In vivo real-time dosimetric verification in high dose rate prostate brachytherapy.

PURPOSE: To evaluate the performance of a diode array in the routine verification of planned dose to points inside the rectum from prostate high dose rate (HDR) brachytherapy using a real-time planning system. METHODS: A dosimetric study involving 28 patients was undertaken where measured doses received during treatment were compared to those calculated by the treatment planning system (TPS). After the ultrasound imaging required for treatment planning had been recorded, the ultrasound probe was replaced with a geometric replica that contained an 8 mm diameter cylindrical cavity in which a PTW diode array type 9112 was placed. The replica probe was then positioned inside the rectum with the individual diode positions determined using fluoroscopy. Dose was then recorded during the patients' treatment and compared to associated coordinates in the planning system. RESULTS: Factors influencing diode response and experimental uncertainty were initially investigated to estimate the overall uncertainty involved in dose measurements, which was determined to be +/- 10%. Data was acquired for 28 patients' first fractions, 11 patients' second fractions, and 13 patients' third fractions with collection dependent upon circumstances. Deviations between the diode measurements and predicted values ranged from -42% to +35% with 71% of measurements experiencing less than a 10% deviation from the predicted values. If the +/- 10% measurement uncertainty was combined with a tolerated dose discrepancy of +/- 10% then over 95% of the diode results exhibited agreement with the calculated data to within +/- 20%. It must also be noted that when large dose discrepancies were apparent they did not necessarily occur for all five diodes in the one measurement. CONCLUSIONS: This technique provided a method that could be utilized to detect gross errors in dose delivery of a real-time prostate HDR plan. Limitations in the detection system used must be well understood if meaningful results are to be achieved.

Early management of prostate cancer.

Prostate cancer is now the commonest cancer diagnosed in Australia. In 2005 there were 5913 men diagnosed with prostate cancer in New South Wales alone (31% of male cancers; 17% of all cancers). However, that year there were only 980 deaths from prostate cancer in NSW, and so prostate cancer dropped to be the fourth commonest cause of cancer death, ahead of breast cancer with 877 deaths. This discrepancy is a major cause of the angst experienced in the detection and management of prostate cancer. What is needed is a way to separate the significant prostate cancers from the insignificant ones, and accept that identifying them is a very different issue to managing them aggressively.

Adoption of hypofractionated radiation therapy for early breast cancer in private practice: the GenesisCare experience 2014­2016.

INTRODUCTION: Cancer Australia guidelines recommend that hypofractionation should be considered for women over the age of 50 years with early breast cancer. GenesisCare is the largest provider of radiation therapy services in Australia. This study aimed to investigate variation in hypofractionation across 4 states encompassing the period when the most recent guidelines had been released. METHODS: Patients with T1 N0 and T2 N0 breast cancer who received radiation therapy as adjuvant therapy after breast conservation surgery between 2014 and 2016 were reviewed. Patient, treatment and disease-related variables were included in the univariate and multivariate models together with other potential explanatory variables such as the state, in which the patient was treated, radiation oncologist and distance from the treatment centre. RESULTS: Of 3374 patients included, 44% received a hypofractionated schedule. There was an increase in the use of hypofractionation from 32% in 2014 to 56% in 2016. Older patients were more likely to receive a hypofractionated treatment schedule - 75% for patients 80 years and over. Multivariate modelling revealed older age, year of treatment, higher T stage and grade, chemotherapy and the individual radiation oncologist (and state) as independent predictors of the use of hypofractionation. There was no difference in hypofractionation based on laterality. CONCLUSIONS: Guidelines from Cancer Australia may impact clinician behaviour. The influence of the individual radiation oncologist remains paramount, and their practice is affected by their immediate colleagues. Subsequent analysis of hypofractionation rates after presentation of these data has resulted in a significant increase in its use.

Volume not number of metastases: Gamma Knife radiosurgery management of intracranial lesions from an Australian perspective.

BACKGROUND AND PURPOSE: To assess the response of the first cohort of patients treated with Gamma Knife radiosurgery in Australia. MATERIALS AND METHODS: A prospectively collected cohort of 180 patients with intracranial metastases from different primaries was treated between August 2010 and July 2017. Survival was calculated using the Kaplan-Meier's method. Cox regression was used for multivariate analysis. RESULTS: Currently 141 patients (78.3%) have died of their disease. The median survival for the group as a whole was 9.2 months, with observed differences resulting from the volume of tumor burden (11.4 months for volumes <3.2 cm3 to 5.16 months for volume >9.1 cm3). Overall 2-year survival was 20.7%. CONCLUSION: Results from the first Gamma Knife radiosurgery center in Australia showed that the treatment is feasible and effective, consistent with the international experience. For patients with larger numbers of intracranial metastases, the total volume of the intracranial burden may be of more significance in predicting outcomes. While there appeared to be a difference in survival by histologic origin, this could be related to concurrent systemic immunotherapy available for certain tumors.

