Assessing ISUP prostate cancer grade groups in patients treated with definitive dose escalated external beam radiation.

PURPOSE: The five grade group system has been validated for men treated with radical prostatectomy. However, the prognostic value for men treated with radiation therapy is uncertain, with prior studies utilising old techniques and doses. We aimed to validate the International Society of Urological Pathology (ISUP) groupings for men treated with contemporary radiation therapy. METHODS: Men with localised prostate cancer treated with image-guided, dose-escalated (≥78 Gy) external beam radiation were identified across four institutions. Primary outcome was time to biochemical failure. Harrell's C index assessed performance of the ISUP system against other grading stratifications. RESULTS: 2205 men were included, withmedian follow-up of 5.6 years. Seven-year actuarial rates of biochemical failure for grade groups 1-5 were 9.3%, 10.4%, 13.2%, 12.4% and 23.4%. On multivariate analysis, hazard ratios for biochemical failure were1.19, 1.00, 1.10, 1.05 and 2.10 for grade groups 1-5, relative to 2. P values were only significant for grade group 5. Harrell's C index favoured an alternative three group model (comprising Gleason scores [6 and 3 + 4 = 7] vs [4 + 3 = 7 and 8] vs [9 and 10]) over ISUP grade groups. CONCLUSIONS: The ISUP grade groups were not validated in a contemporary cohort treated with dose-escalated, image-guided radiation therapy. Grade groups 1-4 were not statistically different from each other; however, grade group 5 had a significantly worse prognosis. We identified a new three group model that better predicted biochemical outcomes. Further work is requiredto validate optimal groupings for modern radiation therapy and investigate the contrasting prognostic capability of grade groups in surgical and radiation therapy patients.

The role of large volume re-irradiation with Bevacizumab in chemorefractory high grade glioma.

BACKGROUND AND PURPOSE: Current practice in re-irradiation (reRT) of previously treated high-grade gliomas (HGG) has generally been limited to small volume reRT with stereotactic procedures. Less evidence exists for large volume reRT involving treatment volumes equivalent to that used at initial diagnosis. The primary aim of this study was to investigate the outcome of large volume reRT delivered in combination with Bevacizumab (BEV) in patients with recurrent chemorefractory HGG. METHODS AND MATERIALS: Patients with HGG managed with reRT were entered prospectively into a database. Clinicopathological features were recorded including timing of reRT, use of BEV and Dosimetric data. Median survival following reRT was the primary endpoint and association with clinicopathological factors was assessed with cox regression models. RESULTS: Sixty seven patients in total were managed with reRT, 51 patients had glioblastoma and 16 had anaplastic glioma. The median PTV was 145.3 cm3. Median OS post reRT was 7.8 months (95% CI 6.3-9.2 months) in the total cohort and 7.5 months (95% CI: 6.6-8.3 months) for GBM patients. In multivariate analysis of the whole cohort, IDH1 mutation status (p = 0.041) and ECOG status prior to reRT (<0.001) were significantly associated with OS. In terms of safety and toxicity, the majority of patients (66.5%) were ECOG 0-2 three months after treatment. In total, four episodes of suspected radiation necrosis occurred, all in patients treated without upfront BEV. CONCLUSION: Large volume reRT with bevacizumab is a feasible late salvage option in patients with recurrent HGG and offers meaningful prolongation of survival with low toxicity.

Results of a Prospective Dose Escalation Study of Linear Accelerator-Based Virtual Brachytherapy (BOOSTER) for Prostate Cancer; Virtual HDR Brachytherapy for Prostate Cancer.

PURPOSE: To demonstrate feasibility and toxicity of linear accelerator-based stereotactic radiation therapy boost (SBRT) for prostate cancer, mimicking a high-dose-rate brachytherapy boost. METHODS AND MATERIALS: A phase 1 sequential dose escalation study of SBRT compared 20 Gy, 22 Gy, and 24 Gy to the prostate and 25 Gy, 27.5 Gy, and 30 Gy to the gross tumor volume in 2 fractions, combined with 46 Gy in 23 fractions of external beam radiation. Feasibility of dose escalation (volume receiving 125% and 150% of the dose) while meeting organ-at-risk dose constraints, grade 2 acute and late gastrointestinal and genitourinary toxicity, and freedom from biochemical failure were secondary endpoints. RESULTS: Thirty-six men with intermediate- and high-risk prostate cancer were enrolled with a median follow-up of 24 months. Sixty-four percent of patients had high-risk features. Nine men were enrolled to dose level 1, 6 to level 2, and 6 to level 3. Another 15 patients were treated at dose level 3 on the continuation study. Dose level 3 achieved superior 125% (23.75 Gy) and 150% (28.5 Gy) dose compared to dose levels 1 and 2, with minimal differences in organ-at-risk doses. Kaplan-Meier estimate of freedom from biochemical failure at 3 years was 93.3%. There were no late grade 2 or 3 gastrointestinal events. The late grade 2 genitourinary toxicity at 2 years was 19.3%. Prostate-specific membrane antigen positron emission tomography was performed at 2 years with no local recurrences. CONCLUSIONS: We have shown that a linear accelerator-based SBRT boost for prostate cancer is feasible and can achieve doses comparable to high-dose-rate boost up to the 150% isodose volumes. Rectal, bladder, and urethral doses remained low, and long-term toxicity was the same as or better than previous reports from high-dose-rate or low-dose-rate boost protocols.

