Urethra-Sparing Stereotactic Body Radiation Therapy for Prostate Cancer: Quality Assurance of a Randomized Phase 2 Trial.

PURPOSE: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer. METHODS AND MATERIALS: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared. RESULTS: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P < .001). Furthermore, the use of VMAT yielded better dosimetric results than IMRT for urethra planning-risk volume D98% (31.1 vs 30.8 Gy, P < .0001), PTV D2% (37.9 vs 38.7 Gy, P < .0001), homogeneity index (0.09 vs 0.10, P < .0001), Dice similarity coefficient (0.83 vs 0.80, P < .0001), and bladder wall V50% (24.5% vs 33.5%, P = .0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P <.0001). The inclusion of SV in the PTV negatively affected the rectal wall V90% (9.1% vs 10.4%, P = .0003) and V80% (13.2% vs 15.7%, P = .0003). CONCLUSIONS: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.

Twice- vs. thrice-weekly moderate hypofractionated radiotherapy for prostate cancer: does overall treatment time matter?

PURPOSE: To evaluate the influence of overall treatment time (OTT) in disease control, acute, and long-term side effects with moderate hypofractionated external beam radiotherapy (RT) for prostate cancer (PCa) delivered either twice- or thrice-a-week. METHODS: 157 patients with localized PCa were treated consecutively with 56 Gy in 4 Gy/fraction delivered either twice (86 patients, from 2003 to 2010, group-1) or thrice a week (71 patients, from 2010 to 2017, group-2) using IMRT or VMAT techniques. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the CTCAE v3.0 grading scale. Median follow-up was 110 and 56 months for groups 1 and 2, respectively. RESULTS: At 6 weeks, patients treated thrice-a-week experienced higher acute ≥ grade-2 GU toxicity compared to those treated twice a week (25.4% vs 5.8%, p = 0.001) even though none presented ≥ grade-3 GU or GI toxicity in the thrice-a-week group. The 5-year ≥ grade-2 late GU toxicity-free survival was higher in group-1 (95.9 ± 2.3%) than in group-2 (81.5 ± 4.9%, p = 0.003), while no differences in ≥ grade-2 late GI toxicity-free survival were observed between both groups (97.5 ± 1.7% vs. 97 ± 2.1% for groups 1 and 2, respectively). The 5-year biochemical relapse-free survival (bRFS) was not different for patients treated twice compared to those treated thrice-a-week (80.6 ± 4.5% vs. 85.3 ± 4.8%, respectively, p = 0.441), as much as for patients treated in > 5 weeks vs. those treated in ≤ 5 weeks (81.3 ± 4.4% vs. 84.4 ± 5.1%, respectively, p = 0.584). CONCLUSIONS: In this retrospective hypothesis-generating analysis, less vs. more than 5 weeks OTT may increase acute and late GU toxicities without significantly improving bRFS in patients treated to high effective doses (> 80 Gy) with moderate hypofractionated RT. Prospective trials evaluating the impact of OTT on hypofractionated schedules for PCa are warranted.

Urethra-sparing stereotactic body radiotherapy for prostate cancer: how much can the rectal wall dose be reduced with or without an endorectal balloon?

BACKGROUND: This is a dosimetric comparative study intended to establish appropriate low-to-intermediate dose-constraints for the rectal wall (Rwall) in the context of a randomized phase-II trial on urethra-sparing stereotactic body radiotherapy (SBRT) for prostate cancer. The effect of plan optimization on low-to-intermediate Rwall dose and the potential benefit of an endorectal balloon (ERB) are investigated. METHODS: Ten prostate cancer patients, simulated with and without an ERB, were planned to receive 36.25Gy (7.25Gyx5) to the planning treatment volume (PTV) and 32.5Gy to the urethral planning risk volume (uPRV). Reference plans with and without the ERB, optimized with respect to PTV and uPRV coverage objectives and the organs at risk dose constraints, were further optimized using a standardized stepwise approach to push down dose constraints to the Rwall in the low to intermediate range in five sequential steps to obtain paired plans with and without ERB (Vm1 to Vm5). Homogeneity index for the PTV and the uPRV, and the Dice similarity coefficient (DSC) for the PTV were analyzed. Dosimetric parameters for Rwall including the median dose and the dose received by 10 to 60% of the Rwall, bladder wall (Bwall) and femoral heads (FHeads) were compared. The monitor units (MU) per plan were recorded. RESULTS: Vm4 reduced by half D30%, D40%, D50%, and Dmed for Rwall and decreased by a third D60% while HIPTV, HIuPRV and DSC remained stable with and without ERB compared to Vmref. HIPTV worsened at Vm5 both with and without ERB. No statistical differences were observed between paired plans on Rwall, Bwall except a higher D2% for Fheads with and without an ERB. CONCLUSIONS: Further optimization to the Rwall in the context of urethra sparing prostate SBRT is feasible without compromising the dose homogeneity to the target. Independent of the use or not of an ERB, low-to-intermediate doses to the Rwall can be significantly reduced using a four-step sequential optimization approach.

