Stereotactic Radiation for the Comprehensive Treatment of Oligometastases (SABR-COMET): Extended Long-Term Outcomes.

PURPOSE: Long-term randomized data assessing the effect of ablative therapies in patients with oligometastases are lacking. The Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastases (SABR-COMET) randomized phase 2 trial was originally designed with 5 years of follow-up, but the trial was amended in 2016 to extend follow-up to 10 years. Herein we report oncologic outcomes beyond 5 years. METHODS AND MATERIALS: Patients were eligible if they had a controlled primary tumor and 1 to 5 metastases, with all metastases amenable to SABR. Patients were randomized in a 1:2 ratio between palliative standard-of-care treatment (control arm) versus SABR to all metastases plus standard of care (SABR arm). The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), toxicity, quality of life (using the Functional Assessment of Cancer Therapy: General [FACT-G]), and time to new metastases. RESULTS: Ninety-nine patients were randomized between 2012 and 2016 (n = 33 in arm 1 vs n = 66 in arm 2). Primary tumor sites included lung (n = 18), breast (n = 18), colon (n = 18), prostate (n = 16), and other (n = 29). Eight-year OS was 27.2% in the SABR arm versus 13.6% in the control arm (hazard ratio, 0.50; 95% confidence interval, 0.30-0.84; P = .008). Eight-year PFS estimates were 21.3% versus 0.0%, respectively (hazard ratio, 0.45; 95% confidence interval, 0.28-0.72; P < .001). Rates of grade ≥ 2 acute or late toxic effects were 30.3% versus 9.1% (P = .019), with no new grade 3 to 5 toxic effects. FACT-G quality of life scores declined over time in both arms, but there were no differences in quality of life scores between arms. The use of systemic therapy overall was similar between arms, but patients in the SABR arm were less likely to require cytotoxic chemotherapy (33.3% vs 54.6%, respectively, P = .043). CONCLUSIONS: SABR achieved durable improvements in OS and PFS, with no new major toxicity signals with extended follow-up. A minority of patients randomized to the SABR arm (21.3%) achieved > 5 years of survival without recurrence.

Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE): A Phase 3 Randomized Clinical Trial.

IMPORTANCE: Palliative thoracic radiotherapy (RT) can alleviate local symptoms associated with advanced non-small cell lung cancer (NSCLC), but esophagitis is a common treatment-related adverse event. Whether esophageal-sparing intensity-modulated RT (ES-IMRT) achieves a clinically relevant reduction in esophageal symptoms remains unclear. OBJECTIVE: To examine whether ES-IMRT achieves a clinically relevant reduction in esophageal symptoms compared with standard RT. DESIGN, SETTING, AND PARTICIPANTS: Palliative Radiation for Advanced Central Lung Tumors With Intentional Avoidance of the Esophagus (PROACTIVE) is a multicenter phase 3 randomized clinical trial that enrolled patients between June 24, 2016, and March 6, 2019. Data analysis was conducted from January 23, 2020, to October 22, 2021. Patients had up to 1 year of follow-up. Ninety patients at 6 tertiary academic cancer centers who had stage III/IV NSCLC and were eligible for palliative thoracic RT (20 Gy in 5 fractions or 30 Gy in 10 fractions) were included. INTERVENTIONS: Patients were randomized (1:1) to standard RT (control arm) or ES-IMRT. Target coverage was compromised to ensure the maximum esophagus dose was no more than 80% of the RT prescription dose. MAIN OUTCOMES AND MEASURES: The primary outcome was esophageal quality of life (QOL) 2 weeks post-RT, measured by the esophageal cancer subscale (ECS) of the Functional Assessment of Cancer Therapy: Esophagus questionnaire. Higher esophageal cancer subscale scores correspond with improved QOL, with a 2- to 3-point change considered clinically meaningful. Secondary outcomes included overall survival, toxic events, and other QOL metrics. Intention-to-treat analysis was used. RESULTS: Between June 24, 2016, and March 6, 2019, 90 patients were randomized to standard RT or ES-IMRT (median age at randomization, 72.0 years [IQR, 65.6-80.3]; 50 [56%] were female). Thirty-six patients (40%) received 20 Gy and 54 (60%) received 30 Gy. For the primary end point, the mean (SD) 2-week ECS score was 50.5 (10.2) in the control arm (95% CI, 47.2-53.8) and 54.3 (7.6) in the ES-IMRT arm (95% CI, 51.9-56.7) (P = .06). Symptomatic RT-associated esophagitis occurred in 24% (n = 11) of patients in the control arm vs 2% (n = 1) in the ES-IMRT arm (P = .002). In a post hoc subgroup analysis based on the stratification factor, reduction in esophagitis was most evident in patients receiving 30 Gy (30% [n = 8] vs 0%; P = .004). Overall survival was similar with standard RT (median, 8.6; 95% CI, 5.7-15.6 months) and ES-IMRT (median, 8.7; 95% CI, 5.1-10.2 months) (P = .62). CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, ES-IMRT did not significantly improve esophageal QOL but significantly reduced the incidence of symptomatic esophagitis. Because post hoc analysis found that reduced esophagitis was most evident in patients receiving 30 Gy of RT, these findings suggest that ES-IMRT may be most beneficial when the prescription dose is higher (30 Gy). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02752126.

