Bilateral metallic hip implants: Are avoidance sectors necessary for pelvic VMAT treatments?

PURPOSE: Metallic hip implants (MHI) are common in elderly patients. For pelvic cancers radiotherapy, conventional approaches consist of MHI avoidance during treatment planning, which leads, especially in case of bilateral MHI, to a decreased quality or increased complexity of the treatment plan. The aim of this study is to investigate the necessity of using avoidance sectors (AvSe) using a 2-arcs coplanar pelvic volumetric modulated arc-therapy (VMAT) planning. METHODS: We evaluated: (1) The dose calculation error of a static 6MV open beam traversing a MHI; (2) The magnitude of an error's decrease within the planning target volume (PTV) for a 360° VMAT treatment without AvSe as compared to the static open beam; (3) The dosimetric influence of MHI misalignment generated by patient's repositioning rolls during image-guided radiotherapy (IGRT). RESULTS: (1) In the static 6MV beam configuration, for distances between 0.5cm and 6cm from the MHI, the median (maximum, number of points) dose calculation error was -1.55% (-2.5%, 11); (2) Compared to the static open beam, in the 360° VMAT treatment without AvSe a simulated error was decreased by a factor of 4.4/2.4 (median/minimum); (3) MHI anterior-posterior misalignment exceeding 0.6cm, resulted in error at PTV surface of >2%. CONCLUSIONS: A standard 2 coplanar arcs 360° VMAT treatment, with dedicated artifact reduction algorithms applied, decreased the error of static beam traversing MHI, in patients presenting a bilateral MHI and might be used to treat the pelvic region without MHI avoidance.

3D printing for dosimetric optimization and quality assurance in small animal irradiations using megavoltage X-rays.

PURPOSE: New therapeutic options in radiotherapy (RT) are often explored in preclinical in-vivo studies using small animals. We report here on the feasibility of modern megavoltage (MV) linear accelerator (LINAC)-based RT for small animals using easy-to-use consumer 3D printing technology for dosimetric optimization and quality assurance (QA). METHODS: In this study we aimed to deliver 5×2Gy to the half-brain of a rat using a 4MV direct hemi-field X-ray beam. To avoid the beam's build-up in the target and optimize dosimetry, a 1cm thick, customized, 3D-printed bolus was used. A 1:1 scale copy of the rat was 3D printed based on the CT dataset as an end-to-end QA tool. The plan robustness to HU changes was verified. Thermoluminescent dosimeters (TLDs), for both MV irradiations and for kV imaging doses, and a gafchromic film were placed within the phantom for dose delivery verifications. The phantom was designed using a standard treatment planning software, and was irradiated at the LINAC with the target aligned using kV on-board imaging. RESULTS: The plan was robust (dose difference<1% for HU modification from 0 to 250). Film dosimetry showed a good concordance between planned and measured dose, with the steep dose gradient at the edge of the hemi-field properly aligned to spare the contralateral half-brain. In the treated region, the mean TLDs percentage dose differences (±2 SD) were 1.3% (±3.8%) and 0.9% (±1.7%) beneath the bolus. The mean (±2 SD) out-of-field dose measurements was 0.05Gy (±0.02Gy) for an expected dose of 0.04Gy. Imaging doses (2mGy) still spared the contralateral-brain. CONCLUSIONS: Use of consumer 3D-printers enables dosimetry optimization and QA assessment for small animals MV RT in preclinical studies using standard LINACS.

Image-guided total-body irradiation with a movable electronic portal imaging device for bone marrow transplant conditioning.

INTRODUCTION: To prevent radiation pneumonitis following total body irradiation (TBI) clinicians usually use lung shield blocks. The correct position of these shields relative to the patient's lungs is usually verified via mega-voltage imaging and computed radiographic (CR) films. In order to improve this time-consuming procedure, we developed in our department a dedicated, movable, real-time imaging system for image-guided TBI. MATERIAL & METHODS: The system consists of an electronic portal imaging device (EPID) mounted on a dedicated support whose motion along a rail can be controlled from the linac console outside the bunker room. Images are acquired online using a stand-alone console. To test the system efficacy we retrospectively analyzed data of lung blocks positioning from two groups of 10 patients imaged with EPID or CR-films, respectively. RESULTS: The median number of portal images per fraction was 2 (range 1-5) and 1 (range 1-2) for the EPID and the CR-film system, respectively. The minimum time required for an EPID image acquisition, without interpretation and no need of patient position correction in the bunker, was 20seconds against 214seconds for the CR-film. Lung shielding positioning in the right-left and superior-inferior directions was improved using the EPID system (p<0.01). CONCLUSIONS: Compared to CR-films, our movable real-time imaging EPID system is a simple technical solution able to reduce the minimum imaging time for lung shielding by a factor of 10. With the increased possibility to acquire more images as compared to CR-film system the EPID system has the potential to improve patient alignment, as well as patient's comfort and overall setup time.