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.

Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter?

PURPOSE: This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. METHODS AND MATERIALS: 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk ≤20% (Roach index) were treated twice weekly to the prostate ± seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 × 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 × 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. RESULTS: There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade ≥2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 ± 2.3% and 78.2 ± 5.1% (P=.001), respectively. The 5-year grade ≥2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 ± 1.3% and 85.1 ± 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 ± 4.7%, worse than patients treated with 60 Gy (93.2 ± 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 ± 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). CONCLUSIONS: A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 × 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control.

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.

Proton beam radiotherapy versus fractionated stereotactic radiotherapy for uveal melanomas: A comparative study.

PURPOSE: A comparative treatment planning study was undertaken between proton and photon therapy in uveal melanoma to assess the potential benefits and limitations of these treatment modalities. A fixed proton horizontal beam (OPTIS) and intensity-modulated spot-scanning proton therapy (IMPT), with multiple noncoplanar beam arrangements, was compared with linear accelerator-based stereotactic radiotherapy (SRT), using a static and a dynamic micromultileaf collimator and intensity-modulated RT (IMRS). METHOD AND MATERIALS: A planning CT scan was performed on a brain metastasis patient, with a 3-mm acquisition slice spacing and the patient looking at a luminous spot with the eyes in three different positions (neutral and 25 degrees right and left). Four different gross tumor volumes were defined for each treatment technique. These target scenarios represented different locations (involving vs. not involving the macula and temporal vs. nasal) and volumes (10 x 6 mm vs. 16 x 10 mm) to challenge the proton and photon treatment techniques. The planning target volume was defined as the gross tumor volume plus 2 mm laterally and 3 mm craniocaudally for both modalities. A dose homogeneity of 95-99% of the planning target volume was used as the "goal" for all techniques. The dose constraint (maximum) for the organs at risk (OARs) for both the proton and the SRT photon plans was 27.5, 22.5, 20, and 9 CGE-Gy for the optic apparatus, retina, lacrimal gland, and lens, respectively. The dose to the planning target volume was 50 CGE-Gy in 10 CGE-Gy daily fractions. The plans for proton and photon therapy were computed using the Paul Scherrer Institute and BrainSCAN, version 5.2 (BrainLAB, Heimstetten, Germany) treatment planning systems, respectively. Tumor and OARs dose-volume histograms were calculated. The results were analyzed using the dose-volume histogram parameters, conformity index (CI(95%)), and inhomogeneity coefficient. RESULTS: Target coverage of all simulated uveal melanomas was equally conformal with the photon and proton modalities. The median CI(95%) value was 1.74, 1.86, and 1.83 for the static, dynamic, and IMSRT plans, respectively. With proton planning, the median CI(95%) was 1.88 for OPTIS and substantially improved with IMPT in some tumor cases (median CI(95%), 1.29). The tumor dose homogeneity in the proton plans was, however, always better than with SRT photon planning (median inhomogeneity coefficient 0.1 and 0.15 vs. 0.46, 0.41, and 0.23 for the OPTIS and IMPT vs. the static, dynamic, and IMSRT plans, respectively). Compared with the photon plans, the use of protons did not lead to a substantial reduction in the homolateral OAR total integral dose in the low- to high-dose level, except for the lacrimal gland. The median maximal dose and dose at the 10% volume with the static, dynamic, and IMSRT plans was 33-30.8, 31.8-28, and 35.8-49 Gy, respectively, for the lacrimal gland, a critical organ. For protons, only the OPTIS plans were better, with a median maximal dose and dose at the 10% volume using OPTIS and IMPT of 19.2 and 8.8 and 25.6 and 23.6 CGE, respectively. The contralateral OARs were completely spared with the proton plans, but the median dose delivered to these structures was 1.2 Gy (range, 0-6.3 Gy) with the SRT photon plans. CONCLUSION: These results suggest that the use of SRT photon techniques, compared with protons, can result in similar levels of dose conformation. IMPT did not increase the degree of conformality for this small tumor. Tumor dose inhomogeneity was, however, always increased with photon planning. Except for the lacrimal gland, the use of protons, with or without intensity modulation, did not increase homolateral OAR dose sparing. The dose to all the contralateral OARs was, however, completely eliminated with proton planning.