Is SABR Cost-Effective in Oligometastatic Cancer? An Economic Analysis of the SABR-COMET Randomized Trial.

PURPOSE: The phase 2 randomized study SABR-COMET demonstrated that in patients with controlled primary tumors and 1 to 5 oligometastatic lesions, SABR was associated with improved progression-free survival (PFS) compared with standard of care (SoC), but with higher costs and treatment-related toxicities. The aim of this study was to assess the cost-effectiveness of SABR versus SoC in this setting. METHODS AND MATERIALS: A Markov model was constructed to perform a cost-utility analysis from the Canadian health care system perspective. Utility values and transition probabilities were derived from individual-level data from the SABR-COMET trial. One-way, 2-way, and probabilistic sensitivity analyses were performed. Costs were expressed in 2018 CAD. A separate analysis based on US payer's perspective was performed. An incremental cost-effectiveness ratio (ICER) at a willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY) was used. RESULTS: In the base case scenario, SABR was cost-effective at an ICER of $37,157 per QALY gained. This finding was most sensitive to the number of metastatic lesions treated with SABR (ICER: $28,066 per QALY for 2, increasing to $64,429 per QALY for 5), difference in chemotherapy use (ICER: $27,173-$53,738 per QALY), and PFS hazard ratio (HR) between strategies (ICER: $31,548-$53,273 per QALY). Probabilistic sensitivity analysis revealed that SABR was cost-effective in 97% of all iterations. Two-way sensitivity analysis demonstrated a nonlinear relationship between the number of lesions and the PFS HR. To maintain cost-effectiveness for each additional metastasis, the HR must decrease by approximately 0.047. The US cost analysis yielded similar results, with an ICER of $54,564 (2018 USD per QALY) for SABR. CONCLUSIONS: SABR is cost-effective for patients with 1 to 5 oligometastatic lesions compared with SoC.

Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial.

PURPOSE: The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data that test this paradigm are lacking. METHODS: We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 v 4-5) and randomized in a 1:2 ratio between palliative standard-of-care (SOC) treatments (arm 1) and SOC plus SABR (arm 2). We used a randomized phase II screening design with a primary end point of overall survival (OS), using an α of .20 (wherein P < .20 indicates a positive trial). Secondary end points included progression-free survival (PFS), toxicity, and quality of life (QOL). Herein, we present long-term outcomes from the trial. RESULTS: Between 2012 and 2016, 99 patients were randomly assigned at 10 centers internationally. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% in arm 1 (95% CI, 6% to 34%) versus 42.3% in arm 2 (95% CI, 28% to 56%; stratified log-rank P = .006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years with last patient censored) and 17.3% in arm 2 (95% CI, 8% to 30%; P = .001). There were no new grade 2-5 adverse events and no differences in QOL between arms. CONCLUSION: With extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL.

Treatment of patients with glomus jugulare tumours (GJT) and its subjective effect on quality of life (QoL) measures.

