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Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk, 0.05; HR no high-risk, 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT. ispartof: JOURNAL OF CLINICAL ONCOLOGY vol:40 issue:29 pages:3377-+ ispartof: location:United States status: published

5025 Background: Prospective reports suggest metastasis directed therapy (MDT) in oligometastatic castration sensitive prostate cancer (omCSPC) is associated with improved treatment outcomes. Here we present long term outcomes of the phase II STOMP and ORIOLE trials and assess the ability of a high-risk (HiRi) mutational signature to provide prognostic and predictive information regarding MDT response. Methods: Patients with omCSPC (< 3 lesions) enrolled on STOMP (n = 62) and ORIOLE (n = 54) randomized to MDT or observation were pooled. The primary endpoint was progression-free survival (PFS) defined as either PSA or radiographic progression, initiation of androgen deprivation, or death. Secondary endpoint was radiographic PFS (rPFS) defined as radiographic progression or death. Both were calculated using the Kaplan-Meier method and stratified by treatment group. Next generation sequencing (NGS) was performed to identify a HiRi mutational signature defined as pathogenic mutations within ATM, BRCA1/2, Rb1, or TP53. Cox proportional hazards regressions were fit to calculate hazard ratios (HR) and assess the prognostic and predictive values of HiRi mutational status. Results: Median follow-up was 52.5 months. Median PFS was prolonged with MDT (11.9 months) compared to observation (5.9 months) with a pooled HR of 0.44 (95% CI, 0.29 – 0.66, p-value < 0.001). MDT was associated with PSA decrease in a majority of patients (84%) as compared to the observation group (41%). On NGS, the incidence of a pathogenic mutation in a HiRi gene was 24.3%. HiRi mutation was prognostic for PFS -- in those without a HiRi mutation median PFS was 11.9 months compared to 5.9 months in those with a HiRi mutation (HR of 1.74, p = 0.06). HiRi mutation was also prognostic for rPFS -- those without a high-risk mutation experienced median rPFS of 22.6 months compared to 10.0 months in those with a high-risk mutation (HR 2.62, p < 0.01). Tumors without a HiRi mutation treated with MDT experienced the longest PFS (13.4 months) while those with a HiRi randomized to observation experienced the shortest PFS (2.8 months). Stratifying by both treatment arms and HiRi status appeared to show a differential benefit to MDT, with those with HiRi mutations experiencing a larger relative magnitude of benefit to treatment: (HiRi mutation: HR of 0.05, p < 0.01; no HiRi mutation: HR of 0.42, p = 0.01; p interaction, 0.12) suggesting a HiRi mutational status can provide information regarding differential response to treatment. Conclusions: Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained benefit to MDT over observation. A HiRi mutational signature appears prognostic for outcomes in omCSPC and those with HiRi might have a relatively larger magnitude of response to MDT. Future studies are needed to optimize patient selection. Clinical trial information: NCT02680587.

Purpose Retrospective studies suggest that metastasis-directed therapy (MDT) for oligorecurrent prostate cancer (PCa) improves progression-free survival. We aimed to assess the benefit of MDT in a randomized phase II trial. Patients and Methods In this multicenter, randomized, phase II study, patients with asymptomatic PCa were eligible if they had had a biochemical recurrence after primary PCa treatment with curative intent, three or fewer extracranial metastatic lesions on choline positron emission tomography–computed tomography, and serum testosterone levels > 50 ng/mL. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions (surgery or stereotactic body radiotherapy). Surveillance was performed with prostate-specific antigen (PSA) follow-up every 3 months, with repeated imaging at PSA progression or clinical suspicion for progression. Random assignment was balanced dynamically on the basis of two factors: PSA doubling time (≤ 3 v > 3 months) and nodal versus non-nodal metastases. The primary end point was androgen deprivation therapy (ADT)–free survival. ADT was started at symptomatic progression, progression to more than three metastases, or local progression of known metastases. Results Between August 2012 and August 2015, 62 patients were enrolled. At a median follow-up time of 3 years (interquartile range, 2.3-3.75 years), the median ADT-free survival was 13 months (80% CI, 12 to 17 months) for the surveillance group and 21 months (80% CI, 14 to 29 months) for the MDT group (hazard ratio, 0.60 [80% CI, 0.40 to 0.90]; log-rank P = .11). Quality of life was similar between arms at baseline and remained comparable at 3-month and 1-year follow-up. Six patients developed grade 1 toxicity in the MDT arm. No grade 2 to 5 toxicity was observed. Conclusion ADT-free survival was longer with MDT than with surveillance alone for oligorecurrent PCa, suggesting that MDT should be explored further in phase III trials.

