Sean Bydder

Radiotherapy for Liver Metastases: A Review of Evidence

Over the past decade, there has been an increasing use of radiotherapy (RT) for the treatment of liver metastases. Most often, ablative doses are delivered to focal liver metastases with the goal of local control and ultimately improving survival. In contrast, low-dose whole-liver RT may be used for the palliation of symptomatic diffuse metastases. This review examines the available clinical data for both approaches. The review found that RT is effective both for local ablation of focal liver metastases and for palliation of patients with symptomatic liver metastases. However, there is a lack of a high level of evidence from randomized clinical trials.

Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma: A retrospective multicenter study of the Australasian Radiation Oncology Lymphoma Group

The curative potential of radiotherapy (RT) alone as initial treatment for patients with Stage I–II lymphocyte‐predominant Hodgkin lymphoma (LPHL) has not been defined well.

Prognostic Significance of Microsatellite Instability and Ki-ras Mutation Type in Stage II Colorectal Cancer

Objectives: The survival of stage II colorectal cancer (CRC) patients is approximately 70% at 5 years. Identification of the patient subgroup at high risk for tumour recurrence and death would allow more informed use of chemotherapy for this stage of disease. Several clinical and pathological factors have been reported to associate with worse survival. In the present study we investigated the prognostic significance of two major genetic alterations in CRC: microsatellite instability (MSI+) and the type of Ki-ras mutation. Methods: PCR-based molecular techniques were used to screen for MSI+ and Ki-ras mutation in 396 stage II CRC patients with an average follow-up time of 75 months. Clinicopathological information was obtained by retrospective review of pathology reports. Results: Prominent vascular invasion was identified in 19% of cases and was found to be an independent prognostic factor for poor outcome (relative risk = 2.08, 95% confidence interval: 1.22–3.57, p = 0.008). The MSI+ phenotype was found in 23% of proximal tumours and Ki-ras mutations in 38% of the overall series. Neither MSI+ nor the type of Ki-ras mutation showed prognostic significance in this cohort of stage II CRC. Conclusions: MSI+ and Ki-ras mutation type are not useful markers for the identification of high-risk stage II CRC patients. Further prospective and/or cohort studies are required to determine whether these molecular changes have predictive value for survival benefit from 5-fluorouracil-based adjuvant chemotherapy.

Outcome for patients with malignant pleural mesothelioma referred for trimodality therapy in Western Australia

Introduction: Trimodality therapy (TMT), consisting of extrapleural pneumonectomy (EPP), preoperative or postoperative combination chemotherapy, and high-dose hemithoracic radiotherapy, is the only therapy reported to achieve long-term survival in selected patients with malignant pleural mesothelioma (MPM). Thus, TMT was introduced as an option for such patients in Western Australia in 2004. However, TMT has never been compared with non-TMT therapy in the same patient population, thereby introducing a potential for selection bias. Method: We performed a retrospective review of all patients referred for TMT consisting of EPP, adjuvant chemotherapy, and hemithoracic radiotherapy at a quaternary referral institution. Patient eligibility for referral for TMT was based on patients’ tolerability for pneumonectomy, epithelioid subtype, and computed tomography and positron emission tomography scanning indicating operable disease, with the exclusion of extrapleural lymphadenopathy and metastatic disease (clinical stage T1-3N0-1M0). Eligible patients consenting to TMT also underwent a surgical staging procedure (bilateral thoracoscopy, mediastinoscopy, and laparoscopy) to confirm eligibility before EPP. Results: Thirty-six patients have been referred for TMT since 2004, and there has been a median of 27 months follow-up; of 31 patients having surgical staging, eight were ineligible for EPP and one declined EPP. Of the 22 planned for EPP, 18 underwent EPP and four had unresectable disease at surgery. There was one death in hospital six days post-EPP and another death postdischarge and 28 days post-EPP (30-day mortality 11%); 15 of 16 EPP survivors received adjuvant chemotherapy and 14 completed adjuvant radiotherapy. Pathologic analysis of the 18 resected EPP specimens revealed N2 disease in seven patients (39%) and nonepithelioid subtype in six patients (33%). Local recurrence did not occur among EPP survivors; however, 56% (9 of 16 patients) developed distant recurrence. Median and 1-year survival did not differ between the 18 EPP patients and 18 non-EPP patients (20.4 versus 20.7 months and 76 versus 78%, respectively; p = NS). Discussion: In this case series, we could not demonstrate a survival benefit for patients in the EPP group compared with that in the non-EPP group. After surgical staging, 26% of patients were ineligible for TMT. Thus, surgical staging is essential before proceeding with EPP. Despite aggressive imaging and surgical staging, 39% of patients will have N2 disease and 18% will have unresectable disease at operation. Although complete locoregional control was achieved with TMT, distant recurrence affected most EPP survivors despite careful patient selection and a high rate of completion of adjuvant therapy. We conclude that TMT for operable epithelioid MPM requires further assessment in randomized controlled trials.

The impact of case discussion at a multidisciplinary team meeting on the treatment and survival of patients with inoperable non-small cell lung cancer.

Patients with inoperable non‐small cell lung cancer diagnosed and managed at a single institution over a one‐year period were identified. Those whose case had been discussed at a multidisciplinary meeting had better survival than those whose case was not discussed (mean survival; 280 days vs. 205 days, log‐rank P= 0.048).

