a median total dose of 57.6 Gy was delivered. Five patients were treated with re-irradiation, of which 4 were treated with fractionated regimens; total dose was 28.8 Gy, 30 Gy, 40 Gy, and 56 Gy in 1.8 to 2 Gy single fractions. RESULTS: Clinical symptoms improved in 18 patients (46%), remained unchanged in 10 patients (26%), and worsening of sequelae was observed in only 1 patient, which was associated with tumor progression. Actuarial local control was 97% at 10 years. Overall survival was 89% at 5 years and 87% at 10 years. Deaths were not disease-related except in 3 patients with tumor progression. No secondary malignancies were observed. CONCLUSION: RT has been established as a treatment alternative for patients with glomus tumors. Long-term local control is very high, with good clinical response to treatment. Head Neck, 2013.