Is prone free breathing better than supine deep inspiration breath-hold for left whole-breast radiotherapy? A dosimetric analysis.

PURPOSE: The advantage of prone setup compared with supine for left-breast radiotherapy is controversial. We evaluate the dosimetric gain of prone setup and aim to identify predictors of the gain. METHODS: Left-sided breast cancer patients who had dual computed tomography (CT) planning in prone free breathing (FB) and supine deep inspiration breath-hold (DiBH) were retrospectively identified. Radiation doses to heart, lungs, breasts, and tumor bed were evaluated using the recently developed mean absolute dose deviation (MADD). MADD measures how widely the dose delivered to a structure deviates from a reference dose specified for the structure. A penalty score was computed for every treatment plan as a weighted sum of the MADDs normalized to the breast prescribed dose. Changes in penalty scores when switching from supine to prone were assessed by paired t-tests and by the number of patients with a reduction of the penalty score (i.e., gain). Robust linear regression and fractional polynomials were used to correlate patients' characteristics and their respective penalty scores. RESULTS: Among 116 patients identified with dual CT planning, the prone setup, compared with supine, was associated with a dosimetric gain in 72 (62.1%, 95% CI: 52.6-70.9%). The most significant predictors of a gain with the prone setup were the breast depth prone/supine ratio (>1.6), breast depth difference (>31 mm), prone breast depth (>77 mm), and breast volume (>282 mL). CONCLUSION: Prone compared with supine DiBH was associated with a dosimetric gain in 62.1% of our left-sided breast cancer patients. High pendulousness and moderately large breast predicted for the gain.

Mild hyperthermia by MR-guided focused ultrasound in an ex vivo model of osteolytic bone tumour: optimization of the spatio-temporal control of the delivered temperature.

BACKGROUND: Magnetic resonance guided focused ultrasound was suggested for the induction of deep localized hyperthermia adjuvant to radiation- or chemotherapy. In this study we are aiming to validate an experimental model for the induction of uniform temperature elevation in osteolytic bone tumours, using the natural acoustic window provided by the cortical breakthrough. MATERIALS AND METHODS: Experiments were conducted on ex vivo lamb shank by mimicking osteolytic bone tumours. The cortical breakthrough was exploited to induce hyperthermia inside the medullar cavity by delivering acoustic energy from a phased array HIFU transducer. MR thermometry data was acquired intra-operatory using the proton resonance frequency shift (PRFS) method. Active temperature control was achieved via a closed-loop predictive controller set at 6 °C above the baseline. Several beam geometries with respect to the cortical breakthrough were investigated. Numerical simulations were used to further explain the observed phenomena. Thermal safety of bone heating was assessed by cross-correlating MR thermometry data with the measurements from a fluoroptic temperature sensor inserted in the cortical bone. RESULTS: Numerical simulations and MR thermometry confirmed the feasibility of spatio-temporal uniform hyperthermia (± 0.5 °C) inside the medullar cavity using a fixed focal point sonication. This result was obtained by the combination of several factors: an optimal positioning of the focal spot in the plane of the cortical breakthrough, the direct absorption of the HIFU beam at the focal spot, the "acoustic oven effect" yielded by the beam interaction with the bone, and a predictive temperature controller. The fluoroptical sensor data revealed no heating risks for the bone and adjacent tissues and were in good agreement with the PRFS thermometry from measurable voxels adjacent to the periosteum. CONCLUSION: To our knowledge, this is the first study demonstrating the feasibility of MR-guided focused ultrasound hyperthermia inside the medullar cavity of bones affected by osteolytic tumours. Our results are considered a promising step for combining adjuvant mild hyperthermia to external beam radiation therapy for sustained pain relief in patients with symptomatic bone metastases.

[Sexual health after radiotherapy]. / La santé sexuelle après radiothérapie.

The impact of locoregional toxicity after radiotherapy on sexual function is the objective of this review. We explore those organs affected by cancer that are obviously implied in patients' intimate lives : cancers of the breast, prostate, pelvic region, and ENT region. However, we strongly believe that any patient diagnosed with cancer, and treated for one, could by all means be exposed to psychological and somatic changes leading to deterioration of their sexuality.

