Long-term results of radiation therapy oncology group 9903: A randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck
Shenouda G.,McGill University |
Zhang Q.,Data Management |
Ang K.K.,University of Houston |
Machtay M.,University Hospitals of Cleveland |
And 11 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2015
Purpose This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). Methods and Materials The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm. Results A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. Conclusions This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out. © 2015 Elsevier Inc.
Dayes I.,McMaster University |
Rumble R.B.,Cancer Care Ontarios Program in Evidence based Care |
Bowen J.,Northeastern Ontario Regional Cancer Center |
Dixon P.,Queen's University |
Warde P.,Radiation Treatment Program
Clinical Oncology | Year: 2012
Intensity-modulated radiotherapy (IMRT) is a newer method of radiotherapy that uses beams with multiple intensity levels for any single beam, allowing concave dose distributions and tighter margins than those possible using conventional radiotherapy. IMRT is ideal for treating complex treatment volumes and avoiding close proximity organs at risk that may be dose limiting and provides increased tumour control through an escalated dose and reduces normal tissue complications through organ at risk sparing. Given the potential advantages of IMRT and the availability of IMRT-enabled treatment planning systems and linear accelerators, IMRT has been introduced in a number of disease sites. This systematic review examined the evidence for IMRT in the treatment of breast cancer to quantify the potential benefits of this new technology and to make recommendations for radiation treatment programmes considering adopting this technique. Providing that avoidance of acute adverse effects associated with radiation is an outcome of interest, then IMRT is recommended over tangential radiotherapy after breast-conserving surgery, based on a review of six published reports including 2012 patients. There were insufficient data to recommend IMRT over standard tangential radiotherapy for reasons of oncological outcomes or late toxicity. Future research should focus on studies with longer follow-up and provide data on late toxicity and disease recurrence rates. © 2012 The Royal College of Radiologists.
Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck
PubMed | McGill University, University of Pennsylvania, University of Houston, New York University and 9 more.
Type: Clinical Trial, Phase III | Journal: International journal of radiation oncology, biology, physics | Year: 2015
This paper reports long-term results of RTOG 9903,to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa).The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5g/dL (12.5g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10days before RT was initiated in the RT+EPO arm.A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1g/dL. In the RT+EPO arm, the mean hemoglobin level at 4weeks increased by 1.66g/dL, whereas it decreased by 0.24g/dL in the RT arm. With a median follow-up of 7.95years (range: 1.66-10.08years) for surviving patients and 3.33years for all patients (range: 0.03-10.08years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT+EPO and RT arms, respectively. Late toxicity was not different between the 2 arms.This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.
Bissett R.J.,Northeastern Ontario Regional Cancer Center
Chronic diseases in Canada | Year: 2010
Radon is a radioactive gas that emanates from uranium-bearing soil and porous rock. Although radon is most highly concentrated in areas of high uranium concentration, the presence of trace amounts of uranium in most ground sources means that all humans are exposed to radon to some degree. Radon migrates out of soil and rock into the surrounding air, resulting in accumulation in poorly ventilated or closed areas. Such areas represent the primary environments in which humans are exposed to radioactivity from radon to experience detrimental health effects. There is no convincing evidence that any cancers other than lung cancer are associated with exposure to radon. There is, on the other hand, consistent evidence of a substantially elevated risk of lung cancer among Canadians exposed to radon in certain occupational settings, particularly uranium mining. While the combined evidence for a positive association between residential radon exposure and lung cancer is less compelling, the inherent methodological difficulties in mounting such studies may render it impossible for any single study to detect the relationship more conclusively. The best available evidence to date from pooled analyses indicates a positive, but weak association between residential radon and lung cancer risk. Residential radon is of critical importance because it is ubiquitous; a small excess risk that may exist in relation to radon exposures encountered in a residential setting translates into the potential for a far greater number of excess cancers in the general population than does exposure of a relatively small number of miners, even though the latter may be exposed to much higher levels of ionizing radiation. Fortunately, a number of techniques are available to homeowners to reduce radon concentrations in their homes.
