Radiation Oncology - Latest Articles

Clinical application of tumor volume in advanced nasopharyngeal carcinoma to predict outcome

Ching-Chih Lee — 2010-03-11T00:00:00Z

Background: Current staging systems have limited ability to adjust optimal therapy in advanced nasopharyngeal carcinoma (NPC). This study aimed to delineate the correlation between tumor volume, treatment outcome and chemotherapy cycles in advanced NPC. Methods: A retrospective review of 110 patients with stage III-IV NPC was performed. All patients were treated first with neoadjuvant chemotherapy, then concurrent chemoradiation, and followed by adjuvant chemotherapy as being the definitive therapy. Gross tumor volume of primary tumor plus retropharyngeal nodes (GTVprn) was calculated to be an index of treatment outcome. Results: GTVprn had a close relationship with survival and recurrence in advanced NPC. Large GTVprn (more tnan 13 ml) was associated with a significantly poorer local control, lower distant metastasis-free rate, and poorer survival. In patients with GTVprn more than 13 ml, overall survival was better after 4 cycles of chemotherapy than after less than 4 cycles. Conclusions: The incorporation of GTVprn can provide more information to adjust treatment strategy.

Hypofractionated radiotherapy for lung tumors with online cone beam CT guidance and active breathe control

Yali Shen — 2010-02-27T00:00:00Z

Background: To study the set-up errors, PTV margin and toxicity of cone beam CT (CBCT) guided hypofractionated radiotherapy with active breathing control (ABC) for patients with non-small cell lung cancer (NSCLC) or metastatic tumors in lung. Methods: 32 tumors in 20 patients were treated. Based on the location of tumor, dose per fraction given to tumor was divided into three groups: 12 Gy, 8 Gy and 6 Gy. ABC is applied for every patient. During each treatment, patients receive CBCT scan for online set-up correction. The pre- and post-correction setup errors between fractions, the interfractional and intrafractional, set-up errors, PTV margin as well as toxicity are analyzed. Results: The pre-correction systematic and random errors in the left-right (LR), superior-inferior (SI), anterior-posterior (AP) directions were 3.7 mm and 5.3 mm, 3.1 mm and 2.1 mm, 3.7 mm and 2.8 mm, respectively, while the post-correction residual errors were 0.6 mm and 0.8 mm, 0.8 mm and 0.8 mm, 1.2 mm and 1.3 mm, respectively. There was an obvious intrafractional shift of tumor position. The pre-correction PTV margin was 9.5 mm in LR, 14.1 mm in SI and 8.2 mm in AP direction. After CBCT guided online correction, the PTV margin was markedly reduced in all three directions. The post-correction margins ranged 1.5 to 2.1 mm. The treatment was well tolerated by patients, of whom there were 4 (20%) grade1-2 acute pneumonitis, 3 (15%) grade1 acute esophagitis, 2 (10%) grade1 late pneumonitis and 1 (5%) grade1 late esophagitis. Conclusion: The positioning errors for lung SBRT using ABC were significant. Online correction with CBCT image guidance should be applied to reduce setup errors and PTV margin, which may reduce radiotherapy toxicity of tissues when ABC was used.

Intensity modulated radiotherapy (IMRT) in benign giant cell tumors - a single institution case series and a short review of the literature

Falk Roeder — 2010-02-26T00:00:00Z

Background: Giant cell tumors are rare neoplasms, representing less than 5 % of all bone tumors. The vast majority of giant cell tumors occurs in extremity sites and is treated by surgery alone. However, a small percentage occurs in pelvis, spine or skull bones, where complete resection is challenging. Radiation therapy seems to be an option in these patients, despite the lack of a generally accepted dose or fractionation concept. Here we present a series of five cases treated with high dose IMRT.Patients and MethodsFrom 2000 and 2006 a total of five patients with histologically proven benign giant cell tumors have been treated with IMRT in our institution. Two patients were male, three female, and median age was 30 years (range 20 - 60). The tumor was located in the sacral region in four and in the sphenoid sinus in one patient. All patients had measurable gross disease prior to radiotherapy with a median size of 9 cm. All patients were treated with IMRT to a median total dose of 64 Gy (range 57.6 Gy to 66 Gy) in conventional fractionation. Results: Median follow up was 46 months ranging from 30 to 107 months. Overall survival was 100%. One patient developed local disease progression three months after radiotherapy and needed extensive surgical salvage. The remaining four patients have been locally controlled, resulting in a local control rate of 80%. We found no substantial tumor shrinkage after radiotherapy but in two patients morphological signs of extensive tumor necrosis were present on MRI scans. Decline of pain and/or neurological symptoms were seen in all four locally controlled patients. The patient who needed surgical salvage showed markedly reduced pain but developed functional deficits of bladder, rectum and lower extremity due to surgery. No severe acute or late toxicities attributable to radiation therapy were observed so far. Conclusion: IMRT is a feasible option in giant cells tumors not amendable to complete surgical removal. In our case series local control was achieved in four out of five patients with marked symptom relief in the majority of cases. No severe toxicity was observed.