L'évaluation de l'impact locorégional après un traitement de radiothérapie sur la fonction sexuelle est l'objectif de cet article. Nous passerons en revue les organes atteints de cancer dont l'implication dans la vie intime des patients nous a semblé la plus parlante : les cancers du sein, de la prostate, de la région pelvienne et de la sphère ORL. Néanmoins, nous sommes convaincus que tout patient avec un diagnostic de cancer, et traité pour celui-ci, peut être exposé à des séquelles psychologiques et somatiques entraînant une baisse de sa sexualité.

The ADAPP trial: a two-year longitudinal multidisciplinary intervention study for prostate cancer frail patients on androgen deprivation associated to curative radiotherapy.

BACKGROUND: Androgen deprivation (AD) therapy combined to radiotherapy (RT) is a curative therapeutic option for patients with non-metastatic locally advanced or aggressive intermediate prostate cancer (PC), though with a range of nutritional, physical, and psychological side effects. A multidisciplinary care program was created to help frail patients to prevent and manage those side effects. MATERIAL AND METHODS: We conducted a longitudinal interventional study in frail patients, presenting either cardiovascular/pulmonary comorbidities, old age (≥75 years), vulnerability ratings, or balance impairment. Patients were treated by AD and RT and, benefited from nutritional coaching, supervised biweekly 45 minute physical training, and psychological counseling for two years. Treatment outcomes included PC-related quality of life (QoL), body mass index, fat mass index, and fat-free mass index derived from bioelectrical impedance analysis, Six-Minute Walk Test, Timed Up&Go, handgrip strength, Hospital Anxiety and Depression scale, Mini Mental State Examination. Measures were repeated after zero, three, six, nine, 12, 18, 24 months, and 12-months post-study follow-up. A prospective mixed-model design was used to assess longitudinal outcome. RESULTS: Regression analyses revealed no significant change over the two years, including post-study follow-up. Means of QoL, nutritional, physical, as well as psychological variables remained stable over more than two years in the 35 men aged 74 (range 68-76) years. CONCLUSION: The expected side effects of AD and RT were not observed in frail PC patients who followed this multidisciplinary care program.

Impact of hydrogel spacer injections on interfraction prostate motion during prostate cancer radiotherapy.

Background The dosimetric advantage of prostate-rectum spacers to displace the anterior rectal wall outside of the high-dose radiation regions has been clearly established in prostate cancer radiotherapy (RT). The aim of this study was to assess the impact of hydrogel spacer (HS) in the interfraction prostate motion in patients undergoing RT for prostate cancer. Material and methods Twenty prostate cancer patients implanted with three fiducial markers (FM) with (n = 10) or without (n = 10) HS were analyzed. Displacements between the prostate isocenter based on the FM's position and the bony anatomy were quantified in the left-right (LR), anterior-posterior (AP), superior-inferior (SI) axes by offline analyses of 122 cone beam computed tomography scans. Group systematic (M), systematic (Σ) and random (σ) setup errors were determined. Results In patients with or without HS, the overall mean interfraction prostate displacements were 0.4 versus -0.4 mm (p = 0.0001), 0.6 versus 0.6 mm (p = 0.85), and -0.6 mm versus -0.3 mm (p = 0.48) for the LR, AP, and SI axes, respectively. Prostate displacements >5 mm in the AP and SI directions were similar for both groups. No differences in M, Σ and σ setup errors were observed in the three axes between HS + or HS- patients. Conclusions HS implantation does not significantly influence the interfraction prostate motion in patients treated with RT for prostate cancer. The major expected benefit of HS is a reduction of the high-dose levels to the rectal wall without influence in prostate immobilization.

Whole-breast irradiation with or without a boost for patients treated with breast-conserving surgery for early breast cancer: 20-year follow-up of a randomised phase 3 trial.