Cerebellopontine angle (CPA) tumours account for 6-10% of intracranial tumours. The most common CPA tumours are vestibular schwannomas (VS), also known as acoustic neuromas, benign tumours of the vestibulocochlear nerve. Less common but symptomatic skull base lesions are glomus jugulare tumours (GJT), of which approximately 40% are identified as CPA tumours. Initial symptoms for GJT may include hearing loss and tinnitus and progress to various cranial nerve dysfunctions. Three well-accepted treatment modalities for such tumours include surgical resection, radiotherapy and/or conservative management employing serial MR or CT imaging. Patients' quality of life may be impacted by different treatment methods, so treatment decisions should be client centered.

Surface Dosimetry of Patients Undergoing Total Body Irradiation: A Retrospective Analysis for Quality Assurance.

Total body irradiation (TBI) is used prior to bone marrow transplantation as part of the conditioning regimen in selected patients. A linear accelerator-based technique was used at our treatment centre between June, 2004 and August, 2015. Patients were treated supine with extended source-to-surface distance (SSD) lateral fields, and prescription dose was 12 Gy delivered in six fractions, two fractions per day. Dose was prescribed to midplane at the level of the umbilicus and monitor units were calculated manually based on measured beam data. Dose variation within 10% of the prescribed midplane dose is considered acceptable for TBI treatment. This was achieved in our clinic by using compensators to account for missing tissue in the head and neck and lower leg regions. Lung attenuators were routinely used to correct for internal inhomogeneity, which resulted from low density lung tissue. The purpose of this study was to determine whether dose variation was within acceptable limits for these patients as part of a quality assurance process. Following chart review, 129 patients who received six-fraction TBI from 2004 to 2015 were included in this study. Patients receiving single fraction treatment were excluded. Metal oxide semiconductor field effect transistors (MOSFET) dosimetry was used to measure surface dose at four or five locations during patients' first fraction of TBI. Dosimetry was repeated during the second fraction for any site with variation greater than 10%. Statistical analysis was carried out on patient data, diagnosis and dosimetry measurements. Of the 129 patients who met the inclusion criteria, 50 were diagnosed with acute myelogenous leukemia, 30 with acute lymphoblastic leukemia and 11 with chronic myelogenous leukemia. The rest of the patients were diagnosed with lymphoma or myelodysplastic syndromes. The mean percent variation in dosimetry measurements taken at the specific locations ranged between 3.5% and 8.3%. The highest variation was found in measurements performed on the cheek. A high percentage of all dosimetry readings (85.5%) was within the acceptable range of +10% from the expected value. The highest number of individual readings taken at a specific location that fell outside this range were found at the cheek. We conclude that the linear accelerator delivered TBI at our centre meets the acceptable limits of dose variation over an 11-year period.

Quality of Life Outcomes After Stereotactic Ablative Radiation Therapy (SABR) Versus Standard of Care Treatments in the Oligometastatic Setting: A Secondary Analysis of the SABR-COMET Randomized Trial.

PURPOSE: Randomized data assessing the longitudinal quality of life (QoL) impact of stereotactic ablative radiation therapy (SABR) in the oligometastatic setting are lacking. METHODS AND MATERIALS: We enrolled patients who had a controlled primary malignancy with 1 to 5 metastatic lesions, with good performance status and life expectancy >6 months. We randomized in a 1:2 ratio between standard of care (SOC) treatment (SOC arm) and SOC plus SABR to all metastatic lesions (SABR arm). QoL was measured using the Functional Assessment of Cancer Therapy-General. QoL changes over time and between groups were assessed with linear mixed modeling. RESULTS: Ninety-nine patients were randomized. Median age was 68 years (range, 43-89), and 60% were male. The most common primary tumor types were breast (n = 18), lung (n = 18), colorectal (n = 18), and prostate (n = 16). Most patients (n = 92) had 1 to 3 metastases. Median follow-up was 26 months. Because of the previously reported inferior survival of the SOC arm, the time for attrition in QoL respondents to <10% of subjects was shorter in the SOC versus SABR arm (30 vs 42 months). In the whole cohort, QoL declined over time after randomization: There were significant declines in total Functional Assessment of Cancer Therapy-General score over time compared with baseline (P < .001) owing to declines in physical and functional subscales (both P < .001), with no declines in social and emotional subscales. However, the magnitudes of decline were small, and clinically meaningful changes were not seen at most time points. Comparison between arms showed no differences in QoL between the SABR and SOC arms in total score (P = .42) or in the physical (P = .98), functional (P = .59), emotional (P = .82), or social (P = .17) subscales. CONCLUSIONS: For patients with oligometastases, average QoL declines slowly over time regardless of treatment approach, although the changes are small in magnitude. The use of SABR, compared with SOC, was not associated with a QoL detriment.