Pelvic Lymph Node Irradiation Including Pararectal Sentinel Nodes for Prostate Cancer Patients: Treatment Optimization Comparing Intensity Modulated X-rays, Volumetric Modulated Arc Therapy, and Intensity Modulated Proton Therapy.

We aimed to assess the dosimetric impact of advanced delivery radiotherapy techniques using either intensity modulated x-ray beams (IMXT), volumetric modulated arc therapy (VMAT), or intensity modulated proton therapy (IMPT), for high-risk prostate cancer patients with sentinel nodes in the pararectal region. Twenty high-risk prostate cancer patients were included in a prospective trial evaluating sentinel nodes on pelvic SPECT acquisition. To be eligible for the dosimetric study, patients had to present with pararectal sentinel nodes usually not included in the clinical target volume encompassing the pelvic lymph nodes. Radiotherapy-plans including the prostate, the seminal vesicles, and the pelvic lymph nodes with the pararectal sentinel nodes were optimized for 6 eligible patients. IMXT and IMPT were delivered with 7 and 3 beams respectively and VMAT with 2 arcs. Results were assessed with Dose-Volume Histograms and predictive normal tissue complication probabilities (NTCPs) models between the three competing treatment modalities aiming to deliver a total dose of 50.4 Gy in 1.8 Gy daily fractions. Target coverage was optimized with IMPT when compared to IMXT and VMAT. Coverage of the sentinel node was slightly better with IMXT (D98% 5 57.3 ± 5.1 Gy) when compared with VMAT (D98% 5 56.2 ± 4.1 Gy). The irradiation of rectal, bladder, small bowel, and femoral heads volumes was significantly reduced with IMPT when compared to IMXT and VMAT. NTCPs rates for rectal and bladder ≥ grade-3 late toxicity were better with IMPT (0.4 ± 0.0% and 0.0 ± 0.0%) compared with IMXT (4.6 ± 3.3% and 1.4 ± 1.1%), and VMAT (4.5 ± 4.0% and 1.6 ± 1.6%), respectively. Acceptable dose-volume distributions and low rectal and urinary NTCPs were estimated to geometrically complex pelvic volumes such as the ones proposed in this study using IMXT, VMAT and IMPT. IMPT succeeded, however, to propose the best physical and biological treatment plans compared to both X-ray derived plans.

In vivo quality assurance of volumetric modulated arc therapy for ano-rectal cancer with thermoluminescent dosimetry and image-guidance.

OBJECTIVE: To assess in vivo dose distribution using cone-beam computed tomography scans (CBCTs) and thermoluminescent dosimeters (TLDs) in patients with anal or rectal cancer treated with volumetric modulated arc therapy (VMAT). METHODS: Intracavitary (IC) in vivo dosimetry (IVD) was performed in 11 patients using adapted endorectal probes containing TLDs, with extra measurements at the perianal skin (PS) for anal margin tumors. Measured doses were compared to calculated ones obtained from image fusion of CBCT with CT treatments plans. RESULTS: A total of 55 IC and 6 PS measurements were analyzed. IC TLD median planned and measured doses were 1.81 Gy (range, 0.25-2.02 Gy) and 1.82 Gy (range, 0.19-2.12 Gy), respectively. In comparison to the planned doses all IC TLD dose measurements differed by a median dose of 0.02 Gy (range, -0.11/+0.19 Gy, p=0.102) (median difference of 1.1%, range -6.1%/+10.6%). Overall, 95% of IC measurements were within ±7.7% of the expected percentage doses and only 1 value was above +10%. For PS measurements, only one was not within ±7.7% of expected values (i.e., -8.9%). CONCLUSIONS: Image guidance using CBCT for IVD with TLDs is helpful to validate the delivered doses in patients treated with VMAT for ano-rectal tumors.

