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355 Background: We aimed to develop and to validate a multi-institutional nomogram of outcomes for PSMA-PET based salvage radiotherapy (sRT) following radical prostatectomy (RP) for patients with recurrent or persistent prostate cancer (PCa). Methods: Data from patients with a detectable post-RP prostate-specific antigen (PSA) treated with sRT with or without concurrent androgen-deprivation therapy (ADT) were obtained from 11 academic institutions from 5 countries. All patients had a PSMA-PET scan prior sRT and patients with distant metastases on PET were excluded from this analysis. The freedom from biochemical failure (FFBF) rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse (BR) was defined as PSA nadir +0.2 ng/ml after sRT. Results: Overall, 1029 patients (training set n=821, external validation set n=208) with a median follow-up of 33 months were included. On PSMA-PET, 427 (42%) and 313 (30%) patients had local and nodal recurrences, respectively. Elective pelvic lymphatics were irradiated in 368 (36%) patients. All patients received sRT to the prostatic fossa receiving a dose of 70 Gy in 103 (10%), 551 (54%) and 375 (36%) patients, respectively. Androgen deprivation therapy (ADT) was given in 325 (32%) patients. On multivariable Cox regression analysis, pre-SRT PSA, ISUP grade, pT stage, surgical margins, ADT use, sRT dose and nodal recurrence on PSMA PET were associated with FFBF. The nomogram concordance index was 0.7 for FFBF in external validation. Conclusions: We present an externally validated contemporary nomogram which can estimate individual patient outcomes after PSMA-PET guided sRT. Positive lymph nodes on PSMA-PET seem to be a new risk factor for BR after sRT.

367 Background: Salvage radiotherapy (SRT) alone or in combination with androgen deprivation therapy (ADT) is the only curative treatment option for patients with biochemical recurrence after radical prostatectomy (RP) for prostate cancer. An undetectable post SRT PSA in patients without ADT (8). Our findings indicate that ADT could be withheld in a proportion of patients that are candidates for ADT based on their risk factors but achieve an undetectable PSA after SRT. Prospective studies are needed to confirm these results.

5084 Background: Current management of HRLPC includes long-term ADT with primary RT. Despite definitive primary treatment, these pts have a high risk of metastasis and death. The phase 3 ATLAS study (NCT02531516) is investigating whether treatment intensification with the addition of APA to neoadjuvant and adjuvant treatment with gonadotropin-releasing hormone agonist (GnRHa) and external beam radiation therapy (EBRT) will improve metastasis-free survival (MFS) in high-risk pts. Here we describe (1) the distribution of baseline characteristics in this high-risk pt population and (2) the application of different RT regimens reflecting recent international guidelines and clinical practice changes for pts with HRLPC. Methods: Eligible HRLPC pts (Gleason score [GS] ≥ 8 or 7 and prostate-specific antigen [PSA] ≥ 20 ng/mL and stage ≥ cT2c), with ECOG PS 0/1 and Charlson Comorbidity Index (CCI) ≤ 3 are stratified by GS, pelvic nodal status, use of brachytherapy boost, and region; pts are randomized 1:1 to APA or PBO plus GnRHa for 30 (28-d) treatment cycles. Study treatment is applied neoadjuvant/concurrent to RT with APA 240 mg/d vs bicalutamide 50 mg/d for 4 cycles; another 26 cycles are completed adjuvantly after RT with APA 240 mg/d vs PBO. Primary end point is MFS (time from randomization to first distant metastasis on CT/MRI/bone scan by independent central review blinded to treatment or death from any cause). Imaging is conducted at baseline and q6m from biochemical failure until MFS. The protocol has been amended to include PET imaging (PSMA, fluciclovine, or choline). Results: Pts (N = 1503) were randomized at 266 sites in 24 countries in North America, Latin America, Europe, and Asia. The study is fully enrolled, but ongoing. Baseline characteristics for the total population: median age, 67 yrs; ECOG PS 0/1; 89%/11%; tumor classification at study entry: high-risk, 66%/very high–risk, 34%; median PSA, 6.3 ng/mL; cT2, 44%/cT3, 50%; cN1, 13%. In 90% of ATLAS pts, RT used was standard EBRT to prostate/pelvis over 6-8 weeks (cumulative 78-81 Gy); in 10%, recent hypofractionation schedules (per CHHiP or NRG/RTOG 0415) were applied (20x3 Gy/d or 28x2.5 Gy/d). 5.6% of pts had EBRT combined with brachytherapy (per ASCENDE-RT). Conclusions: Baseline characteristics of the ATLAS study population are reflective of pts with high- and very high–risk features and pelvic nodal involvement undergoing primary RT in clinical practice. The RT schedules applied reflect recent evidence and guideline changes for the use of hypofractionation in this pt population. ATLAS is an example of how RT can be included in phase 3 trials of HRLPC, in combination with next-generation androgen receptor inhibitors (eg, APA). Clinical trial information: NCT02531516.

