Scott Carruthers

Adjuvant radiotherapy versus observation alone for patients at risk of lymph-node field relapse after therapeutic lymphadenectomy for melanoma: a randomised trial

BACKGROUND The use of radiotherapy after therapeutic lymphadenectomy for patients with melanoma at high risk of further lymph-node field and distant recurrence is controversial. Decisions for radiotherapy in this setting are made on the basis of retrospective, non-randomised studies. We did this randomised trial to assess the effect of adjuvant radiotherapy on lymph-node field control in patients who had undergone therapeutic lymphadenectomy for metastatic melanoma in regional lymph nodes. METHODS This randomised controlled trial included patients from 16 hospitals in Australia, New Zealand, the Netherlands, and Brazil. To be eligible for this trial, patients had to be at high risk of lymph-node field relapse, judged on the basis of number of nodes involved, extranodal spread, and maximum size of involved nodes. After lymphadenectomy, randomisation was done centrally by computer and patients assigned by telephone in a ratio of 1:1 to receive adjuvant radiotherapy of 48 Gy in 20 fractions or observation, with institution, lymph-node field, number of involved nodes, maximum node diameter, and extent of extranodal spread as minimisation factors. Participants, those giving treatment, and those assessing outcomes were not masked to treatment allocation. The primary endpoint was lymph-node field relapse (as a first relapse), analysed for all eligible patients. The study is registered at ClinicalTrials.gov, number NCT00287196. The trial is now closed and follow-up discontinued. FINDINGS 123 patients were randomly allocated to the adjuvant radiotherapy group and 127 to the observation group between March 20, 2002, and Sept 21, 2007. Two patients withdrew consent and 31 had a major eligibility infringement as decided by the independent data monitoring committee, resulting in 217 eligible for the primary analysis (109 in the adjuvant radiotherapy group and 108 in the observation group). Median follow-up was 40 months (IQR 27-55). Risk of lymph-node field relapse was significantly reduced in the adjuvant radiotherapy group compared with the observation group (20 relapses in the radiotherapy group vs 34 in the observation group, hazard ratio [HR] 0·56, 95% CI 0·32-0·98; p=0·041), but no differences were noted for relapse-free survival (70 vs 73 events, HR 0·91, 95% CI 0·65-1·26; p=0·56) or overall survival (59 vs 47 deaths, HR 1·37, 95% CI 0·94-2·01; p=0·12). The most common grade 3 and 4 adverse events were seroma (nine in the radiotherapy group vs 11 in the observation group), radiation dermatitis (19 in the radiotherapy group), and wound infection (three in the radiotherapy group vs seven in the observation group). INTERPRETATION Adjuvant radiotherapy improves lymph-node field control in patients at high risk of lymph-node field relapse after therapeutic lymphadenectomy for metastatic melanoma. Adjuvant radiotherapy should be discussed with patients at high risk of relapse after lymphadenectomy. FUNDING National Health and Medical Research Council of Australia, Cancer Australia, Melanoma Institute Australia, Cancer Council of South Australia.

Adjuvant lymph-node field radiotherapy versus observation only in patients with melanoma at high risk of further lymph-node field relapse after lymphadenectomy (ANZMTG 01.02/TROG 02.01) : 6-year follow-up of a phase 3, randomised controlled trial

BACKGROUND Adjuvant radiotherapy is recommended for patients with melanoma after lymphadenectomy. We previously showed this treatment reduced risk of repeat lymph-node field cancer in patients with a high risk of recurrence but had no effect on overall survival. Here, we aim to update the relapse and survival data from that trial and assess quality of life and toxic effects. METHODS In the ANZMTG 01.02/TROG 02.01 randomised controlled trial, we enrolled patients who had undergone lymphadenectomy for a palpable lymph-node field relapse and were at high risk of recurrence at 16 hospitals (11 in Australia, three in New Zealand, one in Netherlands, and one in Brazil). We randomly assigned patients (1:1) to adjuvant radiotherapy (48 Gy in 20 fractions, given over a maximum of 30 days) or observation, stratified by institution, areas of lymph-node field (parotid and cervical, axilla, or groin), number of involved nodes (≤3 vs >3), maximum involved node diameter (≤4 cm vs >4 cm), and extent of extracapsular extension (none, limited, or extensive). Participants, those giving treatment, and those assessing outcomes were not masked to treatment allocation, but participants were unaware of each others treatment allocation. In this follow-up, we assessed outcomes every 3 months from randomisation for the first 2 years, then every 6 months up to 5 years, then annually. The primary endpoint was lymph-node field relapse as a first relapse, assessed in patients without major eligibility infringements (determined by an independent data monitoring committee). We assessed late adverse effects (occurring >90 days after surgery or start of radiotherapy) with standard criteria in the as-treated population. This study is registered with ClinicalTrials.gov, number NCT00287196. FINDINGS Between March 21, 2003, and Nov 15, 2007, we randomly assigned 123 patients to adjuvant radiotherapy (109 eligible for efficacy assessments) and 127 to observation (108 eligible). The final follow-up date was Nov 15, 2011. Median follow-up was 73 months (IQR 61-91). 23 (21%) relapses occurred in the adjuvant radiotherapy group compared with 39 (36%) in the observation group (adjusted hazard ratio [HR] 0·52 [95% CI 0·31-0·88], p=0·023). Overall survival (HR 1·27 [95% CI 0·89-1·79], p=0·21) and relapse-free survival (0·89 [0·65-1·22], p=0·51) did not differ between groups. Minor, long-term toxic effects from radiotherapy (predominantly pain, and fibrosis of the skin or subcutaneous tissue) were common, and 20 (22%) of 90 patients receiving adjuvant radiotherapy developed grade 3-4 toxic effects. 18 (20%) of 90 patients had grade 3 toxic effects, mainly affecting skin (nine [10%] patients) and subcutaneous tissue (six [7%] patients). Over 5 years, a significant increase in lower limb volumes was noted after adjuvant radiotherapy (mean volume ratio 15·0%) compared with observation (7·7%; difference 7·3% [95% CI 1·5-13·1], p=0·014). No significant differences in upper limb volume were noted between groups. INTERPRETATION Long-term follow-up supports our previous findings. Adjuvant radiotherapy could be useful for patients for whom lymph-node field control is a major issue, but entry to an adjuvant systemic therapy trial might be a preferable first option. Alternatively, observation, reserving surgery and radiotherapy for a further recurrence, might be an acceptable strategy. FUNDING National Health and Medical Research Council of Australia, Cancer Council Australia, Melanoma Institute Australia, and the Cancer Council South Australia.