Focal radiation therapy for limited brain metastases is associated with high rates of local control and low subsequent whole brain radiation therapy.

BACKGROUND: Assess clinical outcomes of focal radiotherapy (RT) in patients with limited brain metastasis (LBM) with whole brain RT (WBRT) avoidance. METHODS: Patients diagnosed with LBM were entered into a database between January 2010 and February 2017. Patients were recommended WBRT avoidance with focal therapy and three-monthly magnetic resonance imaging. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, initial-site failure (ISF), distant brain relapse (DBF), leptomeningeal disease and rate of WBRT. Analysis involved Kaplan-Meier survival estimate with log-rank tests and Cox-regression analysis. RESULTS: One hundred and sixty-six patients were managed with median follow-up of 13 months and median overall survival of 15 months (95% confidence interval (CI) 10.8-19.2). Eighty-three patients had central nervous system (CNS) relapse with median progression-free survival of 11 months (95% CI 6.7-15.3), of which most failures were DBF (83.1%) with 27 ISF (32.5%). Of the ISFs, 12 (43%) had surgery alone, six had chemotherapy alone and nine received RT. Surgery or chemotherapy alone compared with RT had a significantly higher incidence of ISF with a hazard ratio of 4.96 (P < 0.0001, 95% CI 2.10-11.83) and 6.54 (P = 0.001, 95% CI 2.26-18.87), respectively. WBRT was utilized in only 24 patients, with 83% patients free of WBRT at 12 months. On univariate analysis, number of metastases (P = 0.04), symptomatic extracranial disease (P = 0.04) and early CNS relapse within 6 months (P < 0.01) had worse survival. No grade 3-4 toxicity events were noted in 129 patients undergoing RT. CONCLUSION: Focal RT has a low rate of ISF with low toxicity in patients with LBMs. CNS progression was mainly DBF with low rates of salvage WBRT.

Delineating biochemical failure with 68Ga-PSMA-PET following definitive external beam radiation treatment for prostate cancer.

BACKGROUND AND PURPOSE: We investigated the role of 68Ga-PSMA-PET (PSMA) to determine the location of disease recurrence in those with a rising PSA following definitive external beam radiation treatment (EBRT). MATERIALS AND METHODS: 538men were treated with image guided EBRT to a dose of 78 or 82Gy between 2007 and 2014. Patients at least 24months post EBRT with biochemical failure (nadir+2) underwent PSMA scanning. Local recurrence (LR) was defined as increased uptake within the prostate or seminal vesicles. Distant disease included lymph node (LN), bone or visceral metastases. RESULTS: 419men formed the study cohort. Median follow-up was 50months, 70 patients (17%) had biochemical failure (BF), 13 of whom have died. Of the 57 survivors, 5 had metastases detected on conventional scans; 2 were lost to follow up. 48men (of 50 candidates) underwent PSMA; in all cases, the PSMA was unequivocally positive. Of the 48 positive scans, 25 patients (52%) failed beyond the prostate - 5 in bones, 16LN, 3 in both, and 1 in the lungs. Fifteen men (31%) failed within the gland and in either LN (11), bones (3), or both (1). Eight (17%) had an isolated LR, which represents 2% of patients managed with definitive EBRT and followed for at least 2years. CONCLUSIONS: PSMA was positive in all patients with BF. Site of failure following dose-escalated EBRT was generally distant. Isolated LR (on PSMA) occurred in only 8 of 419 patients post-EBRT.

Benchmarking clinical practice quality: an audit of ipsilateral breast tumor recurrence in patients managed for T1/T2 breast carcinoma.

AIM: Breast conserving surgery and adjuvant radiotherapy has equivalent oncological outcomes to mastectomy and is the standard of care for treatment of early-stage invasive breast cancer. Auditing is an essential component of ongoing quality assurance and clinical governance. It also serves to identify patient and tumor factors that have prognostic and therapeutic implications. The aim of this paper is to report on the clinical audit of treatment outcomes for patients undergoing adjuvant radiation treatment for early breast cancer at the Northern Sydney Cancer Care Centre. METHODS: A total of 1252 patients with T1/2 breast cancer received adjuvant radiation treatment between January 2003 and December 2010. Medical records, including the departmental database, were reviewed to extract pathological, treatment, patient and clinical details. RESULTS: Median follow-up was 54 months (mean 56.4 months). Sixty-six (5.27%) patients died from breast cancer, and 27 (2.16%) patients died from other disease. Twenty-three (1.84%) patients were alive with metastatic disease, 7 (0.56%) patients were alive following ipsilateral breast tumor recurrence and 7 (0.56%) patients were alive with nodal recurrence. 9 (0.72%) patients were alive with contralateral breast cancer. Documented rates of late toxicity were low: 6.8% of patients had grade 1 late toxicity and 1.6% of patients had grade 2-3 late toxicity. CONCLUSION: Our ipsilateral breast tumor recurrence rate of 0.56% is well within international standards, as is our toxicity rate. We propose that centralized data collection be implemented on a nation-wide level for breast cancer patients undergoing radiotherapy. Further research is planned to identify potential markers of radio-resistance, and allow tailoring of treatment technique to optimize oncological outcome.