Weidong Kong

Association Between Time to Initiation of Adjuvant Chemotherapy and Survival in Colorectal Cancer: A Systematic Review and Meta-analysis

CONTEXT Adjuvant chemotherapy (AC) improves survival among patients with resected colorectal cancer. However, the optimal timing from surgery to initiation of AC is unknown. OBJECTIVE To determine the relationship between time to AC and survival outcomes via a systematic review and meta-analysis. data sources: MEDLINE (1975 through January 2011), EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched to identify studies that described the relationship between time to AC and survival. STUDY SELECTION Studies were only included if the relevant prognostic factors were adequately described and either comparative groups were balanced or results adjusted for these prognostic factors. DATA EXTRACTION Hazard ratios (HRs) for overall survival and disease-free survival from each study were converted to a regression coefficient (β) and standard error corresponding to a continuous representation per 4 weeks of time to AC. The adjusted β from individual studies were combined using a fixed-effects model. Inverse variance (1/SE(2)) was used to weight individual studies. Publication bias was investigated using the trim and fill approach. RESULTS We identified 10 eligible studies involving 15,410 patients (7 published articles, 3 abstracts). Nine of the studies were cohort or population based and 1 was a secondary analysis from a randomized trial of chemotherapy. Six studies reported time to AC as a binary variable and 4 as 3 or more categories. Meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both overall survival (HR, 1.14; 95% confidence interval [CI], 1.10-1.17) and disease-free survival (HR, 1.14; 95% CI, 1.10-1.18). There was no significant heterogeneity among included studies. Results remained significant after adjustment for potential publication bias and when the analysis was repeated to exclude studies of largest weight. CONCLUSION In a meta-analysis of the available literature on time to AC, longer time to AC was associated with worse survival among patients with resected colorectal cancer.

Temporal trends in the incidence and survival of cancers of the upper aerodigestive tract in Ontario and the United States

The Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology and End Results (SEER) databases were used to describe temporal trends in the incidence and survival of squamous cancers of the upper aerodigestive tract (UADT) in Ontario and the US between 1984 and 2001. Between the 1984–86 and 1999–01 periods, the age‐adjusted incidence rate of all first primary cancers of the UADT decreased from 11.6 (11.2–12.0) to 8.8 (8.5–9.1) in Ontario and 13.0 (12.7–13.3) to 10.2 (10.0–10.4) in the US. Significant decreases in incidence were observed in many UADT sites but there was no significant change in the incidence of cancer of the oropharynx in either the US or Canada. Over the same period, the 5‐year relative survival for all UADT cancers increased from 49.2% (47.2–51.2%) to 57.1%(55.0–59.1%) in Ontario and from 48.1% (46.9–49.3%) to 52.4% (51.2–53.6%) in the US. This significant improvement in the outcome of UADT cancer was largely due to a dramatic increase in the 5‐year relative survival for cancers of the oropharynx from 31.1% (27.1–35.1%) to 53.6% (49.3–57.9%) in Ontario and from 35.3% (32.9–37.8%) to 51.0% (48.7–53.3%) in the US. Smaller increases in survival were observed in cancers of the oral cavity, nasopharynx, and hypopharynx, but there was no evidence of any increase in survival for cancer of the larynx. These results are consistent with the hypothesis that there has been a major change in the etiology of cancer of the oropharynx in Canada and the US and a concomitant change in its response to therapy.

Adjuvant Chemotherapy for Non–Small-Cell Lung Cancer in the Elderly: A Population-Based Study in Ontario, Canada

