Endorectal MRI assessment of local relapse after surgery for prostate cancer: A model to define treatment field guidelines for adjuvant radiotherapy in patients at high risk for local failure.

PURPOSE: To assess the role of endorectal magnetic resonance imaging (MRI) in defining local relapse after radical prostatectomy for prostate cancer to help to reassess the clinical target volume (CTV) for adjuvant postprostatectomy radiotherapy. METHODS AND MATERIALS: Sixty patients undergoing an endorectal MRI before salvage radiotherapy were selected. Spatial coordinates of the relapses were assessed using two reference points: the inferior border of the pubic symphysis (point 1) and the urethro-vesical anastomosis (point 2). Every lesion on MRI was delineated on the planning computed tomography and center of mass coordinates were plotted in two separate diagrams (along the x, y, and z axes) with the urethro-vesical anastomosis as the coordinate origin. An "ideal" CTV was constructed, centered at a point defined by the mathematical means of each of the three coordinates with dimensions defined as twice 2 standard deviations in each of the three axes. The dosimetric impact of the new CTV definition was evaluated in six adjuvantly treated patients. RESULTS: The ideal CTV center of mass was located at coordinates 0 (x), -5 (y), and -3 (z) mm with SDs of 6 (x), 6 (y), and 9 (z) mm, respectively. The CTV size was 24 (x) x 24 (y) x 36 (z) mm. Significant rectal sparing was observed with the new CTV. CONCLUSIONS: A CTV with an approximately cylindrical shape (approximately 4 x 3 cm) centered 5 mm posterior and 3 mm inferior to the urethro-vesical anastomosis was defined. Such CTV may reduce the irradiation of normal nontarget tissue in the pelvis potentially improving treatment tolerance.

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.

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.