A novel, multi-active emollient for the prevention of acute radiation dermatitis in breast cancer patients: a randomized clinical trial.

PURPOSE: To investigate the efficacy of a novel, multi-active emollient in preventing and managing acute radiation dermatitis (ARD) in breast cancer patients undergoing moderate hypofractionated (HF) radiotherapy (RT) compared to standard of care. METHODSA: A monocentric, open-label, randomized clinical trial (RCT) with breast cancer patients receiving moderate HF (dose: 40.05-55.86 Gy, fractions: 15-21) was conducted between January 2022 and May 2023. The experimental group received the novel emollient, while the control group received the standard skin care. Patients applied the skin care products twice daily during the complete RT course. The primary outcome was the severity of ARD at the final RT session measured by the modified Radiation Therapy Oncology Group (RTOG) criteria. Secondary outcomes included patient symptoms, quality of life (QoL), and treatment satisfaction. RESULTS: A total of 100 patients with 50 patients per group were enrolled. In the control group, 50% of the patients developed RTOG grade 1 ARD and 48% grade 2 or higher, while in the experimental group, the severity of ARD was significantly lower with 82% grade 1 and 16% grade 2 ARD (P = .013, χ2-test). The frequency and severity of xerosis were significantly lower in the experimental compared to the control group (Ps ≤ .036, Mann Whiney U test). The impact of ARD on the QoL was low, and treatment satisfaction was high in both groups, with no significant difference. CONCLUSION: This RCT shows that the novel, multi-active emollient significantly reduced the ARD RTOG grade. Research in a more diverse patient population is warranted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04929808 (11/06/2021).

Focal Boost to the Intraprostatic Tumor in External Beam Radiotherapy for Patients With Localized Prostate Cancer: Results From the FLAME Randomized Phase III Trial.

PURPOSE: This study investigates whether focal boosting of the macroscopic visible tumor with external beam radiotherapy increases biochemical disease-free survival (bDFS) in patients with localized prostate cancer. PATIENTS AND METHODS: In the phase III, multicenter, randomized controlled Focal Lesion Ablative Microboost in Prostate Cancer trial, 571 patients with intermediate- and high-risk prostate cancer were enrolled between 2009 and 2015. Patients assigned to standard treatment received 77 Gy (fractions of 2.2 Gy) to the entire prostate. The focal boost arm received an additional simultaneous integrated focal boost up to 95 Gy (fractions up to 2.7 Gy) to the intraprostatic lesion visible on multiparametric magnetic resonance imaging. Organ at risk constraints were prioritized over the focal boost dose. The primary end point was 5-year bDFS. Secondary end points were disease-free survival (DFS), distant metastases-free survival, prostate cancer-specific survival, overall survival, toxicity, and health-related quality of life. RESULTS: Median follow-up was 72 months. Biochemical DFS was significantly higher in the focal boost compared with the standard arm (hazard ratio 0.45, 95% CI, 0.28 to 0.71, P < .001). At 5-year follow-up bDFS was 92% and 85%, respectively. We did not observe differences in prostate cancer-specific survival (P = .49) and overall survival (P = .50). The cumulative incidence of late genitourinary and GI toxicity grade ≥ 2 was 23% and 12% in the standard arm versus 28% and 13% in the focal boost arm, respectively. Both for late toxicity as health-related quality of life, differences were small and not statistically significant. CONCLUSION: The addition of a focal boost to the intraprostatic lesion improved bDFS for patients with localized intermediate- and high-risk prostate cancer without impacting toxicity and quality of life. The Focal Lesion Ablative Microboost in Prostate Cancer study shows that a high focal boost strategy to improve tumor control while respecting organ at risk dose constraints is effective and safe.

Benefits of Elective Para-Aortic Radiotherapy for pN1 Prostate Cancer Using Arc Therapy (Intensity-Modulated or Volumetric Modulated Arc Therapy): Protocol for a Nonrandomized Phase II Trial.