10 Background: Multiple randomized phase II trials suggest that metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa) improves progression-free survival, but the majority of trials lack longer follow-up. We present the updated 5-year results from the STOMP-trial. Methods: In this multicentre, randomised, phase II study, asymptomatic PCa patients were eligible in case of a biochemical recurrence following primary PCa treatment with curative intent and presenting with up to 3 extracranial on choline PET-CT and a serum testosterone levels > 50 ng/ml. Patients were randomly assigned (1:1) to either surveillance or MDT of all detected lesions. Randomisation was balanced dynamically on two factors: PSA doubling time (≤3 vs. > 3 months) and nodal vs non-nodal metastases. The primary endpoint was androgen deprivation therapy (ADT)-free survival. Castrate resistant prostate cancer-free survival (CRPC) was a secondary endpoint. Tests were performed two-sided; p values less than 0.20 were deemed significant. Results: The 5-year ADT-free survival was 8% for the surveillance group and 34% for the MDT group (Figure 1, hazard ratio 0.57 [80% CI: 0.38-0.84], log-rank p = 0.06). There was no significant difference in effect for the different stratification factors (interaction test). The 5-year CRPC-free survival was 53% for the surveillance group and 76% for the MDT group (hazard ratio 0.62 [80% CI: 0.35−1.09]; log−rank p = 0.27). At a median follow for survival of 5.3 years (IQR 4.3-6.3), the 5-year overall survival was 85%, with 6 out of 14 deaths attributed to prostate cancer. Conclusions: The updated STOMP trial outcomes confirm the earlier reported significant difference in ADT free survival in favor of the MDT group compared to surveillance. Prostate-cancer related mortality is low within the first 5 years of diagnosis of oligorecurrent prostate cancer. Clinical trial information: NCT01558427.

BACKGROUND. In non-castrate prostate cancer (PCa), the prognostic value of the number of metastases on prostate cancer-specific survival (PCSS) is not well studied. METHODS. We retrospectively analyzed the medical records of 1,206 patients, referred for radiotherapy of the prostate (bed) following diagnosis of PCa. Distant metastases (nodal, skeletal, and/or visceral) developed in 121 patients following curative treatment, of which 80 with complete records were not castrated at time of metastasis. The treatment at time of metastases was androgen deprivation therapy (ADT; n ¼22), active surveillance (n ¼10) or metastasis-directed therapy (MDT; n ¼48). Cox-regression analyses were used to examine the influence of different variables on PCSS. RESULTS. The median follow-up from primary PCa treatment was 6.9 years with a median interval from diagnosis to first metastatic event of 4.1 year (range: 0.2–15 years). The primary site of metastases was limited to lymph nodes (48%), bone (39%), and viscera (1%) or a combination (12%). Median PCSS from diagnosis of noncastrate metastases was 6.6 years (95% confidence interval [CI], 5.6–7.7 years). A longer premetastatic PSA doubling time (DT) (hazard ratio [HR] 0.73; 95% CI: 0.57–0.92), a lower number of metastases at first presentation (HR 1.07; 95% CI: 1.02–1.12) and pattern of metastatic spread (HR 3.6; 95% CI: 1.13–11.8 for extensive vs. minimal) were associated with improved PCSS. CONCLUSION. A longer PSA DT, involvement of nodes or axial skeleton and a lower number of metastases are associated with an improved PCSS in non-castrated patients developing metastases. Prostate # 2013 Wiley Periodicals, Inc.