Six year experience of external beam radiotherapy, brachytherapy boost with a 1Ci (192)Ir source, and neoadjuvant hormonal manipulation for prostate cancer.

PURPOSE: To present preliminary outcomes of pulsed dose rate brachytherapy (PDR-BT), external beam radiotherapy (EBRT), and hormonal manipulation, for prostate cancer. PATIENTS AND METHODS: Between December 1999 and January 2005, 165 consecutive patients with Stage T1-T3, N0, M0 prostate cancer were treated. Hormones were used in every patient. Median follow-up was 36 months. Risk groups were low (either Stage < or =T2a, +/- Gleason score < or =6, +/- Prostate-Specific Antigen [PSA] level < or =10 ng/mL); intermediate (either Stage T2b,c, +/- Gleason score 7, +/- PSA 10-20 ng/mL); and high (either Stage T3, +/- Gleason score 8-10, +/- PSA >20 ng/mL). RESULTS: At 3 years, Radiotherapy Oncology Group (RTOG) Grade 3 and 4 genito-urinary toxicity was 4% and 1.4%; RTOG Grade 3 and 4 gastro-intestinal toxicity was 2.6% and 0%, respectively. Erectile preservation was 61%. Overall survival was 93% (154 of 165) and cause-specific survival was 98% (162 of 165). At 3 years, disease free survival (DFS) was 93% (153 of 165). DFS for low-, intermediate-, and high-risk groups was 100%, 97%, and 81%, respectively (chi(2) (2) = 16.02, p = 0.0003). The nadir plus 2 ng/mL definition (chi(2) (2) = 14.49, p = 0.0007) best predicted clinical failure, having the lowest false-positive rate (3 of 165). The nadir plus 2 ng/mL PSA-progression-free survival (PSA-PFS) rate was 100%, 95%, and 87% for the low-, intermediate, and high-risk groups, respectively. Overall ASTRO PSA-PFS rate was 88%. CONCLUSIONS: Pulsed dose rate brachytherapy plus EBRT is effective in treating localized prostate cancer, with acceptable toxicity. However, a median 5-year PSA-PFS follow-up is required before providing a solid recommendation. This preliminary information supports continued use.

Follicular Thyroid Adenoma Showing Avid Uptake on 68Ga PSMA-HBED-CC PET/CT.

68Ga-prostate-specific membrane antigen (PSMA) PET/CT imaging is a relatively new imaging technique used to evaluate the extent of disease in prostate carcinoma. Various other neoplasms may also express PSMA and show uptake on PSMA PET/CT scan. We report a case of a 62-year-old man who had a PSMA PET/CT scan for restaging of prostate carcinoma. A PSMA-avid thyroid lesion was identified, and subsequent tissue sampling confirmed the diagnosis of follicular thyroid adenoma. It is important to be aware of this possibility to avoid scan misinterpretation. Tissue biopsy of PSMA-avid thyroid lesions should be considered to exclude a primary thyroid neoplasm.

Schwannoma Showing Avid Uptake on 68Ga-PSMA-HBED-CC PET/CT.

Ga prostate-specific membrane antigen (PSMA) PET/CT is a relatively new and highly sensitive imaging modality used in staging metastatic prostate cancer. We report a case of a 65-year-old man with newly diagnosed prostate carcinoma who had a PSMA PET/CT scan for staging of his disease. A PSMA-avid right pelvic mass was identified anterior to the sacrum. Surgical removal and histopathological examination of this lesion revealed the diagnosis of schwannoma. It is important to be aware that schwannoma may also show avid uptake on PSMA PET/CT scan and may potentially lead to an incorrect diagnosis of metastatic prostate carcinoma.

Does prostate-specific antigen nadir predict longer-term outcomes of prostate cancer after neoadjuvant and adjuvant androgen deprivation therapy in conjunction with brachytherapy?

