Radiation Oncology - Latest articles

Analysis of health related quality of life (HRQoL) of patients with clinically localized prostate cancer, one year after treatment with external beam radiotherapy (EBRT) alone versus EBRT and high dose rate brachytherapy (HDRBT)

2008-07-15

: Purpose: Prostate cancer is the leading form of cancer diagnosed among North American men. Most patients present with localized disease, which can be effectively treated with a variety of different modalities. These are associated with widely different acute and late effects, which can be both physical and psychological in nature. Health related quality of life (HRQOL) concerns are therefore important for these patients for selecting between the various treatment options. Methods and Materials: 117 patients with localized prostate cancer were invited to participate in a quality of life assessment self reported survey. 111 patients consented and participated in the survey, one year after completion of their treatment. 88 patients received EBRT and 23 received EBRT and HDRBT. Quality of life (QOL) was compared in the two groups, by using a modified version of Functional Assessment of Cancer Therapy-Prostate (FACT-P) survey instrument. Results: One year after completion of treatment, there was no significant difference in overall quality of life between patients who received EBRT alone and those who received a combination of EBRT and HDRBT. For each component of the modified FACT-P survey, i.e. physical, social/family, emotional, and functional well-being; there were no statistically significant differences in the mean scores between these two groups. Conclusions: This small study shows that there is no significant difference in quality of life at one year post-treatment, in patients treated with EBRT alone versus combined EBRT and HDRBT. Key words: Radiotherapy, Health Related Quality of Life (HRQOL), High Dose Rate Brachytherapy, Prostate cancer

In vitro studies on the modification of low-dose hyper-radiosensitivity in prostate cancer cells by incubation with genistein and estradiol

2008-07-14

Background: As the majority of prostate cancers (PC) express estrogen receptors, we evaluated the combination of radiation and estrogenic stimulation (estrogen and genistein) on the radiosensitivity of PC cells in vitro. Methods: PC cells LNCaP (androgen-sensitive) and PC-3 (androgen-independent) were evaluated. Estrogen receptor (ER) expression was analyzed by means of immunostaining. Cells were incubated in FCS-free media with genistein 10 uM and estradiol 10 uM 24h before irradiation and up to 24h after irradiation. Clonogenic survival, cell cycle changes, and expression of p21 were assessed. Results: LNCaP expressed both ER-alpha and ER-beta, PC-3 did not. Incubation of LNCaP and PC-3 with genistein resulted in a significant reduction of clonogenic survival. Incubation with estradiol exhibited in low concentrations (0.01 uM) stimulatory effects, while higher concentrations did not influence survival. Both genistein 10 uM and estradiol 10 uM increased low-dose hyper-radiosensitivity [HRS] in LNCaP, while hormonal incubation abolished HRS in PC-3. In LNCaP cells hormonal stimulation inhibited p21 induction after irradiation with 4 Gy. In PC-3 cells, the proportion of cells in G2/M was increased after irradiation with 4 Gy. Conclusion: We found an increased HRS to low irradiation doses after incubation with estradiol or genistein in ER-alpha and ER-beta positive LNCaP cells. This is of high clinical interest, as this tumor model reflects a locally advanced, androgen dependent PC. In contrast, in ER-alpha and ER-beta negative PC-3 cells we observed an abolishing of the HRS to low irradiation doses by hormonal stimulation. The effects of both tested compounds on survival were ER and p53 independent. Since genistein and estradiol effects in both cell lines were comparable, neither ER- nor p53-expression seemed to play a role in the linked signalling. Nevertheless both compounds targeted the same molecular switch. To identify the underlying molecular mechanisms, further studies are needed.