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.

Multicentre validation of IMRT pre-treatment verification: comparison of in-house and external audit.

BACKGROUND AND PURPOSE: We performed a multicentre intercomparison of IMRT optimisation and dose planning and IMRT pre-treatment verification methods and results. The aims were to check consistency between dose plans and to validate whether in-house pre-treatment verification results agreed with those of an external audit. MATERIALS AND METHODS: Participating centres used two mock cases (prostate and head and neck) for the intercomparison and audit. Compliance to dosimetric goals and total number of MU per plan were collected. A simple quality index to compare the different plans was proposed. We compared gamma index pass rates using the centre's equipment and methodology to those of an external audit. RESULTS: While for the prostate case, all centres fulfilled the dosimetric goals and plan quality was homogeneous, that was not the case for the head and neck case. The number of MU did not correlate with the plan quality index. Pre-treatment verifications results of the external audit did not agree with those of the in-house measurements for two centres: being within tolerance for in-house measurements and unacceptable for the audit or the other way round. CONCLUSIONS: Although all plans fulfilled dosimetric constraints, plan quality is highly dependent on the planner expertise. External audits are an excellent tool to detect errors in IMRT implementation and cannot be replaced by intercomparison using results obtained by centres.

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.

Hypofractionated extracranial stereotactic radiotherapy boost for gynecologic tumors: a promising alternative to high-dose rate brachytherapy.

The purpose of this study is to report toxicity and outcome results in patients with gynaecological tumours treated with a final boost using extra-cranial stereotactic radiotherapy (SRT) with a linac-based micro-multileaf collimator technique as an alternative to high-dose rate brachytherapy (HDR-BT). Since January 2002, 26 patients with either endometrial (n = 17) or cervical (n = 9) cancer were treated according to this protocol: 45-50.4 Gy external radiotherapy (RT) to the pelvic +/- para-aortic regions followed by a final SRT boost of 2 x 7 Gy to the vaginal vault (4-7 day interval between fractions). Median age was 62 years (37-74 range). Fifteen patients were diagnosed with adenocarcinoma, 7 with squamous-cell carcinoma, and 4 with sarcoma. FIGO stage I (n = 17), stage II (n = 7), and stage III (n = 2). Toxicity was scored according to RTOG/EORTC criteria. No severe (> grade-3) acute urinary or low-gastrointestinal (GI) toxicity was observed during treatment and up to 3 months after treatment completion. Moderate (grade < or = 3) acute urinary or low-GI toxicity was observed in 23% and 35% of patients, respectively. After a median follow-up of 47 months (4-77, range), late urinary, low-GI, and sexual > or = grade-2 (worst score) has been reported in 4%, 12% and 29.4% of patients, respectively. The 3-year loco-regional failure-free and overall survival rates were 96% and 95%, respectively. Preliminary results on feasibility, tolerance, and outcome with SRT are encouraging and may be considered a sound alternative to HDR-BT for gynecologic tumors.

Boosting the tumor bed from deep-seated tumors in early-stage breast cancer: a planning study between electron, photon, and proton beams.