BACKGROUND: In patients with prostate cancer (PCa) with histopathologically proven pelvic lymph node (LN) metastasis (pN1) after extended pelvic lymph node dissection (ePLND), multimodality treatment consisting of treatment of the primary tumor and whole pelvic radiotherapy (WPRT) combined with androgen deprivation therapy (ADT) offers promising results, leading to better cause-specific survival rates compared with ADT alone. However, in case more than one pelvic LN is invaded by the tumor, approximately 40% of the patients relapse biochemically and clinically. Clinical relapse is present in the para-aortic LNs (M1a disease) in up to 77% of the relapsing cases. OBJECTIVE: We hypothesize that, based on the evidence that positive LNs represent the door to hematogenous dissemination, elective para-aortic irradiation will reduce the development of both retroperitoneal nodal (M1a) and distant metastasis (M1b or M1c disease), postpone the need for palliative ADT, and prolong the time to castration-refractory disease. METHODS: To test this hypothesis, we will conduct a prospective, nonrandomized phase II trial to study the efficacy of additional elective para-aortic radiotherapy (PART) in pN1 patients compared with those who were historically treated with adjuvant WPRT alone. We aim to include 137 patients with PCa and presence of pN1 disease after ePLND. With this number of patients, an improvement of 15% in the 5-year clinical relapse-free survival can be detected with a power of 80%. RESULTS: Recruitment of patients for this trial started in 2017 and will be completed approximately by March 2020. CONCLUSIONS: This is the first phase II trial to investigate the benefits of an elective PART in patients with PCa. The results of this trial will potentially serve as a sound base for a later randomized phase III trial. All participants are given a PART information sheet and required to give written informed consent. Results are expected to be published in a peer-reviewed journal. TRIAL REGISTRATION: ClinicalTrials.gov NCT03079323; https://clinicaltrials.gov/ct2/show/NCT03079323 (Archived by WebCite at http://www.webcitation.org/73ELimv1d). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/11256.

Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial.

PURPOSE: To compare toxicity rates in patients with localized prostate cancer treated with standard fractionated external beam radiotherapy (EBRT) with or without an additional integrated boost to the macroscopically visible tumour. MATERIAL AND METHODS: FLAME is a phase 3 multicentre RCT (NCT01168479) of patients with pathologically confirmed localized intermediate or high-risk prostate cancer. The standard treatment arm (n = 287) received a dose to the entire prostate of 77 Gy in 35 fractions. The dose-escalated treatment arm (n = 284) received 77 Gy in 35 fractions to the entire prostate, with an integrated boost up to 95 Gy to the multi-parametric MRI-defined (macroscopic) tumour within the prostate. Treatment related toxicity was measured using the CTCAE version 3.0. Grade 2 or worse GU or GI events up to two years were compared between groups by presenting proportions and by Generalized Estimating Equations (GEE) analyses for repeated measures. RESULTS: Ninety percent of the 571 men randomly assigned between September 2009 and January 2015 had high-risk disease (Ash 2000), of whom nearly 66% were prescribed hormonal therapy up to three years. Median follow-up was 55 months at the time of this analysis. Toxicity prevalence rates for both GI and GU increased until the end of treatment and regressed thereafter, with no obvious differences across treatment groups. Late cumulative GI toxicity rates were 11.1% and 10.2% for the standard and dose-escalated group, respectively. These rates were 22.6% and 27.1% for GU toxicity. GEE analyses showed that both GU toxicity and GI toxicity (≥grade 2) up to two years after treatment were similar between arms (OR 1.02 95%CI 0.78-1.33p = 0.81 and (OR 1.19 95%CI 0.82-1.73p = 0.38), respectively. CONCLUSIONS: In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation technique is safe and feasible.

Do refined consensus guidelines improve the uniformity of clinical target volume delineation for rectal cancer? Results of a national review project.

In a previous national central review project, 74% of the rectal cancer clinical target volumes (CTVs) needed a modification. In a follow-up initiative, we evaluated whether the use of refined international consensus guidelines improves the uniformity of CTV delineation in clinical practice.

Prostate tumor delineation using multiparametric magnetic resonance imaging: Inter-observer variability and pathology validation.

BACKGROUND AND PURPOSE: Boosting the dose to the largest (dominant) lesion in radiotherapy of prostate cancer may improve treatment outcome. The success of this approach relies on the detection and delineation of tumors. The agreement among teams of radiation oncologists and radiologists delineating lesions on multiparametric magnetic resonance imaging (mp-MRI) was assessed by measuring the distances between observer contours. The accuracy of detection and delineation was determined using whole-mount histopathology specimens as reference. MATERIAL AND METHODS: Six observer teams delineated tumors on mp-MRI of 20 prostate cancer patients who underwent a prostatectomy. To assess the inter-observer agreement, the inter-observer standard deviation (SD) of the contours was calculated for tumor sites which were identified by all teams. RESULTS: Eighteen of 89 lesions were identified by all teams, all were dominant lesions. The median histological volume of these was 2.4cm(3). The median inter-observer SD of the delineations was 0.23cm. Sixty-six of 69 satellites were missed by all teams. CONCLUSION: Since all teams identify most dominant lesions, dose escalation to the dominant lesion is feasible. Sufficient dose to the whole prostate may need to be maintained to prevent under treatment of smaller lesions and undetected parts of larger lesions.

