Hypofractionated conformal radiotherapy for pediatric diffuse intrinsic pontine glioma (DIPG): A randomized controlled trial

Background

The pediatric diffuse intrinsic pontine glioma (DIPG) outcome remains dismal despite multiple therapeutic attempts.

Purpose

To compare the results of treatment of pediatric diffuse intrinsic pontine glioma (DIPG) using hypofractionated versus conventional radiotherapy.

Patients and methods

Seventy-one newly diagnosed DIPG children were randomized into hypofractionated (HF) (39 Gy/13 fractions in 2.6 weeks) and conventional (CF) arm (54 Gy/30 fractions in 6 weeks).

Results

The median and one-year overall survival (OS) was 7.8 months and 36.4 ± 8.2% for the hypofractionated arm, and 9.5 and 26.2 ± 7.4% for the conventional arm respectively. The 18-month OS difference was 2.2%. The OS hazard ratio (HR) was 1.14 (95% CI: 0.70–1.89) (p = 0.59).The hypofractionated arm had a median and one-year progression-free survival (PFS) of 6.6 months and 22.5 ± 7.1%, compared to 7.3 and 17.9 ± 7.1% for the conventional arm. The PFS HR was 1.10 (95% CI: 0.67–1.90) (p = 0.71). The 18-month PFS difference was 1.1%. These differences exceed the non-inferiority margin.The immediate and delayed side effects were not different in the 2 arms.

Conclusions

Hypofractionated radiotherapy offers lesser burden on the patients, their families and the treating departments, with nearly comparable results to conventional fractionation, though not fulfilling the non-inferiority assumption.     

Parotid gland as a risk organ in whole brain radiotherapy

Background and purpose

Since the introduction of CT-based simulation for use in whole brain radiotherapy (WBRT), we have observed that a large volume of the parotid glands is included in the radiation fields. The purpose of this study is to analyze the dose-volume statistics of the parotid glands in patients undergoing WBRT.

Materials and methods

Thirty-two patients received WBRT using CT-based simulation with bilateral two-field arrangement. Daily fraction was 3 Gy with total dose of 30 Gy in 2 weeks. We analyzed the radiation dose from WBRT to the parotid glands.

Results

Average of the mean parotid dose was 17.5 Gy (range, 10.5-26.2) for both glands. Mean parotid doses ?20 and ?25 Gy were observed in 22 (34.4%) and 4 (6.3%) of 64 individual glands. The numbers of patients with a mean parotid dose of both glands ?20 Gy and ?25 Gy were 12 (37.5%) and 1 (3.1%), respectively.

Conclusions

Mean parotid dose was variable in patients with WBRT. According to the parotid dose and combined potential risk factors, parotid glands can be regarded as a risk organ in WBRT for improvement of patient quality of life.     

Hypofractionated accelerated CT-guided interstitial Ir-HDR-Brachytherapy as re-irradiation in inoperable recurrent cervical lymphadenopathy from head and neck cancer

Background

Despite significant improvements in the treatment of head and neck cancer (HNC), lymph node recurrences remain a clinical challenge after primary radiotherapy. The value of interstitial (IRT) brachytherapy (BRT) for control of lymph node recurrence remains unclear. In order to clarify its role a retrospective review was undertaken on the value of computed tomography (CT)-guided IRT high-dose-rate (HDR)-BRT in isolated recurrent disease from HNC.

Patients and methods

From 2000 to 2007, 74 patients were treated for inoperable recurrent cervical lymphadenopathy. All patients had previously been treated with radical radiotherapy or chemoradiation with or without surgery. The HDR-BRT delivered a median salvage dose of 30.0 Gy (range, 12.0-36.0 Gy) in twice-daily fractions of 2.0-5.0 Gy in 71 patients and of 30.0 Gy (range, 10.0-36.0 Gy) in once-daily fractions of 6.0-10.0 Gy in three patients.

Results

The overall and disease-free survival rates at one, two and three years were 42%, 19%, 6%, and 42%, 37% and 19%, respectively. The local control probability at one, two and three years was 67% at all three time points. Grade III-IV complications occurred in 13% of patients.

Conclusions

In patients with inoperable recurrent neck disease from HNC, hypofractionated accelerated CT-guided IRT-HDR-BRT can play an important role in providing palliation and tumor control.     