PURPOSE Non-small-cell lung cancer (NSCLC) is predominantly a disease of the elderly. Retrospective analyses of the National Cancer Institute of Canada Clinical Trials Group JBR.10 trial and the Lung Adjuvant Cisplatin Evaluation (LACE) meta-analysis suggest that the elderly benefit from adjuvant chemotherapy. However, the elderly were under-represented in these studies, raising concerns regarding the reproducibility of the study results in clinical practice. PATIENTS AND METHODS By using the Ontario Cancer Registry, we identified 6,304 patients with NSCLC who were treated with surgical resection from 2001 to 2006. Registry data were linked to electronic treatment records. Uptake of chemotherapy was compared across age groups: younger than 70, 70 to 74, 75 to 79, and ≥ 80 years. As a proxy of survival benefit from chemotherapy, we compared survival of patients diagnosed from 2004 to 2006 with survival of those diagnosed from 2001 to 2003. Hospitalization rates within 6 to 24 weeks of surgery served as a proxy of severe chemotherapy-related toxicity. RESULTS In all, 2,763 (43.8%) of 6,304 surgical patients were elderly (age ≥ 70 years). Uptake of adjuvant chemotherapy in the elderly increased from 3.3% (2001 to 2003) to 16.2% (2004 to 2006). Among evaluable elderly patients, 70% received cisplatin and 28% received carboplatin-based regimens. Requirements for dose adjustments or drug substitutions were similar across age groups. Hospitalization rates within 6 to 24 weeks of surgery were similar across age groups (28.0% for patients age < 70 years; 27.8% for patients age ≥ 70 years; P = .54). Four-year survival of elderly patients increased significantly (47.1% for patients diagnosed from 2001 to 2003; 49.9% for patients diagnosed from 2004 to 2006; P = .01). Survival improved in all subgroups except patients age ≥ 80 years. CONCLUSION Uptake of adjuvant chemotherapy for NSCLC increased in patients age 70 years or older following reporting of pivotal adjuvant chemotherapy trials, but it remained below that for patients younger than age 70 years. Adoption of adjuvant chemotherapy appears to be associated with significant survival benefit in the elderly (age ≥ 70 years), with tolerability apparently similar to that of patients who are younger than age 70 years.

Adoption of adjuvant chemotherapy for non-small-cell lung cancer: a population-based outcomes study.

PURPOSE Since 2004, several clinical trials have demonstrated that adjuvant chemotherapy (ACT) improves survival in patients with early-stage non-small-cell lung cancer (NSCLC). Here, we evaluate the uptake of ACT and its impact on outcomes in the general population of Ontario, Canada. METHODS All patients diagnosed with NSCLC in Ontario from 2001 to 2006 who underwent surgical resection (n = 6,304) were identified using the Ontario Cancer Registry. We linked electronic records of treatment to the registry. We described uptake of ACT and compared survival of all patients with surgically resected NSCLC diagnosed from 2001 to 2003 with patients diagnosed from 2004 to 2006. As a proxy measure of ACT-related toxicity, we evaluated hospitalizations within 6 months of surgery. RESULTS Demographic, disease, and treatment-related characteristics did not differ between the 2001 to 2003 and 2004 to 2006 study cohorts. Over the study period, the proportion of patients receiving ACT increased from 7% (192 of 2,950 patients) to 31% (1,032 of 3,354 patients; P < .001). The proportion of patients admitted to hospital within 6 months of surgery remained stable and (36% in the 2001 to 2003 cohort and 37% in the 2004 to 2006 cohort). However, within 2 years of surgery, there was a 33% reduction in the proportion of patients admitted to hospital with metastatic disease (P < .001). During the study period, there was a substantial improvement in 4-year survival among surgically resected patients, from 52.5% (2001 to 2003) to 56.1% (2004 to 2006; P = .001). CONCLUSION There has been a rapid uptake of ACT for NSCLC, which was not associated with an increased rate of hospitalization. The adoption of ACT was associated with a substantial improvement in overall survival, suggesting that the benefits seen in clinical trials are generalizable to the general population.

