[Show abstract][Hide abstract] ABSTRACT: Background:
To retrospectively access outcome and prognostic parameters of linear accelerator-based stereotactic radiosurgery in brain metastases from malignant melanoma.
Between 1990 and 2011 140 brain metastases in 84 patients with malignant melanoma (median age 56 years) were treated with stereotactic radiosurgery. At initial stereotactic radiosurgery 48 % of patients showed extracerebral control. The median count of brain metastases in a single patient was 1, the median diameter was 12 mm. The median dose applied was 20 Gy/80 % isodose enclosing.
The median follow-up was 7 months and the median overall survival 9 months. The 6-, 12- and 24 month overall survival rates were 71 %, 39 % and 25 % respectively. Cerebral follow-up imaging showed complete remission in 20 brain metastases, partial remission in 39 brain metastases, stable disease in 54 brain metastases, progressive disease in 24 brain metastases and pseudo-progression in 3 brain metastases. Median intracerebral control was 5.3 months and the 6- and 12-month intracerebral progression-free survival rates 48 % and 38 %, respectively. Upon univariate analysis, extracerebral control (log-rank, p < 0.001), the response to stereotactic radiosurgery (log-rank, p < 0.001), the number of brain metastases (log-rank, p = 0.007), the recursive partitioning analysis class (log-rank, p = 0.027) and the diagnosis-specific graded prognostic assessment score (log-rank, p = 0.011) were prognostic for overall survival. The most common clinical side effect was headache common toxicity criteria grade I. The most common radiological finding during follow-up was localized edema within the stereotactic radiosurgery high dose region.
Stereotactic radiosurgery is a well-tolerated and effective treatment option for brain metastases in malignant melanoma and was able to achieve local remissions in several cases. Furthermore, especially patients with controlled extracerebral disease and a low count of brain metastases seem to benefit from this treatment modality. Prospective trials analysing the effects of combined stereotactic radiosurgery and new systemic agents are warranted.
BMC Cancer 07/2015; 15(1):537. DOI:10.1186/s12885-015-1517-1 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Novel techniques in radiation oncology have significantly improved the therapeutic window in locally advanced pancreatic cancer LAPC. In about one third of the patients, chemoradiation can lead to secondary resectability, contributing to an increase in outcome. Dose-escalation approaches using stereotactic body radiotherapy (SBRT) or advanced treatments such as intensity-modulated radiotherapy (IMRT) can exploit the biological benefits of hypofractionation, or use "dose painting" approaches to target defined subvolumes. Prognostic subgroups of patients have been identified, based on molecular markers such as CA 19-9, nutritional factors, diabetes or immunological properties of tumor and normal tissue.
The aim of the present manuscript is to summarize data on downsizing for locally advanced pancreatic cancer (LAPC) and to elucidate the role of individualized radiotherapy (iRT).
Future concepts focus on iRT based on prognostic factors leading to a true personalized treatment.
Langenbeck s Archives of Surgery 07/2015; DOI:10.1007/s00423-015-1309-8 · 2.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: With the development of more conformal and precise radiation techniques such as Intensity-Modulated Radiotherapy (IMRT), Stereotactic Body Radiotherapy (SBRT) and Image-Guided Radiotherapy (IGRT), patients with hepatic tumors could be treated with high local doses by sparing normal liver tissue. However, frequently occurring large HCC tumors are still a dosimetric challenge in spite of modern high sophisticated RT modalities. This interventional clinical study has been set up to evaluate the value of different fiducial markers, and to use the modern imaging methods for further treatment optimization using physical and informatics approaches.
Surgically implanted radioopaque or electromagnetic markers are used to detect tumor local-ization during radiotherapy. The required markers for targeting and observation during RT can be implanted in a previously defined optimal position during the oncologically indicated operation. If there is no indication for a surgical resection or open biopsy, markers may be inserted into the liver or tumor tissue by using ultrasound-guidance. Primary study aim is the detection of the patients´ anatomy at the time of RT by observation of the marker position during the indicated irradiation (IGRT). Secondary study aims comprise detection and recording of 3D liver and tumor motion during RT. Furthermore, the study will help to develop technical strategies and mechanisms based on the recorded information on organ motion to avoid inaccurate dose application resulting from fast organ motion and deformation.
This is an open monocentric non-randomized, prospective study for the evaluation of organ motion using interstitial markers or implantable radiotransmitter. The trial will evaluate the full potential of different fiducial markers to further optimize treatment of moving targets, with a special focus on liver lesions.