Effect of prolonging radiation delivery time on retention of gammaH2AX

Vitali Moiseenko, Judit P Banáth, Cheryl Duzenli and Peggy L Olive — 2008-06-27

Background and purposeCompared to conventional external beam radiotherapy, IMRT requires significantly more time to deliver the dose. Prolonging dose delivery potentially increases DNA repair which would reduce the biological effect. We questioned whether retention of γH2AX, a measure of lack of repair of DNA damage, would decrease when dose delivery was protracted.Materials and methodsExponentially growing SiHa cervical carinoma cells were irradiated with 6 MV photons in a water tank using a VarianEX linear accelerator. Cells held at 37°C received 2 Gy in 0.5 min and 4 Gy in 1 min. To evaluate effect of dose delivery prolongation, 2 and 4 Gy were delivered in 30 and 60 min. After 24 h recovery, cells were analyzed for clonogenic survival and for residual γH2AX as measured using flow cytometry. Results: Increasing the dose delivery time from 0.5 or 1 min to 30 or 60 min produced a signficant increase in cell survival from 0.45 to 0.48 after 2 Gy, and from 0.17 to 0.20 after 4 Gy. Expression of residual γH2AX decreased from 1.27 to 1.22 relative to background after 2 Gy and 1.46 to 1.39 relative to background after 4 Gy, but differences were not statistically significant. The relative differences in the slopes of residual γH2AX versus dose for acute versus prolonged irradiation bordered on significant (p = 0.055), and the magnitude of the change was consistent with the observed increase in surviving fraction. Conclusion: These results support the concept that DNA repair underlies the increase in survival observed when dose delivery is prolonged. They also help to establish the limits of sensitivity of residual γH2AX, as measured using flow cytometry, for detecting differences in response to irradiation.

A psychoeducational intervention reduces the need for anesthesia during radiotherapy for young childhood cancer patients

2008-06-04

Background: Radiotherapy (RT) has become an important treatment modality in pediatric oncology, but its delivery to young children with cancer is challenging and general anesthesia is often needed. Methods: To evaluate whether a psychoeducational intervention might reduce the need for anesthesia, 223 consecutive pediatric cancer patients receiving 4141 RT fractions during 244 RT courses between February 1989 and January 2006 were studied. Whereas in 154 RT courses corresponding with 2580 RT fractions patients received no psychoeducational intervention (group A), 90 RT courses respectively 1561 RT fractions were accomplished by using psychoeducational intervention (group B). This tailored psychoeducational intervention in group B included a play program and interactive support by a trained nurse according to age to get familiar with staff, equipment and procedure of radiotherapy. Results: Group A did not differ significantly from group B in age at RT, gender, diagnosis, localization of RT and positioning during RT. Whereas 33 (21.4%) patients in group A got anesthesia, only 8 (8.9%) patients in group B needed anesthesia. The median age of cooperating patients without anesthesia decreased from 3.2 to 2.7 years. In both uni- and multivariate analyses the psychoeducational intervention significantly and independently reduced the need for anesthesia. Conclusion: We conclude that a specifically tailored psychoeducational intervention is able to reduce the need for anesthesia in children undergoing RT for cancer. This results in lower costs and increased cooperation during RT.

Reproducibility and geometric accuracy of the fixster system during hypofractionated stereotactic radiotherapy

2008-05-28

Background: Hypofractionated radiotherapy has been used for the treatment of AVMs and brain metastases. Hypofractionation necessitates the use of a relocatable stereotactic frame that has to be applied on several occasions. The stereotactic frame needs to have a high degree of reproducibility, and patient positioning is crucial to achieve a high accuracy of the treatment. Methods: In this study we have, by radiological means, evaluated the reproducibility of the isocenter in consecutive treatment sessions using the Fixster frame. Deviations in the X, Y and Z-axis were measured in 10 patients treated with hypofractionated radiotherapy. Results: The mean deviation in the X-axis was 0.4 mm (range -2.1 – 2.1, median 0.7 mm) and in the Y-axis -0.3 mm (range -1.4 – 0.7, median -0.2 mm). The mean deviation in the Z-axis was -0.6 (range -1.4 – 1.4, median 0.0 mm). Conclusion: There is a high degree of reproducibility of the isocenter during successive treatment sessions with HCSRT using the Fixster frame for stereotactic targeting. The high reducibility enables a safe treatment using hypofractionated stereotactic radiotherapy.

High-dose intensity-modulated radiotherapy for prostate cancer using daily fiducial marker-based position verification: acute and late toxicity in 331 patients

2008-05-21

We evaluated the acute and late toxicity after high-dose intensity-modulated radiotherapy (IMRT) with fiducial marker-based position verification for prostate cancer. Between 2001 and 2004, 331 patients with prostate cancer received 76 Gy in 35 fractions using IMRT combined with fiducial marker-based position verification. The symptoms before treatment (pre-treatment) and weekly during treatment (acute toxicity) were scored using the Common Toxicity Criteria (CTC). The goal was to score late toxicity according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) scale with a follow-up time of at least three years. Twenty-two percent of the patients experienced pre-treatment grade ≥ 2 genitourinary (GU) complaints and 2% experienced grade 2 gastrointestinal (GI) complaints. Acute grade 2 GU and GI toxicity occurred in 47% and 30%, respectively. Only 3% of the patients developed acute grade 3 GU and no grade ≥ 3 GI toxicity occurred. After a mean follow-up time of 47 months with a minimum of 31 months for all patients, the incidence of late grade 2 GU and GI toxicity was 21% and 9%, respectively. Grade ≥ 3 GU and GI toxicity rates were 4% and 1%, respectively, including one patient with a rectal fistula and one patient with a severe hemorrhagic cystitis (both grade 4). In conclusion, high-dose intensity-modulated radiotherapy with fiducial marker-based position verification is well tolerated. The low grade ≥ 3 toxicity allows further dose escalation if the same dose constraints for the organs at risk will be used.