BACKGROUND: Since the introduction of breast-conserving treatment, various radiation doses after lumpectomy have been used. In a phase 3 randomised controlled trial, we investigated the effect of a radiation boost of 16 Gy on overall survival, local control, and fibrosis for patients with stage I and II breast cancer who underwent breast-conserving treatment compared with patients who received no boost. Here, we present the 20-year follow-up results. METHODS: Patients with microscopically complete excision for invasive disease followed by whole-breast irradiation of 50 Gy in 5 weeks were centrally randomised (1:1) with a minimisation algorithm to receive 16 Gy boost or no boost, with minimisation for age, menopausal status, presence of extensive ductal carcinoma in situ, clinical tumour size, nodal status, and institution. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was overall survival in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT02295033. FINDINGS: Between May 24, 1989, and June 25, 1996, 2657 patients were randomly assigned to receive no radiation boost and 2661 patients randomly assigned to receive a radiation boost. Median follow-up was 17.2 years (IQR 13.0-19.0). 20-year overall survival was 59.7% (99% CI 56.3-63.0) in the boost group versus 61.1% (57.6-64.3) in the no boost group, hazard ratio (HR) 1.05 (99% CI 0.92-1.19, p=0.323). Ipsilateral breast tumour recurrence was the first treatment failure for 354 patients (13%) in the no boost group versus 237 patients (9%) in the boost group, HR 0.65 (99% CI 0.52-0.81, p<0.0001). The 20-year cumulative incidence of ipsilatelal breast tumour recurrence was 16.4% (99% CI 14.1-18.8) in the no boost group versus 12.0% (9.8-14.4) in the boost group. Mastectomies as first salvage treatment for ipsilateral breast tumour recurrence occurred in 279 (79%) of 354 patients in the no boost group versus 178 (75%) of 237 in the boost group. The cumulative incidence of severe fibrosis at 20 years was 1.8% (99% CI 1.1-2.5) in the no boost group versus 5.2% (99% CI 3.9-6.4) in the boost group (p<0.0001). INTERPRETATION: A radiation boost after whole-breast irradiation has no effect on long-term overall survival, but can improve local control, with the largest absolute benefit in young patients, although it increases the risk of moderate to severe fibrosis. The extra radiation dose can be avoided in most patients older than age 60 years. FUNDING: Fonds Cancer, Belgium.

First imaging results of an intraindividual comparison of (11)C-acetate and (18)F-fluorocholine PET/CT in patients with prostate cancer at early biochemical first or second relapse after prostatectomy or radiotherapy.

PURPOSE: (18)F-Fluorocholine (FCH) and (11)C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers. METHODS: The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤ 3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤ 5 ng/ml) or RP and salvage RT (9 patients, PSA ≤ 5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307 ± 16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994 ± 72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results. RESULTS: PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen's kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later. CONCLUSION: Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging.

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.

Determinants and effects of positive surgical margins after prostatectomy on prostate cancer mortality: a population-based study.

BACKGROUND: The objective of this population-based study was to assess patient, physician and tumour determinants associated with positive surgical margins after prostatectomy, and to assess the effects of positive surgical margins on prostate cancer-specific survival. METHODS: We included 1'254 prostate cancer patients recorded at the Geneva Cancer Registry who had radical prostatectomy during 1990-2008. To assess factors associated with positive margins, we used logistic regression. We assessed the effects of positive margins on prostate cancer-specific survival by Cox proportional hazard models accounting for numerous other prognostics factors including prostate and tumour volume, the total percentage of tumour, radiotherapy, surgical approach and surgeon's caseload. RESULTS: Among men undergoing prostatectomy, 479 (38%) had positive margins. In the multivariate logistic regression analysis, period, clinical- and pathological T stage, Prostate Specific Antigen (PSA) level, Gleason score and percentage of tumour in the prostate were significantly associated to positive margins. Ten-year prostate cancer-specific survival was 96.6% for the negative margins group and 92.0% for the positive margins group (log rank p = 0.008). In the Cox survival analysis adjusted for tumour characteristics, surgical margin status per se was not an independent prognostic factor while age, pathological T, PSA level and Gleason score remained associated with prostate cancer-specific survival. CONCLUSIONS: More aggressive tumour characteristics were strong determinants for positive margins. Furthermore, surgical margin status per se was not an independent prognostic factor for prostate cancer-specific survival after adjusting by the gravity of the disease in the multivariate analysis.

Planning for the future: cancer incidence projections in Switzerland up to 2019.

BACKGROUND: Projections of the national burden of cancer play a key role in planning cancer control programmes and investments. We present projections of cancer incidence rates and cases for the period up to 2015-2019 in Switzerland. METHODS: Projections were based on cancer incidence data estimated from cancer registries for the 1989-2009 periods and demographic projections of the Federal Statistical Office. Age-specific incidence rates were modelled as a function of age, period-birth cohort using NORDPRED. RESULTS: Up to 2019 the incidence of all cancers combined is expected to decrease slightly for both sexes. Nevertheless, the overall number of cases is predicted to increase. The number of male cancer cases will increase by 30%, from 20005 in 2005-2009 to 25910/year in 2015-2019. For females the number will increase by 20%, from 16913 to 20359/year in 2015-2019. Changes in the population size and structure will be responsible for most of the increase. Among men, the largest increase is observed for melanoma (+54%), thyroid (+45%), non-Hodgkin lymphoma (+43%), and prostate (+37%). Prostate cancer will contribute with 8083 cases, colorectal cancer with 2908 and lung cancer with 2791. For women, cases of lung and oral cavity cancers will increase by +48% and +38%, respectively; those of thyroid by +45% and non-Hodgkin lymphoma by +36%. The sites with the most cancer predicted are breast (5870), colorectal and lung (over 2000 each), melanoma (1341) and corpus uteri (1040). The overall annual cancer burden predicted for 2015-19 is of 46269 new cases in Switzerland. CONCLUSIONS: Substantial investments appear to be needed in Switzerland cancer services to meet and fill absolute increased demand driven by aging population.

