Chen Z, King W, Pearcy R, Kerba M, Mackillop WJThe relationship between waiting time for radiotherapy and clinical outcome: a systemic review of the literature. Radioth Oncol 87: 3-16

Queen's Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
Radiotherapy and Oncology (Impact Factor: 4.36). 05/2008; 87(1):3-16. DOI: 10.1016/j.radonc.2007.11.016
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To synthesize the direct clinical evidence relating waiting times (WTs) for radiotherapy (RT) to the outcomes of RT.
We did a systematic review of the literature between 1975 and 2005 to identify clinical studies describing the relationship between WTs and outcomes of RT. Only high quality (HQ) studies that had adequately controlled for confounding factors were included in the primary analysis. WTs that had originally been reported as a categorical variable were converted to a continuous variable based on the distribution of WTs in each category. Meta-analyses were done using a fixed-effect model.
The systematic review identified 44 relevant studies. Meta-analyses of 20 HQ studies of local control demonstrated a significant increase in the risk of local failure with increasing WT, RRlocal recurrence/month =1.14, 95% Confidence Intervals (CI): 1.09-1.21. For post-operative RT for breast cancer; RRlocal recurrence/month =1.11, 95%CI: 1.04-1.19. For post-operative RT for head and neck cancer, RRlocal recurrenc/month =1.28, 95%CI: 1.08-1.52. For definitive RT for head and neck cancer, RRlocal recurrence/month =1.15, 95%CI: 1.02-1.29. There was little evidence of any association between WTs and the risk of distant metastasis. Meta-analyses of the 6 HQ studies of breast cancer showed RRmetastasis/month =1.04, 95%CI: 0.98-1.09. Meta-analyses of 4 HQ studies of breast cancer showed no significant decrease in survival with increasing WT, RRdeath/month =1.06, 95%CI: 0.97-1.16, but there was a marginally significant decrease in survival in 4 HQ studies of head and neck cancer, RRdeath/month =1.16, 95%CI: 1.02-1.32.
The risk of local recurrence increases with increasing WTs for RT. The increase in local recurrence rate may translate into decreased survival in some clinical situations. WTs for RT should be as short as reasonably achievable.

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Available from: Marc Kerba, Oct 02, 2014
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    • "Accordingly, our multivariable Cox regression model showed that longer waiting time, was significantly related to a higher hazard of dying. A similar relationship was found in a review by Chen [18] in patients with an HNSCC treated with radiotherapy. Intuitively , this probably is due to progression of the tumor to a more advanced stage, considering the rapid growth of HNSCCs [31] [32]. "
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    ABSTRACT: Waiting to start treatment has been shown to be associated with tumor progression and upstaging in head and neck squamous cell carcinomas (HNSCCs). This diminishes the chance of cure and might lead to unnecessary mortality. We investigated the association between waiting times and survival in the Netherlands and assessed which factors were associated to longer waiting times. Patient (age, sex, socioeconomic status (SES), tumor (site, stage) and treatment (type, of institute of diagnosis/treatment) characteristics for patients with HNSCC who underwent treatment were extracted from the Netherlands Cancer Registry (NCR) for 2005-2011. Waiting time was defined as the number of days between histopathological diagnosis and start of treatment. Univariable and multivariable Cox regression was used to evaluate survival. In total, 13,140 patients were included, who had a median waiting time of 37days. Patients who were more likely to wait longer were men, patients with a low SES, oropharynx tumors, stage IV tumors, patients to be treated with radiotherapy or chemoradiation, and patients referred for treatment to a Head and Neck Oncology Center (HNOC) from another hospital. The 5-year overall survival was 58% for all patients. Our multivariable Cox regression model showed that longer waiting time, was significantly related to a higher hazard of dying (p<0.0001). This is the first large population-based study showing that longer waiting time for surgery, radiotherapy or chemoradiation is a significant negative prognostic factor for HNSCC patients. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Oral Oncology 12/2014; 51(3). DOI:10.1016/j.oraloncology.2014.12.003 · 3.61 Impact Factor