Androgen deprivation and high-dose radiotherapy for oligometastatic prostate cancer patients with less than five regional and/or distant metastases.

BACKGROUND: Substantial survival may be observed with oligometastatic prostate cancer. Combining androgen deprivation (AD) and high-dose external beam radiotherapy (RT) to isolated regional or distant lesions may be proposed for these patients and the outcome of this strategy is the purpose of the present report. MATERIAL AND METHODS: From 2003 to 2010, 50 prostate cancer patients were diagnosed with synchronous (n = 7) or metachronous (n = 43) oligometastases (OM). Among the relapsing patients, the recurrence occurred after radical prostatectomy in 33 patients and curative RT (± AD) in 10 patients. The median age at diagnosis was 63 years (range, 48-82). All patients underwent a bone scan and 18F-choline or 11C-acetate PET-CT at the time of diagnosis or relapse, showing regional and/or distant nodal and bone and/or visceral metastases in 33 and 17 patients, respectively. The median delivered effective dose was 64 Gy. All but one patient received neo-adjuvant and concomitant AD. RESULTS: After a median follow-up of 31 months (range, 9-89) the three-year biochemical relapse-free survival (bRFS), clinical failure-free survival, and overall survival rates were 54.5%, 58.6% and 92%, respectively. No grade 3 toxicity was observed. Improved bRFS was found to be significantly associated with the number of OM. The three-year bRFS was 66.5% versus 36.4% for patients with 1 and > 1 OMs (p = 0.031). A normalised total dose (NTD in 2 Gy/fraction, alpha/beta = 2 Gy) above 64 Gy was also correlated with a better three-year bRFS compared to lower doses: 65% vs. 41.8%, respectively (p = 0.005). On multivariate analysis, only the NTD > 64 Gy retained statistical significance (HR: 0.37, 95% CI 0.15-0.93). CONCLUSION: Oligometastatic patients may be successfully treated with short AD and high-dose irradiation to the metastatic lesions. High dose improves bRFS. Such a treatment strategy may hypothetically succeed to prolong the failure-free interval between two consecutive AD courses.

High-dose-rate brachytherapy boost to the dominant intra-prostatic tumor region: hemi-irradiation of prostate cancer.

BACKGROUND: To assess the feasibility, toxicity, and outcome of prostate hemi-irradiation with a high-dose-rate brachytherapy (HDR-BT) boost for patients presumed to harbor dominant intra-prostatic tumors in a single lobe. METHODS: After 3D conformal external radiotherapy (3DCRT) to 64-64.4 Gy, 77 patients with non-metastatic locally aggressive prostate cancer have been treated from 2000 to 2004, with HDR-BT using temporary open MRI-guided (192) Ir implants, to escalate the dose in the boost region. Twenty patients (26%) had one lobe involvement (i.e., one sided endorectal MRI, rectal examination, and biopsies) and were boosted to one side of the gland only. A dose of 12, 14, and 16 Gy in two fractions was delivered to 5, 6, and 9 patients, respectively. RESULTS: After a median follow-up 69 months, no differences in late rectal toxicity were observed between the unilaterally and bilaterally irradiated cohorts. Although, grade 2 late urinary toxicity was worse in the hemi-irradiated group (P = 0.03), severe grade ≥3 late urinary toxicity at 5 years was not different: 10% versus 8.8% in the unilaterally and bilaterally irradiated cohorts, respectively. Grade 4 late urinary toxicity, however, was exclusively observed in patients boosted to both lobes (5/57, 8.8%). Five-year biochemical relapse-free survival was 79.7% versus 70.5% for the unilateral and bilateral boost groups, respectively (P = 0.99). CONCLUSION: Prostate hemi-irradiation with a HDR-BT boost to the dominant tumor region may be considered when rectal examination, MRI, and biopsies suggest one lobe involvement. Nevertheless, strict dosimetric optimization is needed in order to further reduce the risk of late severe toxicity.

Intensity modulated radiation therapy or stereotactic fractionated radiotherapy for infratentorial ependymoma in children: a multicentric study.

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques.

Twice-weekly hypofractionated intensity-modulated radiotherapy for localized prostate cancer with low-risk nodal involvement: toxicity and outcome from a dose escalation pilot study.