Hypofractionated Accelerated Radiotherapy with Concurrent Carboplatin for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Aims

Hypofractionated accelerated radiotherapy with concurrent carboplatin utilises both advantages of altered fractionation and synchronous chemotherapy to maximise local control in locally advanced head and neck cancer. Such fractionation schedules are increasingly used in the intensity-modulated radiotherapy era and the aim of this study was to determine the outcome of hypofractionated accelerated radiotherapy with carboplatin.

Materials and methods

One hundred and fifty consecutive patients with squamous cell carcinoma of the larynx, oropharynx, oral cavity and hypopharynx (International Union Against Cancer [IUAC] stage II-IV) treated with 55 Gy in 20 fractions over 25 days with concurrent carboplatin were analysed. Outcome measures were 2 year overall survival, local control and disease-free survival.

Results

The median follow-up in surviving patients was 25 months. IUAC stages: II n = 15; III n = 42; IV n = 93. Two year overall survival for all patients was 74.9% (95% confidence interval 66.0-81.7%). Two year local control was 78.3% (95% confidence interval 69.6-84.8%). Two year disease-free survival was 67.2% (95% confidence interval 58.3-74.7%). There were 135 patients with stage III and IV disease. For these patients, the 2 year overall survival, local control and disease-free survival were 74.3% (95% confidence interval 64.7-81.6%), 79.1% (95% confidence interval 69.8-85.9%) and 67.6% (95% confidence interval 58.0-75.4%), respectively. Prolonged grade 3 and 4 mucositis seen at ≥4 weeks were present in 9 and 0.7%, respectively. Late feeding dysfunction (determined by dependence on a feeding tube at 1 year) was seen in 13% of the surviving patients at 1 year.

Conclusion

Hypofractionated accelerated radiotherapy with concurrent carboplatin achieves a high local control. This regimen should be considered for a radiotherapy dose-escalation study using intensity-modulated radiotherapy.     

Radiation-induced rib fractures after hypofractionated stereotactic body radiation therapy of non-small cell lung cancer: A dose- and volume-response analysis

Background and purpose

The aim of this study is to analyse the dose-response and the volume-response of radiation-induced rib fractures after hypofractionated stereotactic body radiation therapy (SBRT).

Materials and methods

During the period 1998-2005, 68 patients with medically inoperable stage I non-small cell lung cancer (NSCLC) were treated with hypofractionated SBRT to 45 Gy in 3 fractions. Among the 33 patients with complete treatment records and radiographic follow-up exceeding 15 months (median: 29 months), 13 fractures were found in seven patients. Identifying all ribs receiving at least 21 Gy, 81 ribs (13 with and 68 without fracture) in 26 patients were separately contoured and their dose-volume histograms (DVHs) were obtained. The DVHs were assessed with the mean dose and cut-off models. Maximum likelihood estimation was used to fit dose-response and volume-response curves to each model.

Results

It was possible to quantify the risk of radiation-induced rib fracture using response curves and information contained in the DVHs. Absolute volumes provided better fits than relative volumes and dose-response curves were more suitable than volume-response curves. For the dose given by the 2 cm³ cut-off volume, D_2cm3, the logistic dose-response curve for three fractions was parameterised by D₅₀ = 49.8 Gy and γ₅₀ = 2.05. Consequently, for a median follow-up of 29 months, if D_2cm3 < 3 × 7.0 Gy the risk is close to 0, and the 5% and 50% risks are given by D_2cm3 = 3 × 9.1 Gy and 3 × 16.6 Gy, respectively.

Conclusions

In this group of patients, the risk for radiation-induced rib fracture following hypofractionated SBRT was related to the dose to 2 cm³ of the rib.     

Efficacy of a hypofractionated schedule in electron beam radiotherapy for epithelial skin cancer: Analysis of 434 cases

Background and purpose

Efficacy of radiotherapy for epithelial skin cancer was evaluated and treatment outcomes of two electron beam fractionation schedules were compared.

Materials and methods

Outcome data of 434 epithelial skin cancers in 333 patients were analysed; 332 were basal cell carcinomas (BCCs) and 102 squamous cell carcinomas (SCCs). Patients were treated with electron beam, and received either 54 Gy in 18 fractions (n = 159) or 44 Gy in 10 fractions (n = 275). Local recurrence free (LRF) rates were analysed as well as metastases free rates, cancer specific survival (CSS) and cosmetic result.

Results

Median follow-up was 42.8 months. For BCC, actuarial 3-year LRF rates were 97.6% for tumours treated with 54 Gy and 96.9% for 44 Gy. In SCC 3-year LRF rates were 97.0% for 54 Gy and 93.6% for 44 Gy (n.s.).T stage was found to be the only significant factor for recurrence (p = 0.036). Three-year CSS was 98% for SCC and 100% for BCC.

