Arts Undergraduate Handbook 2009

PURPOSE: Anemia is associated with poor tumor control. It was previously observed that accelerated radiotherapy combined with carbogen breathing and nicotinamide (ARCON) can correct this adverse outcome in patients with head and neck cancer. The purpose of this study was to validate this observation based on data from a randomized trial. EXPERIMENTAL DESIGN: Of 345 patients with cT2-4 laryngeal cancer, 174 were randomly assigned to accelerated radiotherapy and 171 to ARCON. Hemoglobin levels, measured before treatment, were defined as low when <7.5 mmol/L for women and <8.5 mmol/L for men. The hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies. Data were analyzed 2 years after inclusion of the last patient. RESULTS: Pretreatment hemoglobin levels were available and below normal in 27 of 173 (16%) accelerated radiotherapy and 27 of 167 (16%) ARCON patients. In patients with normal pretreatment, hemoglobin levels treatment with ARCON had no significant effect on 5-year loco-regional control (LRC, 79% versus 75%; P = 0.44) and disease-free survival (DFS, 75% vs. 70%; P = 0.46) compared with accelerated radiotherapy. However, in patients with low pretreatment, hemoglobin levels ARCON significantly improved 5-year LRC (79% vs. 53%; P = 0.03) and DFS (68% vs. 45%; P = 0.04). In multivariate analysis including other prognostic factors, pretreatment hemoglobin remained prognostic for LRC and DFS in the accelerated radiotherapy treatment arm. No correlation between pretreatment hemoglobin levels and pimonidazole uptake was observed. CONCLUSION: Results from the randomized phase III trial support previous observations that ARCON has the potential to correct the poor outcome of cancer patients with anemia (ClinicalTrials.gov number, NCT00147732). Clin Cancer Res; 20(5); 1345-54. (c)2014 AACR

ARCON for laryngeal cancer

Contains fulltext : 155622.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 17 maart 2016Promotor : Kaanders, J.H.A.M. Co-promotor : Span, P.N

Acute toxicity profile of craniospinal irradiation with intensity-modulated radiation therapy in children with medulloblastoma: A prospective analysis

Contains fulltext : 152450.pdf (publisher's version ) (Open Access)BACKGROUND: To report on the acute toxicity in children with medulloblastoma undergoing intensity-modulated radiation therapy (IMRT) with daily intrafractionally modulated junctions. METHODS: Newly diagnosed patients, aged 3-21, with standard-risk (SR) or high-risk (HR) medulloblastoma were eligible. A dose of 23.4 or 36.0Gy in daily fractions of 1.8Gy was prescribed to the craniospinal axis, followed by a boost to the primary tumor bed (54 or 55.8Gy) and metastases (39.6-55.8Gy), when indicated. Weekly, an intravenous bolus of vincristine was combined for patients with SR medulloblastoma and patients participating in the COG-ACNS-0332 study. Common toxicity criteria (CTC, version 2.0) focusing on skin, alopecia, voice changes, conjunctivitis, anorexia, dysphagia, gastro-intestinal symptoms, headache, fatigue and hematological changes were scored weekly during radiotherapy. RESULTS: From 2010 to 2014, data from 15 consecutive patients (SR, n = 7; HR, n = 8) were collected. Within 72 h from onset of treatment, vomiting (66 %) and headache (46 %) occurred. During week 3 of treatment, a peak incidence in constipation (33 %) and abdominal pain/cramping (40 %) was observed, but only in the subgroup of patients (n = 9) receiving vincristine (constipation: 56 vs 0 %, P = .04; pain/cramping: 67 vs 0 %, P = .03). At week 6, 73 % of the patients developed faint erythema of the cranial skin with dry desquamation (40 %) or moist desquamation confined to the skin folds of the auricle (33 %). No reaction of the skin overlying the spinal target volume was observed. CONCLUSIONS: Headache at onset and gastro-intestinal toxicity, especially in patients receiving weekly vincristine, were the major complaints of patients with medulloblastoma undergoing craniospinal irradiation with IMRT

Outcome and toxicity profile after brachytherapy for squamous cell carcinoma of the nasal vestibule

Contains fulltext : 153558.pdf (Publisher’s version ) (Closed access)BACKGROUND: The purpose of this study was to evaluate outcome and toxicity profile after primary brachytherapy for squamous cell carcinoma of the nasal vestibule. METHODS: A retrospective study was conducted for patients with Wang classification T1 to 2 cN0 squamous cell carcinoma of the nasal vestibule who received primary treatment with brachytherapy between 1992 and 2010. Tumor control, acute skin, mucosal, and late cartilage toxicity were scored. RESULTS: Of 60 patients (T1, 50; T2, 10), 38 were treated with an interstitial implant and 22 by a mold technique. The 3-year local, regional, and locoregional control rates were 91%, 93%, and 84%, respectively. Tumor diameter <1.5 cm resulted in a better local (p = .02) and regional (p = .05) control. The cumulative incidence of moist skin desquamation and confluent mucositis was 64% and 82%, respectively. The actuarial incidence of chondritis and/or chondronecrosis was 19%. CONCLUSION: Primary brachytherapy for Wang T1 to 2 squamous cell carcinoma of the nasal vestibule offers excellent tumor control rates with acceptable toxicity and preservation of anatomy. (c) 2014 Wiley Periodicals, Inc. Head Neck 37: 1297-1303, 2015