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    • "Chen at al. showed in a systematic review that a delay in starting radiotherapy for head and neck cancer was significantly associated with higher recurrence rates and lower survival. They found an absolute increase in the risk of local recurrence of 3,7% per month delay [20]. The median intervals presented in those studies were all less than 2 months. "
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) has a high incidence in Indonesia. Previous study in Yogyakarta revealed a complete response of 29% and a median overall survival of less than 2 years. These poor treatment outcome are influenced by the long diagnose-to-treatment interval to radiotherapy (DTI) and the extended overall treatment time of radiotherapy (OTT). This study reveals insight why the OTT and DTI are prolonged. All patients treated with curative intent radiotherapy for NPC between July 2011 until October 2012 were included. During radiotherapy a daily diary was kept, containing information on DTI, missed radiotherapy days, the reason for missing and length of OTT. Sixty-eight patients were included. The median DTI was 106 days (95% CI: 98-170). Fifty-nine patients (87%) finished the treatment. The median OTT for radiotherapy was 57 days (95% CI: 57-65). The main reason for missing days was an inoperative radiotherapy machine (36%). Other reasons were patient's poor condition (21%), public holidays (14%), adjustment of the radiation field (7%), power blackout (3%), inoperative treatment planning system (2%) and patient related reasons (9%). Patient's insurance type was correlated to DTI in disadvantage for poor people. Yogyakarta has a lack of sufficient radiotherapy units which causes a delay of 3-4 months, besides the OTT is extended by 10-12 days. This influences treatment outcome to a great extend. The best solution would be creating sufficient radiotherapy units and better management in health care for poor patients. The growing economy in Indonesia will expectantly in time enable these solutions, but in the meantime solutions are needed. Solutions can consist of radiation outside office hours, better maintenance of the facilities and more effort from patient, doctor and nurse to finish treatment in time. These results are valuable when improving cancer care in low and middle income countries.
    PLoS ONE 01/2014; 9(1):e85959. DOI:10.1371/journal.pone.0085959 · 3.23 Impact Factor
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    • "Patients who had a pathological diagnosis elsewhere and referred to our institute for treatment (65%) even had an average total treatment delay of 45 days. As reported by Chen et al. [28] in patients with radiotherapy as their single treatment modality, we expected a negative impact of lengthy waiting times on patient outcome. On the contrary, we found that patients treated within 30 days had significantly the worst outcome, a relationship that was found earlier by Leon et al. [29]. "
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    ABSTRACT: The increasing volume of head and neck squamous cell carcinoma (HNSCC) patients can lead to longer intervals between histopathological diagnosis and primary treatment. This could cause psychological distress to the patient, but more importantly could possibly lead to tumor progression and decreased survival. Accordingly, this study investigates these relationships. The correlation of professional delay and clinical characteristics of 2493 patients, treated between 1990 and 2011 with oral, oropharyngeal, hypopharyngeal and laryngeal SCC, was investigated. Patients were divided in two groups based on treatment delay, defined as the interval between histopathological diagnosis and initial treatment. Univariate and multivariate proportional hazards models were used to assess disease specific survival (DSS) and disease free survival (DFS). Year of diagnosis, tumor site and therapy were significantly related to treatment delay. Tumor stage was not related to treatment delay. Multivariate regression models revealed that the group with a delay of more than 30days had a better DSS (HR .838, CI .697-.922, p=.041) and DFS (HR .816, CI .702-.947), p=.007) than the group treated within 30days. In our study, treatment delay up to 90days is not related to impaired survival. This argument can be used extremely cautiously to comfort patients who have to wait several weeks for treatment. Although, possible tumor progression during treatment delay could have led to increased morbidity subsequent to more extensive treatment. Also, possible negative psychological impact of delay in treatment should not be underestimated.
    Oral Oncology 01/2014; 50(4). DOI:10.1016/j.oraloncology.2013.12.018 · 3.61 Impact Factor
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