Conclusions

Electron beam irradiation is a safe and effective treatment modality for epithelial skin cancer. In view of a similar efficacy and patient convenience of the hypofractionated schedule, 44 Gy in 10 fractions can be regarded the radiation schedule of choice.     

Evaluation of early metabolic responses in rectal cancer during combined radiochemotherapy or radiotherapy alone: Sequential FDG-PET-CT findings

Background and purpose

The purpose of this study was to prospectively investigate metabolic changes of rectal tumors after 1 week of treatment of either radiochemotherapy (28 × 1.8 Gy + Capecitabine) (RCT) or hypofractionated radiotherapy (5 × 5 Gy) alone (RT).

Materials and methods

Fourty-six rectal cancer patients, 25 RCT- and 21 RT-patients, were included in this study. Sequential FDG-PET-CT scans were performed for each of the included patients both prior to treatment and after the first week of treatment. Consecutively, the metabolic treatment response of the tumor was evaluated.

Results

For the patients referred for pre-operative RCT, significant reductions of SUV_mean (p < 0.001) and SUV_max (p < 0.001) within the tumor were found already after the first week of treatment (8 Gy biological equivalent dose (BED). In contrast, 1 week of treatment with RT alone did not result in significant changes in the metabolic activity of the tumor (p = 0.767, p = 0.434), despite the higher applied RT dose of 38.7 Gy BED.

Conclusions

Radiochemotherapy of rectal cancer leads to significant early changes in the metabolic activity of the tumor, which was not the case early after hypofractionated radiotherapy alone, despite the higher radiotherapy dose given. Thus, the chemotherapeutic agent Capecitabine might be responsible for the early metabolic treatment responses during radiochemotherapy in rectal cancer.     

A study of middle ear function in the treatment of nasopharyngeal carcinoma with IMRT technique

Purpose

This study evaluates the difference in damage to middle ear function with CRT and IMRT techniques in the treatment of nasopharyngeal carcinoma (NPC). We explore the isthmus of the Eustachian tube (ET) as the key anatomic site for the prevention of radiation-induced otitis media with effusion.

Methods and materials

Eighty-two patients with NPC were divided into two groups: 40 patients treated with CRT and 42 patients treated with IMRT. The difference between dosage over the middle ear cavity and the isthmus of the ET was evaluated in both CRT group and IMRT group. All patients underwent hearing tests including pure tone audiometry and impedance audiometry before and after RT.

Results

The dosage difference to the middle ear cavity and isthmus between these two groups was statistically significant (p < 0.05). The difference in hearing test results between these two groups was also statistically significant (p < 0.05). If we limited the dose to the middle ear cavity under 34 Gy and the dose to the isthmus under 53 Gy with IMRT, we may decrease radiation-induced OME even with the larger 2.25 Gy fraction size.

Conclusions

IMRT may have better protected the middle ear function compared with the CRT technique, even with larger fraction sizes than for the conventional CRT technique.     

Dosimetric predictor identification for radiation-induced liver disease after hypofractionated conformal radiotherapy for primary liver carcinoma patients with Child-Pugh Grade A cirrhosis

Purpose

Radiation-induced liver disease (RILD) is the most severe complication in liver cancer treatment. The aim of this study was to identify dosimetric predictors for RILD in primary liver carcinoma (PLC) patients with Child-Pugh Grade A cirrhosis after hypofractionated conformal radiotherapy (CRT).

Methods and materials

A total of 114 eligible patients (mean age 45 years old) were enrolled and treated. The mean gross tumor volume (GTV) was (378.3 ± 308.1) cm³. A median dose of 53 Gy was delivered to the PLC by hypofractionated CRT (three fractions/week) with a median fraction size of 4.6 Gy (range: 4-6 Gy).

Results

Patients were followed up for 1-79 months (median 19 months) after the completion of irradiation. RILD was diagnosed in nine (7.9%) patients. Univariate analyses revealed that GTV and the percentage of normal liver volume receiving more than 5-40 Gy irradiations (V_5-40) were related to the risk of developing RILD. Multivariate analyses demonstrated that only GTV and V₂₀ were independent predictors. Using V₂₀ as the predictor for RILD, the accuracy, sensitivity, and specificity was 76.3%, 88.9%, and 75.2%, respectively.