Abara E.,Richmond Hill Urology Practice and Prostate Institute |
Chivulescu I.,McMaster University |
Clerk N.,York Central Hospital |
Cano P.,Northeastern Ontario Regional Cancer Center |
Goth A.,Sensenbrener Hospital
Journal of the Canadian Urological Association | Year: 2010
Localized renal cell carcinoma (RCC) responds well to surgery. Patients often question how long they have to be on surveillance after their surgery. Several follow-up patterns have been described in the literature. Until 2009, no published established Canadian guidelines existed to assist Canadian health-care practitioners in the surveillance of these patients. We present 3 cases of RCC that recurred 10 years or longer after the initial nephrectomy. These cases emphasize the need for careful long-term follow-up, as recommended in the Canadian Urological Association guidelines. We also discuss the optimism of prolonged disease survival in the era of novel therapeutic agents that target angiogenesis. © 2010 Canadian Urological Association.
Alexander A.,British Columbia Cancer Agency |
Crook J.,Princess Margaret Hospital |
Jones S.,British Columbia Cancer Agency |
Malone S.,Ottawa Regional Cancer Center |
And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010
Purpose: To ascertain whether biochemical response to neoadjuvant androgen-deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the critical determinant of benefit in the multimodal treatment of localized prostate cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8-month trial with a pre-RT, post-hormone PSA (PRPH-PSA) ≤0.1 ng/ml vs those >0.1 ng/ml. Methods and Materials: From 1995 to 2001, 378 men with localized prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On univariate analysis, survival indices were compared between those with a PRPH-PSA ≤0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including treatment arm, risk group, and gleason Score. Multivariate analysis identified independent predictors of outcome. Results: Biochemical disease-free survival (bDFS) was significantly higher for those with a PRPH-PSA ≤0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in survival indices was observed between treatment arms. There was no difference in bDFS between patients in the 3- and 8-month arms with a PRPH-PSA ≤0.1 ng/ml nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk patients with PRPH-PSA ≤0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0% vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA (p = 0.041), Gleason score (p = 0.001), initial PSA (p = 0.025), and T-stage (p = 0.003), not ADT duration, as independent predictors of outcome. Conclusion: Biochemical response to neoadjuvant ADT before RT, not duration, appears to be the critical determinant of benefit in the setting of combined therapy. Individually tailored ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing the duration of ADT and its related toxicities. © 2010 Elsevier Inc. All rights reserved.
Crump M.,University of Toronto |
Herst J.,Northeastern Ontario Regional Cancer Center |
Baldassarre F.,McMaster University |
Sussman J.,Juravinski Cancer Center |
And 3 more authors.
Blood | Year: 2015
Case 1. Anne is a 23-year-old nursing student who presents with bilateral cervical, left supraclavicular, and left axillary adenopathy. Computed tomography (CT) scan of the thorax reveals a 6-cm anterior mediastinal mass. Biopsy of the left supraclavicular lymph node reveals classical nodular sclerosis Hodgkin lymphoma. A complete blood count is normal and the erythrocyte sedimentation rate (ESR) is 25 mm/h. CT scan of the abdomen/pelvis show normal liver and spleen and no evidence of abdominal lymphadenopathy. You are asked to advise her on the role of radiation therapy in her treatment plan. Case 2. John is a 48-year-old teacher who presents with chest pain following a hockey game. A chest radiograph reveals mediastinal widening, and a contrast-enhancedCT scan shows a 7.5-cm anterior mediastinalmass, with enlarged paratracheal and right hilar lymph nodes. Image-guided core biopsy of the mediastinal mass is diagnostic for classical Hodgkin lymphoma. The hemoglobin is 130 g/L, white blood cell count and platelets are normal, and the ESR is 35 mm/h. John asks you about the role of radiotherapy in the management of his lymphoma. © 2015 by The American Society of Hematology.