PURPOSE: To evaluate the toxicity and preliminary outcome of patients with localized prostate cancer treated with twice-weekly hypofractionated intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: Between 2003 and 2006, 82 prostate cancer patients with a nodal involvement risk ≤20% (Roach index) have been treated to the prostate with or without seminal vesicles with 56 Gy (4 Gy/fraction twice weekly) and an overall treatment time of 6.5 weeks. Acute and late genitourinary (GU) and gastrointestinal (GI) toxicities were scored according to the Radiation Therapy Oncology Group (RTOG) grading system. Median follow-up was 48 months (range, 9-67 months). RESULTS: All patients completed the treatment without interruptions. No patient presented with Grade ≥3 acute GU or GI toxicity. Of the patients, 4% presented with Grade 2 GU or GI persistent acute toxicity 6 weeks after treatment completion. The estimated 4-year probability of Grade ≥2 late GU and GI toxicity-free survival were 94.2% ± 2.9% and 96.1% ± 2.2%, respectively. One patient presented with Grade 3 GI and another patient with Grade 4 GU late toxicity, which were transitory in both cases. The 4-year actuarial biochemical relapse-free survival was 91.3% ± 5.9%, 76.4% ± 8.8%, and 77.5% ± 8.9% for low-, intermediate-, and high-risk groups, respectively. CONCLUSIONS: In patients with localized prostate cancer, acute and late toxicity were minimal after dose-escalation administering twice-weekly 4 Gy to a total dose of 56 Gy, with IMRT. Further prospective trials are warranted to further assess the best fractionation schemes for these patients.

Dose escalation study with two different hypofractionated intensity modulated radiotherapy techniques for localized prostate cancer: acute toxicity.

To assess acute gastrointestinal (GI) and genitourinary (GU) toxicities in patients with localized prostate cancer treated with a sequential dose escalation hypofractionated intensity-modulated radiotherapy (IMRT) study using two different delivery methods. Since 2003, 88 and 48 patients were sequentially treated to 56 Gy and to 60 Gy (4 Gy/fraction twice weekly), respectively. IMRT with 6 MV beams was delivered with five fields in Geneva and with nine in Barcelona. Acute GI and GU side effects were scored weekly during treatment and 6 weeks after treatment completion using the Radiation Therapy Oncology Group (RTOG) toxicity scale. Clinical, technical, and dosimetric parameters were analyzed in order to assess for a potential correlation with toxicity. Grade 1-2, GU and GI toxicities during and 6 weeks after treatment completion were 64%, and 24%, and 35% and 12%, respectively. Only one Grade 4 GU toxicity, consisting of transitory urinary obstruction, was observed. Patients treated to 60 Gy in Geneva presented a higher rate of Grade 1-2 GU toxicity (p = 0.01), while patients treated to both 56 and 60 Gy in Barcelona presented a higher Grade 1-2 GI toxicity (p = 0.02). A lower rate of rectal toxicity was observed in the subgroup of 22 patients treated with a rectal balloon (p = 0.02). The use of androgen deprivation therapy was associated with a higher rate of Grade 1-2 GU toxicity after the end of the treatment (p = 0.02). Dose escalation with either 14 _ 4 Gy or 15 _ 4 Gy delivered with two different IMRT techniques is feasible and is associated with a tolerable acute toxicity.

Unilateral radiotherapy for tonsil cancer: potential dose distribution optimization with a simple two-field intensity-modulated radiation therapy beam arrangement.

BACKGROUND AND PURPOSE: To evaluate the feasibility and dosimetric optimization potential of a unilateral two-field intensity-modulated radiotherapy (IMRT) technique in the curative treatment of lateralized tonsil cancer. MATERIALS AND METHODS: Six patients with lateralized tonsillar carcinoma were treated unilaterally with a two-field IMRT technique (oblique-anterior and oblique-posterior fields, with or without collimator and couch rotation). Alternative IMRT plans using seven non-opposed coplanar fields were compared with the two-field plans for each patient. RESULTS: Planning target volume (PTV) coverage was excellent with the two-field technique, using a relatively low number of monitor units (MU) (median, 441; range, 309-550). Dose constraints were respected for all organs at risk (OAR). Mean doses to contralateral parotid and submandibular glands were 3.9 and 17.7 Gy, respectively. Seven-field IMRT provided similar PTV coverage, with statistically significant better dose homogeneity and conformality. However, the mean delivered dose to the contralateral parotid (3.9 vs. 9.0 Gy, p=0.001) as well as the mean number of MU (437 vs. 814, p=0.002) and consequently machine time were lower with two-field IMRT. CONCLUSIONS: Unilateral two-field IMRT is a simple and feasible technique providing excellent tumor coverage and optimal OAR sparing while reducing the number of MU and treatment time.