Purpose Combined-modality treatment consisting of four to six cycles of chemotherapy followed by involved-field radiotherapy (IFRT) is the standard of care for patients with early unfavorable Hodgkin's lymphoma (HL). It is unclear whether treatment results can be improved with more intensive chemotherapy and which radiation dose needs to be applied. Patients and Methods Patients age 16 to 75 years with newly diagnosed early unfavorable HL were randomly assigned in a 2 × 2 factorial design to one of the following treatment arms: four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) + 30 Gy of IFRT; four cycles of ABVD + 20 Gy of IFRT; four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPbaseline) + 30 Gy of IFRT; or four cycles of BEACOPPbaseline + 20 Gy of IFRT. Results With a total of 1,395 patients included, the freedom from treatment failure (FFTF) at 5 years was 85.0%, overall survival was 94.5%, and progression-free survival was 86.0%. BEACOPPbaseline was more effective than ABVD when followed by 20 Gy of IFRT (5-year FFTF difference, 5.7%; 95% CI, 0.1% to 11.3%). However, there was no difference between BEACOPPbaseline and ABVD when followed by 30 Gy of IFRT (5-year FFTF difference, 1.6%; 95% CI, −3.6% to 6.9%). Similar results were observed for the radiotherapy question; after four cycles of BEACOPPbaseline, 20 Gy was not inferior to 30 Gy (5-year FFTF difference, −0.8%; 95% CI, −5.8% to 4.2%), whereas inferiority of 20 Gy cannot be excluded after four cycles of ABVD (5-year FFTF difference, −4.7%; 95% CI, −10.3% to 0.8%). Treatment-related toxicity occurred more often in the arms with more intensive therapy. Conclusion Moderate dose escalation using BEACOPPbaseline did not significantly improve outcome in early unfavorable HL. Four cycles of ABVD should be followed by 30 Gy of IFRT.

Purpose Local failure after radical prostatectomy (RP) is common in patients with cancer extending beyond the capsule. Two randomized trials demonstrated an advantage for adjuvant radiotherapy (RT) compared with a wait-and-see policy. We conducted a randomized, controlled clinical trial to compare RP followed by immediate RT with RP alone for patients with pT3 prostate cancer and an undetectable prostate-specific antigen (PSA) level after RP. Methods After RP, 192 men were randomly assigned to a wait-and-see policy, and 193 men were assigned to immediate postoperative RT. Eligible patients had pT3 pN0 tumors. Patients who did not achieve an undetectable PSA after RP were excluded from treatment according to random assignment (n = 78; 20%). Of the remaining 307 patients, 34 patients on the RT arm did not receive RT and five patients on the wait-and-see arm received RT. Therefore, 114 patients underwent RT and 154 patients were treated with a wait-and-see policy. The primary end point was biochemical progression-free survival. Results Biochemical progression-free survival after 5 years in patients with undetectable PSA after RP was significantly improved in the RT group (72%; 95% CI, 65% to 81%; v 54%, 95% CI, 45% to 63%; hazard ratio = 0.53; 95% CI, 0.37 to 0.79; P = .0015). On univariate analysis, Gleason score more than 6 and less than 7, PSA before RP, tumor stage, and positive surgical margins were predictors of outcome. The rate of grade 3 to 4 late adverse effects was 0.3%. Conclusion Adjuvant RT for pT3 prostate cancer with postoperatively undetectable PSA significantly reduces the risk of biochemical progression. Further follow-up is needed to assess the effect on metastases-free and overall survival.