Conclusions

Our data suggest that V₂₀ is the unique significant dosimetric predictor for RILD risks in PLC patients with Child-Pugh Grade A cirrhosis after hypofractionated CRT.     

Nomogram to predict ipsilateral breast relapse based on pathology review from the EORTC 22881-10882 boost versus no boost trial

Background and purpose

The EORTC 22881-10882 trial showed that for patients treated with breast conserving therapy (BCT), a 16 Gy boost dose significantly improved local control, but increased the risk of breast fibrosis. A model to estimate the risk of ipsilateral breast relapse (IBR) already exists, but now a model has been developed which takes boost treatment into account and is based on centrally reviewed pathology.

Materials and methods

A Cox model was developed based on central pathology review data and clinical data of 1603 patients from the EORTC 22881-10882 trial with a median follow-up of 11.5 years. From a predefined set of variables, predictors with a maximal effect on 10-year IBR rate >4% were retained in the model. Bootstrap re-sampling was used to assess model calibration and discrimination. The results are presented in the form of a nomogram.

Results

Apart from young age and no boost, presence of DCIS adjacent to the invasive tumor was associated with increased risk of IBR (HR 1.96, p = 0.001). Patients with high grade invasive tumors were younger than patients with low/intermediate grade (p < 0.0001). The nomogram includes histologic grade, DCIS, tumor diameter, age, tamoxifen, chemotherapy, and boost with a concordance probability estimate of 0.68.

Conclusions

The nomogram for predicting IBR 10 years after BCT includes seven factors, with young age, presence of DCIS and boost treatment as the most dominant factors. The nomogram estimates IBR and confirms the importance of a boost dose. Combined with a model to predict fibrosis published previously, the nomogram presented here may assist in decision making for individual patients.     

Intensity modulated radiotherapy in the management of sacral chordoma in primary versus recurrent disease

Purpose

To investigate treatment outcome in patients suffering from sacral chordoma after intensity modulated radiotherapy (IMRT) for primary versus recurrent disease.

Material/methods

We report on 34 patients with histologically proven sacral chordoma. Seventeen patients were treated at time of initial diagnosis with post-operative IMRT (n = 13) or with IMRT alone (n = 4). Seventeen patients were treated in recurrent disease after surgery (n = 11) or with radiotherapy alone (n = 6). Median total dose to the boost volume (PTV2) was 66 Gy (range, 72-54) with 2 Gy per fraction using an integrated boost concept. Median dose to target volume (PTV1) was 54 Gy in 1.8 Gy.

Results

Local control was 35% (12/34) and overall survival 74% (25/34) after a median follow-up of 4.5 years. Actuarial local control was 79%, 55% and 27% after 1, 2 and 5 years, respectively. Local control was significantly higher in patients treated for primary tumors (p < 0.03) and in total doses >60 Gy (p < 0.01). Actuarial overall survival was 97%, 91% and 70% after 1, 2 and 5 years, respectively.

Conclusion

These data demonstrate that local control after IMRT is higher in patients treated for primary tumors and using higher radiation doses. Therefore, we recommend radiotherapy as part of initial treatment in sacral chordoma.     

Accelerated partial-breast irradiation using high-dose-rate interstitial brachytherapy: 12-year update of a prospective clinical study

Background and purpose

To report the 12-year updated results of accelerated partial-breast irradiation (APBI) using multicatheter interstitial high-dose-rate (HDR) brachytherapy (BT).

Patients and methods

Forty-five prospectively selected patients with T1N0-N1mi, nonlobular breast cancer without the presence of an extensive intraductal component and with negative surgical margins were treated with APBI after breast-conserving surgery (BCS) using interstitial HDR BT. A total dose of 30.3 Gy (n = 8) and 36.4 Gy (n = 37) in seven fractions within 4 days was delivered to the tumour bed plus a 1-2 cm margin. The median follow-up time was 133 months for surviving patients. Local and regional control, disease-free (DFS), cancer-specific (CSS), and overall survival (OS), as well as late side effects, and cosmetic results were assessed.

Results

Four (8.9%) ipsilateral breast tumour recurrences were observed, for a 5-, 10-, and 12-year actuarial rate of 4.4%, 9.3%, and 9.3%, respectively. A total of two regional nodal failures were observed for a 12-year actuarial rate of 4.4%. The 12-year DFS, CSS, and OS was 75.3%, 91.1%, and 88.9%, respectively. Grade 3 fibrosis was observed in one patient (2.2%). No patient developed grade 3 teleangiectasia. Fat necrosis requiring surgical intervention occurred in one woman (2.2%). Cosmetic results were rated excellent or good in 35 patients (77.8%).