Survival Differences in Patients With Metastatic Colorectal Cancer and With Single Site Metastatic Disease at Initial Presentation: Results From South Australian Clinical Registry for Advanced Colorectal Cancer

BACKGROUND Colorectal cancer is the third most common cancer in Australia. The median overall survival for metastatic colorectal cancer is nearly 2 years. However, there may be survival differences based on site of metastatic disease. METHODS Data was collected from the South Australian Registry for Advanced Colorectal Cancer. A total of 1207 patients with single site metastatic disease at initial diagnosis were subclassified into 6 subgroups: liver only (n = 780), pelvic only (n = 148), lung only (n = 142), lymph node only (n = 95), bone only (n = 32), and brain only (n = 10). Univariate and multivariate parametric survival analyses were performed. RESULTS Median overall survival was 20.3 months for the whole group. The overall survival for lung-only metastases group was 41.1 months followed by liver- and pelvic-only disease groups (22.8 and 23.8 months, respectively). Patients with isolated bone-only and brain-only metastases had poor overall survival (5.1 and 5.7 months, respectively). On multivariate analysis, prognosis was superior for the lung-only group. CONCLUSIONS Lung only group had the longest median overall survival. Bone and brain sites had a poor outlook. Site of metastatic disease at initial presentation may be prognostic.

Radiation treatment compliance in the Indigenous population: The pilot Northern Territory experience and future directions

There is a perception that Indigenous patients are less likely to attend radiotherapy treatment. This study sought to determine if a difference in radiotherapy treatment compliance rates exists between Indigenous and non‐Indigenous patients. Secondly, we aimed to ascertain which patient, disease and treatment factors affect compliance in Indigenous patients.

External evaluation of the Radiation Therapy Oncology Group brachial plexus contouring protocol: several issues identified.

The aims of the study were to evaluate interobserver variability in contouring the brachial plexus (BP) using the Radiation Therapy Oncology Group (RTOG)‐approved protocol and to analyse BP dosimetries.

Prospective randomized trial of neoadjuvant chemotherapy during the ‘wait period’ following preoperative chemoradiotherapy for rectal cancer: results of the WAIT trial

The aim was to determine whether the addition of additional cycles of chemotherapy during the ‘wait period’ following neoadjuvant chemoradiotherapy for rectal cancer improves the pathological complete response (pCR) rate.

Brain metastasis in advanced colorectal cancer: results from the South Australian metastatic colorectal cancer (SAmCRC) registry

Objective: Brain metastasis is considered rare in metastatic colorectal cancer (mCRC); thus, surveillance imaging does not routinely include the brain. The reported incidence of brain metastases ranges from 0.6% to 3.2%. Methods: The South Australian mCRC Registry (SAmCRC) was analyzed to assess the number of patients presenting with brain metastasis during their lifetime. Due to small numbers, a descriptive analysis is presented. Results: Only 59 patients of 4,100 on the registry at the time of analysis had developed brain metastasis (1.4%). The clinical characteristics of those with brain metastasis were as follows: the median age was 65.3 years and 51% were female. Where the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation status of the tumor was known, the majority harbored a KRAS mutation (55%); 31 (53%) underwent craniotomy and 55 (93%) underwent whole-brain radiotherapy. The median survival time from diagnosis of brain metastasis was 4.2 months (95% confidence interval 2.9–5.5). Patients who underwent craniotomy and radiotherapy had superior survival compared to those who underwent whole-brain radiotherapy (8.5 months vs. 2.2 months, respectively). Data from the SAmCRC (a population-based registry) confirm that brain metastases are rare and the median time to development is approximately 2 years. Conclusions: Brain metastasis is a rare outcome in advanced CRC. Patients within the registry tended to be female, young in age, and harbored with higher rates of KRAS mutations. Whether routine surveillance brain scanning should be considered remains controversial given the relative rarity of developing brain metastases in mCRC and ultimately, most patients with central nervous system involvement die from their extracranial disease.

Long-term prospective assessment of quality of life and lymphedema after inguinal or inguinal and pelvic lymphadenectomy for recurrent melanoma in the groin

Book Society of Surgical Oncology 69 Annual Cancer Symposium Boston, Massachusetts