6028Background: We performed an open label phase 2 trial and investigated the efficacy and toxicity of additional cetuximab during and after adjuvant radiochemotherapy (RCT) in head and neck cancer...

TPS5087Background: At present, high-risk localized and locally advanced prostate cancer (PC) patients receiving primary radiation therapy (RT) and long-term androgen deprivation therapy (ADT; gonad...

e12049 Background: One of the most common complications in breast surgery is seroma formation. The origin of seroma formation remains unclear, but omitting a wound drain in breast surgery has been ...

153 Background: Biochemical recurrence (BCR) after radical prostatectomy (RP) is usually defined at a PSA >0.2 ng/ml. BCR may precede clinical progression by years. Though salvage radiotherapy (SRT) is recommend to be initiated at PSA 0.2 ng/ml) within a median time of 7 months. Subsequent PSA rise to >0.3, >0.4, and >0.6 ng/ml was recorded in 174 (58%), 123 (41%), and 24 (8%) men, respectively. Twenty-four (8%) men developed metastases. In cohort 2, 112 men received SRT at PSA between 0.03 and 0.2 ng/ml, and 86 at 0.2-0.499 ng/ml. The latter group, had a poorer 10-years BCR-free Kaplan-Meier rate, 43% vs. 66% (p=0.051). Together with pT0.1 ng/ml after RP will subsequently progress to PSA >0.2 ng/ml. Improved progression free survival can be achieved, if SRT is administered at a PSA

207 Background: Salvage radiotherapy (SRT) is a curative approach in recurrent prostate cancer after radical prostatectomy. The outcome depends on various parameters. We report the long term results of SRT with special respect to the course of PSA after SRT. Methods: Between 1997 and 2007, 307 patients received SRT with 66.6 (N=240) or 70.2 Gy (N=67) using CT-based 3D planning. The median pre-SRT PSA was 0.297 ng/ml. Post-SRT progression was defined as either PSA rising >0.2 ng/ml above nadir, or hormone treatment, or clinical recurrence. Data were analyzed with the Kaplan-Meier method (Logrank-test) and with multivariate Cox regression. Results: Patients were followed up for median 7.2 (max. 14.4) years. Recurrence occurred in median 9.4 months post-RP. In 112 patients, SRT was administered before their PSA reached 0.2 ng/ml, 195 men were above that threshold. After SRT, 222 patients achieved a PSA nadir

32 Background: In the ARO 96-02 trial, patients with pT3 prostate cancer were randomly assigned before achieving an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP) to receive a wait and see policy (arm A) or adjuvant radiotherapy (RT) (arm B). If the undetectable PSA level was not achieved, patients were excluded by protocol and received RT with 66 Gy (arm C). Methods: Three hundred eighty eight patients with pT3-4 pN0 prostate cancer with positive or negative surgical margins were recruited; 78 retained a detectable PSA (median 0.6 ng/mL, range 0.05-5.6 ng/mL) after RP; 74 of them were irradiated with 66 Gy to the prostatic fossa. Radiotherapy was applied in median 86 days post-RP. Results: Compared to patients in arm A and B, the patients with persisting PSA after RP had higher preoperative PSA values (p