Intensity-modulated radiation therapy (IMRT) vs. 3D conformal radiotherapy (3DCRT) in locally advanced rectal cancer (LARC): dosimetric comparison and clinical implications

Leire Arbea — 2010-02-26T00:00:00Z

Purpose: To compare target dose distribution, comformality, normal tissue avoidance, and irradiated body volume (IBV) in 3DCRT using classic anatomical landmarks (c3DCRT), 3DCRT fitting the PTV (f3DCRT), and intensity-modulated radiation therapy (IMRT) in patients with locally advanced rectal cancer (LARC).Methods and Materials: Fifteen patients with LARC underwent c3DCRT, f3DCRT, and IMRT planning. Target definition followed the recommendations of the ICRU reports No. 50 and 62. OAR (SB and bladder) constraints were D5 50 Gy and Dmax < 55 Gy. PTV dose prescription was defined as PTV95 [greater than or equal to]45 Gy and PTVmin [greater than or equal to] 35 Gy. Target coverage was evaluated with the D95, Dmin, and Dmax. Target dose distribution and comformality was evaluated with the homogeneity indices (HI) and Conformity Index (CI). Normal tissue avoidance of OAR was evaluated with the D5 and V40. IBV at 5 Gy (V5), 10 Gy (V10), and 20 Gy (V20) were calculated. Results: The mean GTV95, CTV95, and PTV95 doses were significantly lower for IMRT plans. Target dose distribution was more inhomogeneous after IMRT planning and 3DCRTplans had significantly lower CI. The V40 and D5 values for OAR were significantly reduced in the IMRT plans .V5 was greater for IMRT than for f3DCRT planning (p<0.05) and V20 was smaller for IMRT plans(p<0.05). Conclusions: IMRT planning improves target conformity and decreases irradiation of the OAR at the expense of increased target heterogeneity. IMRT planning increases the IBV at 5 Gy or less but decreases the IBV at 20 Gy or more.

Cytokines levels, Severity of acute mucositis and the need of PEG tube installation during chemo-radiation for head and neck cancer - a prospective pilot study

Amichay Meirovitz — 2010-02-25T00:00:00Z

Background: The purpose of this pilot study was to detect a correlation between serum cytokine levels and severity of mucositis, necessitating installation of a percutaneous endoscopic gastrostomy tube (PEG) in head and neck (H&N) cancer patients receiving combined chemo-radiation therapy.Patients and MethodsFifteen patients with H&N epithelial cancer were recruited to this study. All patients received radiotherapy to the H&N region, with doses ranging from 50-70 Gy. Chemotherapy with cisplatin, carboplatin, 5-fluorouracil and taxanes was given to high-risk patients, using standard chemotherapy protocols. Patients were evaluated for mucositis according to WHO common toxicity criteria, and blood samples were drawn for inflammatory (IL-1, IL-6, IL-8, TNF-α) and anti-inflammatory (IL-10) cytokine levels before and during treatment. Results: A positive correlation was found between IL-6 serum levels and severity of mucositis and dysphagia; specifically, high IL-6 levels at week 2 were correlated with a need for PEG tube installation. A seemingly contradictory correlation was found between low IL-8 serum levels and a need for a PEG tube. Conclusion: These preliminary results, indicating a correlation between IL-6 and IL-8 serum levels and severity of mucositis and a need for a PEG tube installation, justify a large scale study.