Stereotactic ablative radiotherapy for the comprehensive treatment of 4-10 oligometastatic tumors (SABR-COMET-10): study protocol for a randomized phase III trial.

BACKGROUND: Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment option for patients with oligometastatic disease. SABR delivers precise, high-dose, hypofractionated radiotherapy, and achieves excellent rates of local control for primary tumors or metastases. A recent randomized phase II trial evaluated SABR in a group of patients with a small burden of oligometastatic disease (mostly with 1-3 metastatic lesions), and found that SABR was associated with benefits in progression-free survival and overall survival. The goal of this phase III trial is to assess the impact of SABR in patients with 4-10 metastatic cancer lesions. METHODS: One hundred and fifty-nine patients will be randomized in a 1:2 ratio between the control arm (consisting of standard of care palliative-intent treatments), and the SABR arm (consisting of standard of care treatment + SABR to all sites of known disease). Randomization will be stratified by two factors: histology (Group 1: prostate, breast, or renal; Group 2: all others), and type of pre-specified systemic therapy (Group 1: immunotherapy/targeted; Group 2: cytotoxic; Group 3: observation). SABR is to be completed within 2 weeks, allowing for rapid initiation of systemic therapy. Recommended SABR doses are 20 Gy in 1 fraction, 30 Gy in 3 fractions, or 35 Gy in 5 fractions, chosen to minimize risks of toxicity. The primary endpoint is overall survival, and secondary endpoints include progression-free survival, time to development of new metastatic lesions, quality of life, and toxicity. Translational endpoints include assessment of circulating tumor cells, cell-free DNA, and tumor tissue as prognostic and predictive markers, including assessment of immunological predictors of response and long-term survival. DISCUSSION: This study will provide an assessment of the impact of SABR on clinical outcomes and quality of life, to determine if long-term survival can be achieved for selected patients with 4-10 oligometastatic lesions. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT03721341 . Date of registration: October 26, 2018.

Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial.

BACKGROUND: The oligometastatic paradigm suggests that some patients with a limited number of metastases might be cured if all lesions are eradicated. Evidence from randomised controlled trials to support this paradigm is scarce. We aimed to assess the effect of stereotactic ablative radiotherapy (SABR) on survival, oncological outcomes, toxicity, and quality of life in patients with a controlled primary tumour and one to five oligometastatic lesions. METHODS: This randomised, open-label phase 2 study was done at 10 hospitals in Canada, the Netherlands, Scotland, and Australia. Patients aged 18 or older with a controlled primary tumour and one to five metastatic lesions, Eastern Cooperative Oncology Group score of 0-1, and a life expectancy of at least 6 months were eligible. After stratifying by the number of metastases (1-3 vs 4-5), we randomly assigned patients (1:2) to receive either palliative standard of care treatments alone (control group), or standard of care plus SABR to all metastatic lesions (SABR group), using a computer-generated randomisation list with permuted blocks of nine. Neither patients nor physicians were masked to treatment allocation. The primary endpoint was overall survival. We used a randomised phase 2 screening design with a two-sided α of 0·20 (wherein p<0·20 designates a positive trial). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, number NCT01446744. FINDINGS: 99 patients were randomised between Feb 10, 2012, and Aug 30, 2016. Of 99 patients, 33 (33%) were assigned to the control group and 66 (67%) to the SABR group. Two (3%) patients in the SABR group did not receive allocated treatment and withdrew from the trial; two (6%) patients in the control group also withdrew from the trial. Median follow-up was 25 months (IQR 19-54) in the control group versus 26 months (23-37) in the SABR group. Median overall survival was 28 months (95% CI 19-33) in the control group versus 41 months (26-not reached) in the SABR group (hazard ratio 0·57, 95% CI 0·30-1·10; p=0·090). Adverse events of grade 2 or worse occurred in three (9%) of 33 controls and 19 (29%) of 66 patients in the SABR group (p=0·026), an absolute increase of 20% (95% CI 5-34). Treatment-related deaths occurred in three (4·5%) of 66 patients after SABR, compared with none in the control group. INTERPRETATION: SABR was associated with an improvement in overall survival, meeting the primary endpoint of this trial, but three (4·5%) of 66 patients in the SABR group had treatment-related death. Phase 3 trials are needed to conclusively show an overall survival benefit, and to determine the maximum number of metastatic lesions wherein SABR provides a benefit. FUNDING: Ontario Institute for Cancer Research and London Regional Cancer Program Catalyst Grant.