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterized by mucinous peritoneal disease arising from disseminated peritoneal adenomucinosis. Primary treatment involves a combination of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). There is no consensus on the proper treatment of recurrent PMP. In selected patients, repeated cytoreductive surgery with or without HIPEC might improve outcome. However, every repeated debulking procedure becomes less effective with increased morbidity. We present a case of a patient with intestinal obstruction caused by recurrent pseudomyxoma peritonei. We treated the patient with whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy (IMAT) to a total dose of 33 Gy, delivered in 22 daily fractions. The treatment was well tolerated and resulted in resolution of the obstruction for a period of 24 months. To the best of our knowledge, we present the first case report showing the possibility of resolving intestinal obstruction with WAPRT in a patient with recurrent PMP. It is our opinion that WAPRT delivered by IMAT, in analogy with ovarian cancer, should be considered as a palliative treatment option in managing patients with recurrent PMP especially in case of obstruction.

IntroductionSince the addition of chemotherapy to radiotherapy, the survival rates of locally advanced cervical cancer (LACC) have improved but are still disappointing. Therefore, the idea of surgery after chemoradiation in case of LACC or bulky disease was adopted. One of the concerns regarding surgery following chemoradiotherapy is surgery-related morbidity.AimThe objectives of this study were to investigate the feasibility of surgery after advanced radiotherapy techniques such as intensity-modulated arc therapy (IMAT) and to describe the morbidity.MethodsThis was a prospective study of primary inoperable LACC patients primary treated with IMAT, in most cases combined with weekly cisplatin. Then the resectability was reevaluated. If resectable patients were treated with Wertheim type 2 surgery ± pelvic lymphadenectomy (on positron emission tomography–computed tomography indication). If tumor is not resectable, patients were treated with brachytherapy.ResultsSince 2006, 41 consecutive patients were included. After neoadjuvant IMAT, 34 were considered resectable and underwent surgery, whereas 7 proceeded with brachytherapy. The operative mortality rate was nil. There were no major perioperative complications. No ureter, bladder, or bowel injuries occurred. No postoperative urinary/digestive fistulae or stenoses were noted. Eleven patients had postoperatively urinary retention problems. At the time of discharge, 5 patients still needed self-catheterization. All problems resolved within 3 months. In 4 cases, we saw significant lymphoceles. In all patients intended to treat, overall survival and disease-free survival at 3 years were 63% and 74%. In the Wertheim group, overall survival and disease-free survival at 3 years were 81% and 91%.ConclusionsCompleting surgery after chemoradiation therapy (with IMAT) for LACC or bulky disease is feasible, and complication rates are comparable with those of primary surgery for cervical cancer.

Background We investigated whether repeated stereotactic body radiotherapy (SBRT) of oligometastatic disease is able to defer the initiation of palliative androgen deprivation therapy (ADT) in patients with low-volume bone and lymph node metastases. Patients and Methods Patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary end point. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic or in case of a prostate specific antigen elevation above 50 ng/mL in the absence of metastases. Secondary end points were local control, clinical progression-free survival, and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events. Results We treated 24 patients with a median follow-up of 24 months. Ten patients started with ADT resulting in a median ADT-FS of 38 months. The 2-year local control and clinical progression-free survival was 100% and 42%, respectively. Eleven and 3 patients, respectively, required a second and third salvage treatment for metachronous low-volume metastatic disease. No grade 3 toxicity was observed. Conclusion Repeated salvage SBRT is feasible, well tolerated and defers palliative ADT with a median of 38 months in patients with limited bone or lymph node PCa metastases.

