A novel case of hereditary leiomyomatosis- associated renal cell carcinoma with metastasis to pituitary gland.

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare genetic disorder characterised by a germline mutation of the fumarate hydratase (FH) gene, in which affected individuals have a high likelihood of developing cutaneous leiomyomas, uterine leiomyomas and renal cell cancer (RCC). HLRCC-associated RCC is characterised by presentation at a younger age than the sporadic form, its aggressive nature and rapid metastatic potential. We present the case of a 50 year old woman with FH mutation, a history of early onset symptomatic uterine leiomyomas, and RCC with the first reported case of an isolated metastasis to the pituitary gland.

Optimal management in optic nerve sheath meningioma - A multicentre study and pooled data analysis.

Optic nerve sheath meningiomas (ONSMs) are rare, benign neoplasms of the anterior visual pathway. The optimal modality of radiotherapy for treatment has not yet been established. This is the first study to show significant difference in visual outcomes between radiotherapy subtypes in the management of ONSM. We performed a retrospective analysis of visual outcomes and side effects in ONSM patients treated with radiotherapy at three centres in Sydney, Australia, between 2000 and 2016. 15 patients with ONSM were included, and visual outcomes (visual acuity, visual fields, colour vision, OCT retinal nerve fibre layer thickness and radiological tumour response) and treatment toxicities were assessed. Pooled data analysis of available studies was also performed. Statistical analysis was performed with binomial, two-tailed chi-squared tests and Fisher exact tests. In our cohort a significant majority experienced improved visual field (p = 0.046), stable or improved visual acuity (p = 0.0017) and colour vision (p = 0.015) after fractionated radiotherapy. Pooled analysis with strict inclusion criteria found 3D conformal radiotherapy to offer significantly poorer visual acuity compared to fractionated stereotactic radiotherapy (p = 0.008). When all published studies were included, stereotactic radiosurgery was superior to 3D conformal methods (p = 0.035), and equivalent to other fractionated methods. 3D conformal methods also had significantly higher rates of long-term side effects. These results support the use of fractionated radiotherapy and radiosurgery for ONSM treatment, however 3D conformal methods cannot be recommended.

78Gy with Fiducial Marker Image-Guided Radiotherapy in Prostate Cancer: Single Center Analysis of 301 Patients.

AIM: In prostate cancer, fiducial marker image-guided radiotherapy (FMIGRT) allows correction of setup errors and interfraction physiological motion resulting in improved accuracy of target and sparing of at risk organs. We aim to report outcomes and toxicities observed in patients treated with dose escalation to 78Gy with FMIGRT in our center. METHODS AND MATERIALS: Retrospective review of consecutive patients with histologically confirmed T1-4N0M0 localized prostate cancer treated with dose escalation to 78Gy with FMIGRT in our center. All patients had 3-D conformal radiotherapy. Duration of androgen deprivation therapy use was tailored to risk group. Toxicity was scored according to CTCAE.v04. Kaplan-Meier analysis was performed for freedom from biochemical failure (FFBF), prostate cancer-specific survival and overall survival. RESULTS: Median follow-up was 48.6 months. Median duration of androgen deprivation therapy was 6 and 23 months in the intermediate- and high-risk group, respectively. FFBF at 5 years was 88.8%. FFBFs when stratified to risk groups were 100% for low risk, 88.9% for low-intermediate risk, 89.9% for high-intermediate risk and 85.4% for high risk, respectively. Acute severe toxicity (grade≥3) rate for both genitourinary (GU) and gastrointestinal (GI) was 1%. Late moderate-to-severe toxicity (grade≥2) rates for GU and GI were 15% and 17%, respectively, with severe (grade≥3) toxicity rate for GU and GI at 2% and 3%, respectively. CONCLUSION: Dose escalation to 78Gy with FMIGRT in our series achieved good FFBF at 5 years with low acute and late toxicity rates. These results provide a good comparator cohort to our current use of image-guided intensity modulated radiotherapy.

High-dose-rate brachytherapy boost for prostate cancer: Outcomes and genitourinary toxicity.

AIMS: To report disease outcomes and late urinary toxicity profile. To assess the impact of changing technique and evolving quality assurance on genitourinary toxicity rates. METHODS AND MATERIALS: One hundred eighty patients were treated with external beam radiation therapy and high-dose-rate brachytherapy (HDRB) for localized intermediate- and high-risk prostate cancer, between December 2002 and February 2012. The HDRB technique evolved over the period of this study, from 19.5 Gy/3 (n = 68), to 17 Gy/2 (n = 40), 18 Gy/2 (n = 39), and most recently 19 Gy/2 (n = 33). In the two fraction cohort, 68 patients underwent additional correction for catheter displacement before each fraction. RESULTS: With a median followup of 5.2 years, 5-year freedom from failure was 93.7% for intermediate, and 76.0% for high risk patients. The 3- and 6-year cumulative stricture incidence for all patients was 7.8% and 15.3%, respectively. There was no statistically significant difference in stricture rate for the four dose levels used nor between the three fractions and the two fraction technique overall. The 19 Gy/2 fractionation group had the lowest 3-year stricture rate (3.0%). The addition of correction for intrafraction catheter displacement did not result in a statistically significant difference in stricture rates, although the severity of strictures has been reduced. CONCLUSIONS: Our biochemical control is consistent with other similar series. We found no increase in late urinary toxicity with a two fraction, two implant HDRB technique compared with three fractions. The HDRB dose did not correlate with stricture rates in our series. Correction of intra-fraction catheter displacement did not lead to a statistically significant reduction in stricture rates, although may have mitigated the effects of dose escalation.