Testing the portal imager GLAaS algorithm for machine quality assurance

G Nicolini, E Vanetti, A Clivio, A Fogliata, G Boka and L Cozzi — 2008-05-21

Background: To report about enhancements introduced in the GLAaS calibration method to convert raw portal imaging images into absolute dose matrices and to report about application of GLAaS to routine radiation tests for linac quality assurance procedures programmes. Methods: Two characteristic effects limiting the general applicability of portal imaging based dosimetry are the over-flattening of images (eliminating the "horns" and "holes" in the beam profiles induced by the presence of flattening filters) and the excess of backscattered radiation originated by the detector robotic arm supports. These two effects were corrected for in the new version of GLAaS formalism and results are presented to prove the improvements for different beams, detectors and support arms. GLAaS was also tested for independence from dose rate (fundamental to measure dynamic wedges).With the new corrections, it is possible to use GLAaS to perform standard tasks of linac quality assurance. Data were acquired to analyse open and wedged fields (mechanical and dynamic) in terms of output factors, MU/Gy, wedge factors, profile penumbrae, symmetry and homogeneity. In addition also 2D Gamma Evaluation was applied to measurement to expand the standard QA methods. GLAaS based data were compared against calculations on the treatment planning system (the Varian Eclipse) and against ion chamber measurements as consolidated benchmark. Measurements were performed mostly on 6 MV beams from Varian linacs. Detectors were the PV-as500/IAS2 and the PV-as1000/IAS3 equipped with either the robotic R- or Exact- arms. Results: Corrections for flattening filter and arm backscattering were successfully tested. Percentage difference between PV-GLAaS measurements and Eclipse calculations relative doses at the 80% of the field size, for square and rectangular fields larger than 5 × 5 cm2 showed a maximum range variation of -1.4%, + 1.7% with a mean variation of <0.5%. For output factors, average percentage difference between GLAaS and Eclipse (or ion chamber) data was -0.4 ± 0.7 (-0.2 ± 0.4) respectively on square fields. Minimum, maximum and average percentage difference between GLAaS and Eclipse (or ion chamber) data in the flattened field region were: 0.1 ± 1.0, 0.7 ± 0.8, 0.1 ± 0.4 (1.0 ± 1.4, -0.3 ± 0.2, -0.1 ± 0.2) respectively. Similar minimal deviations were observed for flatness and symmetry.For Dynamic wedges, percentage difference of MU/Gy between GLAaS and Eclipse (or ion chamber) was: -1.1 ± 1.6 (0.4 ± 0.7). Minimum, maximum and average percentage difference between GLAaS and Eclipse (or ion chamber) data in the flattened field region were: 0.4 ± 1.6, -1.5 ± 1.8, -0.1 ± 0.3 (-2.2 ± 2.3, 2.3 ± 1.2, 0.8 ± 0.3) respectively.For mechanical wedges differences of transmission factors were <1.6% (Eclipse) and <1.1% (ion chamber) for all wedges. Minimum, maximum and average percentage difference between GLAaS and Eclipse (or ion chamber) data in the flattened field region were: -1.3 ± 0.7, -0.7 ± 0.7, -0.2 ± 0.2 (-0.8 ± 0.8, 0.7 ± 1.1, 0.2 ± 0.3) respectively. Conclusion: GLAaS includes now efficient methods to correct for missing "horns" and "holes" induced by flattening filter in the beam and to compensate for excessive backscattering from the support arm. These enhancements allowed to use GLAaS based dosimetric measurement to perform standard tasks of Linac quality assurance with reliable and consistent results. This fast method could be applied to routine practice being also fast in usage and because it allows the introduction of new analysis tools in routine QA by means, e.g., of the Gamma Index analysis.