[Opening of the Geneva University Hospital Prostate Cancer Center]. / Création du Centre du cancer de la prostate des HUG.

In 2014, Geneva University Hospital has opened the first certified prostate cancer Center of western Switzerland. It incorporates 29 entities implicated in the diagnosis and treatment of this disease, thereby assuring that all available ressources are made available to patients, regardless of the division to which they were initially referred. The main strength of the Center lies in the synergy generated by its multidisciplinary tumor board. Furthermore, regular conferences, staff meetings, propectively held registers and the yearly re-certification audit support its constant quality improvement.

Urethra-Sparing Prostate Cancer Stereotactic Body Radiation Therapy: Sexual Function and Radiation Dose to the Penile Bulb, the Crura, and the Internal Pudendal Arteries From a Randomized Phase 2 Trial.

PURPOSE: Erectile dysfunction (ED) is a common side effect after prostate cancer stereotactic body radiation therapy (SBRT). We aimed to assess the correlation between the dose to the penile bulb (PB), internal pudendal arteries (IPA), and crura with the development of ED after ultrahypofractionation as part of a phase 2 clinical trial of urethra-sparing prostate SBRT. METHODS AND MATERIALS: Among the 170 patients with localized prostate cancer from 9 centers included in the trial, 90 men with Common Terminology Criteria for Adverse Events version 4.03 grade 0 to 1 ED (ED-) at baseline treated with 36.25 Gy in 5 fractions were selected for the present analysis. Doses delivered to the PB, crura, and IPA were analyzed and correlated with grade 2 to 3 ED (ED+) development. The effect on quality of life, assessed by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-PR25) questionnaire, was reported. RESULTS: After a median follow-up of 6.5 years, 43% (n = 39) of the patients developed ED+, and 57% (n = 51) remained ED-. The dose delivered to the crura was significantly higher in ED+ patients than in ED- patients (7.7 vs 3.6 Gy [P = .014] for the Dmean and 18.5 vs 7.2 Gy [P = .015] for the D2%, respectively). No statistically significant difference between ED+ and ED- patients was observed for the dose delivered to the PB and IPA. The median ED+-free survival was worse in patients receiving a crura Dmean ≥ 4.7 versus < 4.7 Gy (51.5% vs 71.7%, P = .005) and a crura D2% > 12 versus ≤ 12 Gy (54.9% vs 68.9%, P = .015). No ED+-free survival differences were observed for doses delivered to the PB and IPA. Decline in EORTC QLQ-PR25 sexual functioning was significantly more pronounced in patients with higher doses to the crura. CONCLUSIONS: By keeping a Dmean and D2% to crura below 4.7 and 12 Gy, respectively, the risk of developing ED+ after prostate SBRT may be significantly reduced.

ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial.

PURPOSE: To assess in a prospective, multicenter, single-arm phase I/II study the early safety and efficacy profile of single fraction urethra-sparing stereotactic body radiotherapy (SBRT) for men with localized prostate cancer. MATERIAL AND METHODS: Patients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone were recruited. A single-fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra. Intrafraction motion was monitored using intraprostatic electromagnetic transponders with intra-fraction correction of displacements exceeding 3 mm. Genitourinary (GU), gastrointestinal (GI), and sexual toxicity during the first 18 months were evaluated using the CTCAE v4.0 grading scale. Quality of life was assessed using the International Prostate Symptom Score, the Expanded Prostate Cancer Index composite 26 score, and the International Index of Erectile Function score. RESULTS: Among the 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction without protocol deviations, and 34 had a minimal follow-up of 18 months. The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 (<3% with grade 2), with a 12 % grade 2 flare at month 18. Gl toxicity was mild in the acute phase, with no grade ≥ 2 events (12 % grade 1 at month 6). Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18. Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18. Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24. After a median follow-up time of 26 months, 3 biochemical failures (7 %) were observed at month 17, 21 and 30. CONCLUSIONS: In this multicenter phase I/II trial, we demonstrated that a 19 Gy single-fraction urethra-sparing SBRT is feasible and associated with an acceptable toxicity rate, mostly returning to the baseline at week-12 and with a symptoms flare between months 12 and 18. Longer follow-up is needed to assess the potential long-term adverse effects and the disease control efficacy.