A Small Tolerance for Catheter Displacement in High–Dose Rate Prostate Brachytherapy is Necessary and Feasible

PURPOSE We examined catheter displacement in patients treated with fractionated high-dose rate (HDR) brachytherapy boost for prostate cancer and the impact this had on tumor control probability (TCP). These data were used to make conclusions on an acceptable amount of displacement. METHODS AND MATERIALS The last 20 patients treated with HDR brachytherapy boost for prostate cancer at our center in 2007 were replanned using simulated interstitial catheter displacements of 3, 6, 9, and 12 mm with originally planned dwell times. The computer-modeled dose-volume histograms for the clinical target volumes were exported and used to calculate the TCP of plans with displaced needles relative to the original plan. Actual catheter displacements were also measured before and after manual adjustment in all patients treated in 2007. RESULTS In the 20 patients who were replanned for caudal catheter displacements of 3, 6, 9, and 12 mm, the median relative TCP was 0.998, 0.964, 0.797, and 0.265, respectively (p < 0.01 when all medians were compared). All patients replanned with a 3-mm displacement, compared with only 75% with a 6-mm displacement, had a relative TCP greater than 0.950. In the 91 patients treated in 2007, before adjustment, 82.3% of fractions had a displacement greater than 3 mm compared with 12.2% of fractions after adjustment. CONCLUSIONS Catheter displacement in HDR brachytherapy significantly compromises the TCP. The tolerance for these movements should be small (< or =3 mm). Correcting these displacements to within acceptable limits is feasible.

Comparison of DVH data from multiple radiotherapy treatment planning systems

This study examined the variation of dose-volume histogram (DVH) data sourced from multiple radiotherapy treatment planning systems (TPSs). Treatment plan exports were obtained from 33 Australian and New Zealand centres during a dosimetry study. Plan information, including DVH data, was exported from the TPS at each centre and reviewed in a digital review system (SWAN). The review system was then used to produce an independent calculation of DVH information for each delineated structure. The relationships between DVHs extracted from each TPS and independently calculated were examined, particularly in terms of the influence of CT scan slice and pixel widths, the resolution of dose calculation grids and the TPS manufacturer. Calculation of total volume and DVH data was consistent between SWAN and each TPS, with the small discrepancies found tending to increase with decreasing structure size. This was significantly influenced by the TPS model used to derive the data. For target structures covered with relatively uniform dose distributions, there was a significant difference between the minimum dose in each TPS-exported DVH and that calculated independently.

Catheter Tract Metastasis Associated With Indwelling Pleural Catheters

BACKGROUND Indwelling pleural catheters (IPCs) are commonly used to manage malignant effusions. Tumor spread along the catheter tract remains a clinical concern for which limited data exist. We report the largest series of IPC-related catheter tract metastases (CTMs) to date, to our knowledge. METHODS This is a single-center, retrospective review of IPCs inserted over a 44-month period. CTM was defined as a new, solid chest wall lesion over the IPC insertion site and/or the tunneled subcutaneous tract that was clinically compatible with a malignant tract metastasis. RESULTS One hundred ten IPCs were placed in 107 patients (76.6% men; 60% with mesothelioma). CTM developed in 11 cases (10%): nine with malignant pleural mesothelioma and two with metastatic adenocarcinoma. CTM often developed late (median, 280 days; range, 56-693) post-IPC insertion. Seven cases had chest wall pain, and six received palliative radiotherapy to the CTM. Radiotherapy was well tolerated, with no major complications and causing no damage to the catheters. Longer interval after IPC insertion was the sole significant risk factor for development of CTM (OR, 2.495; 95% CI, 1.247-4.993; P = .0098) in the multivariate analyses. CONCLUSIONS IPC-related CTM is uncommon but can complicate both mesothelioma and metastatic carcinomas. The duration of interval after IPC insertion is the key risk factor identified for development of CTM. Symptoms are generally mild and respond well to radiotherapy, which can be administered safely without removal of the catheter.

An international survey on liver metastases radiotherapy

Abstract Background. An international survey of radiation therapy (RT) of liver metastases was undertaken by the Liver Cancer Workgroup of the Third International Consensus on Metastases Workshop at the 2010 American Society for Radiation Oncology (ASTRO) meeting. Material and methods. Canadian, European, Australian, New Zealand and American centers participated in this online survey. The survey had four objectives: 1) to describe the practice patterns for RT of liver metastases; 2) to report on the use of low-dose RT for symptomatic liver metastases; 3) to report on the use of technology; and 4) to describe the regional differences in the management of liver metastases. Results. A total of 69 individuals treating liver metastases with radiotherapy responded to the survey. Regional response rates ranged from 39% to 50%. The primary professional affiliation of all respondents was evenly distributed amongst ASTRO, CARO, ESTRO and TROG/RANZCR. A 36% increase in the average annual number of referrals over the past five years is reported. The majority of referrals were for radical RT. The most common technologies used were 4D-CT (61%), SBRT (55%), IGRT (50%), and/or IMRT (28%). A uniform treatment approach was not found. The most commonly employed radical regimens were 45 Gy in 3 fractions, 40–50 Gy in 5 fractions, and 45 Gy in 15 fractions. Palliative regimens included 20 Gy in 5 fractions, 30 Gy in 10 fractions, 8 Gy in 1 fraction, and 10 Gy in 2 fractions. Conclusions. This survey suggests radiation oncologists will be seeing more referrals for liver RT. The majority of experience in liver metastases RT is with radical SBRT for focal metastases rather than low-dose palliative RT for symptom control. There is significant variation in technology utilization and dose regimens. Prospective studies or registries may allow for comparison of regimens and identification of parameters to optimize patient selection.

PROSPECTIVE TRIAL OF INTRAOPERATIVE RADIATION TREATMENT FOR BREAST CANCER

Background:  A new device, Intrabeam, is available for intraoperative radiotherapy. We have prospectively examined its feasibility and tolerability in delivering adjuvant breast cancer treatment.