Treatment outcomes and incidence of brain metastases in pulmonary large cell neuroendocrine carcinoma.

INTRODUCTION: Large cell neuroendocrine carcinoma (LCNEC) is a rare type of high-grade pulmonary neuroendocrine tumor. The study objective is to investigate its survival outcomes, incidence of brain metastases, and patterns of recurrence. METHODS: This is a single center study of patients with pathologic diagnosis of pulmonary LCNEC. Patient data were collected retrospectively and analyzed, including survival, incidence of brain metastases, and patterns of recurrence. RESULTS: Of 87 patients (stages I: 24, II: 14, III: 23, IV: 26), 52 were managed curatively and 35 palliatively. The median follow-up time was 17.3 months (range 0.6-89.5) for those treated with curative intent and 7.0 months (range 0.1-28.6) for those treated palliatively. The 2- and 5-year overall survival (OS) rates are 48.4% and 25.5% for the curative group, with a median OS of 13.5 months. In the palliative group, the OS are 30.8% at 1 year and 6.8% at 2 years, with a median OS of 7.0 months. Thirty-eight of 52 (73%) patients treated with curative intent had disease relapse, with the common sites being regional lymph nodes (20), brain (18), bones (11), and liver (9). The incidence of brain recurrence among those managed curatively are 21.4% and 41.3%, respectively at 1 and 2 years. Of 18 patients experiencing brain metastases, 14 developed them as part of a first relapse. CONCLUSIONS: LCNEC's survival outcomes are poor. The incidence of brain metastases is higher than what is observed for other types of nonsmall cell lung cancers. Prophylactic cranial irradiation should be investigated as a means of improving outcomes.

Quality of life related to symptomatic outcomes in patients with vestibular schwannomas: A Canadian Centre perspective.

Patients with vestibular schwannomas (VS) typically present with hearing loss and tinnitus as well as variable cranial nerve dysfunctions. Surgical resection, stereotactic radiotherapy and/or conservative management employing serial magnetic resonance or computed tomography imaging serve as the main treatment options. Quality of life (QoL) may be impacted by the extent of tumour burden and exacerbated or relieved by treatment. Subjective assessment and quality of life inventories provide valuable information in client centered approaches with important implications for treatment. The intention of QoL measurements affecting VS patients within a clinical setting is to facilitate discussions regarding treatment options and objectively evaluate patient- centered clinical outcomes in a naturalistic setting.

Energy-dependent OAR sparing and dose conformity for total marrow irradiation of obese patients.

PURPOSE: To investigate the effect on target coverage and organs at risk sparing by using 10 versus 6 MV for VMAT total marrow irradiation of obese patients. METHODS AND MATERIALS: Twenty-six total marrow irradiation, TMI, treatment plans delivered between December 2014 and June 2017 were reviewed and 10 were chosen for replanning based on patient characteristics and plan metrics. Beam geometry and isocenter placement were conserved, energy was changed from 6 to 10 MV and plans were reoptimized. Resulting dose distributions were compared to original plans to evaluate any potential advantage of choosing one energy over the other. RESULTS: Target coverage and total monitor units were consistent between the 6 and 10 MV plans when averaged over all ten patients. Improvement in the conformity index (-11.0%, P = 0.009) when using 10 MV was statistically significant compared to the 6 MV plans. Volumes of normal tissue receiving 50%, 75%, and 90% Rx all decreased for the 10 MV plans compared to the original 6 MV plans. The mean dose to individual OARs decreased significantly for all investigated structures except for the lenses, oral cavity, and genitalia. The largest decreases in Dmean were found for the rectum (22.4%, P = 0.004) and bladder (18.1%, P = 0.005). The three highest priorities for sparing during plan optimization (lungs, liver, and heart), showed decreases of 7.6%, 16.1%, and 13.0%. CONCLUSIONS: Use of a higher energy 10 MV beam provided similar dose to target while achieving increased OAR and normal tissue sparing for the patients reviewed in this study.