Recurrence pattern after [(18)F]fluoroethyltyrosine-positron emission tomography-guided radiotherapy for high-grade glioma: a prospective study.

PURPOSE: To assess the failure pattern observed after (18)F fluoroethyltyrosine (FET) planning after chemo- and radiotherapy (RT) for high-grade glioma. METHODS: All patients underwent prospectively RT planning using morphological gross tumour volumes (GTVs) and biological tumour volumes (BTVs). The post-treatment recurrence tumour volumes (RTVs) of 10 patients were transferred on their CT planning. First, failure patterns were defined in terms of percentage of RTV located outside the GTV and BTV. Second, the location of the RTV with respect to the delivered dose distribution was assessed using the RTV's DVHs. Recurrences with >95% of their volume within 95% isodose line were considered as central recurrences. Finally, the relationship between survival and GTV/BTV mismatches was assessed. RESULTS: The median percentages of RTV outside the GTV and BTV were 41.8% (range, 10.5-92.4) and 62.8% (range, 34.2-81.1), respectively. The majority of recurrences (90%) were centrally located. Using a composite target volume planning formalism, the degree of GTV and BTV mismatch did not correlate with survivorship. CONCLUSIONS: The observed failure pattern after FET-PET planning and chemo-RT is primarily central. The target mismatch-survival data suggest that using FET-PET planning may counteract the possibility of BTV-related progression, which may have a detrimental effect on survival.

Hypofractionated boost with high-dose-rate brachytherapy and open magnetic resonance imaging-guided implants for locally aggressive prostate cancer: a sequential dose-escalation pilot study.

PURPOSE: To evaluate the feasibility, tolerance, and preliminary outcome of an open MRI-guided prostate partial-volume high-dose-rate brachytherapy (HDR-BT) schedule in a group of selected patients with nonmetastatic, locally aggressive prostatic tumors. METHODS AND MATERIALS: After conventional fractionated three-dimensional conformal external radiotherapy to 64-64.4 Gy, 77 patients with nonmetastatic, locally aggressive (e.g., perineural invasion and/or Gleason score 8-10) prostate cancer were treated from June 2000 to August 2004, with HDR-BT using temporary open MRI-guided (192)Ir implants, to escalate the dose in the boost region. Nineteen, 21, and 37 patients were sequentially treated with 2 fractions of 6 Gy, 7 Gy, and 8 Gy each, respectively. Neoadjuvant androgen deprivation was given to 62 patients for 6-24 months. Acute and late toxicity were scored according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scoring system. RESULTS: All 77 patients completed treatment as planned. Only 2 patients presented with Grade > or =3 acute urinary toxicity. The 3-year probability of Grade > or =2 late urinary and low gastrointestinal toxicity-free survival was 91.4% +/- 3.4% and 94.4% +/- 2.7%, respectively. Rates of 3-year biochemical disease-free survival (bDFS) and disease-specific survival were 87.1% +/- 4.1% and 100%, respectively. CONCLUSIONS: Boosting a partial volume of the prostate with hypofractionated HDR-BT for aggressive prostate cancer was feasible and showed limited long-term toxicity, which compared favorably with other dose-escalation methods in the literature. Preliminary bDFS was encouraging if one considers the negatively selected population of high-risk patients in this study.

[(18)F]Fluoroethyltyrosine- positron emission tomography-guided radiotherapy for high-grade glioma.