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

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

Importance and determinants of Gleason score undergrading on biopsy sample of prostate cancer in a population-based study.

BACKGROUND: In this population-based study, we investigated the degree of concordance between Gleason scores obtained from prostate biopsies and those obtained from prostatectomy specimens, as well as the determinants of biopsy understaging. METHODS: We considered for this study all 371 prostate cancer patients recorded at the Geneva Cancer Registry diagnosed from 2004 to 2006 who underwent a radical prostatectomy. We used the kappa statistic to evaluate the Gleason score concordance from biopsy and prostatectomy specimens. Logistic regression was used to determine the parameters that predict the undergrading of the Gleason score in prostate biopsies. RESULTS: The kappa statistic between biopsy and prostatectomy Gleason score was 0.42 (p < 0.0001), with 67% of patients exactly matched, and 26% (n = 95) patients with Gleason score underestimated by the biopsy. In a multi-adjusted model, increasing age, advanced clinical stage, having less than ten biopsy cores, and longer delay between the two procedures, were all independently associated with biopsy undergrading. In particular, the proportion of exact match increased to 72% when the patients had ten or more needle biopsy cores. The main limitation of the study is that both biopsy and prostatectomy specimens were examined by different laboratories. CONCLUSIONS: The data show that concordance between biopsy and prostatectomy Gleason scores lies within the classic clinical standards in this population-based study. The number of biopsy cores appears to strongly impact on the concordance between biopsy and radical prostatectomy Gleason score.

Every-Other-Day Versus Once-a-Week Urethra-Sparing Prostate Stereotactic Body Radiation Therapy: 5-Year Results of a Randomized Phase 2 Trial.

PURPOSE: The objective of this study was to present the 5-year results from a prospective, multicenter, phase 2 randomized trial of every-other-day (EOD) versus once-a-week (QW) urethra-sparing stereotactic body radiation therapy for localized prostate cancer. METHODS AND MATERIALS: Between 2012 and 2015, 170 patients with cT1c-3aN0M0 prostate cancer from 9 European institutions were randomized to 36.25 Gy in 5 fractions (6.5 Gy/fraction to the urethra) delivered either EOD (arm A, n = 84) or QW (arm B, n = 86). The median follow-up was 78 months (interquartile range, 66-89 months) and 77 months (interquartile range, 66-82 months) for arms A and B, respectively. RESULTS: Among the 165 patients treated and retained for the final analysis (arm A, n = 82; arm B, n = 83), acute toxicity (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 scale) was mild or absent, with no differences between arms. The 5-year grade 2 or greater genitourinary toxicity-free survival was 75.9% and 76.1% for arms A and B, respectively (P = .945), whereas the 5-year grade 2 or greater gastrointestinal toxicity-free survival was 89% and 92% for arms A and B, respectively (P = .596). No changes in European Organisation for Research and Treatment of Cancer QLQ-PR25 scores were observed in both arms for genitourinary, gastrointestinal, and sexual domains at 5-year follow-up compared with baseline. At the last follow-up, biochemical failure was observed in 14 patients in the EOD arm and in 7 patients in the QW arm, with a 5-year biochemical relapse-free survival rate of 92.2% and 93% for arms A and B, respectively (P = .13). CONCLUSIONS: Stereotactic body radiation therapy for prostate cancer with a 10% dose reduction to urethra was associated with a minimal effect on urinary function and quality of life regardless of an EOD or QW fractionation schedule. Biochemical control so far has been encouraging and much alike in both study arms, although longer follow-up is probably needed to assess the true value of overall treatment time on disease outcome.

Five-Fraction Proton Therapy for the Treatment of Skull Base Chordomas and Chondrosarcomas: Early Results of a Prospective Series and Description of a Clinical Trial.

