Dose-adapted salvage radiotherapy after radical prostatectomy based on an erMRI target definition model: toxicity analysis.

BACKGROUND: To assess treatment tolerance by patients treated with a dose-adapted salvage radiotherapy (SRT) protocol based on an multiparametric endorectal magnetic resonance imaging (erMRI) failure definition model after radical prostatectomy (RP). MATERIAL AND METHODS: A total of 171 prostate cancer patients recurring after RP undergoing erMRI before SRT were analyzed. A median dose of 64 Gy was delivered to the prostatic bed (PB) with, in addition, a boost of 10 Gy to the suspected relapse as visualized on erMRI in 131 patients (76.6%). Genitourinary (GU) and gastrointestinal (GI) toxicities were scored using the RTOG scale. RESULTS: Grade ≥ 3 GU and GI acute toxicity were observed in three and zero patients, respectively. The four-year grade ≥ 2 and ≥ 3 late GU and GI toxicity-free survival rates (109 patients with at least two years of follow-up) were 83.9 ± 4.7% and 87.1 ± 4.2%, and 92.1 ± 3.6% and 97.5 ± 1.7%, respectively. Boost (p = 0.048) and grade ≥ 2 acute GU toxicity (p = 0.008) were independently correlated with grade ≥ 2 late GU toxicity on multivariate analysis. CONCLUSIONS: A dose-adapted, erMRI-based SRT approach treating the PB with a boost to the suspected local recurrence may potentially improve the therapeutic ratio by selecting patients that are most likely expected to benefit from SRT doses above 70 Gy as well as by reducing the size of the highest-dose target volume. Further prospective trials are needed to investigate the use of erMRI in SRT as well as the role of dose-adapted protocols and the best fractionation schedule.

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.

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.

Results of Dose-adapted Salvage Radiotherapy After Radical Prostatectomy Based on an Endorectal MRI Target Definition Model.

OBJECTIVES: To assess the outcome of patients treated with a dose-adapted salvage radiotherapy (SRT) protocol based on an endorectal magnetic resonance imaging (erMRI) failure definition model after radical prostatectomy (RP). METHODS: We report on 171 relapsing patients after RP who had undergone an erMRI before SRT. 64 Gy were prescribed to the prostatic bed with, in addition, a boost of 10 Gy to the suspected local relapse as detected on erMRI in 131 patients (76.6%). RESULTS: The 3-year biochemical relapse-free survival (bRFS), local relapse-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival were 64.2±4.3%, 100%, 85.2±3.2%, 100%, and 99.1±0.9%, respectively. A PSA value >1 ng/mL before salvage (P=0.006) and an absence of biochemical progression during RT (P=0.001) were both independently correlated with bRFS on multivariate analysis. No significant difference in 3-year bRFS was observed between the boost and no-boost groups (68.4±4.6% vs. 49.7±10%, P=0.251). CONCLUSIONS: A PSA value >1 ng/mL before salvage and a biochemical progression during RT were both independently correlated with worse bRFS after SRT. By using erMRI to select patients who are most likely expected to benefit from dose-escalated SRT protocols, this dose-adapted SRT approach was associated with good biochemical control and outcome, serving as a hypothesis-generating basis for further prospective trials aimed at improving the therapeutic ratio in the salvage setting.

RapidArc, intensity modulated photon and proton techniques for recurrent prostate cancer in previously irradiated patients: a treatment planning comparison study.

BACKGROUND: A study was performed comparing volumetric modulated arcs (RA) and intensity modulation (with photons, IMRT, or protons, IMPT) radiation therapy (RT) for patients with recurrent prostate cancer after RT. METHODS: Plans for RA, IMRT and IMPT were optimized for 7 patients. Prescribed dose was 56 Gy in 14 fractions. The recurrent gross tumor volume (GTV) was defined on 18F-fluorocholine PET/CT scans. Plans aimed to cover at least 95% of the planning target volume with a dose > 50.4 Gy. A maximum dose (DMax) of 61.6 Gy was allowed to 5% of the GTV. For the urethra, DMax was constrained to 37 Gy. Rectal DMedian was < 17 Gy. Results were analyzed using Dose-Volume Histogram and conformity index (CI90) parameters. RESULTS: Tumor coverage (GTV and PTV) was improved with RA (V95% 92.6 +/- 7.9 and 83.7 +/- 3.3%), when compared to IMRT (V95% 88.6 +/- 10.8 and 77.2 +/- 2.2%). The corresponding values for IMPT were intermediate for the GTV (V95% 88.9 +/- 10.5%) and better for the PTV (V95%85.6 +/- 5.0%). The percentages of rectal and urethral volumes receiving intermediate doses (35 Gy) were significantly decreased with RA (5.1 +/- 3.0 and 38.0 +/- 25.3%) and IMPT (3.9 +/- 2.7 and 25.1 +/- 21.1%), when compared to IMRT (9.8 +/- 5.3 and 60.7 +/- 41.7%). CI90 was 1.3 +/- 0.1 for photons and 1.6 +/- 0.2 for protons. Integral Dose was 1.1 +/- 0.5 Gy*cm3 *105 for IMPT and about a factor three higher for all photon's techniques. CONCLUSION: RA and IMPT showed improvements in conformal avoidance relative to fixed beam IMRT for 7 patients with recurrent prostate cancer. IMPT showed further sparing of organs at risk.