e15199^ Background: The current approach in patients with high-risk localised or locally advanced PCa is ADT prior to radiotherapy, which improves disease-specific and overall survival vs radiotherapy alone. Whether degarelix, a GnRH antagonist performs comparably with the use of GnRH agonist under flare protection in neoadjuvant settings has not yet been investigated. Methods: Patients with intermediate to high risk PCa were randomised (3:1) to receive either degarelix or goserelin plus bicalutamide (G+B) for 12 wks. The primary endpoint was the percentage reduction from baseline in prostate volume at wk 12 as measured by TRUS. The non-inferiority margin was -10%. Other endpoints included changes in the IPSS, testosterone and PSA. Results: 177 in the degarelix and 62 patients in the G+B arm have completed the trial. 62% and 38% of the patients had localised and locally advanced PCa, respectively. The primary endpoint was successfully met establishing noninferiority between the two treatments in terms of prostate volume reduction at wk 12 (Table). Conclusions: Degarelix was equally effective as prostate shrinking neoadjuvant hormone therapy in patients with intermediate to high risk PCa, but elicited more pronounced LUTS relief compared with G+B after 12 wks of treatment. Possible explanations may involve more pronounced effects on the tumour per se or differences in the action of these drugs on peripheral GnRH receptors expressed in the prostate and the urinary bladder. [Table: see text]

e16033 Background: The prognosis for HNC patients (pts) after surgical treatment and adjuvant chemoradiation (CRT) is unsatisfactory in case of close resection margin 2 d1-d5 + d29-33) were given concurrently to postoperative RT using an integrated boost IMRT-technique (1.8/2.0/2.2Gy QD) to a total dose of 61.6 Gy. CTX started 7 days prior CRT with a loading dose of 400 mg/m2 followed by weekly CTX (250 mg/m2) during CRT. Maintenance CTX started after completion of CRT plus CTX with 500 mg/m² every 2 weeks over a 6-month period. Results: 55 of 80 planned pts (46 male, 9 female, mean age 55.6, range 29-70 years) have finished CRT, 50 are evaluable for toxicity. Concurrent CRT plus CTX was associated with grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reaction outside the radiation portals in 46%, 28%, and 14% of pts, respectively. One toxic death occurred (peritonitis at day 57). CTX was terminated in 10% of all pts (allergic reactions) after the first application. In 22% of all pts CTX was discontinued during the last 2 weeks or at the end of CRT. Of those pts embarking on maintenance therapy, 80% were still on CTX after 3 and 63% after 5 months. 48% completed 6 months maintenance therapy. Conclusions: Adjuvant CRT in combination with CTX followed by maintenance CTX is feasible with toxicity in the expected range. Compliance to maintenance CTX was satisfactory during the first 3-5 months.

612 Background: The influence of consensus recommendations and guidelines for local-regional therapy of early breast cancer on survival of patients is still not clear. We therefore sought to explore whether adherence to evidence based practice guidelines can improve outcome of the disease. Methods: The study population includes 2,680 patients who received primary therapy for early breast cancer at the University of Ulm Medical School. Patients were categorized according to guideline adherence and the influence on survival was calculated by Cox proportional hazard analyses. Model adjustments include prognostic factors, type of treatment, age, and co-existing morbidity. Results: Overtreatment with mastectomy (ME) and non-undertreatment with ME were associated with increased risk of death (hazard ratio [HR] =2.00, 95% confidence interval (CI) 1.47–2.71, HR=1.46, CI 1.12 - 1.92, respectively); however, a non-significant increase in risk was calculated after model adjustment for postoperative irradiation. Over...

5161 Background: Salvage radiotherapy (SRT) is used to treat patients with biochemical failure after radical prostatectomy. A biochemical response in about 65% of patients was demonstrated, but a s...