Final analysis of a prospective trial on functional imaging for nodal staging in patients with prostate cancer at high risk for lymph node involvement.

PURPOSE: Accurate staging modalities to diagnose lymph node involvement in patients with prostate cancer (PCa) are lacking. We wanted to prospectively assess sensitivity, specificity, and positive predictive value (PPV) and negative predictive value of (11)C-choline positron emission tomography (PET)-computed tomography (CT) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for nodal staging in patients with PCa at high risk for lymph node involvement. MATERIAL AND METHODS: In total, 75 patients with a risk≥10% but<35% for lymph node (LN) metastases (Partin tables) who had N0 lesions based on the findings of contrast-enhanced CT scans were included. Patients underwent (11)C-choline PET-CT and DW MRI before surgery, which consisted of a superextended lymph node dissection followed by radical prostatectomy. LNs were serially sectioned and histopathologically examined after pankeratin staining. These results were used as the gold standard to compare with the imaging results. RESULTS: Of 1,665 resected LNs (median = 21, range: 7-49), 106 affected LNs (median = 2, range: 1-10) were found in 37 of 75 patients (49%). On a region-based analysis, we found a low sensitivity of 8.2% and 9.5% and a PPV of 50.0% and 40.0% for (11)C-choline PET-CT and DW MRI, respectively. The patient-based analysis showed a sensitivity of 18.9% and 36.1% for and a PPV of 63.6% and 86.7% (11)C-choline PET-CT and DW MRI, respectively. Even when both imaging modalities were combined, sensitivity values remained too low to be clinically useful. CONCLUSIONS: Because of the low sensitivity, there is no indication for routine clinical use of either (11)C-choline PET-CT or DW MRI for LN staging in patients with PCa, in whom CT scan findings were normal.

Reliability of sentinel node procedure for lymph node staging in prostate cancer patients at high risk for lymph node involvement.

AIM: To investigate the reliability of a sentinel node (SN) procedure for nodal staging in prostate cancer (PCa) patients at high risk for lymph node (LN) involvement. MATERIAL AND METHODS: Seventy-four patients with localized prostate adenocarcinoma, who were clinically node-negative and had a risk of LN involvement of ≥ 10% (Partin tables), were prospectively enrolled. Upon intraprostatic 99mTc-nanocolloid injection, they underwent planar scintigraphy and SPECT imaging. Surgical removal of the SN, located by means of a gamma probe, was completed with a superextended LN dissection (seLND) as a reference and followed by radical prostatectomy. RESULTS: In total, 470 SN (median 6, IQR 3-9) were scintigraphically detected of which 371 (median 4, IQR 2-6) were located by gamma probe and selectively removed during surgery (79%). Histopathology confirmed LN metastases in 37 patients (50%) having 106 affected LN in total (median number per patient 2, IQR 1-4). Twenty-eight patients were node positive (N+) based on the analysis of the resected SN. However, the seLND that was performed as a reference revealed nine additional N+ patients resulting in a sensitivity of 76% (28/37). In total, 15 of 37 patients (41%) had metastases in SN only and could have been spared seLND to remove all affected nodes. CONCLUSION: We found a relatively low sensitivity when addressing the SN procedure for nodal staging in PCa patients at high risk for LN involvement. Importantly, only less than half of the N+ patients could have been spared a seLND to remove all affected lymphoid tissue.

Dosimetric adaptive IMRT driven by fiducial points.