Hemizygosity for Atm and Brca1 influence the balance between cell transformation and apoptosis

Fengtao Su — 2010-02-22T00:00:00Z

Background: In recent years data from both mouse models and human tumors suggest that loss of one allele of genes involved in DNA repair pathways may play a central role in genomic instability and carcinogenesis. Additionally several examples in mouse models confirmed that loss of one allele of two functionally related genes may have an additive effect on tumor development. To understand some of the mechanisms involved, we examined the role of monoallelic loss or Atm and Brca1 on cell transformation and apoptosis induced by radiation. Methods: Cell transformation and apoptosis were measured in mouse embryo fibroblasts (MEF) and thymocytes respectively. Combinations of wild type and hemizygous genotypes for ATM and BRCA1 were tested in various comparisons. Results: Haploinsufficiency of either ATM or BRCA1 resulted in an increase in the incidence of radiation-induced transformation of MEF and a corresponding decrease in the proportion of thymocytes dying an apoptotic death, compared with cells from wild-type animals. Combined haploinsufficiency for both genes resulted in an even larger effect on apoptosis. Conclusions: Under stress, the efficiency and capacity for DNA repair mediated by the ATM/BRCA1 cell signalling network depends on the expression levels of both proteins.

Neo-adjuvant chemo-radiation of rectal cancer with Volumetric Modulated Arc Therapy: summary of technical and dosimetric features and early clinical experience

Antonella Richetti — 2010-02-19T00:00:00Z

Background: To report about initial technical and clinical experience in preoperative radiation treatment of rectal cancer with volumetric modulated arcs with the RapidArc(R) (RA) technology. Methods: Twenty-five consecutive patients (pts) were treated with RA. All showed locally advanced rectal adenocarcinoma with stage T2-T4, N0-1. Dose prescription was 44Gy in 22 fractions (or 45Gy in 25 fractions). Delivery was performed with single arc with a 6MV photon beam. Twenty patients were treated preoperatively, five did not receive surgery. Twenty-three patients received concomitant chemotherapy with oral capecitabine. A comparison with a cohort of twenty patients with similar characteristics treated with conformal therapy (3DC) is presented as well. Results: From a dosimetric point of view, RA improved conformality of doses (CI95=1.1 vs. 1.4 for RA and 3DC), presented similar target coverage with lower maximum doses, significant sparing of femurs and significant reduction of integral and mean dose to healthy tissue. From the clinical point of view, surgical reports resulted in a down-staging in 41% of cases. Acute toxicity was limited to Grade 1-2 diarrhoea in 40% and Grade 3 in 8% of pts for RA pts, 45% and 5% for 3DC pts, compatible with known effects of concomitant chemotherapy. RA treatments were performed with an average of 2.0 vs. 3.4 min of 3DC. Conclusion: RA proved to be a safe, qualitatively advantageous treatment modality for rectal cancer, showing some improved results in dosimetric aspects.

Whole brain radiotherapy with a conformational external beam radiation boost for lung cancer patients with 1-3 brain metastasis: a multi institutional study

Nathalie Casanova — 2010-02-18T00:00:00Z

Background: To determine the outcome of patients with brain metastasis (BM) from lung cancer treated with an external beam radiotherapy boost (RTB) after whole brain radiotherapy (WBRT). Methods: A total of 53 BM patients with lung cancer were treated sequentially with WBRT and RTB between 1996 and 2008 according to our institutional protocol. Mean age was 58.8 years. The median KPS was 90. Median recursive partitioning analysis (RPA) and graded prognostic assessment (GPA) grouping were 2 and 2.5, respectively. Surgery was performed on 38 (71%) patients. The median number of BM was 1 (range, 1-3). Median WBRT and RTB combined dose was 39 Gy (range, 37.5 - 54). Median follow-up was 12.0 months. Results: During the period of follow-up, 37 (70%) patients died. The median overall survival (OS) was 14.5 months. Only 13 patients failed in the brain. The majority of patients (n = 29) failed distantly. The 1-year OS, -local control, extracranial failure rates were 61.2%, 75.2% and 60.8%, respectively. On univariate analysis, improved OS was found to be significantly associated with total dose (≤ 39 Gy vs. > 39 Gy; p < 0.01), age < 65 (p < 0.01), absence of extracranial metastasis (p < 0.01), GPA ≥ 2.5 (p = 0.01), KPS ≥ 90 (p = 0.01), and RPA < 2 (p = 0.04). On multivariate analysis, total dose (p < 0.01) and the absence of extracranial metastasis (p = 0.03) retained statistical significance. Conclusions: The majority of lung cancer patients treated with WBRT and RTB progressed extracranially. There might be a subgroup of younger patients with good performance status and no extracranial disease who may benefit from dose escalation after WBRT to the metastatic site.