To report on toxicity after postoperative intensity-modulated arc therapy (IMAT) for cervical (CC) and endometrial cancer (EC).Twenty-four CC and 41 EC patients were treated with postoperative IMAT. If indicated, para-aortic lymph node irradiation (preventive or when affected, PALN) and/or concomitant cisplatin (40 mg/m(2), weekly) was administered. The prescribed dose for IMAT was 45 Gy (CC, 25 fractions) and 46 Gy (EC, 23 fractions), followed by a brachytherapeutic boost if possible. Radiation-related toxicity was assessed prospectively. The effect of concomitant cisplatin and PALN irradiation was evaluated.Regarding acute toxicity (n = 65), Grade 3 and 2 acute gastrointestinal toxicity was observed in zero and 63% of patients (79% CC, 54% EC), respectively. Grade 3 and 2 acute genitourinary toxicity was observed in 1% and 18% of patients, respectively. Grade 2 (21%) and 3 (12%) hematologic toxicity (n = 41) occurred only in CC patients. Seventeen percent of CC patients and 2% of EC patients experienced Grade 2 fatigue and skin toxicity, respectively. Adding cisplatin led to an increase in Grade2 nausea (57% vs. 9%; p = 0.01), Grade 2 nocturia (24% vs. 4%; p = 0.03), Grade ≥ 2 hematologic toxicity (38% vs. nil, p = 0.003), Grade ≥ 2 leukopenia (33% vs. nil, p = 0.009), and a strong trend toward more fatigue (14% vs. 2%; p = 0.05). Para-aortic lymph node irradiation led to an increase of Grade 2 nocturia (31% vs. 4%, p = 0.008) and a strong trend toward more Grade2 nausea (44% vs. 18%; p = 0.052). Regarding late toxicity (n = 45), no Grade 3 or 4 late toxicity occurred. Grade 2 gastrointestinal toxicity, genitourinary toxicity, and fatigue occurred in 4%, 9%, and 1% of patients. Neither concomitant cisplatin nor PALN irradiation increased late toxicity rates.Postoperative IMAT for EC or CC is associated with low acute and late toxicity. Concomitant chemotherapy and PALN irradiation influences acute but not late toxicity.

Objective To report on the value of magnetic resonance imaging (MRI) and 2-deoxy-2-[18] fluoro-D-glucose positron emission tomography computed tomography (18FDG PET-CT) in predicting resectability and pathological response of primary locally advanced cervical cancer after neoadjuvant intensity-modulated arc therapy (IMAT) with or without cisplatin (C). Methods and Materials Twenty-seven patients with International Federation of Gynecology and Obstetrics stages IB2 to IVA cervical cancer were treated with IMAT-C followed by extrafascial hysterectomy (EH). All patients received MRI and 18FDG PET-CT after IMAT-C. The end points of this study were to: Assess the ability of MRI to predict negative surgical margins (R0). Assess the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MRI in predicting the following situation at the EH specimen: “no residual disease or minimal microscopically visible residual tumor.” Assess the sensitivity, specificity, PPV, and NPV value of 18FDG PET-CT in predicting “no residual viable tumor cells” at the EH specimen. Results An R0 resection was obtained in all patients. None of the EH specimens contained macroscopically visible tumor. In 13 patients, no viable tumor cells were found and only 14 had residual microscopic disease. Twenty-four of 27 MRIs were able to correctly predict R0 resection. A negative MRI was 100% predictive for the end point “R0 resection.” The specificity and NPV of MRI (end point 2) were 74% and 100%, respectively. No sensitivity or PPV could be calculated. The sensitivity, specificity, PPV, and NPV of 18FDG PET-CT were 29%, 62%, 44%, and 44%, respectively (end point 3). Conclusions A negative MRI after IMAT-C predicts 100% correctly for R0 resection. The role of 18FDG PET-CT in predicting viable tumor cells at EH specimen is at least debatable.

The goal of this work was to evaluate the feasibility and outcome of intensity-modulated arc therapy ± cisplatin (IMAT ± C) followed by hysterectomy for locally advanced cervical cancer.A total of 30 patients were included in the study. The primary tumour and PET-positive lymph node(s) received a simultaneous integrated boost. Four weeks after IMAT ± C treatment, response was evaluated. Resection consisted of hysterectomy with or without lymphadenectomy. Tumour response, acute and late radiation toxicity, postoperative morbidity and outcome were evaluated.All hysterectomy specimens were macroscopically tumour-free with negative resection margins; pathological complete response was 40%. In 2 patients, one resected lymph node was positive. There was no excess in postoperative morbidity. Apart from two grade 3 hematologic toxicities, no grade 3 or 4 acute radiation toxicity was observed. No grade 3, 1 grade 4 (4%) intestinal, and 4 grade 3 (14%) urinary late toxicities were observed. The 2-year local and regional control rates were 96% and 100%, respectively. The 2-year distant control rate was 92%. Actuarial 2-year progression free survival rate was 89%. Actuarial 1- and 2-year overall survival rates were 96% and 91%, while 3-year overall survival was 84%.Surgery after IMAT ± C is feasible with low postoperative morbidity and radiation toxicity. Local, regional, distant control and survival rates are promising.