BACKGROUND: To compare morphological gross tumor volumes (GTVs), defined as pre- and postoperative gadolinium enhancement on T1-weighted magnetic resonance imaging to biological tumor volumes (BTVs), defined by the uptake of (18)F fluoroethyltyrosine (FET) for the radiotherapy planning of high-grade glioma, using a dedicated positron emission tomography (PET)-CT scanner equipped with three triangulation lasers for patient positioning. METHODS: Nineteen patients with malignant glioma were included into a prospective protocol using FET PET-CT for radiotherapy planning. To be eligible, patients had to present with residual disease after surgery. Planning was performed using the clinical target volume (CTV = GTV union or logical sum BTV) and planning target volume (PTV = CTV + 20 mm). First, the interrater reliability for BTV delineation was assessed among three observers. Second, the BTV and GTV were quantified and compared. Finally, the geometrical relationships between GTV and BTV were assessed. RESULTS: Interrater agreement for BTV delineation was excellent (intraclass correlation coefficient 0.9). Although, BTVs and GTVs were not significantly different (p = 0.9), CTVs (mean 57.8 +/- 30.4 cm(3)) were significantly larger than BTVs (mean 42.1 +/- 24.4 cm(3); p < 0.01) or GTVs (mean 38.7 +/- 25.7 cm(3); p < 0.01). In 13 (68%) and 6 (32%) of 19 patients, FET uptake extended >or= 10 and 20 mm from the margin of the gadolinium enhancement. CONCLUSION: Using FET, the interrater reliability had excellent agreement for BTV delineation. With FET PET-CT planning, the size and geometrical location of GTVs and BTVs differed in a majority of patients.

Stereotactic radiotherapy for ocular melanoma: initial experience using closed eyes for ocular target immobilization.

To assess the reliability and target positioning reproducibility with eyes closed in uveal melanoma patients treated with a micromultileaf-based linear accelerator dedicated for stereotactic radiotherapy. Five consecutive patients treated with curative radiotherapy for uveal melanoma were monitored for positioning reproducibility with resimulation CT scans performed every two days while on treatment (23 resimulation CTs available). All patients underwent MRIs of the orbits before simulation to help to define the target and organs at risk (e.g., lenses, optic nerves, ciliary bodies, and lacrimal glands) in the simulation CT (MRI-to-CT bone registration). Patients were simulated, resimulated, and treated with eyes closed. Patient #1 was treated with 5 daily fractions while patients #2 to #5, were treated with 10 daily fractions. We chose the lens of the tumor-bearing eye as the structure to be controlled, assuming that correct repositioning of the lens should be a valid surrogate for correctness of target repositioning. Displacements (mean and standard deviations, SD) of the lens in the three axes were measured for each patient. Systematic and standard errors were calculated. Planning target volume (PTV) margins were estimated according to McKenzie et al. [Phys Med Biol 45, 3331-3342 (2000)]. For both AP-PA and left-right shifts calculated SD were always below 1 mm, except for patient #4, who was treated with a non-customized bolus that pushed the globe backwards in a random fashion. In ideal set-up conditions PTV margins around the target were estimated to be 3 mm. Asking patients to close their eyes is a simple and reliable immobilization procedure when treating ocular tumors with stereotactic radiotherapy. Margins of 3 mm around the target may be necessary to safely treat these tumors under ideal set-up conditions.

Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells.

OBJECTIVE: This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs) could enhance the radiosensitivity of three different human colorectal adenocarcinoma cell lines. To understand the underlying mechanisms, the effects of omega-3 PUFAs on the cell growth, survival, and apoptosis were evaluated alone or in combination with an antioxidant (vitamin E) and compared with the effects of omega-6 PUFAs. METHODS: LS174T, CO112, and Caco-2 cell survival was assessed by clonogenic assay after a 3-d pretreatment with omega-3/omega-6 PUFAs and/or vitamin E before a single X-ray exposure to 4 Gy. Cell growth and viability were measured by double fluorescence-activated cell sorter analyses using propidium iodide and fluorescein isothiocyanate-conjugated annexin V. Student's t test or multivariable linear regression analyses were used for comparison. RESULTS: Preincubation with 30 to 100 micromol/L of omega-3 PUFAs induced a dose-dependent additive decrease in cell survival after irradiation (P < 0.05). Evaluation of the underlying mechanisms indicated that omega-3 PUFAs mainly decreased the cell number via apoptosis induction. Moreover, formation of lipid peroxidation products and modulation of cyclooxygenase II activity seemed to be involved, because coincubation with 10 micromol/L vitamin E abolished the effect of 50 micromol/L of omega-3 PUFAs (P < 0.05), whereas omega-6 PUFAs could partly mimic omega-3 PUFA effects. CONCLUSION: These observations suggest that omega-3 PUFAs may be potential candidates as nutritional adjuvants to enhance the efficacy of human colorectal cancer radiotherapy.