[Show abstract][Hide abstract] ABSTRACT: The benefits of new innovations in glioblastoma therapies should not be curtailed as a result of delays in commencement of radiation therapy, caused by clinical circumstances as well as diagnostic procedures. This study evaluates whether delays in chemo-radiotherapy after surgery, while determining O6-methylguanine-DNA-methyltransferase (MGMT) promoter status, affect the survival rates of patients with glioblastoma (GBM).
Our sample comprised 50 GBM patients in a retrospective analysis of three prospective studies that focused on combined radiotherapy and required MGMT promoter-status testing as inclusion criteria. Results were compared with a reference group of 127 favourable GBM cases (Karnofsky performance-status scale ≥ 70), in which the patients underwent standard postoperative chemo-radiotherapy with temozolomide. Survival time was calculated using the Kaplan-Meier method, and a multivariate analysis of the delays between surgical and radiotherapy procedures was performed using the Cox regression model.
The study group's median overall survival time was 16.2 months (with a range of 2 to 56 months), versus the reference group's survival time of 18.2 months (with a range of 1 to 92 months) (p = 0.64). The delay between surgery and radiotherapy was increased by 8 days in the study patients (p < 0.001), with a median delay of 35 days (range: 18-49 days) corresponding to the typical 27-day delay (range: 5-98 days) for those in the reference group. Univariate and multivariate analyses did not show any negative association between survival time and delaying radiation therapy to determine MGMT-promoter status; commencement of radiation therapy sooner than 24 days after surgery was the threshold for significantly decreased overall survival (p = 0.01) and progression-free (p = 0.03) survival.
Delaying postoperative chemoradiation for GBM patients-carried out in order to determine MGMT-promoter status-did not have a negative impact on survival time. Indeed, the data of the present study shows that initiating radiation therapy sooner than 24 days after surgery has a negative impact on progression and survival.
BMC Cancer 07/2015; 15(1):558. DOI:10.1186/s12885-015-1545-x · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to assess the importance of surrounding tissues for the delineation of moving targets in tissue-specific phantoms and to find optimal settings for lung, soft tissue, and liver tumors.
Tumor movement was simulated by a water-filled table tennis ball (target volume, TV). Three phantoms were created: corkboards to simulate lung tissue (lung phantom, LunPh), animal fat as fatty soft tissue (fatty tissue phantom, FatPh), and water enhanced with contrast medium as the liver tissue (liver phantom, LivPh). Slow planning three-dimensional compute tomography images (3D-CTs) were acquired with and without phantom movements. One-dimensional tumor movement (1D), three-dimensional tumor movement (3D), as well as a real patient's tumor trajectories were simulated. The TV was contoured using two lung window settings, two soft-tissue window settings, and one liver window setting. The volumes were compared to mathematical calculated values.
TVs were underestimated in all phantoms due to movement. The use of soft-tissue windows in the LivPh led to a significantunderestimation of the TV (70.8 % of calculated TV). When common window settings [LunPh + 200 HU/-1,000 HU (upper window/lower window threshold); FatPh: + 240 HU/-120 HU; LivPh: + 175 HU/+ 50 HU] were used, the contoured TVs were: LivPh, 84.0 %; LunPh, 93.2 %, and FatPh, 92.8 %. The lower window threshold had a significant impact on the size of the delineated TV, whereas changes of the upper threshold led only to small differences.
The decisive factor for window settings is the lower window threshold (for adequate TV delineation in the lung and fatty-soft tissue it should be lower than density values of surrounding tissue). The use of a liver window should be considered.
Strahlentherapie und Onkologie 06/2015; 191(9). DOI:10.1007/s00066-015-0862-y · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The primary objective was to assess the different reasons for refusal of surgical resection (SR) in patients with esophageal squamous cell cancer (ESCC), who were initially planned for neoadjuvant radiochemotherapy (N-RCT) + SR, but SR was not performed after N-RCT.
From 1988 to 2011, 311 patients with ESCC were treated with N-RCT in a tertiary referral center for esophageal diseases. Fifty-three patients were analyzed who received RCT with 40-45 Gy and concomitant chemotherapy in neoadjuvant intention, but in whom the treatment was stopped or switched to definitive RCT due to progression, patient decision, or new findings.