Purpose To retrospectively review our experience with whole abdominopelvic radiotherapy (WAPRT) using intensity-modulated arc therapy in the palliative treatment of chemotherapy-resistant ovarian cancer with bulky peritoneal disease. Methods and Materials Between April 2002 and April 2008, 13 patients were treated with WAPRT using intensity-modulated arc therapy. We prescribed a dose of 33 Gy to be delivered in 22 fractions of 1.5 Gy to the abdomen and pelvis. All patients had International Federation of Gynecology and Obstetrics Stage III or IV ovarian cancer at the initial diagnosis. At referral, the median age was 61 years, and the patients had been heavily pretreated with surgery and chemotherapy. All patients had symptoms from their disease, including gastrointestinal obstruction or subobstruction in 6, minor gastrointestinal symptoms in 2, pain in 4, ascites in 1, and vaginal bleeding in 2. A complete symptom or biochemical response required complete resolution of the patient's symptoms or cancer antigen-125 level. A partial response required ≥50% resolution of these parameters. The actuarial survival was calculated from the start of radiotherapy. Results The median overall survival was 21 weeks, with a 6-month overall survival rate of 45%. The 9 patients who completed treatment obtained a complete symptom response, except for ascites (partial response). The median and mean response duration (all symptoms grouped) was 24 and 37 weeks, respectively. Of the 6 patients presenting with obstruction or subobstruction, 4 obtained a complete symptom response (median duration, 16 weeks). Conclusion WAPRT delivered using intensity-modulated arc therapy offers important palliation in the case of peritoneal metastatic ovarian cancer. WAPRT resolved intestinal obstruction for a substantial period.

A predictive technique in the management of patients with cancer could improve the therapeutic index by allowing better individualization of treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique that can provide anatomical and physiological information on the tumor and its microenvironment. We studied the effect of chemotherapy (gemcitabine), anti-angiogenesis therapy (sunitinib) and radiotherapy on the kinetics of DCE-MRI parameters in a preclinical model of pancreatic cancer using P846, a new low-diffusible contrast agent. Mice underwent DCE-MRI before treatment (MRI1), after 1 week of treatment (MRI2), and after 1 additional week (MRI3). Combined treatment with radiotherapy and sunitinib had a synergistic effect on tumor growth. In radiotherapy/sunitinib-treated mice, a decrease in K(trans) at MRI2 predicted its superior antivascular and antitumor effect at an early time. An increased K(trans) at MRI2, as seen in gemcitabine- and gemcitabine/sunitinib-treated mice, reflects increased permeability for P846 and might predict a smaller therapeutic effect at this early time. This study shows that the kinetics of DCE-MRI parameters depends on the contrast agent used. P846 appears to be a promising low-diffusible agent to monitor therapeutic effects in this preclinical cancer model, but further studies are needed to compare its behavior with Gd-DTPA and macromolecular-weight contrast agents. Sunitinib as a radiosensitizer is promising for future clinical trials in human pancreatic cancer.

Background: Metastases-directed therapy (MDT) with surgery or stereotactic body radiotherapy (SBRT) is emerging as a new treatment option for prostate cancer (PCa) patients with a limited number of metastases (≤3) at recurrence – so called “oligometastases”. One of the goals of this approach is to delay the start of palliative androgen deprivation therapy (ADT), with its negative impact on quality of life. However, the lack of a control group, selection bias and the use of adjuvant androgen deprivation therapy prevent strong conclusions from published studies. The aim of this multicenter randomized phase II trial is to assess the impact of MTD on the start of palliative ADT compared to patients undergoing active surveillance. Methods/Design: Patients with an oligometastatic recurrence, diagnosed on choline PET/CT after local treatment with curative intent, will be randomised in a 1:1 ratio between arm A: active surveillance only and arm B: MTD followed by active surveillance. Patients will be stratified according to the location of metastasis (node vs. bone metastases) and PSA doubling time (≤3 vs. > 3 months). Both surgery and SBRT are allowed as MDT. Active surveillance means 3-monthly PSA testing and re-imaging at PSA progression. The primary endpoint is ADT-free survival. ADT will be started in both arms at time of polymetastatic disease (>3 metastatic lesions), local progression or symptoms. The secondary endpoints include progression-free survival, quality of life, toxicity and prostate-cancer specific survival. Discussion: This is the first randomized phase 2 trial assessing the possibility of deferring palliative ADT with MDT in oligometastatic PCa recurrence. Trial registration: Clinicaltrials.gov identifier: NCT01558427

