Citations

TPS389 Background: Recent data have shown that up to 25% of patients with advanced prostate cancer, including mCRPC, have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM, or another homologous recombination DNA repair gene. Such mutations can be used as a molecular marker to select patients for targeted treatment with poly(ADP-ribose) polymerase inhibitors (PARPis), which are lethal to cells with HRD. Treatment with PARPis has shown preliminary evidence of antitumor activity in patients with mCRPC and a mutation in a homologous recombination DNA repair gene (Mateo et al. N Engl J Med. 2015;373:1697-708). These data provide a compelling rationale for evaluating rucaparib, a potent inhibitor of PARP1, PARP2, and PARP3, in patients with mCRPC associated with HRD. Methods: TRITON3 (NCT02975934) is a randomized, phase 3 study evaluating rucaparib 600 mg BID vs physician’s choice of abiraterone, enzalutamide, or docetaxel in patients with mCRPC and a deleterious germline or somatic BRCA1, BRCA2, or ATM mutation (identified by prior local testing or central testing during screening). Patients must have progressed on androgen receptor signaling–directed therapy in the mCRPC setting; prior PARPi treatment or chemotherapy for mCRPC are exclusion criteria. Patients will be randomly assigned in a 2:1 ratio to either rucaparib or physician’s choice, with the possibility for cross over from the comparator treatment to rucaparib upon radiographic progression confirmed by independent radiology review. The primary endpoint is radiographic progression-free survival (modified RECIST v1.1/PCWG3 criteria) assessed by independent radiology review. Secondary endpoints include objective response rate, duration of response, patient-reported outcomes, overall survival, and safety. Pretreatment blood samples collected from all patients will enable development of a noninvasive plasma-based companion diagnostic to select patients who may benefit from rucaparib treatment. Patients (≈400) will be enrolled at > 100 sites worldwide. Clinical trial information: NCT02975934.

TPS388 Background: Up to 25% of patients with advanced prostate cancer, including mCRPC, have a deleterious germline or somatic mutation in BRCA1, BRCA2, ATM or another homologous recombination (HR) DNA repair gene that can serve as a molecular marker to select those who may respond to poly(ADP-ribose) polymerase inhibitors (PARPis). PARPis are lethal to cells with HRD, and PARPi treatment has shown preliminary evidence of an antitumor effect in patients with mCRPC who harbor a mutation in an HR DNA repair gene (Mateo et al. N Engl J Med. 2015;373:1697-708). These data provide a compelling rationale for evaluating rucaparib, a potent PARP1, PARP2 and PARP3 inhibitor, in patients with mCRPC associated with HRD. Methods: TRITON2 (NCT02952534) is a phase 2 study evaluating rucaparib 600 mg BID in patients with mCRPC. Patients with a deleterious germline or somatic BRCA1, BRCA2 or ATM mutation (per prior local test or central test during screening) will be enrolled into 1 of 2 cohorts based on the presence or absence of measurable visceral and/or nodal disease. An exploratory cohort will enroll patients with an alteration in any of 12 other prespecified HR genes (eg, RAD51C, RAD51D and PALB2), with or without measurable visceral and/or nodal disease. Patients must have progressed on androgen receptor signaling–directed therapy and 1 prior taxane-based chemotherapy for mCRPC. Patients who received prior treatment with a PARPi, mitoxantrone, cyclophosphamide or platinum-based chemotherapy are excluded. The primary endpoint is objective response rate measured using modified RECIST v1.1/PCWG3 for patients with soft-tissue disease and prostate-specific antigen response for patients with nonmeasurable disease. Secondary endpoints include duration of response, radiographic progression-free survival, overall survival, clinical benefit rate and safety. Pretreatment blood samples collected from all patients will enable development of a plasma-based companion diagnostic to select patients who may benefit from rucaparib treatment. Patients (≈160) will be enrolled at > 100 sites worldwide. Clinical trial information: NCT02952534.