Effectiveness and toxicity of hypofractionated high-dose intensity-modulated radiotherapy versus 2- and 3-dimensional radiotherapy in incurable head and neck cancer

BACKGROUND: This retrospective study evaluates efficacy and tolerability of high-dose hypofractionated radiotherapy (RT) in patients with head and neck cancer. METHODS: All patients with head and neck cancer treated between September 2003 and September 2013 with 12 x 4 Gy RT were included. Two and 3D-RT or intensity-modulated radiotherapy (IMRT) were used. Overall survival (OS), tumor response, and palliative effect were evaluated. RESULTS: Palliative effect occurred in 63% of 81 included patients, lasted a median of 4.6 months, and was correlated with tumor response (p = .006). Median OS was 7.2 months. Confluent mucositis occurred more often in patients treated with 2D/3D-RT than IMRT (26% vs 44%; p = .04) and lasted for a median of 2 weeks. CONCLUSION: High-dose hypofractionated RT resulted in meaningful palliation in 63%, lasting for almost 5 months. IMRT should be the technique of choice, as it results in less high-grade toxicity. The 12 x 4 schedule should be opted for patients with reasonable functional capacities and a life expectancy of >6 months. (c) 2015 Wiley Periodicals, Inc. Head Neck 38: E1264-E1270, 2016

Trends in sinonasal cancer in The Netherlands: more squamous cell cancer, less adenocarcinoma. A population-based study 1973-2009

BACKGROUND: Cancer of the nasal cavity or the paranasal sinuses (sinonasal cancer) is rare. Sinonasal cancer has been associated with various occupational risk factors such as exposure to dust of hard wood and leather. Also, a relationship with smoking habits has been suggested. We studied the long term trends in incidence to evaluate a putative effect of past preventive measures or changes in risk factors. DESIGN: A retrospective population-based descriptive study. OBJECTIVE: To interpret the long term trends in incidence of sinonasal cancer in The Netherlands. METHODS: Data of all 3329 patients >15 years registered during 1989-2009 by the Netherlands Cancer Registry (NCR) were analysed, by data of 447 patients registered by the Eindhoven Cancer Registry (ECR) during 1973-2009 were analysed separately. Information on patients and tumour characteristics was obtained from both registries. The incidence was calculated per 1,000,000 person years and standardised using the European Standard Population. RESULTS: Squamous cell carcinoma (SCC) was the most prominent histological type (48%), followed by adenocarcinoma (15%) and melanoma (8%). SCC was more frequently located in the nasal cavity or sinus maxillaris, but adenocarcinoma was more located in the ethmoid sinus. The male incidence increased during 1973-1995 with a peak of 15/1,000,000/year, decreasing since then to 11/1,000,000/year due to a declining incidence of both SCC and adenocarcinoma. In females the incidence remained stable around 5/1,000,000/year up to 2006 and increased to 7.5/1,000,000 in 2009 as a result of more SCC. The male/female ratio for SCC decreased from 2.7 to 2.0, and for adenocarcinoma from 3.4 to 2.8 since 1989. CONCLUSIONS: The higher incidence in males and the different trends in incidence in males and females may reflect differences in previous exposure to risk factors. Adenocarcinoma, related to occupational exposures, tend to decline. The trends in both male and female sinonasal SCC are comparable with the trends in lung cancer

Acute toxicity profile of craniospinal irradiation with intensity-modulated radiation therapy in children with medulloblastoma: A prospective analysis

BACKGROUND: To report on the acute toxicity in children with medulloblastoma undergoing intensity-modulated radiation therapy (IMRT) with daily intrafractionally modulated junctions. METHODS: Newly diagnosed patients, aged 3-21, with standard-risk (SR) or high-risk (HR) medulloblastoma were eligible. A dose of 23.4 or 36.0Gy in daily fractions of 1.8Gy was prescribed to the craniospinal axis, followed by a boost to the primary tumor bed (54 or 55.8Gy) and metastases (39.6-55.8Gy), when indicated. Weekly, an intravenous bolus of vincristine was combined for patients with SR medulloblastoma and patients participating in the COG-ACNS-0332 study. Common toxicity criteria (CTC, version 2.0) focusing on skin, alopecia, voice changes, conjunctivitis, anorexia, dysphagia, gastro-intestinal symptoms, headache, fatigue and hematological changes were scored weekly during radiotherapy. RESULTS: From 2010 to 2014, data from 15 consecutive patients (SR, n = 7; HR, n = 8) were collected. Within 72 h from onset of treatment, vomiting (66 %) and headache (46 %) occurred. During week 3 of treatment, a peak incidence in constipation (33 %) and abdominal pain/cramping (40 %) was observed, but only in the subgroup of patients (n = 9) receiving vincristine (constipation: 56 vs 0 %, P = .04; pain/cramping: 67 vs 0 %, P = .03). At week 6, 73 % of the patients developed faint erythema of the cranial skin with dry desquamation (40 %) or moist desquamation confined to the skin folds of the auricle (33 %). No reaction of the skin overlying the spinal target volume was observed. CONCLUSIONS: Headache at onset and gastro-intestinal toxicity, especially in patients receiving weekly vincristine, were the major complaints of patients with medulloblastoma undergoing craniospinal irradiation with IMRT