The reasons for refusal of SR for these 53 patients were as follows: (1) patients' or physicians' preference for the planned treatment was changed during the N-RCT, such that RCT was continued to a curative dose without a break (group 1, n = 23, 44%); (2) patients were restaged after 4 weeks, and the tumor board decided to continue RCT because R0 resection was unlikely and/or patients were medically unfit (group 2, n = 15, 28%); (3) patients refused continuation of any treatment (group 3, n = 15, 28%). Refusal of SR was significantly more likely in patients with longitudinal tumor dimension >8 cm and those with an Eastern Cooperative Oncology Group performance status score of 2. Median follow-up time from the start of N-RCT was 57 months (range 1-137 months). The survival rates at 2 and 5 years were 36 ± 7% and 27 ± 7%, respectively. Group 1 had significantly longer survival.
The planned N-RCT+SR could not be completed in a considerable number of patients in a tertiary referral center. More strict selection criteria for multimodality treatment including SR could spare some of these patients an incomplete treatment and probably lead to increased utilization of definitive RCT.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the study was to evaluate the effect of radiation therapy and chemoradiation with gemcitabine (GEM) after R1 resection in patients with pancreatic adenocarcinoma (PAC).
We performed a retrospective analysis of 25 patients who were treated with postoperative radiotherapy (RT) or chemoradiation (CRT) after surgery with microscopically positive resection margins for primary pancreatic cancer (PAC). Median age was 60 years (range 34 to 74 years), and there were 17 male and 8 female patients. Fractionated RT was applied with a median dose of 49.6 Gy (range 36 to 54 Gy). Eight patients received additional intraoperative radiotherapy (IORT) with a median dose of 12 Gy.
Median overall survival (mOS) of all treated patients was 22 months (95% confidence interval (CI) 7.9 to 36.1 months) after date of resection and 21.1 months (95% CI 7.6 to 34.6 months) after start of (C)RT. Median progression-free survival (mPFS) was 13.0 months (95% CI 0.93 to 25 months). Grading (G2 vs. G3, P = 0.005) and gender (female vs. male, P = 0.01) were significantly correlated with OS. There was a significant difference in mPFS between male and female patients (P = 0.008). A total of 11 from 25 patients experienced local tumour progression, and 19 patients were diagnosed with either locoregional or distant failure.
We demonstrated that GEM-based CRT can be applied in analogy to neoadjuvant protocols in the adjuvant setting for PAC patients at high risk for disease recurrence after incomplete resection. Patients undergoing additive CRT have a rather good OS and PFS compared to historical control patient groups.
World Journal of Surgical Oncology 04/2015; 13(1):149. DOI:10.1186/s12957-015-0560-3 · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heat shock protein 70 (Hsp70) is frequently overexpressed in tumor cells. An unusual cell surface localization could be demonstrated on a large variety of solid tumors including lung, colorectal, breast, squamous cell carcinomas of the head and neck, prostate and pancreatic carcinomas, glioblastomas, sarcomas and hematological malignancies, but not on corresponding normal tissues. A membrane (m)Hsp70-positive phenotype can be determined either directly on single cell suspensions of tumor biopsies by flow cytometry using cmHsp70.1 monoclonal antibody or indirectly in the serum of patients using a novel lipHsp70 ELISA. A mHsp70-positive tumor phenotype has been associated with highly aggressive tumors, causing invasion and metastases and resistance to cell death. However, natural killer (NK), but not T cells were found to kill mHsp70-positive tumor cells after activation with a naturally occurring Hsp70 peptide (TKD) plus low dose IL-2 (TKD/IL-2). Safety and tolerability of ex vivo TKD/IL-2 stimulated, autologous NK cells has been demonstrated in patients with metastasized colorectal and NSCLC in a phase I clinical trial. Based on promising clinical results of the previous study, a phase II randomized clinical study was initiated in 2015. The primary objective of this multicenter proof-of-concept trial is to examine whether an adjuvant treatment of NSCLC patients after platinum based radiochemotherapy with TKD/IL-2 activated, autologous NK cells is clinically effective. As a mHsp70-positive tumor phenotype is associated with poor clinical outcome only mHsp70-positive tumor patients will be recruited into the trial. The primary endpoint of this study will be the comparison of the progression-free survival of patients treated with ex vivo activated NK cells compared to patients who were treated with radiochemotherapy alone. As secondary endpoints overall survival, toxicity, quality-of-life and biological responses will be determined in both study groups.