PURPOSE: To evaluate whether nadir prostate-specific antigen (nPSA), time to nPSA (TnPSA), and nPSA 3-years post-treatment are prognostic for prostate cancer (PC) in patients treated with temporary brachytherapy plus external beam radiation therapy (EBRT) and hormonal manipulation. METHODS AND MATERIALS: We retrospectively analyzed our database of 253 patients with Stage T1-T3 N0M0 PC who underwent brachytherapy with temporary brachytherapy plus EBRT. All patients received neoadjuvant androgen deprivation for a median of 6 months. Treatment consisted of three pulses of pseudo pulsed-dose-rate brachytherapy to a median dose of 18Gy with 50.4Gy in 28 fractions of EBRT. Treatment took place between December 1999 and March 2006. RESULTS: At a median of 6-years followup, nPSA value was a predictor of biochemical control. Rising nPSA categories of <0.01, 0.01-<0.05, 0.05-≤0.1, 0.1-≤ 1.0, or >1.0 ng/mL correlated with a deteriorating 5-year biochemical control (nBED) by the Phoenix definition of 100%, 90.0%, 82.5%, 64.3%, and 10%, respectively. A highly statistically significant relationship between nPSA value and subsequent clinical failure is also demonstrated. The relationship between TnPSA and nBED was strongly significant (p<0.0001), with a significantly longer nPSA for patients who had Phoenix nBED. A PSA of <1.5 ng/mL achieved 3-year post radiation therapy was prognostic for biochemical and clinical disease control (p<0.0001). CONCLUSION: The nPSA, TnPSA, and reaching a PSA cutoff level of <1.5 ng/mL at 3 years post-treatment can provide useful prognostic information on long-term biochemical and clinical control of PC in patients treated with pseudo PDR, EBRT, and hormone manipulation.

Reducing shield thickness and backscattered radiation using a multilayered shield for 6­10 MeV electron beams.

Intraoral and external electron shields used in radiotherapy are designed to minimize radiation exposure to non-treatment tissue. Sites where shields are used include but are not limited to, the treatment of lips, cheeks and ears whilst shielding the underlying oral cavity, tongue, gingival or temporal region. A commonly known and published effect, concerns the enhancement in dose that can occur on the beam side on an electron shield caused by an increase in electron backscatter radiation. In this work a lead shield has been designed incorporating copper, aluminium and wax in a step down filter arrangement to minimise backscatter whilst minimizing overall shield thickness for better clinical setup and ease of use. For electron beams ranging from 6 to 10 MeV, a standard shield design of 4 mm lead, 0.6 mm copper, 1.0 mm aluminium and 1.5 mm wax (3.1 mm added filtration, 7.1 mm total thickness) provided adequate backscatter and transmission reduction to match a standard 4.5 mm lead and 10 mm wax (total thickness 14.5 mm) electron shield. Dose enhancement values of no more than 10 % were measured utilising this shield design with a 50 % reduction in shield thickness. The thinner shield will not only allow easier patient set up but should be tolerated better by patients when mucosal reactions occur as they place less physical pressure on these sites during treatment due to their smaller size.

Prostate brachytherapy in New South Wales: patterns of care study and impact of caseload on treatment quality.

PURPOSE: We performed the first comprehensive, population-based brachytherapy (BT) Patterns of Care Study in the Australian setting. Herein we report on prostate BT and assess the technical quality of BT practice, focusing on whether a caseload effect could be identified in New South Wales (NSW). MATERIAL AND METHODS: Site visits were made to all radiation oncology departments in NSW that delivered prostate BT, collecting relevant data on NSW residents treated with prostate BT in 2003. Overall quality of NSW prostate BT treatment was assessed using benchmarks including treatment of appropriate prostate cancer disease risk category, absence of (relative) physical contraindications, optimal planned and treated dosimetry, and pre-/post-implant planning/CT. Quality was compared between higher and lower caseload departments. RESULTS: One hundred and fifty-seven (67%) patients underwent temporary BT and 79 (33%) permanent seed BT. Prostate BT was concentrated in five departments, with three of four departments with active programmes treating greater than the recommended 25 cases. Rates of concordance with quality benchmarks were high (85-99%) with no consistent caseload effect identified. CONCLUSIONS: Prostate BT in NSW in 2003 was generally of high quality and a caseload effect on quality could not be identified. This may be because the number of departments was insufficient to determine a caseload effect, or because the prostate BT was largely concentrated in a small number of high caseload departments.

Pituitary metastasis from breast cancer presenting as diabetes insipidus.

An 83-year-old woman developed pituitary metastasis while being treated for metastatic breast cancer. She presented with visual disturbance and headache followed by thirst, nocturia and polyuria. A visual field defect was present. MRI revealed a sellar mass consistent with metastasis to the pituitary gland. She was successfully treated with radiotherapy to the sella and had improvement of her visual symptoms and visual field defect. She then required ongoing treatment for diabetes insipidus. Her symptoms had not shown any sign of recurring up to 9 months after treatment. Pituitary metastases are rare but should be suspected in patients with metastatic cancer who present with features similar to those seen here. With improvements in survival in metastatic breast cancer, pituitary metastases may be seen more commonly and active local treatment is warranted given the possibility of resolution of symptoms related to the pituitary metastases.