(1) Background: Our purpose is to describe the design of a phase II clinical trial on 5-fraction proton therapy for chordomas and chondrosarcomas of the skull base and to present early results in terms of local control and clinical tolerance of the first prospective series. (2) Methods: A dose of 37.5 GyRBE in five fractions was proposed for chordomas and 35 GyRBE in five fractions for chondrosarcomas. The established inclusion criteria are age ≥ 18 years, Karnofsky Performance Status ≥ 70%, clinical target volume up to 50 cc, and compliance with dose restrictions to the critical organs. Pencil beam scanning was used for treatment planning, employing four to six beams. (3) Results: A total of 11 patients (6 chordomas and 5 chondrosarcomas) were included. The median follow-up was 12 months (9-15 months) with 100% local control. Acute grade I-II headache (64%), grade I asthenia and alopecia (45%), grade I nausea (27%), and grade I dysphagia (18%) were described. Late toxicity was present in two patients with grade 3 temporal lobe necrosis. (4) Conclusions: Hypofractionated proton therapy is showing encouraging preliminary results. However, to fully assess the efficacy of this therapeutic approach, future trials with adequate sample sizes and extended follow-ups are necessary.

Clinical impact of 18F-choline PET/CT in patients with recurrent prostate cancer.

PURPOSE: To investigate the clinical value of (18)F-fluorocholine PET/CT (CH-PET/CT) in treatment decisions in patients with recurrent prostate cancer (rPCA). METHODS: The study was a retrospective evaluation of 156 patients with rPCA and CH-PET/CT for restaging. Questionnaires for each examination were sent to the referring physicians 14-64 months after examination. Questions included information regarding initial extent of disease, curative first-line treatment, and the treatment plan before and after CH-PET/CT. Additionally, PSA values at diagnosis, after initial treatment, before CH-PET/CT and at the end of follow-up were also obtained from the questionnaires. RESULTS: Mean follow-up was 42 months. The mean Gleason score was 6.9 at initial diagnosis. Initial treatment was: radical prostatectomy in 110 patients, radiotherapy in 39, and combined prostatectomy and radiotherapy in 7. Median PSA values before CH-PET/CT and at the end of follow-up were 3.40 ng/ml and 0.91 ng/ml. PSA levels remained stable, decreased or were below measurable levels in 108 patients. PSA levels increased in 48 patients. In 75 of the 156 patients (48%) the treatment plan was changed due to the CH-PET/CT findings. In 33 patients the therapeutic plan was changed from palliative treatment to treatment with curative intent. In 15 patients treatment was changed from curative to palliative. In 8 patients treatment was changed from curative to another strategy and in 2 patients from one palliative strategy to another. In 17 patients the treatment plan was adapted. CONCLUSION: CH-PET/CT has an important impact on the therapeutic strategy in patients with rPCA and can help to determine an appropriate treatment.

Urinary toxicity after salvage re-irradiation for prostate cancer local failure after definitive radiotherapy: a clinical and dosimetric prognostic factors analysis.

Purpose: Predictors of long-term toxicity after prostate cancer re-irradiation are scarce. In this study, we retrospectively assessed the impact of clinical/dosimetric data on late genitourinary (GU) toxicity on fourteen radio-recurrent prostate cancer patients treated with salvage radiotherapy (RT). Material and methods: To identify dose parameters and clinical factors potentially associated to severe long-term GU toxicity, study population was stratified in two groups according to toxicity, including one low-grade group (grade ≤ 2, n = 6) and one high-grade group (grade ≥ 3, n = 8). Dose prescription at primary and salvage-RT in 2 Gy equivalent dose (EQD2Gy) per fraction, treatment techniques, and clinical factors potentially associated to severe GU toxicity were analyzed. Results: At salvage-RT, the median EQD2Gy α/ß = 3 Gy was significantly higher in the high-toxicity group (85 Gy, range, 71-85 Gy) compared to the low-toxicity group (77 Gy, range, 61-85 Gy) (p = 0.01). All patients treated using salvage-RT with a brachytherapy (BT) boost and with a baseline Framingham risk-score of > 20% (n = 8) developed severe GU toxicity, while none of the remaining patients developed a grade 3 or more GU toxicity (p = 0.0003). V70 > 0 and V75 > 0 of the primary treatment were associated with an increased rate of toxicity. Conclusions: Our analysis shows that the delivery of doses up to 75-80 Gy (EQD2Gy, α/ß = 3 Gy) in salvage-RT can be safe in terms of severe GU toxicity avoidance. Furthermore, concomitant cardiovascular comorbidities seem to increase the risk to develop severe GU toxicity.