PURPOSE: Intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy have become standard treatments but are more sensitive to anatomical variations than 3D conformal techniques. To correct for inter- and intrafraction anatomical variations, fast and easy to implement methods are needed. Here, the authors propose a full dosimetric IMRT correction that finds a compromise in-between basic repositioning (the current clinical practice) and full replanning. It simplifies replanning by avoiding a recontouring step and a full dose calculation. It surpasses repositioning by updating the preoptimized fluence and monitor units (MU) using a limited number of fiducial points and a pretreatment (CB)CT. To adapt the fluence the fiducial points were projected in the beam's eye view (BEV). To adapt the MUs, point dose calculation towards the same fiducial points were performed. The proposed method is intrinsically fast and robust, and simple to understand for operators, because of the use of only four fiducial points and the beam data based point dose calculations. METHODS: To perform our dosimetric adaptation, two fluence corrections in the BEV are combined with two MU correction steps along the beam's path. (1) A transformation of the fluence map such that it is realigned with the current target geometry. (2) A correction for an unintended scaling of the penumbra margin when the treatment beams scale to the current target size. (3) A correction for the target depth relative to the body contour and (4) a correction for the target distance to the source. The impact of the correction strategy and its individual components was evaluated by simulations on a virtual prostate phantom. This heterogeneous reference phantom was systematically subjected to population based prostate transformations to simulate interfraction variations. Additionally, a patient example illustrated the clinical practice. The correction strategy was evaluated using both dosimetric (CTV mean dose, conformity index) and clinical (tumor control probability, and normal tissue complication probability) measures. RESULTS: Based on the current experiments, the intended target dose and tumor control probability could be assured by the proposed method (TCP ≥ TCP(intended)). Additionally, the conformity index error was more than halved compared to the current clinical practice (ΔCI(95%) from 40% to 16%) resulting in improved organ at risk protection. All the individual correction steps had an added value to the full correction. CONCLUSIONS: A limited number of fiducial points (no organ contours required) and an in-room (CB)CT are sufficient to perform a full dosimetric correction for IMRT plans. In the presence of interfraction variation, the corrected plans show superior dose distributions compared to our current clinical practice.

The role of elective pelvic radiotherapy in clinically node-negative prostate cancer: a systematic review.

The role of elective radiotherapy of the pelvic nodal regions in clinically node-negative prostate cancer patients remains highly controversial. This review will address the difficulty of non-invasive nodal staging, even with more advanced imaging techniques, and will show that surgical staging still finds a relatively high percentage of patients with intermediate- or high-risk prostate cancer that have microscopic tumor invasion in the pelvic nodes. Finally, an overview of the current literature on elective pelvic irradiation will be provided.

18F-MK-9470 PET imaging of the type 1 cannabinoid receptor in prostate carcinoma: a pilot study.

BACKGROUND: Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa). In a prospective study, the feasibility of 18F-MK-9470 positron emission tomography (PET) imaging in patients with primary and metastatic PCa was evaluated. METHODS: Eight patients were included and underwent 18F-MK-9470 PET/CT imaging. For five patients with primary PCa, dynamic PET/CT imaging was performed over three acquisition intervals (0 to 30, 60 to 90 and 120 to 150 min post-injection). In malignant and benign prostate tissue regions, time activity curves of the mean standardized uptake value (SUVmean) were determined as well as the corresponding area under the curve to compare 18F-MK-9470 uptake over time. Muscle uptake of 18F-MK-9470 was used as reference for non-specific binding. Magnetic resonance imaging (MRI) was used as anatomical reference and for delineating intraprostatic tumours. Histological and immunohistochemical (IHC) examination was performed on the whole-mount histopathology sections of four patients who underwent radical prostatectomy to assess the MRI-based tumour versus benign tissue classification. For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. 18F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUVmean values of metastases with these of the contralateral bone tissue. RESULTS: 18F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments. IHC findings of corresponding prostatic histopathological sections indicated weak CB1R expression in locally confined PCa, which was not visualized with 18F-MK-9470 PET. Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher 18F-MK-9470 uptake as compared to the uptake in contralateral normal bone. CONCLUSIONS: 18F-MK-9470 PET could not detect local PCa or bone metastases in the axial skeleton but was able to visualize metastases in the appendicular skeleton. Based on these pilot observations, it seems unlikely that CB1R PET will play a significant role in the evaluation of PCa.

Identification and characterization of nodal metastases in prostate cancer patients at high risk for lymph node involvement.