Highly proliferative neuroendocrine carcinoma – influence of radiotherapy fractionation on tumor response

Anne Hansen Ree — 2008-05-19

A 45-year-old white male presented to our department with postoperative recurrence of gastrointestinal poorly differentiated neuroendocrine carcinoma manifesting as lymph node dissemination and a solitary implantation metastasis in the rectovesical pouch. Following disease progression on chemotherapy, the patient was treated with radiotherapy using either a conventional daily treatment or an accelerated hyperfractionated protocol to separate sites of disease progression. Using serial CT scan assessment, changes in cross-sectional area of the separately treated metastatic lesions were evaluated for determination of therapy response. The accelerated hyperfractionated radiotherapy appeared to limit the rate of tumor growth to a greater degree than the conventional fractionation schedule. Of uttermost importance, in this palliative setting, the patient completed the intensified radiotherapy regimens with acceptable acute toxicity. Given the proliferative capacity of poorly differentiated neuroendocrine carcinomas of the gastrointestinal tract, radiotherapy may be a therapeutic supplement to chemotherapy, which represents the main treatment option in this tumor entity. Importantly, tumors with a capacity for rapid proliferation and regeneration may be particularly sensitive to the use of intensified fractionation protocols in clinical radiotherapy.

The effect of radio-adaptive doses on HT29 and GM637 cells

2008-04-23

Background: The shape of the dose-response curve at low doses differs from the linear quadratic model. The effect of a radio-adaptive response is the centre of many studies and well known inspite that the clinical applications are still rarely considered. Methods: We studied the effect of a low-dose pre-irradiation (0.03 Gy – 0.1 Gy) alone or followed by a 2.0 Gy challenging dose 4 h later on the survival of the HT29 cell line (human colorectal cancer cells) and on the GM637 cell line (human fibroblasts). Results: 0.03 Gy given alone did not have a significant effect on both cell lines, the other low doses alone significantly reduced the cell survival. Applied 4 h before the 2.0 Gy fraction, 0.03 Gy led to a significant induced radioresistance in GM637 cells, but not in HT29 cells, and 0.05 Gy led to a significant hyperradiosensitivity in HT29 cells, but not in GM637 cells. Conclusion: A pre-irradiation with 0.03 Gy can protect normal fibroblasts, but not colorectal cancer cells, from damage induced by an irradiation of 2.0 Gy and the application of 0.05 Gy prior to the 2.0 Gy fraction can enhance the cell killing of colorectal cancer cells while not additionally damaging normal fibroblasts. If these findings prove to be true in vivo as well this may optimize the balance between local tumour control and injury to normal tissue in modern radiotherapy.

Conventionally-fractionated image-guided intensity modulated radiotherapy (IG-IMRT): a safe and effective treatment for cancer spinal metastasis

Youling Gong, Jin Wang, Sen Bai, Xiaoqin Jiang and Feng Xu — 2008-04-22

Background: Treatments for cancer spinal metastasis were always palliative. This study was conducted to investigate the safety and effectiveness of IG-IMRT for these patients. Methods: 10 metastatic lesions were treated with conventionally-fractionated IG-IMRT. Daily kilovoltage cone-beam computed tomography (kV-CBCT) scan was applied to ensure accurate positioning. Plans were evaluated by the dose-volume histogram (DVH) analysis. Results: Before set-up correction, the positioning errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) axes were 0.3 ± 3.2, 0.4 ± 4.5 and -0.2 ± 3.9 mm, respectively. After repositioning, those errors were 0.1 ± 0.7, 0 ± 0.8 and 0 ± 0.7 mm, respectively. The systematic/random uncertainties ranged 1.4–2.3/3.0–4.1 before and 0.1–0.2/0.7–0.8 mm after online set-up correction. In the original IMRT plans, the average dose of the planning target volume (PTV) was 61.9 Gy, with the spinal cord dose less than 49 Gy. Compared to the simulated PTVs based on the pre-correction CBCT, the average volume reduction of PTVs was 42.3% after online correction. Also, organ at risk (OAR) all benefited from CBCT-based set-up correction and had significant dose reduction with IGRT technique. Clinically, most patients had prompt pain relief within one month of treatment. There was no radiation-induced toxicity detected clinically during a median follow-up of 15.6 months. Conclusion: IG-IMRT provides a new approach to treat cancer spinal metastasis. The precise positioning ensures the implementation of optimal IMRT plan, satisfying both the dose escalation of tumor targets and the radiation tolerance of spinal cord. It might benefit the cancer patient with spinal metastasis.