Conclusions

Twelve-year results with APBI using HDR multicatheter interstitial implants continue to demonstrate excellent long-term local tumour control, survival, and cosmetic results with a low-rate of late side effects.     

Whole brain radiotherapy: Prognostic factors and results of a radiation boost delivered through a conventional linear accelerator

Purpose

Assess prognostic factors for overall survival and the potential benefit of a boost in patients treated with whole brain radiation therapy (WBRT).

Methods and materials

From 2002 to 2006, a retrospective analysis was made from 250 unselected consecutive patients with secondary brain metastases from lung cancer, breast cancer and melanoma. Eighteen patients received surgery and were excluded from analysis. Four potential prognostic factors have been studied: primary tumor type, gender, number of metastases and improvement of neurological symptoms after radiation therapy. A subgroup analysis was performed to determine whether an additional boost could potentially improve outcome in patients who presented with less than three metastases, performance status <2, and no surgical resection of their metastasis.

Results

Average follow-up was 10.3 months. Median overall survival was 5.6 months and survival rates at 1 and 2 years were 22.7% and 10%, respectively. Age less than 65 (p < 0.01), neurological improvement after WBRT (p < 0.01), and presence of less than three metastases were significant factors for overall survival in multivariate analysis. When focusing on the selected subgroup (120 assessable patients), median overall survival was 4.0 months in patients with no radiation boost, versus 8.9 months in patients with radiation boost (p = 0.0024).

Conclusions

Survival and prognostic factors were similar to those found in the literature. Boost delivered after WBRT by a conventional particle accelerator could provide a benefit in selected patients, especially for centers that do not have radiotherapy techniques in stereotactic conditions. This warrants further prospective assessment.     

Palliative prostate radiotherapy for symptomatic advanced prostate cancer

Background and purpose

To report the results for the use of short-course palliative radiotherapy to the prostate for localised symptoms.

Materials and methods

Fifty-eight patients were identified from radiotherapy records between 2003 and 2007. Data were collected retrospectively on patients’ demographics, radiotherapy details and response. Symptoms and toxicity were scored, retrospectively, according to the following scale: 0 = no symptoms, 1 = mild symptoms, 2 = moderate symptoms, and 3 = severe symptoms.

Results

All the 58 patients had advanced prostate carcinoma. The median age at radiotherapy was 76.6 years (range 54-91). Fifty-six patients (97%) had hormone refractory disease. Twenty-seven patients (47%) had evidence of metastatic disease. 20Gy in 5 fractions was the most commonly used fractionation. The most frequent baseline symptom was haematuria (54%). Eighty-nine percent (31/35) of the patients had a complete or partial resolution of symptoms at 4 months. Response rates for individual symptoms (including unknown responses) were: rectal symptoms (75%), pelvic pain (69%), urinary obstruction (54%) and haematuria (42%). A >50% reduction in PSA occurred in five patients. Toxicity was mild to moderate only and was self-limiting.

Conclusion

Palliative radiotherapy to the prostate gland for local symptoms appears to be an effective means of palliation with minimal toxic side effects. Prospective studies are now required to assess its benefits in more detail.     

Phase I dose escalation trial of hypofractionated limited-field external beam thoracic radiotherapy for limited-stage small cell carcinoma of the lung

Purpose

To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurrent chemotherapy for limited-stage small cell lung cancer.

Materials and methods

Limited-stage small cell lung cancer patients were prescribed 54, 58, 62 or 65 Gy, all given in 25 daily fractions and commenced on or before the second chemotherapy cycle. Dose level accrual was performed sequentially. Conformal radiotherapy techniques were used and targeted gross disease plus margin. Four cycles of platinum-based chemotherapy were prescribed. Primary endpoint was the rate of acute RT toxicities according to NCI Common Toxicity Criteria scales. The dose which caused unacceptable acute radiotherapy toxicity rates according to pre-defined stopping rules defined the maximal tolerated radiotherapy dose.

Results

Six patients were accrued to each of the 54, 58 and 62 Gy dose levels. There were no radiotherapy-related deaths. No grade 3 toxicities occurred in the 54 and 58 Gy groups. There were 2 grade 3 RT toxicities in the 62 Gy group. There were 14 complete responses. Trial accrual has stopped at the 62 Gy group according to trial stopping rules.

Conclusions

The maximal tolerated hypofractionated thoracic radiotherapy dose in this trial was 58 Gy in 25 daily fractions.     