Whelan T.J.,McMaster University |
Olivotto I.A.,Tom Baker Cancer Center |
Olivotto I.A.,Cancer Agency Vancouver Island Center |
Parulekar W.R.,Queen's University |
And 20 more authors.
New England Journal of Medicine | Year: 2015
Background Most women with breast cancer who undergo breast-conserving surgery receive wholebreast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes. Methods We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodalirradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival. Results Between March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P = 0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P = 0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P = 0.01) and lymphedema (8.4% vs. 4.5%, P = 0.001). Conclusions Among women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. © 2015 Massachusetts Medical Society.
PubMed | Northeastern Ontario Regional Cancer Center
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
3137 Background: Preclinical studies indicate the conventional chemotherapeutic agents given continuously at low doses may provide an improved therapeutic index (RS Kerbel et al, Annals of Oncology 13:12-15, 2002). Cyclophosphamide and vinblastine have been best studied in experimental models where tumor growth retardation is achieved, at least in part, through antiangiogenic mechanisms.50 with advanced solid tumors were enrolled (26 male and 24 female, median age 63 years - range 24 - 85). 43 patients had received at least one prior chemotherapy regimen. Patients were required to have ECOG performance status < 2, a life expectancy of > 3 months and at least one measurable lesion. All patients received cyclophosphamide 50 mg PO daily, weekly injections of vinblastine 3 mg/mOf the 45 evaluable patients, there were 2 complete responses (CR) (4%), 4 partial responses (PR) (9%) for an overall objective response rate of 13%. An additional 6 patients achieved disease stabilization (SD) 6 months (13%). The primary endpoint of clinical benefit (CR + PR + SD 6 months) was, therefore, 26%. The median progression-free survival for all patients was 105 days, and 240 days for patients experiencing clinical benefit. The incidence of grade 3/4 toxicities were as follows: neutropenia 12/2, anaemia 2/0, and thrombocytopenia 1/0. No patients developed grade 3 or 4 nausea, vomiting, mucositis or alopecia.This low-dose regimen consisting of daily oral cyclophosphamide and weekly vinblastine injections given concurrently with rofecoxib is associated with minimal toxicity and provides significant clinical benefit to patients with advanced solid tumors. These results are particularly encouraging given the nature of the study population, and indicate that this regimen merits further investigation in specific disease site studies. [Table: see text].
PubMed | McMaster University, Odette Cancer Center, Grand River Regional Cancer Center, Princess Margaret Cancer Center and 2 more.
Type: Journal Article | Journal: Clinical oncology (Royal College of Radiologists (Great Britain)) | Year: 2016
In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma. We conducted a systematic review searching MEDLINE, EMBASE, the Cochrane Library and other literature sources from 2003 to 2015, and applied the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Two authors independently reviewed and selected studies, and appraised the evidence quality. The document underwent internal and external review by content, methodology experts, a patient representative and clinicians in Ontario. We have issued recommendations for patients with classical Hodgkin lymphoma and with nodular lymphocyte predominant Hodgkin lymphoma; with favourable and unfavourable prognosis; and for the use of positron emission tomography to direct treatment. We have provided our interpretation of the evidence and considerations for implementation. Examples of recommendations are: Patients with early-stage classical Hodgkin lymphoma should not be treated with radiotherapy alone; chemotherapy plus radiotherapy or chemotherapy alone are recommended treatment options for patients with early-stage non-bulky Hodgkin lymphoma; The Working Group does not recommend the use of a negative interim positron emission tomography scan alone to identify patients with early-stage Hodgkin lymphoma for whom radiotherapy can be omitted without a reduction in progression-free survival. Through the use of GRADE, recommendations were geared towards patient important outcomes and their strength reflected the available evidence and its interpretation from the patients point of view.