5060 Background: Adjuvant RT for pT3 R1 or R0 patients (pts.) after RP remains controversial. Results of an EORTC-phase-III- study (with unknown PSA-status after RP) suggested a 20% better biochemical control (bNED) after 5 years for RT. Methods: 385 men with prostate cancer were randomized to either 60 Gy RT (arm A; n=193) or WS (arm B; n=192) before achieving an undetectable PSA. Pts. were stratified for Gleason-score, margin status, neoadjuvant hormonal treatment and stage (pT3A+B vs. C). When the undetectable PSA-level after RP was not achieved, the pts. were stated as progressive disease and left arm A/B and were irradiated. PSA-progression for pts. with undetectable PSA was stated after two consecutive increasing PSA out of the undetectable range. Primary endpoint was bNED. Study was powered to demonstrate a 15% increase in bNED for RT. Results: 78 pts. (20%) did not achieve an undetectable PSA and were stated as progressive disease (arm A: 45 pts., arm B: 33 pts.). Additionally, 34 pts. (23%) from the RT-arm did not receive RT. Therefore, 114 pts. had RT (arm A) and 159 pts. WS (arm B). Median follow up was 53.6 months for arm A and 53.7 months for arm B. BNED at 5 years increased to 72% for arm A (RT) compared with 54% for arm B (WS) (p=0.0015, hazard ratio 0.53). Pts. with a preop. PSA > 10 ng/ml, tumor stage =pT3b, Gleason score =8 as well as positive margins profited significantly from adjuvant RT. The rate of late grade II side effects for the rectum was 1%. Conclusions: Adjuvant radiotherapy for pT3 prostate cancer significantly reduces the risk of biochemical progression after radical prostatectomy. The rate of side effects is very low. No significant financial relationships to disclose.

14556 Background: In pts with PC and biochemical relapse after RP SR is well established. However, the significance of pre-radiotherapeutic variables for guidance of treatment decisions is less clear. We analyzed prognostic factors in a large cohort of pts treated with SR after RP. Methods: 163 pts with PC and persisting PSA-levels (n = 60) or PSA-elevation following undetectable PSA-levels (n = 103) after RP received three-dimensional conformal radiotherapy (RT). None received androgen depriving therapy between prostatectomy and start of RT. We evaluated the impact of age, stage, surgical margin status (SMS), Gleason score and PSA-kinetics by survival and regression analysis. Biochemical progression (BP) was defined as PSA-increases at 3 consecutive time points after the post RT nadir. To detect thresholds for significant prognostic variables, we calculated receiver operating characteristic (ROC) curves. Results: Medians for pre-RT variables were: 11.97 ng/ml for pre-prostatectomy PSA (Pre-OP PSA), 5.4 months for PSA doubling time (PSADT) and 0.339 ng/ml for pre-radiotherapy PSA (Pre-RT PSA). Probability for a projected 4-year PFS was 50% (median follow-up: 33.5 months). Logistic regression revealed a significant impact on the probability of BP for Pre-OP PSA (p = 0.036), PSADT (p = 0.024) and tumor-stage (p = 0.043), whereas Pre-RT PSA and SMS had a significant impact on achievement of undetectable post-RT PSA (p = 0.009 and p = 0.028 respectively). Analysis of ROC-curves for Pre-OP PSA, Pre-RT PSA, PSADT revealed an area under the curve not exceeding 0.704 for any of these parameters. Conclusions: By analyzing ROC-curves we could not detect clear thresholds for PSA kinetic variables. In accordance with recently published data we found similar independent significant variables predicting a therapeutic success. However, we observed a lower median Pre-RT PSA and a higher probability of PFS in our patient cohort. This suggests, that early radiotherapeutic intervention improves PFS. No significant financial relationships to disclose.

9573 Background: Radiotherapy (RT) can induce the expression of P-glycoprotein (gene product of the multidrug resistance [MDR] gene 1), which can lead to a broad cytostatic drug resistance. The kin...

4756 Background: Locally confined prostate cancer can be treated by various treatment options (radical prostatectomy [RP] or radiotherapy [RT]) with comparable results but different possible side e...

2136 Background: Radiotherapy (RT) can induce the expression of P-glycoprotein (P-gp, gene product of the multidrug resistance [MDR] gene 1), which can lead to a broad cytostatic drug resistance. K...