AIM: To investigate whether blood-based markers could be used to identify prostate cancer (PCa) patients harboring lymph node (LN) metastases. In addition, E-cadherin expression was studied within the concept of epithelial mesenchymal plasticity. MATERIAL AND METHODS: Seventy-five patients with clinically localized PCa who underwent a superextended lymphadenectomy followed by radical prostatectomy (RP) were included in this study. Preoperative plasma/serum levels of endoglin, transforming growth factor-ß1 (TGF-ß1), osteopontin, vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), and E-cadherin were measured using commercially available enzyme immunoassays in 47/75 patients and correlated with clinicopathological parameters. E-cadherin expression in the diagnostic biopsies (n = 63), RP specimens (n = 75) and LN metastases (n = 106) was examined by immunohistochemical analysis. RESULTS: Occult LN metastases were present in almost half of the patients (37/75), with a total of 106 affected LN. Preoperative levels of endoglin, TGF-ß1, osteopontin, VEGF, VCAM-1 nor E-cadherin were significantly associated with LN status. Only a positive correlation between plasma endoglin and serum prostate-specific antigen was found (Spearman's r = 0.44; p = 0.002). The majority of biopsies (91.9%) and RP specimens (79.7%) showed strong E-cadherin expression, while in the LN this was found to be much weaker (28.9%). While the staining pattern in the isolated tumor cells (ITC) and micrometastases was mainly homogenous, the macrometastases showed a much more heterogeneous pattern (χ², p < 0.0001). CONCLUSION: In this study, none of the blood-based markers tested could be used for nodal staging in PCa, nor could E-cadherin expression in the tissue. However, the difference in E-cadherin expression pattern between the ITC/micrometastases and the macrometastases may point to another biological behavior. The specific staining pattern seen in the macrometastases could indicate an ongoing mesenchymal epithelial transition, presumed to be a mechanism for metastatic colonization. As the latter is the rate-limiting step in the metastatic process, evaluation of the E-cadherin expression pattern could have potential therapeutic implications.

Mapping of pelvic lymph node metastases in prostate cancer.

BACKGROUND: Opinions about the optimal lymph node dissection (LND) template in prostate cancer differ. Drainage and dissemination patterns are not necessarily identical. OBJECTIVE: To present a precise overview of the lymphatic drainage pattern and to correlate those findings with dissemination patterns. We also investigated the relationship between the number of positive lymph nodes (LN+) and resected lymph nodes (LNs) per region. DESIGN, SETTING, AND PARTICIPANTS: Seventy-four patients with localized prostate adenocarcinoma were prospectively enrolled. Patients did not show suspect LNs on computed tomography scan and had an LN involvement risk of ≥ 10% but ≤ 35% (Partin tables) or a cT3 tumor. INTERVENTION: After intraprostatic technetium-99m nanocolloid injection, patients underwent planar scintigraphy and single-photon emission computed tomography imaging. Then surgery was performed, starting with a sentinel node (SN) procedure and a superextended lymphadenectomy followed by radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Distribution of scintigraphically detected SNs and removed SNs per region were registered. The number of LN+, as well as the percentage LN+ of the total number of removed LNs per region, was demonstrated in combining data of all patients. The impact of the extent of LND on N-staging and on the number of LN+ removed was calculated. RESULTS AND LIMITATIONS: A total of 470 SNs were scintigraphically detected (median: 6; interquartile range [IQR]: 3-9), of which 371 SNs were removed (median: 4; IQR: 2.25-6). In total, 91 LN+ (median: 2; IQR: 1-3) were found in 34 of 74 patients. The predominant site for LN+ was the internal iliac region. An extended LND (eLND) would have correctly staged 32 of 34 patients but would have adequately removed all LN+ in only 26 of 34 patients. When adding the presacral region, these numbers increased to 33 of 34 and 30 of 34 patients, respectively. CONCLUSIONS: Standard eLND would have correctly staged the majority of LN+ patients, but 13% of the LN+ would have been missed. Adding the presacral LNs to the template should be considered to obtain a minimal template with maximal gain. NOTE: This manuscript was invited based on the 2011 European Association of Urology meeting in Vienna.

Multiparametric MRI for prostate cancer localization in correlation to whole-mount histopathology.

PURPOSE: To prospectively evaluate multiparametric magnetic resonance imaging (MRI) for accurate localization of intraprostatic tumor nodules, with whole-mount histopathology as the gold standard. MATERIALS AND METHODS: Seventy-five patients with biopsy-proven, intermediate, and high-risk prostate cancer underwent preoperative T2-weighted (T2w), dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI at 1.5T. Localization of suspicious lesions was recorded for each of 24 standardized regions of interest on the different MR images and correlated with the pathologic findings. Generalized estimating equations (GEE) were used to estimate the sensitivity, specificity, accuracy, positive, and negative predictive value for every MRI modality, as well as to evaluate the influence of Gleason score and pT-stage. Tumor volume measurements on histopathological specimens were correlated with those on the different MR modalities (Pearson correlation). RESULTS: DW MRI had the highest sensitivity for tumor localization (31.1% vs. 27.4% vs. 44.5% for T2w, DCE, and DW MRI, respectively; P < 0.005), with more aggressive or more advanced tumors being more easily detected with this imaging modality. Significantly higher sensitivity values were obtained for the combination of T2w, DCE, and DW MRI (58.8%) as compared to each modality alone or any combination of two modalities (P < 0.0001). Tumor volume can most accurately be assessed by means of DW MRI (r = 0.75; P < 0.0001). CONCLUSION: Combining T2w, DCE, and DW imaging significantly improves prostate cancer localization.