Palliative chemoradiotherapy versus radiotherapy alone for dysphagia in advanced oesophageal cancer: a multicentre randomised controlled trial (TROG 03.01).

BACKGROUND: A short course of radiotherapy is commonly prescribed for palliative relief of malignant dysphagia in patients with incurable oesophageal cancer. We compared chemoradiotherapy with radiotherapy alone for dysphagia relief in the palliative setting. METHODS: This multicentre randomised controlled trial included patients with advanced or metastatic oesophageal cancer who were randomly assigned (1:1) through a computer-generated adaptive biased coin design to either palliative chemoradiotherapy or radiotherapy alone for treatment of malignant dysphagia at 22 hospitals in Australia, Canada, New Zealand, and the UK. Eligible patients had biopsy-proven oesophageal cancer that was unsuitable for curative treatment, symptomatic dysphagia, Eastern Cooperative Oncology Group performance status 0-2, and adequate haematological and renal function. Patients were stratified by hospital, dysphagia score (Mellow scale 1-4), and presence of metastases. The radiotherapy dose was 35 Gy in 15 fractions over 3 weeks for patients in Australia and New Zealand and 30 Gy in ten fractions over 2 weeks for patients in Canada and the UK. Chemotherapy consisted of one cycle of intravenous cisplatin (either 80 mg/m2 on day 1 or 20 mg/m2 per day on days 1-4 of radiotherapy at clinician's discretion) and intravenous fluorouracil 800 mg/m2 per day on days 1-4 of radiotherapy in week 1. Patients were assessed weekly during treatment. The primary endpoint was dysphagia relief (defined as ≥1 point reduction on the Mellow scale at 9 weeks and maintained 4 weeks later), and key secondary endpoints were dysphagia progression-free survival (defined as a worsening of at least 1 point on the Mellow scale from baseline or best response) and overall survival. These endpoints were analysed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00193882. This trial is closed. FINDINGS: Between July 7, 2003, and March 21, 2012, 111 patients were randomly assigned to chemoradiotherapy and 109 patients to radiotherapy. One patient in the chemoradiotherapy group was omitted from analysis because of ineligibility. 50 (45%, 95% CI 36-55) patients in the chemoradiotherapy group and 38 (35%, 26-44) in the radiotherapy group obtained dysphagia relief (difference 10·6%, 95% CI -2 to 23; p=0·13). Median dysphagia progression-free survival was 4·1 months (95% CI 3·5-4·8) versus 3·4 months (3·1-4·3) in the chemoradiotherapy and radiotherapy groups, respectively (p=0·58), and median overall survival was 6·9 months (95% CI 5·1-8·3) versus 6·7 months (4·9-8·0), respectively (p=0·88). Of the 211 patients who commenced radiotherapy, grade 3-4 acute toxicity occurred in 38 (36%) patients in the chemoradiotherapy group and in 17 (16%) patients in the radiotherapy group (p=0·0017). Anaemia, thrombocytopenia, neutropenia, oesophagitis, diarrhoea, nausea and vomiting, and mucositis were significantly worse in patients who had chemoradiotherapy than in patients who had radiotherapy. INTERPRETATION: Palliative chemoradiotherapy showed a modest, but not statistically significant, increase in dysphagia relief compared with radiotherapy alone, with minimal improvement in dysphagia progression-free survival and overall survival with chemoradiotherapy but at a cost of increased toxicity. A short course of radiotherapy alone should be considered a safe and well tolerated treatment for malignant dysphagia in the palliative setting. FUNDING: National Health and Medical Research Council, Canadian Cancer Society Research Institute, Canadian Cancer Trials Group, Trans Tasman Radiation Oncology Group, and Cancer Australia.

Scalp Seeding Post Craniotomy and Radiosurgery for Solitary Brain Metastasis: A Case Report and Systematic Review.