Fractionated stereotactic radiotherapy boost for gynecologic tumors: an alternative to brachytherapy?

PURPOSE: A brachytherapy (BT) boost to the vaginal vault is considered standard treatment for many endometrial or cervical cancers. We aimed to challenge this treatment standard by using stereotactic radiotherapy (SRT) with a linac-based micromultileaf collimator technique. METHODS AND MATERIALS: Since January 2002, 16 patients with either endometrial (9) or cervical (7) cancer have been treated with a final boost to the areas at higher risk for relapse. In 14 patients, the target volume included the vaginal vault, the upper vagina, the parametria, or (if not operated) the uterus (clinical target volume [CTV]). In 2 patients with local relapse, the CTV was the tumor in the vaginal stump. Margins of 6-10 mm were added to the CTV to define the planning target volume (PTV). Hypofractionated dynamic-arc or intensity-modulated radiotherapy techniques were used. Postoperative treatment was delivered in 12 patients (2 x 7 Gy to the PTV with a 4-7-day interval between fractions). In the 4 nonoperated patients, a dose of 4 Gy/fraction in 5 fractions with 2 to 3 days' interval was delivered. Patients were immobilized in a customized vacuum body cast and optimally repositioned with an infrared-guided system developed for extracranial SRT. To further optimize daily repositioning and target immobilization, an inflated rectal balloon was used during each treatment fraction. In 10 patients, CT resimulation was performed before the last boost fraction to assess for repositioning reproducibility via CT-to-CT registration and to estimate PTV safety margins around the CTV. Finally, a comparative treatment planning study between BT and SRT was performed in 2 patients with an operated endometrial Stage I cancer. RESULTS: No patient developed severe acute urinary or low-intestinal toxicity. No patient developed urinary late effects (>6 months). One patient with a vaginal relapse previously irradiated to the pelvic region presented with Grade 3 rectal bleeding 18 months after retreatment. A second patient known to suffer from irritable bowel syndrome presented with Grade 1 abdominal pain after treatment. The estimated PTV margins around the CTV were 9-10 mm with infrared marker registration. External SRT succeeded in improving dose homogeneity to the PTV and in reducing the maximum dose to the rectum, when compared to BT. CONCLUSION: These results suggest that the use of external SRT to deliver a final boost to the areas at higher risk for relapse in endometrial or cervical cancer is feasible, well tolerated, and may well be considered an acceptable alternative to BT.

Target repositioning optimization in prostate cancer: is intensity-modulated radiotherapy under stereotactic conditions feasible?

PURPOSE: To assess repositioning reproducibility of the prostate when treatment setup conditions before radiotherapy (RT) are optimized and internal organ motion is reduced with an endorectal inflatable balloon. METHODS AND MATERIALS: Thirty-two patients were treated with 64 Gy to the prostate and seminal vesicles using a three-dimensional conformal radiotherapy technique, followed by a boost (two fractions of 5-8 Gy, 3-5 days apart) delivered to a reduced prostate volume (the peripheral tumor bearing zone with 3-mm margins) using intensity-modulated RT. A commercially available infrared-guided stereotactic repositioning system and a rectal balloon were used. Further improvement in repositioning could be obtained with a stereoscopic X-ray registration device matching the pelvic bones during treatment with the corresponding bones in the planning computed tomography (CT). To simulate repositioning reproducibility, CT resimulation was performed before the last boost fraction. Prostate repositioning was reassessed, first after CT-to-CT fusion with the stereotactic metallic body markers of the infrared-guided system, and second after CT-to-CT registration of the pelvic bony structures. RESULTS: Standard deviations of the prostate (CTV) center of mass shifts in the three axes ranged from 2.2 to 3.6 mm with body marker registration and from 0.9 to 2.5 mm with pelvic bone registration. The latter improvement was significant, particularly in the right-to-left axis (3.5-fold improvement). In 10 patients, systematic rectal probe repositioning errors (i.e., >20-mL probe volume variations or >8-mm probe shifts in the perpendicular axes) were detected. Target repositioning was reassessed excluding these 10 patients. An additional improvement was observed in the anteroposterior axis with 1.7 times and 1.5 times reduction of the standard deviation with body markers and pelvic bone registrations, respectively. CONCLUSIONS: Infrared-guided target repositioning for prostate cancer can be optimized with a stereoscopic X-ray positioning device mostly in the right-to-left axis. An optimally positioned inflatable rectal probe further optimizes target repositioning mostly along the anteroposterior axis. Thus a planning target volume with a margin of 2 (right-to-left), 4 (anteroposteriorly), and 6 (craniocaudally) mm around the CTV can be recommended under optimal setup conditions with pelvic bone registration and optimal repositioning of an inflated rectal balloon.