153 Background: To identify sites and patterns of prostate cancer (PCa) recurrence following primary PCa treatment with 18F-choline PET/CT and estimate the number of patients potentially eligible for metastasis-directed therapy (MDT, defined as patients with up to 3 metastatic lesions). Methods: Between 7/7/2011 and 7/6/2016, 229 patients underwent a 18F-choline PET/CT for a biochemical PCa recurrence for potential inclusion in a randomized phase II-trial (STOMP). The trial randomizes patients with oligorecurrent (Orec) PCa between active surveillance (AS) and MDT. Patients were eligible for the trial in case of biochemical recurrence following primary prostate cancer treatment, up to 3 extracranial metastases and testosterone > 50 ng/ml. Patterns of recurrence were classified as local (prostate or prostate bed), distant (N1, M1a/b/c) or a combination of both. The number of lesions were counted per scan and patients with up to 3 distant lesions with or without a local recurrence were considered as ORec vs > 3 lesions as polyrecurrent (PRec). Results: A total number of 229 patients underwent 277 choline PET-CTs, resulting in 208 patients (91%) with a recurrence and 21 patients (9%) without any detectable recurrence. Twenty-two men (10%) had a local recurrence and 186 men (81%) had a distant recurrence, which was combined with a local recurrence in 17 men. Of the 186 patients, 131 (57%) were considered as ORec and 55 (24%) as PRec at median PSA values of 3.4 and 5.4 ng/ml, respectively (p < 0.003). ORec were categorized as N1: 16%, M1a: 8%, M1b: 13%, M1c: 2% or a combination of sites: 17% (Figure 1). Fifty-eight patients had 1 lesion (25%), 39 2 lesions (17%) and 34 3 lesions (15%). Men with ORec PCa were treated with AS, MDT or palliative ADT in respectively 27%, 27% and 1% of the cases. Sixty-two of ORec men (27%) agreed to be randomized in the STOMP-trial. PRec were categorized as N1: 2%, M1a: 1%, M1b: 3%, M1c: 1% or a combination: 17% (Figure 1). Thirteen patients had 4 lesion (6%), 9 5 lesions (4%) and 33 > 5 lesions (18%) Conclusions: Two out of three PCa recurrences on 18F-choline PET-CT are potentially salvageable with local therapy and/or metastasis-directed therapy. Clinical trial information: NCT01558427.

This work evaluated SU11248 (sunitinib) as a potential therapeutic agent, alone or in combination with the cytotoxic agent gemcitabine or radiotherapy in a murine model of pancreatic cancer. Panc02 cells were injected subcutaneously into HsdOla/MF1 mice (n=222). Treatment was administered during 1 week: sunitinib (SUN), gemcitabine (GEM), radiotherapy (RT), RT+SUN and GEM+SUN. Mice were sacrificed 14 days after treatment. The effect on microvessel density (MVD) was measured by CD31 staining. Apoptosis (sFAS, cleaved caspase-3) and proangiogenic proteins (VEGF, PlGF, EGF) were measured with ELISA and immunohistochemistry. At day 14, tumors in all groups increased significantly despite treatment. Only after RT/SUN treatment tumor growth slowed down, although the accretion was still significant (P=0.033). Highest levels of apoptosis were seen in GEM/SUN, RT/SUN and RT treated mice (respectively P