Chemotherapy for children with medulloblastoma

BACKGROUND: Post-surgical radiotherapy (RT) in combination with chemotherapy is considered as standard of care for medulloblastoma in children. Chemotherapy has been introduced to improve survival and to reduce RT-induced adverse effects. Reduction of RT-induced adverse effects was achieved by deleting (craniospinal) RT in very young children and by diminishing the dose and field to the craniospinal axis and reducing the boost volume to the tumour bed in older children. OBJECTIVES: Primary objectives: 1. to determine the event-free survival/disease-free survival (EFS/DFS) and overall survival (OS) in children with medulloblastoma receiving chemotherapy as a part of their primary treatment, as compared with children not receiving chemotherapy as part of their primary treatment; 2. to determine EFS/DFS and OS in children with medulloblastoma receiving standard-dose RT without chemotherapy, as compared with children receiving reduced-dose RT with chemotherapy as their primary treatment.Secondary objectives: to determine possible adverse effects of chemotherapy and RT, including long-term adverse effects and effects on quality of life. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 7), MEDLINE/PubMed (1966 to August 2013) and EMBASE/Ovid (1980 to August 2013). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases (August 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating the above treatments in children (aged 0 to 21 years) with medulloblastoma. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, data extraction and risk of bias assessment. We performed analyses according to the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions. Where possible, we pooled results. MAIN RESULTS: The search identified seven RCTs, including 1080 children, evaluating treatment including chemotherapy and treatment not including chemotherapy. The meta-analysis of EFS/DFS not including disease progression during therapy as an event in the definition showed a difference in favour of treatment including chemotherapy (hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.54 to 0.91; P value = 0.007; 2 studies; 465 children). However, not including disease progression as an event might not be optimal and the finding was not confirmed in the meta-analysis of EFS/DFS including disease progression during therapy as an event in the definition (HR 1.02; 95% CI 0.70 to 1.47; P value = 0.93; 2 studies; 300 children). Two individual studies using unclear or other definitions of EFS/DFS also showed no clear evidence of difference between treatment arms (one study with unclear definition of DFS: HR 1.67; 95% CI 0.59 to 4.71; P value = 0.34; 48 children; one study with other definition of EFS: HR 0.84; 95% CI 0.58 to 1.21; P value = 0.34; 233 children). In addition, it should be noted that in one of the studies not including disease progression as an event, the difference in DFS only reached statistical significance while the study was running, but due to late relapses in the chemotherapy arm, this significance was no longer evident with longer follow-up. There was no clear evidence of difference in OS between treatment arms (HR 1.06; 95% CI 0.67 to 1.67; P value = 0.80; 4 studies; 332 children). Out of eight reported adverse effects, of which seven were reported in one study, two (severe infections and fever/neutropenia) showed a difference in favour of treatment not including chemotherapy (severe infections: risk ratio (RR) 5.64; 95% CI 1.28 to 24.91; P value = 0.02; fever/neutropenia: RR not calculable; Fisher's exact P value = 0.01). There was no clear evidence of a difference between treatment arms for other adverse effects (acute alopecia: RR 1.00; 95% CI 0.92 to 1.08; P value = 1.00; reduction in intelligence quotient: RR 0.78; 95% CI 0.46 to 1.30; P value = 0.34; secondary malignancies: Fisher's exact P value = 0.5; haematological toxicity: RR 0.54; 95% CI 0.20 to 1.45; P value = 0.22; hepatotoxicity: Fisher's exact P value = 1.00; treatment-related mortality: RR 2.37; 95% CI 0.43 to 12.98; P value = 0.32; 3 studies). Quality of life was not evaluated. In individual studies, the results in subgroups (i.e. younger/older children and high-risk/non-high-risk children) were not univocal.The search found one RCT comparing standard-dose RT with reduced-dose RT plus chemotherapy. There was no clear evidence of a difference in EFS/DFS between groups (HR 1.54; 95% CI 0.81 to 2.94; P value = 0.19; 76 children). The RCT did not evaluate other outcomes and subgroups.The presence of bias could not be ruled out in any of the studies. AUTHORS' CONCLUSIONS