Patient positioning based on a radioactive tracer implanted in patients with localized prostate cancer: a performance and safety evaluation.

PURPOSE: To evaluate the performance and safety of a radiation therapy positioning system (RealEye) based on tracking a radioactive marker (Tracer) implanted in patients with localized prostate cancer. METHODS AND MATERIALS: We performed a single-arm multi-institutional trial in 20 patients. The iridium-192 ((192)Ir)-containing Tracer was implanted in the patient together with 4 standard gold seed fiducials. Patient prostate-related symptoms were evaluated with the International Prostate Symptom Score (IPSS) questionnaire. Computed tomography (CT) was performed for treatment planning, during treatment, and after treatment to evaluate the migration stability of the Tracer. At 5 treatment sessions, cone beam CT was performed to test the positioning accuracy of the RealEye. RESULTS: The Tracer was successfully implanted in all patients. No device or procedure-related adverse events occurred. Changes in IPSS scores were limited. The difference between the mean change in Tracer-fiducial distance and the mean change in fiducial-fiducial distance was -0.39 mm (95% confidence interval [CI] upper boundary, -0.22 mm). The adjusted mean difference between Tracer position according to RealEye and the Tracer position on the CBCT for all patients was 1.34 mm (95% CI upper boundary, 1.41 mm). CONCLUSIONS: Implantation of the Tracer is feasible and safe. Migration stability of the Tracer is good. Prostate patients can be positioned and monitored accurately by using RealEye.

Is there an additional value of ¹¹C-choline PET-CT to T2-weighted MRI images in the localization of intraprostatic tumor nodules?

PURPOSE: To investigate the additional value of (11)C-choline positron emission tomography (PET)-computed tomography (CT) to T2-weighted (T2w) magnetic resonance imaging (MRI) for localization of intraprostatic tumor nodules. METHODS AND MATERIALS: Forty-nine prostate cancer patients underwent T2w MRI and (11)C-choline PET-CT before radical prostatectomy and extended lymphadenectomy. Tumor regions were outlined on the whole-mount histopathology sections and on the T2w MR images. Tumor localization was recorded in the basal, middle, and apical part of the prostate by means of an octant grid. To analyze (11)C-choline PET-CT images, the same grid was used to calculate the standardized uptake values (SUV) per octant, after rigid registration with the T2w MR images for anatomic reference. RESULTS: In total, 1,176 octants were analyzed. Sensitivity, specificity, and accuracy of T2w MRI were 33.5%, 94.6%, and 70.2%, respectively. For (11)C-choline PET-CT, the mean SUV(max) of malignant octants was significantly higher than the mean SUV(max) of benign octants (3.69 ± 1.29 vs. 3.06 ± 0.97, p < 0.0001) which was also true for mean SUV(mean) values (2.39 ± 0.77 vs. 1.94 ± 0.61, p < 0.0001). A positive correlation was observed between SUV(mean) and absolute tumor volume (Spearman r = 0.3003, p = 0.0362). No correlation was found between SUVs and prostate-specific antigen, T-stage or Gleason score. The highest accuracy (61.1%) was obtained with a SUV(max) cutoff of 2.70, resulting in a sensitivity of 77.4% and a specificity of 44.9%. When both modalities were combined (PET-CT or MRI positive), sensitivity levels increased as a function of SUV(max) but at the cost of specificity. When only considering suspect octants on (11)C-choline PET-CT (SUV(max) ≥ 2.70) and T2w MRI, 84.7% of these segments were in agreement with the gold standard, compared with 80.5% for T2w MRI alone. CONCLUSIONS: The additional value of (11)C-choline PET-CT next to T2w MRI in detecting tumor nodules within the prostate is limited.

The benefits of including clinical factors in rectal normal tissue complication probability modeling after radiotherapy for prostate cancer.

PURPOSE: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. METHODS AND MATERIALS: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. RESULTS: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was "previous abdominal surgery." As second significant (p = 0.012-0.016) factor, "cardiac history" was included in all three rectal bleeding fits, whereas including "diabetes" was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D(50). Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. CONCLUSIONS: Comparable prediction models were obtained with LKB, RS, and logistic NTCP models. Including clinical factors improved the predictive power of all models significantly.