147 Background: Prostate cancer patients treated with external beam radiation therapy are instructed to present daily with a full bladder to decrease small bowel and bladder toxicity and to increase reproducibility of treatment. However, older patients may have difficulty presenting with full bladders and variation of bladder volume with treatment is unknown. The objective of this study was to assess bladder filling at the time of radiation treatment (RT) using a bladder ultrasound in patients undergoing treatment for prostate cancer. Methods: Patients with prostate cancer were prospectively enrolled prior to CT simulation from January to August 2017. Bladder volume was recorded during CT simulation and daily immediately prior to RT. Patients were instructed to drink 8-12 ounces of water 30-60 minutes prior to RT. Three bladder volume measurements were recorded daily and averaged at the time of each treatment. Average bladder volume during treatment and the number of treatments with low bladder volumes ( < 50cc, < 60cc, and < 100cc) were reported using descriptive statistics. Results: A total of 13 patients completed a median of 42 days of RT during the study period, resulting in 550 daily bladder volumes. Ten patients were treated definitively and 3 with salvage radiation after prostatectomy. The median age of patients in the study was 72 years. Older patients were statistically more likely to present with low bladder volumes, with percentage of treatments with a bladder volume less than 50cc, 60cc, and 100cc being 29%, 42%, and 66% compared to only 4%, 7%, and 18% in patients aged < 70 (P < 0.01). The average bladder volume at the time of CT simulation was 176cc ± 57cc and the average volume during treatment was 140cc± 93cc, which was not statistically different (P = 0.28). The bladder volume did not significantly change over the course of treatment. Conclusions: Older patients (age 70+) with prostate cancer were more likely to present for RT with low bladder volumes in this prospective study. Our findings suggest that older patients should receive extra counseling about bladder filling and/or may require less bladder filling at the time of CT simulation to provide more accurate bowel dosimetry measurements.

AbstractHepatocellular carcinoma (HCC) is the most prevalent primary tumor of the liver, and is steadily becoming one of the most lethal cancers worldwide. Liver resection, which is the recommended procedure for early localized HCC, results in frequent recurrence (50–70%), while the standard of care for late-stage HCC, multikinase inhibitors, only improves survival by a few months. The lack of success for these treatment modalities is attributable, at least in part, to marked phenotypic heterogeneity within the tumor. Intratumoral heterogeneity (ITH) has emerged as a defining characteristic of human tumors, with individual cancer cells displaying distinct differences in properties including growth rate, metastatic capacity, and response to treatment. This heterogeneity, which is unlikely to be captured from a biopsy, impacts outcome because a single treatment targeting one cancer-specific pathway would spare tumor cells having distinct characteristics. Development of effective biomarkers remains a major challenge for similar reasons. Understanding, interpreting, and circumventing the impact of ITH is therefore paramount for developing reliable biomarkers and designing effective individualized treatment strategies for HCC.

BackgroundWith radiotherapy having entered the era of image guidance, or image‐guided radiation therapy (IGRT), imaging procedures are routinely performed for patient positioning and target localization. The imaging dose delivered may result in excessive dose to sensitive organs and potentially increase the chance of secondary cancers and, therefore, needs to be managed.AimsThis task group was charged with: a) providing an overview on imaging dose, including megavoltage electronic portal imaging (MV EPI), kilovoltage digital radiography (kV DR), Tomotherapy MV‐CT, megavoltage cone‐beam CT (MV‐CBCT) and kilovoltage cone‐beam CT (kV‐CBCT), and b) providing general guidelines for commissioning dose calculation methods and managing imaging dose to patients.Materials & MethodsWe briefly review the dose to radiotherapy (RT) patients resulting from different image guidance procedures and list typical organ doses resulting from MV and kV image acquisition procedures.ResultsWe provide recommendations for managing the imaging dose, including different methods for its calculation, and techniques for reducing it. The recommended threshold beyond which imaging dose should be considered in the treatment planning process is 5% of the therapeutic target dose.DiscussionAlthough the imaging dose resulting from current kV acquisition procedures is generally below this threshold, the ALARA principle should always be applied in practice. Medical physicists should make radiation oncologists aware of the imaging doses delivered to patients under their care.ConclusionBalancing ALARA with the requirement for effective target localization requires that imaging dose be managed based on the consideration of weighing risks and benefits to the patient.

Background and aim Thoracic radiation therapy (XRT) for cancer is associated with the development of significant coronary artery disease that may require coronary artery bypass grafting surgery (CABG). Contemporary acute surgical outcomes and long-term postoperative survival of patients with prior XRT have not been well characterised. Methods This was a retrospective, single-centre study of patients with a history of thoracic XRT who required CABG and who were propensity matched against 141 controls who underwent CABG over the same time period. The objectives were to assess early CABG outcomes and long-term survival in patients with prior XRT. Results Thirty-eight patients with a history of previous thoracic XRT underwent CABG from 1994 to 2013. The median time from XRT exposure to surgery was 7.9 years (IQR: 2.5–18.4 years). Perioperative adverse events were similar in the XRT group and controls; however, there was a trends lower utilisation of internal mammary artery (IMA) grafts in the XRT group (89%vs98%, P=0.13). After a median postoperative follow-up of 5.4 years (IQR 0.9–9.4 years), no difference in long-term all-cause mortality was observed. Conclusion Patients with prior thoracic XRT who undergo CABG have similar long-term all-cause mortality compared with controls. Isolated CABG after thoracic XRT is not associated with higher perioperative complications, but IMA graft use may be limited by prior XRT.