HDR brachytherapy combined with external beam radiation for localised prostate cancer: early experience from the Sydney Cancer Centre.

INTRODUCTION: To report the toxicity and early efficacy of high-dose rate brachytherapy (HDR) as a boost to external beam radiation (EBRT) in the treatment of localised prostate cancer. METHODS: Between December 2002 and November 2007, 101 consecutive patients with intermediate or high risk prostate cancer were treated with EBRT plus an HDR boost. The HDR boost was initially delivered in three fractions of 6.5 Gy each via one implant; this was subsequently modified to a two-fraction technique with separate implants 2 weeks apart (8.5 Gy each). Most patients also received at least 3 months of androgen ablation. RESULTS: Our cohort included 65 intermediate risk and 36 high-risk patients. Sixty-seven patients received the three-fraction regime; 34 the two-fraction schedule. Median follow-up was 56 months, at which time 82% of patients were free from failure. The 4-year disease-free survival for intermediate and high-risk groups was 95% and 66%, respectively (overall 85%). Significant acute toxicities included clot retention (eight patients), one traumatic urethral injury, one case of retention requiring suprapubic catheter placement, one case of new onset atrial fibrillation and three cases of pulmonary emboli. At 4 years, the rate of late grade 2 genitourinary toxicity was 8%; two patients experienced grade 3 toxicity. No late grade 3 gastrointestinal toxicity was observed. Potency was preserved in 72% of those patients reporting normal pre-treatment sexual function. CONCLUSIONS: Our cohort experienced toxicity similar to previously published HDR boost series with very promising early efficacy results.

Prostate HDR brachytherapy catheter displacement between planning and treatment delivery.

BACKGROUND AND PURPOSE: HDR brachytherapy is used as a conformal boost for treating prostate cancer. Given the large doses delivered, it is critical that the volume treated matches that planned. Our outpatient protocol comprises two 9 Gy fractions, two weeks apart. We prospectively assessed catheter displacement between CT planning and treatment delivery. MATERIALS AND METHODS: Three fiducial markers and the catheters were implanted under transrectal ultrasound guidance. Metal marker wires were inserted into 4 reference catheters before CT; marker positions relative to each other and to the marker wires were measured from the CT scout. Measurements were repeated immediately prior to treatment delivery using pelvic X-ray with marker wires in the same reference catheters. Measurements from CT scout and film were compared. For displacements of 5mm or more, indexer positions were adjusted prior to treatment delivery. RESULTS: Results are based on 48 implants, in 25 patients. Median time from planning CT to treatment delivery was 254 min (range 81-367 min). Median catheter displacement was 7.5mm (range -2.9-23.9 mm), 67% of implants had displacement of 5mm or greater. Displacements were predominantly caudal. CONCLUSIONS: Catheter displacement can occur in the 1-3h between the planning CT scan and treatment. It is recommended that departments performing HDR prostate brachytherapy verify catheter positions immediately prior to treatment delivery.

Patient-reported outcomes of prostate high-dose-rate brachytherapy boost comparing an outpatient and inpatient protocol: a two-center chronologic cohort study.

PURPOSE: To determine patients' self-reported experiences of outpatient high-dose-rate prostate brachytherapy boost, and compare with previous cohort treated as inpatients. METHODS AND MATERIALS: Using the Prostate Brachytherapy Questionnaire, we previously examined patients' subjective experience of the brachytherapy procedure when it involved one implant and hospitalization with the template in situ for 2 days (Group 1). The protocol was subsequently changed to two implants, 2 weeks apart as outpatients. Fifty-eight patients treated with the new protocol (Group 2) completed the same questionnaire. We compared the self-reported experiences between Groups 1 and 2 and also between the first and second implant for those in Group 2. Our hypothesis was that the worst rated issues in Group 1 might be reduced with the new approach. RESULTS: Group 2 patients were less troubled overall by the procedure (mean scores 2.3 vs. 3.2, p=0.0293). Specifically, they were less troubled by "discomfort" (2.8 vs. 3.8, p=0.0254); "being stuck in bed" (1.7 vs. 4.2 p<0.0001); "feeling helpless" (1.3 vs. 2.8, p=0.0009); "fear of opening my bowels" (2.1 vs. 3.3, p=0.0055); and "fear of coping with the implant" (1.3 vs. 2.5, p=0.0004). There was no significant increase in "thought of implant" or "fear of implant" before the second implant. However, more patients rated worse than expected "fear of passing urine" during the second implant. CONCLUSIONS: Patients rated high-dose-rate brachytherapy less troublesome when delivered as outpatient with two implants, 2 weeks apart than as inpatient over 3 days, despite the additional invasive procedure and anesthesia.