Radiation pneumonitis in patients treated for malignant pulmonary lesions with hypofractionated radiation therapy

Purpose

We evaluated the relationship between the mean lung dose (MLD) and the incidence of radiation pneumonitis (RP) after stereotactic body radiation therapy (SBRT), and compared this with conventional fractionated radiation therapy (CFRT).

Materials and methods

For both SBRT (n = 128) and CFRT (n = 142) patients, RP grade ?2 was scored. Toxicity models predicting the probability of RP as a function of the MLD were fitted using maximum log likelihood analysis. The MLD was NTD (Normalized Total Dose) corrected using an α/β ratio of 3 Gy.

Results

SBRT patients were treated with 6-12 Gy per fraction with a median MLD of 6.4 Gy (range: 1.5-26.5 Gy). CFRT patients were treated with 2 Gy or 2.25 Gy per fraction, the median MLD was 13.2 Gy (range: 3.0-23.0 Gy). The crude incidence rates of RP were 10.9% and 17.6% for the SBRT and CFRT patients, respectively. A significant dose-response relationship for RP was found after SBRT, which was not significantly different from the dose-response relationship for CFRT (p = 0.18).

Conclusion

We derived a significant dose-response relationship between the risk of RP and the MLD for SBRT from the clinical data. This relation was not significantly different from the dose-response relation for CFRT, although statistical analysis was hampered by the low number of patients in the high dose range.     

Dose-response relationship for radiation-induced pneumonitis after pulmonary stereotactic body radiotherapy

Purpose

To evaluate dosimetric factors predictive for radiation-induced pneumonitis (RP) after pulmonary stereotactic body radiotherapy (SBRT).

Materials and methods

A retrospective analysis was performed based on 59 consecutive patients treated with cone-beam CT-based image-guided SBRT for primary NSCLC (n = 21) or pulmonary metastases (n = 54). The majority of patients were treated with radiosurgery of 26 Gy to 80% (n = 29) or three fractions of 12.5 Gy to 65% (n = 40). To correct for different single fraction doses, local doses were converted to 2 Gy equivalent normalized total doses (NTDs) using α/β ratio of 3 Gy for RP. Dose-volume parameters and incidences of RP ? grade II SWOG were fitted using NTCP models.

Results

Eleven patients developed RP grade II. With an average MLD of 10.3 ± 5.6 Gy to the ipsilateral lung, a significant dose-response relationship was observed: the MLD was 12.5 ± 4.3 Gy and 9.9 ± 5.8 Gy for patients with and without development of RP, respectively. Additionally, volumes of the lung exposed to minimum doses between 2.5 and 50 Gy (V_2.5-V₅₀) were correlated with incidences of RP with a continuous decrease of the goodness of fit for higher doses.

Conclusions

The MLD and V_2.5-V₅₀ of the ipsilateral lung were correlated with incidences of RP after pulmonary SBRT.     

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data

Background and purpose

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).

Materials and methods

RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n = 3), while group 2 had PTVs encompassing the entire vertebra (n = 4). Finally, RA delivery parameters in four patients were assessed.

Results

Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V_{10-partial cord} for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min.

Conclusions

Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.     

DNA methylation changes in cells regrowing after fractioned ionizing radiation

Background and purpose

Repeated exposure to ionizing radiation (IR) can result in adaptive reactions. While DNA methylation changes in adaption to repeated stress exposure are established for a variety of drugs, their role in fractioned ionizing radiation is largely unknown.

Material and methods

MCF7 breast cancer cells were treated 5 times a week with IR in fractions of 2 Gy, resulting in total doses of 10 and 20 Gy. Cells were harvested 48 and 72 h after the last irradiation, as well as after a recovery period of at least 14 d. To identify genes differentially methylated in irradiated versus non-irradiated cells, we used methyl-CpG immunoprecipitation (MCIp) followed by global methylation profiling on CpG island microarrays.

Results

MCIp profiling revealed methylation changes in several CpG islands 48 h after FIR with 10 and 20 Gy. Cells receiving a total dose of 10 Gy started regrowing after 14 d and exhibited similar radioresistance as mock-treated cells. Differential methylation of the CpG units associated with FOXC1 (p < 0.001) and TRAPPC9 (p < 0.001) could be confirmed by time-of-flight mass spectrometry (Sequenom).

Conclusions

In summary, these data indicate that regrowth of MCF7 cells after 10 Gy FIR is associated with locus-specific alterations in DNA methylation.