BACKGROUND: Radiosurgery is being increasingly used post craniotomy for brain metastasis, instead of whole-brain radiation. We report a case of scalp metastasis following craniotomy and radiosurgery, along with a systematic review of the literature. METHODS: Our patient was a 70-year-old male who presented with a scalp metastasis, two years after craniotomy and radiosurgery, for a solitary brain metastasis from esophageal carcinoma. Using Medline® (United States National Library of Medicine, Bethesda, MD), we performed a systematic review of the literature to identify cases of isolated scalp metastases following craniotomy for brain lesions. RESULTS: The scalp metastasis was in close proximity to the craniotomy site. Workup did not show any other site of active disease. Biopsy confirmed it to be a metastasis from esophageal carcinoma. The literature review did not yield any case of isolated scalp metastasis following craniotomy and whole-brain radiotherapy or radiosurgery. However, it yielded six cases of isolated scalp metastases following craniotomy for primary brain tumors. CONCLUSION: Isolated scalp metastasis has not been reported following craniotomy and whole-brain radiotherapy for brain metastases. Our patient likely had surgical seeding during craniotomy. These surgically implanted cells could not be ablated because the radiosurgery treatment volume does not cover the surgical tract. Further research is needed to identify risk factors for surgical seeding.

Investigating the Impact of Positron Emission Tomography-Computed Tomography Versus Computed Tomography Alone for High-risk Volume Selection in Head and Neck and Lung Patients Undergoing Radiotherapy: Interim Findings.

INTRODUCTION: The aim of this study was to quantify the impact of positron emission tomography-computed tomography (PET-CT) on clinical target volume (CTV) selection in non-small cell lung cancer (NSCLC) and head and neck squamous cell cancer (HNSCC) cancer patients. METHODS: Eight radiation oncologists with expertise in either NSCLC or HNSCC prospectively contoured target volumes with and without PET-CT findings. All volumes were contoured manually, and computed tomography (CT)-alone contours were identified as gross tumour volume CT and clinical target volume (CTV) CT, whereas those contoured with the aid of PET-CT were GTV PET and CTV PET. PET-CT contours were used for actual treatment delivery. Test treatment plans were generated based on the CT-alone volumes and applied to the final PET-CT contours. PET-CT had an impact if the test plans failed department quality assurance guidelines. For each patient, the dose to critical structures and any changes in the treatment plan were recorded. RESULTS: Eighty patients (49 HNSCC and 31 NSCLC) were analyzed. PET-CT impacted 42.9% of HNSCC cases and 45.2% of NSCLC cases. On average, PET-CT volumes were significantly larger than CT-alone volumes for HNSCC cases (P < .01) but not for NSCLC cases (P = .29). For organs at risk, no statistically significant differences were noted, with the exception of mean parotid dose for the right and left parotids (P = .0137and P = .0330, respectively). CONCLUSIONS: Interim analysis of data found that the use of PET-CT in the radiation therapy planning process impacted CTV selection, resulting in a major change in radiation therapy plans in 43.7% (HNSCC 42.9% and NSCLC 45.2%) of patients.

PET/CT aids the staging of and radiotherapy planning for early-stage extranodal natural killer/T-cell lymphoma, nasal type: a case series.

Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare form of non-Hodgkin lymphoma. Treatment of ENKTL primarily relies on radiation; thus, proper delineation of target volumes is critical. Currently, the ideal modalities for delineation of gross tumor volume for ENKTL are unknown. We describe three consecutive cases of localized ENKTL that presented to the Nova Scotia Cancer Centre in Halifax, Nova Scotia. All patients had a planning CT and MRI as well as a planning FDG-PET/CT in the radiotherapy treatment position, wearing immobilization masks. All patients received radiation alone. In two patients, PET/CT changed not only the stage, but also the target volume requiring treatment. The third patient was unable to tolerate an MRI, but was able to undergo PET/CT, which improved the accuracy of the target volume. PET/CT aided the staging of and radiotherapy planning for our patients and appears to be a promising tool in the treatment of ENKTL.

Radiosurgery scope of practice in Canada: a report of the Canadian association of radiation oncology (CARO) radiosurgery advisory committee.