PURPOSE: To assess the potential dosimetric advantages and drawbacks of photon beams (modulated or not), electron beams (EB), and protons as a boost for the tumor bed in deep-seated early-stage breast cancer. MATERIAL AND METHODS: Planning CTs of 14 women with deep-seated tumors (i.e., > or =4 cm depth) were selected. The clinical target volume (CTV) was defined as the area of architectural distortion surrounded by surgical clips. The planning treatment volume (PTV) was the CTV plus 1cm margin. A dose of 16 Gy in 2 Gy fractions was prescribed. Organs at risk (OARs) were heart, lungs, breasts, and a 5-mm thick skin segment on the breast surface. Dose-volume metrics were defined to quantify the quality of concurrent treatment plans assessing target coverage and sparing of OAR. The following treatment techniques were assessed: photon beams with either static 3D-conformal, dynamic arc (DCA), static gantry intensity-modulated beams (IMRT), or RapidArc (RA); a single conformal EB; and intensity-modulated proton beams (IMPT). The goal for this planning effort was to cover 100% of the CTV with 95% of the prescribed dose and to minimize the volume inside the CTV receiving >107% of the dose. RESULTS: All techniques but DCA and EB achieved the planning objective for the CTV with an inhomogeneity ranging from 2% to 11%. RA showed the best conformity, EB the worst. Contra-lateral breast and lung were spared by all techniques with mean doses <0.5 Gy (zero for protons). The ipsi-lateral lung received a mean dose <10% of that prescribed with photon beams and <2% with IMPT, increasing to 17% with EB. The heart, in left-sided breast tumors, received also the highest dose with EB. The skin was best protected with RA with a mean dose of 5.4 Gy and V(15Gy)=2.4%. CONCLUSIONS: Boosting the tumor bed in early-stage breast cancer with optimized photon or proton beams may be preferred to EB especially for deep-seated targets. The marked OAR (i.e., ipsi-lateral breast, lung, heart, and skin surface) dose-sparing effect may allow for a potential long-term toxicity risk reduction and better cosmesis. DCA or RA may also be considered alternative treatment options for patients eligible for accelerated partial breast irradiation trials.

Hypofractionated boost to the dominant tumor region with intensity modulated stereotactic radiotherapy for prostate cancer: a sequential dose escalation pilot study.

PURPOSE: To evaluate the feasibility, tolerability, and preliminary outcomes in patients with prostate cancer treated according to a hypofractionated dose escalation protocol to boost the dominant tumor-bearing region of the prostate. METHODS AND MATERIALS: After conventional fractionated external radiotherapy to 64 to 64.4 Gy, 50 patients with nonmetastatic prostate cancer were treated with an intensity-modulated radiotherapy hypofractionated boost under stereotactic conditions to a reduced prostate volume to the dominant tumor region. A rectal balloon inflated with 60 cc of air was used for internal organ immobilization. Five, 8, and 8 patients were sequentially treated with two fractions of 5, 6, or 7 Gy, respectively (normalized total dose in 2 Gy/fraction [NTD(2 Gy)] < 100 Gy, low-dose group), whereas 29 patients received two fractions of 8 Gy each (NTD(2 Gy) > 100 Gy, high-dose group). Androgen deprivation was given to 33 patients. Acute and late toxicities were assessed according to the Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) scoring system. RESULTS: Two patients presented with Grade 3 acute urinary toxicity. The 5-year probabilities of >or=Grade 2 late urinary and late low gastrointestinal (GI) toxicity-free survival were 82.2% +/- 7.4% and 72.2% +/- 7.6%, respectively. The incidence and severity of acute or late toxicities were not correlated with low- vs. high-dose groups, pelvic irradiation, age, or treatment with or without androgen deprivation. The 5-year biochemical disease-free survival (b-DFS) and disease-specific survival were 98% +/- 1.9% and 100%, respectively. CONCLUSION: Intensity-modulated radiotherapy hypofractionated boost dose escalation under stereotactic conditions was feasible, and showed excellent outcomes with acceptable long-term toxicity. This approach may well be considered an alternative to high-dose-rate brachytherapy.

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.