To report on the planning procedure, quality control, and clinical implementation of intensity-modulated arc therapy (IMAT) delivering a simultaneous integrated boost (SIB) in patients with primary irresectable cervix carcinoma.Six patients underwent PET-CT (positron emission tomography-computed tomography) and MRI (magnetic resonance imaging) before treatment planning. Prescription (25 fractions) was (1) a median dose (D(50)) of 62, 58 and 56 Gy to the primary tumor (GTV_cervix), primary clinical target volume (CTV_cervix) and its planning target volume (PTV_cervix), respectively; (2) a D(50) of 60 Gy to the PET-positive lymph nodes (GTV_nodes); (3) a minimal dose (D(98)) of 45 Gy to the planning target volume of the elective lymph nodes (PTV_nodes). IMAT plans were generated using an anatomy-based exclusion tool with the aid of weight and leaf position optimization. The dosimetric delivery of IMAT was validated preclinically using radiochromic film dosimetry.Five to nine arcs were needed to create valid IMAT plans. Dose constraints on D(50) were not met in two patients (both GTV_cervix: 1 Gy and 3 Gy less). D(98) for PTV_nodes was not met in three patients (1 Gy each). Film dosimetry showed excellent gamma evaluation. There were no treatment interruptions.IMAT allows delivering an SIB to the macroscopic tumor without compromising the dose to the elective lymph nodes or the organs at risk. The clinical implementation is feasible.

In radiotherapy for prostate cancer, the rectum is considered the dose-limiting organ. The incidence of overlap between the sigmoid colon and/or small bowel and the planning target volume (PTV) as well as the dose to sigmoid colon and small bowel were investigated. The CT data of 75 prostate cancer patients were analyzed. The clinical target volume (CTV) consisted of prostate and seminal vesicles. The PTV was defined as a three-dimensional expansion of the CTV with a 10-mm margin in craniocaudal and a 7-mm margin in the other directions. All patients were planned to a mean CTV dose of at least 76 Gy. Minimum CTV dose was set at 70 Gy. Dose inhomogeneity within the CTV was kept between 12% and 17%. Sigmoid colon was defined upward from the level where the rectum turned in a transverse plane. Contrast-filled small bowel was contoured on all slices where it was visible. The presence of sigmoid colon and/or small bowel in close vicinity to or overlapping with the PTV was recorded. For each case, the dose to the sigmoid colon and small bowel was calculated. The PTV was found to overlap with the sigmoid colon in 60% and with the small bowel in 19% of the cases. In these patients, mean maximum dose to the sigmoid colon was 76.2 Gy (5th–95th percentile: 70.0–80.7 Gy). Mean maximum dose to the small bowel was 74.9 Gy (5th–95th percentile: 68.0–80.0 Gy). When systematically investigating the anatomic position of sigmoid colon and small bowel in patients accepted for prostate irradiation, parts of both organs were often observed in close vicinity to the PTV. Apart from the rectum, these organs may be dose-limiting in prostate radiotherapy.

Purpose/objective To report on toxicity, resection rate and outcome after IMAT ± cisplatin for primary irresectable cervical cancer. Material/methods Fourty one patients with Figo IIB-IVA cervix carcinoma were treated with IMAT ± cisplatin pre-operatively. Pre-treatment work-up included clinical examination and imaging (18FDG-PET/CT and MRI). IMAT dose prescription was as follows: 62 Gy and 60 Gy (Dmed) to the primary tumour and PET/CT-positive lymph nodes respectively; 58 Gy and 56 Gy (Dmed) to CTV (uterus, cervix, upper vaginal 1/3 to 1/2 and parametria) and its PTV; minimal dose of 45 Gy to pelvic lymph nodes. IMAT was delivered in 25 fractions, resulting in a SIB. Within 4 weeks after IMAT, tumour resectability was assessed clinically and radiologically. Wertheim-Meigs hysterectomy was performed within 6-8 weeks after end of IMAT. If irresectable, brachytherapy (BT) was performed. Acute toxicity was scored weekly during IMAT and 1 and 3 months thereafter. Late toxicity scoring started ≥ 6 months after ending IMAT and was scored 3 monthly during the first 2 years, and 6 monthly thereafter. Disease control was evaluated clinically (3-monthly) and with imaging (6-monthly). Results 7/41(17%) were inoperable because of progression (2/7), insufficient response (4/7) or reduced general condition (1/7. Pathology revealed complete response in 14/34 (41%). Surgical margins were free of disease in all cases. There was no postoperative mortality and no excess in morbidity. One patient needed a re-intervention due to large lymphocoeles. At 3 years OS and DFS were 81% and 91% respectively in the wertheim group. Non of patients in the brachytherapy group survived 3 years. Conclusion Wertheim surgery following IMAT ± cisplatin is associated with no mortality and acceptable morbidity IMAT has low toxicity and is excellent in rendering irresectable cervical cancer resectable. Disclosure All authors have declared no conflicts of interest.

