Stereotactic ablative radiotherapy for early stage lung cancer and lung metastases in a New Zealand population.

AIM: Stereotactic ablative radiotherapy (SABR) involves the delivery of high doses of precisely targeted radiation in a shorter time period than conventional radiotherapy. The aim of this study was to compare the outcomes of lung-based SABR in a New Zealand cohort to the global literature. METHODS: A single-institution retrospective analysis was performed on all patients who received lung-based SABR between May 2015 and September 2019 at Waikato Hospital, New Zealand. The study included both early stage lung cancer and lung oligometastases that measured less than 5cm. RESULTS: 102 patients received SABR to 116 lesions. Median follow-up was 19 months. The three-year rate of local control in the primary and metastatic cohorts was 85% and 82%, respectively. This reflects the three-year local control rate of 86% for primary lung cancer in the SPACE trial and the two-year local control rate of 81% for pulmonary oligometastases in a German study. Central primary lung cancer was associated with a higher risk of local recurrence (HR6.4 (1.3-31.5) p=0.02). The three-year progression-free survival rate in patients with early stage lung cancer and oligometastases was 56% and 26%, respectively. Maori patients with primary lung cancer had a significantly worse progression free survival (HR2.4 (1.1-5.1) p=0.03). There were no reported grade three toxicities. CONCLUSION: The use of lung-based SABR in a typical radiotherapy setting in New Zealand mirrors global outcomes.

Contemporary salvage post prostatectomy radiotherapy: Early implementation improves biochemical control.

INTRODUCTION: The optimal time to commence salvage radiotherapy (SRT) for a rising PSA post radical prostatectomy is not known. We wished to assess the impact of index PSA (iPSA) level prior to SRT on rates of biochemical failure (BCF) post treatment. METHODS: Patients referred to our institution for SRT for a rising PSA post surgery were accrued onto a prospective database. Baseline demographic data, tumour and treatment factors were collected including pathologic T and N stage, margin status, Gleason score (GS), lymphovascular space invasion (LVSI), use of androgen deprivation therapy (ADT) and time from surgery to salvage radiotherapy. Our endpoint was time to BCF. RESULTS: Between January 2008 and December 2013, 189 patients received SRT to a mean dose of 69.8 Gy in 34 fractions using Intensity Modulated Radiotherapy (IMRT). Median follow-up was 50 months. For patients with an iPSA of <0.2 ng/mL (n = 92), iPSA ≥ 0.2 to <1.0 ng/mL (n = 75) and ≥ 1.0 ng/mL (n = 22), rates of BCF at 5 years were 28.3%, 44.3% and 73.7% respectively. Compared to the iPSA <0.2 ng/mL group, the hazard ratios for time to BCF for an iPSA ≥ 0.2 to <1.0 ng/mL was 1.73 (P = 0.05) and >1.0 ng/mL was 3.1 (P = 0.002). Factors predicting time to BCF on univariate analysis included iPSA, GS, T stage, PSA nadir post surgery and LVSI. On multivariate analysis, GS, iPSA, use of ADT, T stage, PSA post surgery nadir and margin status remained significant. CONCLUSION: Rising iPSA levels are associated with an increasing risk of biochemical failure after adjusting for known prognostic factors and early salvage post prostatectomy radiotherapy is recommended.

Using individual patient anatomy to predict protocol compliance for prostate intensity-modulated radiotherapy.

If a prostate intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) plan has protocol violations, it is often a challenge knowing whether this is due to unfavorable anatomy or suboptimal planning. This study aimed to create a model to predict protocol violations based on patient anatomical variables and their potential relationship to target and organ at risk (OAR) end points in the setting of definitive, dose-escalated IMRT/VMAT prostate planning. Radiotherapy plans from 200 consecutive patients treated with definitive radiation for prostate cancer using IMRT or VMAT were analyzed. The first 100 patient plans (hypothesis-generating cohort) were examined to identify anatomical variables that predict for dosimetric outcome, in particular OAR end points. Variables that scored significance were further assessed for their ability to predict protocol violations using a Classification and Regression Tree (CART) analysis. These results were then validated in a second group of 100 patients (validation cohort). In the initial analysis of the hypothesis-generating cohort, percentage of rectum overlap in the planning target volume (PTV) (%OR) and percentage of bladder overlap in the PTV (%OB) were highlighted as significant predictors of rectal and bladder dosimetry. Lymph node treatment was also significant for bladder outcomes. For the validation cohort, CART analysis showed that %OR of < 6%, 6% to 9% and > 9% predicted a 13%, 63%, and 100% rate of rectal protocol violations respectively. For the bladder, %OB of < 9% vs > 9% is associated with 13% vs 88% rate of bladder constraint violations when lymph nodes were not treated. If nodal irradiation was delivered, plans with a %OB of < 9% had a 59% risk of violations. Percentage of rectum and bladder within the PTV can be used to identify individual plan potential to achieve dose-volume histogram (DVH) constraints. A model based on these factors could be used to reduce planning time, improve work flow, and strengthen plan quality and consistency.

Increasing tumor thickness is associated with recurrence and poorer survival in patients with Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine tumor usually occurring on sun-exposed skin in elderly patients. Clinical and pathologic factors associated with disease progression and mortality in patients with MCC are poorly defined. Recently, it has been reported that p63 expression in primary MCC is strongly associated with clinical outcome. METHODS: MCC patients diagnosed between July 1, 1993 and July 31, 2009 were identified from the surgical pathology records of the Sydney South West Area Health Service. Clinical, pathologic, treatment, and survival data were obtained and immunohistochemical analyses for p53, p63, and Ki-67 were performed. The associations of clinical and pathologic features with disease-free and disease-specific survival were analyzed. RESULTS: Ninety-five patients were identified (67 males, 28 females; median age at diagnosis of primary MCC 76 [range, 42-93] years). Increasing primary tumor thickness was significantly associated with poorer disease-free survival (5-year survival 18 % in tumors >10 mm thick compared with 69 % for patients with tumors ≤10 mm thick, p = 0.002) and disease-specific survival (5-year survival 74 % in tumors >10 mm thick compared with 97 % for patients with tumors ≤10 mm thick, p = 0.006). There was a strong positive correlation between the Ki-67 index (proportion of Ki-67-positive tumor nuclei) and tumor thickness (r = 0.39, n = 45, p = 0.008). Positive staining for p63 in MCC was infrequent (9 % of primary MCC) and showed no significant association with disease outcome. CONCLUSIONS: Tumor thickness is significantly associated with disease-free survival in MCC. We recommend that primary tumor thickness be routinely recorded in the pathology reports of patients with primary MCC.

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.

Rat-bite fever: a cautionary tale.

We present the first ever report of streptobacillary rat-bite fever in New Zealand. The patient was a young man who was admitted with systemic sepsis. He presented with a high fever, hypotension, and tender axillary lymphadenopathy. He had been bitten by a rat a week earlier. Blood cultures grew Streptobacillus moniliformis, thus confirming the diagnosis. The literature on rat-bite fever is also reviewed.