Maintenance of Sorafenib following combined therapy of three-dimensional conformal radiation therapy/intensity-modulated radiation therapy and transcatheter arterial chemoembolization in patients with locally advanced hepatocellular carcinoma: a phase I/II study

Jian-Dong Zhao — 2010-02-12T00:00:00Z

Background: Three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with or without transcatheter arterial chemoembolization (TACE) for locally advanced hepatocellular carcinoma (HCC) has shown favorable outcomes in local control and survival of locally advanced HCC. However, intra-hepatic spreading and metastasis are still the predominant treatment failure patterns. Sorafenib is a multikinase inhibitor with effects against tumor proliferation and angiogenesis. Maintenance Sorafenib would probably prevent or delay the intrahepatic and extrahepatic spread of HCC after radiotherapy, which provides the rationale for the combination of these treatment modalities.Methods and designPatients with solitary lesion (bigger than 5 cm in diameter) histologically or cytologically confirmed HCC receive TACE (1-3 cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be administered only for the patients with non-progression disease 4 to 6 weeks after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day. Sorafenib will be continuously given for 12 months unless intolerable toxicities and/or tumor progression. If no more than 3 patients discontinue Sorafenib treatment who experience dose-limiting toxicity after necessary dose modification and delay and/or radiation-induced liver disease in the first 15 enrolled patients, the study will recruit second fifteen patients for further evaluating safety and efficacy of treatment. Hypothesis of the current study is that Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE is safe and superior to radiotherapy combined with TACE alone in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in comparison to historical data.DiscussionA recent meta-analysis showed TACE in combination with radiotherapy, improved the survival and the tumor response of patients, and was thus more therapeutically beneficial. In this study, local therapy for HCC is the combination of TACE and radiotherapy. Radiation exposure as a kind of stress might induce the compensatory activations of multiple intracellular signaling pathway mediators, such as PI3K, MAPK, JNK and NF-kB. Vascular endothelial growth factor (VEGF) was identified as one factor that was increased in a time- and dose-dependent manner after sublethal irradiation of HCC cells in vitro, translating to enhanced intratumor angiogenesis in vivo. Therefore, Sorafenib-mediated blockade of the Raf/MAPK and VEGFR pathways might enhance the efficacy of radiation, when Sorafenib is followed sequentially as a maintenance modality. (ClinicalTrials.gov number, NCT00999843.)

Kypho-IORT - a novel approach of intraoperative radiotherapy during kyphoplasty for vertebral metastases

Frederik Wenz — 2010-02-11T00:00:00Z

Background: Instable and painful vertebral metastases in patients with progressive visceral metastases present a common therapeutic dilemma. We developed a novel approach to deliver intraoperative radiotherapy (IORT) during kyphoplasty and report the first treated case.Methods/Results60 year old patient with metastasizing breast cancer under chemotherapy presented with a newly diagnosed painful metastasis in the 12th thoracic vertebra. Under general anaesthesia, a bipedicular approach into the vertebra was chosen with insertion of specially designed metallic sleeves to guide the electron drift tube of the miniature X-ray generator (INTRABEAM, Carl Zeiss Surgical, Oberkochen, Germany). This was inserted with a novel sheet designed for this approach protecting the drift tube. A radiation dose of 8 Gy in 5 mm distance (50 kV X-rays) was delivered. The kyphoplasty balloons (KyphX, Kyphon Inc, Sunnyvale) were inflated after IORT and polymethylmethacrylate cement was injected. The whole procedure lasted less than 90 minutes. Conclusion: In conclusion, this novel, minimally invasive procedure can be performed in standard operating rooms and may become a valuable option for patients with vertebral metastases providing immediate stability and local control. A phase I/II study is under way to establish the optimal dose prescription.