Influence of rectal volume changes during radiotherapy for prostate cancer: a predictive model for mild-to-moderate late rectal toxicity.

PURPOSE: To assess the rectal volume changes during radiotherapy for prostate cancer, to estimate an average rectal dose distribution profile during treatment, and to correlate these parameters with mild-to-moderate late rectal toxicity. MATERIALS AND METHODS: Nine patients with localized prostate cancer underwent virtual CT simulation using a six-field conformal 18-MV photon technique. During treatment, patients underwent weekly pelvic CT scans under simulation conditions. Dosimetries were run with each CT data set using the same beam parameters as in the initial treatment plan. The influence of weekly rectal volume changes on the dose-volume histogram (DVH) profiles was studied. A polynomial function correlating the initial rectal volume with the mean percentage of change in the rectal volume during treatment was used to define a correction factor for rectal DVHs. The model was validated using data from 100 patients treated with 74 Gy according to the same technique. Areas under the curve of the initial rectal DVHs were correlated with toxicity (Radiation Therapy Oncology Group Grade 0 vs. 1-2, Student's t test), with or without the use of the above correction factor. RESULTS: A trend for enlargement of the rectal volume during treatment was observed for most patients in the study with small rectal volumes (<75 cm(3)) at simulation, resulting in an increase in the integral rectal dose by a factor ranging from 1.3 to 2.1. Corrected, but not uncorrected, rectal DVH profiles were strongly predictive of Grade 0 vs. 1-2 late rectal morbidity. CONCLUSIONS: Correcting the area under the curve of the rectal DVH at simulation by a factor that takes into account the projected volume changes during treatment correlates significantly with the probability of mild-to-moderate late rectal toxicity (Grade 1-2). This reliable predictor for mild-to-moderate late rectal morbidity may also be a practical tool for treatment planning.

Dosimetric implications of changes in patient repositioning and organ motion in conformal radiotherapy for prostate cancer.

PURPOSE: To assess the influence of patient repositioning and organ motion on dose distribution within the prostate and the seminal vesicles (clinical target volume, (CTV)). MATERIAL AND METHODS: Nine patients were simulated and treated in the supine position, with an empty bladder, and without immobilization devices. While on treatment, patients underwent weekly pelvic computed tomography (CT) scans under conditions identical to those at simulation. Patients were aligned using lasers on anterior and lateral skin tattoos, onto which lead markers were placed. After each CT scan (n=53) the CTV was redefined by contouring, and a new isocenter was obtained. A six-field technique was used. The field margins around the CTV were 20 mm in the cranio-caudal axis, and 13 mm in the other axes, except in the lateral fields where a 10 mm posterior margin was used. Dose-volume histograms (DVHs) for each organ were compared with those determined at simulation, using the notion of the proportional change in the area under the CTV-DVH curve resulting from a change in treatment plan (cDVH). RESULTS: The reproducibility of the dose distribution was good for the prostate (%cDVH, mean+/-SD: -0.97+/-2.11%) and less than optimal for the seminal vesicles (%cDVH, mean+/-SD: -4.66+/-10.45%). When correlating prostate %cDVH variations with displacements of the isocenter in the Y axis (antero-posterior) the %cDVH exceeded (-)5% in only two dosimetries, both with an isocenter shift of >10 mm. For the seminal vesicles, however, ten out of 53 dosimetries showed a %cDVH exceeding (-) 5%. In nine of these ten dose distribution studies the posterior shift of the isocenter exceeded 8 mm. CONCLUSIONS: Precise targeting of prostate radiotherapy is primarily dependent on careful daily set-up and on random changes in rectal geometry. Margins no less than 10 mm around the prostate and at least 15 mm around the seminal vesicles are probably necessary to insure adequate target coverage with a six-field technique.