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.

(11)C-acetate PET in the early evaluation of prostate cancer recurrence.

PURPOSE: The first aim of the study was to investigate the diagnostic potential of (11)C-acetate PET in the early detection of prostate cancer recurrence. A second aim was the evaluation of early and late PET in this context. METHODS: The study population comprised 32 prostate cancer patients with early evidence of relapse after initial radiotherapy (group A) or radical surgery (group B). The median PSA of group A (n=17) patients was 6 ng/ml (range 2.6-30.2) while that of group B (n=15) was 0.4 ng/ml (range 0.08-4.8). Pelvic-abdominal-thoracic PET was started 2 min after injection of (11)C-acetate and evaluated after fusion with CT. RESULTS: Group A: Taking a SUV(max)> or =2 as the cut-off, PET showed local recurrences in 14/17 patients and two equivocal results. Distant disease was observed in six patients and an equivocal result was obtained in one. Endorectal MRI was positive in 12/12 patients. Biopsy confirmed local recurrence in six of six (100%) patients. PET was positive in five of the six patients with biopsy-proven recurrences, the result in the remaining patient being equivocal. Group B: Among the 15 patients, visual interpretation was positive for local recurrences in five patients and equivocal in four. One obturator lymph node was positive. Endorectal MRI was positive in 11/15 patients and equivocal in two. Positional correlation of positive/equivocal results on PET and endorectal MRI was observed in seven of nine patients. PSA decreased significantly after salvage radiotherapy in 8/14 patients, providing strong evidence for local recurrence. PET of the eight patients responding to RT was positive in three and equivocal in two. CONCLUSION: (11)C-acetate PET was found to be valuable in the early evaluation of prostate cancer relapse. Optimising scanning time and use of modern PET-CT equipment might allow further improvement.

18F-choline and/or 11C-acetate positron emission tomography: detection of residual or progressive subclinical disease at very low prostate-specific antigen values (<1 ng/mL) after radical prostatectomy.

OBJECTIVES: To assess the value of positron emission tomography (PET)/computed tomography (CT) with either (18)F-choline and/or (11)C-acetate, of residual or recurrent tumour after radical prostatectomy (RP) in patients with a prostate-specific antigen (PSA) level of <1 ng/mL and referred for adjuvant or salvage radiotherapy. PATIENTS AND METHODS: In all, 22 PET/CT studies were performed, 11 with (18)F-choline (group A) and 11 with (11)C-acetate (group B), in 20 consecutive patients (two undergoing PET/CT scans with both tracers). The median (range) PSA level before PET/CT was 0.33 (0.08-0.76) ng/mL. Endorectal-coil magnetic resonance imaging (MRI) was used in 18 patients. Nineteen patients were eligible for evaluation of biochemical response after salvage radiotherapy. RESULTS: There was abnormal local tracer uptake in five and six patients in group A and B, respectively. Except for a single positive obturator lymph node, there was no other site of metastasis. In the two patients evaluated with both tracers there was no pathological uptake. Endorectal MRI was locally positive in 15 of 18 patients; 12 of 19 responded with a marked decrease in PSA level (half or more from baseline) 6 months after salvage radiotherapy. CONCLUSIONS: Although (18)F-choline and (11)C-acetate PET/CT studies succeeded in detecting local residual or recurrent disease in about half the patients with PSA levels of <1 ng/mL after RP, these studies cannot yet be recommended as a standard diagnostic tool for early relapse or suspicion of subclinical minimally persistent disease after surgery. Endorectal MRI might be more helpful, especially in patients with a low likelihood of distant metastases. Nevertheless, further research with (18)F-choline and/or (11)C-acetate PET with optimal spatial resolution might be needed for patients with a high risk of distant relapse after RP even at low PSA values.

Endoscopic features of esophageal tuberculosis.

BACKGROUND: Esophageal tuberculosis is rare. Clinical and endoscopic features are variable, diverse, nonspecific, and poorly described. These findings may be confused with those of esophageal cancer and deep fungal infection. METHODS: Medical records from a 5-year period (January 1997 to December 2001) were searched for cases of esophageal tuberculosis. For identified cases, the clinical, radiologic, and endoscopic features were evaluated. OBSERVATIONS: Four cases of esophageal tuberculosis were encountered during the 5-year period studied. Three of the patients presented with dysphagia and weight loss. One patient had aspiration pneumonia and another fatal hematemesis. Endoscopic features included deep and large proximal esophageal ulcers in 2 patients, tracheo-esophageal fistula in one, and nonhealing proximal esophageal ulcer in another patient. CONCLUSION: The present case series indicates that certain endoscopic features, such as deep and large esophageal ulcers, tracheoesophageal fistula, and nonhealing ulcer, are strongly suggestive of tuberculosis-related esophageal lesions.