Long-term outcome for prostate cancer using pseudo pulse-dosed rate brachytherapy, external beam radiotherapy, and hormones.

PURPOSE: We report the long-term outcomes of pulse-dose rate (PDR) brachytherapy used in a nonstandard style (pseudo-PDR) with an high-dose rate brachytherapy technique in conjunction with external beam radiotherapy (EBRT) and hormonal manipulation on prostate cancer (PC). METHODS AND MATERIALS: We treated 253 patients with Stage T1-T3 N0M0 PC, between December 1999 and March 2006. All patients received neoadjuvant androgen deprivation for a median 6 months. Treatment consisted of three pulses of pseudo-PDR brachytherapy to a median dose of 18Gy with 50.4Gy in 28 fractions of EBRT. RESULTS: At a median 6 years followup, (range, 1-11 years), 5-year overall survival was 92%, and PC-specific survival was 96%. The 5-year biochemical control (biochemical no evidence of disease) by the Phoenix definition for low-, intermediate-, and high-risk groups was 95%, 90%, and 71%, respectively (p<0.00001). At 6 years, the incidence of Radiotherapy Oncology Group Grade 2 and 3 genitourinary toxicity was 1% and 6%; Radiotherapy Oncology Group Grade 2 and 3 gastrointestinal toxicity was 4% and 0%. Erectile preservation at 3 years was 58%. The Phoenix definition best predicted clinical failure with a high specificity (94%). CONCLUSIONS: Pseudo-PDR brachytherapy plus EBRT with limited neoadjuvant hormonal manipulation is an effective treatment option in localized PC, with minimal and tolerable morbidity and provides excellent control. This technique of a modified PDR-delivery technique appears as effective as high-dose rate therapy.

The role of radiation therapy in the management of metastatic melanoma in the brain.

Brain metastasis is common in patients with melanoma and represents a significant cause of morbidity and mortality. There have been no specific randomized trials for patients with melanoma brain metastasis, so treatment is based on management of brain metastasis in general and requires multidisciplinary expertise including radiation oncology, neurosurgery, medical oncology, and palliative care. In this paper, we summarize the prognosis, general management, and the role of radiation therapy in the management of metastatic melanoma in the brain.

Automated radiosynthesis of [18F]PBR111 and [18F]PBR102 using the Tracerlab FXFN and Tracerlab MXFDG module for imaging the peripheral benzodiazepine receptor with PET.

[(18)F]PBR111 and [(18)F]PBR102 are selective radioligands for imaging of the Peripheral Benzodiazepine Receptor (PBR). We have developed a fully automated method for the radiosynthesis of [(18)F]PBR111 and [(18)F]PBR102 in the Tracerlab FX(FN) (30±2% radiochemical yield non-decay-corrected for both tracers) and Tracerlab MX(FDG) (25±2% radiochemical yield non-decay-corrected for both tracers) from the corresponding p-toluenesulfonyl precursors. For all tracers, radiochemical purity was >99% and specific activity was >150GBq/µmol after less than 60min of preparation time.

Life-threatening anaphylactoid reaction to amifostine used with concurrent chemoradiotherapy for nasopharyngeal cancer in a patient with dermatomyositis: a case report with literature review.

Dermatomyositis is associated with malignancy in approximately 20-25% of cases. The most common associated cancers are ovarian, lung, pancreatic, stomach, colon and non-Hodgkin's lymphoma. Nasopharyngeal cancer is not common in the Caucasian population; however, there is a much higher incidence in Asian patients. Radiotherapy is the mainstay of treatment for early nasopharyngeal cancer, but combination chemoradiotherapy is becoming more common for patients with advanced disease since the Intergroup trial 0099 demonstrated improved progression-free survival and overall survival for chemoradiotherapy. Increasingly, the cytotoxic agent amifostine is being used prior to radiotherapy in an attempt to decrease associated morbidities. Amifostine has been found to significantly decrease acute and chronic xerostomia but not mucositis. It appears to be selectively protective to salivary glands and kidneys without being tumor protective. The most common side effects associated with amifostine are nausea, vomiting, hypotension, hypocalcemia and allergic reactions. We describe the case of a man with dermatomyositis and stage IV nasopharyngeal cancer treated with chemoradiotherapy and s.c. amifostine. The patient suffered a life-threatening anaphylactoid reaction to amifostine.