Frontiers in Immunology 04/2015; 6:162. DOI:10.3389/fimmu.2015.00162
[Show abstract][Hide abstract] ABSTRACT: Unlabelled:
Curative treatment of pediatric cancer not only focuses on long-term survival, but also on reducing treatment-related side effects. Advantages of particle therapy are mainly due to their physical ability of significantly reducing integral dose.
Between January 2009 and December 2012, we treated 83 pediatric patients (aged 21 and younger) at the Heidelberg Ion Therapy Center at University Hospital of Heidelberg (HIT). In total 56 patients (67%) received proton irradiation, while 25 (30%) patients were treated with carbon ions (C12). Two patients received both treatments (3%). Treatment toxicity was analyzed retrospectively and documented according to the CTCAE/RTOG classification. In a second step, treatment toxicity from ion therapy was analyzed in comparison to treatment toxicity during photon irradiation of a comparable historical group of 19 pediatric patients.
In all patients, particle therapy was tolerated well (median follow-up time 3.7 months), children (20 patients) with at least two follow-up visits showed a median follow-up time of 10.2 months. During the first two months patients mainly suffered from radiogenic skin reaction (63%), mucositis (30%), headache and dizziness (35%) as well as nausea and vomiting (13%). Severe toxicity reaction (grade II-IV) was only seen in patients who had intensive simultaneous chemotherapy or who had undergone several operations in the irradiated area before radiotherapy (18%). Treatment toxicity during ion therapy was comparable to treatment toxicity from photon irradiation of a historical group.
In comparison to conventional therapy, patients with particle therapy do not suffer from increased acute treatment-related toxicity during the first months. More experience with particle therapy will be needed during the next years to help to thoroughly evaluate the high potential of ion therapy.
[Show abstract][Hide abstract] ABSTRACT: To assess the association between dosimetric factors of the lung and incidence of intra- and postoperative mortality among esophageal cancer (EC) patients treated with neoadjuvant radiochemotherapy (N-RCT) followed by surgery (S).
Inclusion criteria were: age < 85 years, no distant metastases at the time of diagnosis, no induction chemotherapy, conformal radiotherapy, total dose ≤ 50.4 Gy, and available dose volume histogram (DVH) data. One-hundred thirty-five patients met our inclusion criteria. Median age was 62 years. N-RCT consisted of 36 - 50.4 Gy (median 45 Gy), 1.8 - 2 Gy per fraction. Concomitant chemotherapy consisted of 5-Fluoruracil (5-FU) and cisplatin in 113 patients and cisplatin and taxan-derivates in 15 patients. Seven patients received a single cytotoxic agent. In 130 patients an abdominothoracal and in 5 patients a transhiatal resection was performed. The following dosimetric parameters were generated from the total lung DVH: mean dose, V5, V10, V15, V20, V30, V40, V45 and V50. The primary endpoint was the rate of intra- and postoperative mortality (from the start of N-RCT to 60 days after surgical resection).
A total of ten postoperative deaths (7%) were observed: 3 within 30 days (2%) and 7 between 30 and 60 days after surgical intervention (5%); no patient died during the operation. In the univariate analysis, weight loss (≥10% in 6 months prior to diagnosis, risk ratio: 1.60, 95%CI: 0.856-2.992, p=0.043), Eastern Cooperative Oncology Group-performance status (ECOG 2 vs. 1, risk ratio: 1.931, 95%CI: 0.898-4.150, p=0.018) and postoperative pulmonary plus non-pulmonary complications (risk ratio: 2.533, 95%CI: 0.978-6.563, p=0.004) were significantly associated with postoperative mortality. There was no significant association between postoperative mortality and irradiated lung volumes. Lung V45 was the only variable which was significantly associated with higher incidence of postoperative pulmonary plus non-pulmonary complications (Exp(B): 1.285, 95%CI 1.029-1.606, p=0.027), but not with the postoperative pulmonary complications (Exp(B): 1.249, 95%CI 0.999-1.561, p=0.051).
Irradiated lung volumes did not show relevant associations with intra- and postoperative mortality of patients treated with moderate dose (36 - 50.4 Gy) conventionally fractionated conformal radiotherapy combined with widely used radiosensitizers. Postoperative mortality was significantly associated with greater weight loss, poor performance status and development of postoperative complications, but not with treatment-related factors. Limiting the volume of lung receiving higher radiation doses appears prudent because of the observed association with risk of postoperative complications.
Journal of Cancer 01/2015; 6(3):254-60. DOI:10.7150/jca.10796 · 3.27 Impact Factor