Purpose: To assess the outcome of prostate cancer (PCa) patients diagnosed with oligometastatic disease at recurrence and treated with stereotactic body radiotherapy (SBRT). Methods: Non-castrate patients with up to 3 synchronous metastases (bone and/or lymph nodes) diagnosed on positron emission tomography - computed tomography, following biochemical recurrence after local curative treatment, were treated with (repeated) SBRT to a dose of 50 Gy in 10 fractions or 30 Gy in 3 fractions. Androgen deprivation therapy-free survival (ADT-FS) defined as the time interval between the first day of SBRT and the initiation of ADT was the primary endpoint. ADT was initiated if more than 3 metastases were detected during follow-up even when patients were still asymptomatic. Secondary endpoints were local control, progression free survival (PFS) and toxicity. Toxicity was scored using the Common Terminology Criteria for Adverse Events. Results: With a median follow-up from time of SBRT of 2 years, we treated 50 patients with 70 metastatic lesions with a local control rate of 100%. The primary involved metastatic sites were lymph nodes (54%), bone (44%), and viscera (2%). The median PFS was 19 mo (95% CI: 13-25 mo) with 75% of recurring patients having

Background and aims To asses the palliative effect of WAPRT using IMAT for patients with chemotherapy-resistant ovarian cancer. Methods Forty-two patients were treated (33Gy; 22 daily fractions). At referral, median [range] age and Karnofsky performance score (KPS) was 59y [31 -76] and 80 [40-90]. Disease-related symptoms were: intestinal (sub)-obstruction (n = 22), minor gastro-intestinal symptoms (n = 2), pain (n = 20), ascites (n = 11), and vaginal bleeding (n = 2). Median [range] CA125 serum level was 421 U/ml [6-13796]. All patients were heavily pre-treated. The actuarial overall survival (OS) and abdominal progression free survival (aPFS) were calculated from the start, response duration from the end of treatment. Results Response rates (completed treatments; n = 30): The median [range] response duration (all symptoms) was 16 weeks [0-139]. For the whole population median [range] OS and aPFS was 4 months [0-32] and 11 weeks [0-142]. For those patients who completed treatment median [range] OS and aPFS was 8 months [2-32] and 17 weeks [4-142]. Patients with a KPS ≥70 ended the treatment significantly more (p Conclusion WAPRT offers important palliation for peritoneal metastasized /platinum resistant ovarian cancer patients. It can resolve intestinal obstruction for a substantial period. Carefull patient selection is mandatory (KPS ≥ 70). Disclosure All authors have declared no conflicts of interest.

14048 Background: This study aimed to determine the role of PET/CT in differentiating pancreatic lesions and changing therapeutic approach. Methods: A retrospective analysis of prospectively collected data of 33 PET/CT scans (Philips, Cleveland, USA) was performed. Scans were made between October 2004 and July 2005 for differentiating primary or recurrent pancreatic disease found on CT, MRI or/and EUS. All PET/CT scans were assessed by a radiologist in co-operation with a nuclearist. Pancreatic lesions were interpreted based on visual assessment and by use of a semi-quantitative evaluation (SUV). These results were correlated with pathological diagnoses or clinical follow-up, dividing patients into 2 groups: ‘positive’ (malignant) versus ‘negative’ (benign disease/no lesion). In each patient therapeutic change after PET/CT was assessed. Results: The patient group consisted of 33 consecutive patients, of whom 14 were female. Median age was 61 years (range 33–76 years). SUV values in malignant lesions were significantly higher than those found in benign lesions [5.77 (95%CI 4.08–7.46) versus 1.76 (95%CI 0.79–2.7), P No significant financial relationships to disclose.

4248 Background: Pancreatic adenocarcinoma carries one of the worst prognoses among all cancers. This study aimed to determine the exact disease free and overall survival data of patients with a pa...