Radiosurgery has a long history in Canada. Since the treatment of the first patient at the McGill University Health Center in 1985, radiosurgery programs have been developed from coast to coast. These have included multidisciplinary teams of radiation oncologists, neurosurgeons, medical physicists, radiation technologists and other health professionals. In 2008, the CARO Board of Directors requested that a working group be formed to define the role of the radiation oncologist in the practice of radiosurgery. Taking into account evolving technology, changing clinical practice and current scope of practice literature, the working group made recommendations as to the role of the radiation oncologists. These recommendations were endorsed by the Canadian Association of Radiation Oncology board of directors in September 2009 and are present herein. It is recognized that patients benefit from a team approach to their care but it is recommended that qualified radiation oncologists be involved in radiosurgery delivery from patient consultation to follow-up. In addition, radiation oncologists should continue to be involved in the administrative aspects of radiosurgery programs, from equipment selection to ongoing quality assurance/quality improvement.

Outcome of stereotactic radiotherapy for patients with uncontrolled acromegaly.

OBJECTIVE: Linear accelerator based stereotactic radiation therapy (SRT) has been used for the treatment of pituitary tumours; however, little is known concerning the use of this modality for the treatment of patients with acromegaly. We have prospectively studied the short-term outcome of SRT in 12 acromegaly patients who failed to achieve biochemical remission despite surgery and/or pharmacologic therapy. METHODS: We identified all patients who had biochemically uncontrolled acromegaly and were treated with SRT between April 2003 and December 2006. All patients were followed prospectively based on a pre-defined protocol that included Goldman visual field examination, MRI of the sella, and pituitary hormone testing at 3, 6, 12 months, and then yearly. RESULTS: A total of 12 patients with acromegaly were treated with SRT. There were 9 females and the median age of the group was 50 years. The median follow-up was 28.5 months during which time the mean tumor volume decreased by 40%, the median GH fell from 4.1 microg/L to 1.3 microg/L (p = 0.003) and the median IGF-1 dropped more than half from 545.5 microg/L to 260.5 microg/L (p = 0.002). Four patients achieved normal, while an additional 2 achieved near-normal, IGF-1 levels. One patient was able to discontinue and two were able to reduce their acromegaly medications while maintaining a normal IGF-1. A new pituitary hormonal deficit was found at 24 months in one patient who developed hypoadrenalism requiring corticosteroid replacement. CONCLUSION: Based on our early experience, we believe that SRT should be considered in treating patients with uncontrolled acromegaly.

Randomized, double-blind, placebo-controlled trial of erythropoietin in non-small-cell lung cancer with disease-related anemia.

PURPOSE: Previous trials have suggested a quality-of-life (QOL) improvement for anemic cancer patients treated with erythropoietin, but few used QOL as the primary outcome. We designed a trial to investigate the effects of epoetin alfa therapy on the QOL of anemic patients with advanced non-small-cell carcinoma of the lung (NSCLC). PATIENTS AND METHODS: A multicenter, randomized, double-blind, placebo-controlled trial was conducted. The proposed sample size was 300 patients. Eligible patients were required to have NSCLC unsuitable for curative therapy and baseline hemoglobin (Hgb) levels less than 121 g/L. Patients were assigned to 12 weekly injections of subcutaneous epoetin alpha or placebo, targeting Hgb levels between 120 and 140 g/L. The primary outcome was the difference in the change in Functional Assessment of Cancer Therapy-Anemia scores between baseline and 12 weeks. RESULTS: Reports of thrombotic events in other epoetin trials prompted an unplanned safety analysis after 70 patients had been randomly assigned (33 to the active arm and 37 to the placebo arm). This revealed a significant difference in the median survival in favor of the patients on the placebo arm of the trial (63 v 129 days; hazard ratio, 1.84; P = .04). The Steering Committee closed the trial. Patient numbers compromised the interpretation of the QOL analysis, but a positive Hgb response was noted with epoetin alfa treatment. CONCLUSION: An unplanned safety analysis suggested decreased overall survival in patients with advanced NSCLC treated with epoetin alfa. Although infrequent, other similar reports highlight the need for ongoing trials evaluating erythropoietin receptor agonists to ensure that overall survival is monitored closely.