Impact of Adoption of Chemoradiotherapy on the Outcome of Cervical Cancer in Ontario: Results of a Population-Based Cohort Study

PURPOSE To describe the adoption of concurrent cisplatin-based chemoradiotherapy (C-CRT), and to evaluate its impact on the outcome of cervical cancer in Ontario. METHODS We used a population-based cancer registry to identify the 4,069 patients with invasive carcinoma of the cervix diagnosed in Ontario between 1992 and 2001. We linked electronic records of treatment to the registry. We described time trends in the use of C-CRT, and we compared survival before and after widespread adoption of C-CRT. RESULTS Over the study period, the proportion of patients treated with primary radical radiotherapy (RT) remained constant at approximately 42%. Between 1992 and 1998, less than 10% of RT cases received chemotherapy. Early in 1999, there was rapid adoption of C-CRT. Between 1999 and 2001, more than 60% of RT cases received C-CRT. There was a contemporaneous increase in overall 3-year survival from 71.1% in the 1995 to 1998 cohort to 75.9% in the 1999 to 2001 cohort (P = .03). There was no change in survival in patients treated with surgery alone. However, there was a significant increase in 3-year survival from 58.6% in the 1995 to 1998 cohort to 69.8% in the 1999 to 2001 cohort (P < .01) in the subpopulation of patients treated with primary RT +/- chemotherapy. CONCLUSION The adoption of C-CRT was associated with a significant improvement in overall survival of cervical cancer at the population level. The magnitude of the benefit of C-CRT in the general population was consistent with the results of the relevant clinical trials.

Perioperative chemotherapy for muscle-invasive bladder cancer: A population-based outcomes study.

Practice guidelines recommend neoadjuvant chemotherapy (NACT) for bladder cancer. However, the evidence in support of adjuvant chemotherapy (ACT) is less robust. Here we describe whether the evidence of efficacy for NACT/ACT was sufficient to change clinical practice and whether the efficacy demonstrated in clinical trials was translated into effectiveness in the general population.

A Population-Based Study of the Fractionation of Postlumpectomy Breast Radiation Therapy

PURPOSE The optimal fractionation schedule of post lumpectomy radiation therapy remains controversial. The objective of this study was to describe the fractionation of post-lumpectomy radiation therapy (RT) in Ontario, before and after the seminal Ontario Clinical Oncology Group (OCOG) trial, which showed the equivalence of 16- and 25-fraction schedules. METHODS AND MATERIALS This was a retrospective cohort study conducted by linking electronic treatment records to a population-based cancer registry. The study population included all patients who underwent lumpectomy for invasive breast cancer in Ontario, Canada, between 1984 and 2008. RESULTS Over the study period, 41,747 breast cancer patients received post lumpectomy radiation therapy to the breast only. Both 16- and 25-fraction schedules were commonly used throughout the study period. In the early 1980s, shorter fractionation schedules were used in >80% of cases. Between 1985 and 1995, the proportion of patients treated with shorter fractionation decreased to 48%. After completion of the OCOG trial, shorter fractionation schemes were once again widely adopted across Ontario, and are currently used in about 71% of cases; however, large intercenter variations in fractionation persisted. CONCLUSIONS The use of shorter schedules of post lumpectomy RT in Ontario increased after completion of the OCOG trial, but the trial had a less normative effect on practice than expected.

Time to adjuvant chemotherapy and survival in non-small cell lung cancer: a population-based study.

The time interval between surgery and initiation of adjuvant chemotherapy (ACT) may impact survival in colorectal and breast cancers. This is the first report describing the association between time to adjuvant chemotherapy (TTAC) and survival in non–small cell lung cancer (NSCLC).

Curative therapy for bladder cancer in routine clinical practice: A population-based outcomes study

AIMS Definitive therapy of bladder cancer involves cystectomy or radiotherapy; controversy exists regarding optimal management. Here we describe the management and outcomes of patients treated in routine practice. MATERIALS AND METHODS Treatment records were linked to the Ontario Cancer Registry to identify all cases of bladder cancer in Ontario treated with cystectomy or radiotherapy in 1994-2008. Practice patterns are described in three study periods: 1994-1998, 1999-2003, 2004-2008. Logistic regression, Cox model and propensity score analyses were used to evaluate factors associated with treatment choice and survival. RESULTS In total, 3879 cases (74%) underwent cystectomy and 1380 (26%) were treated with primary radiotherapy. Cystectomy use increased over time (66, 75, 78%), whereas radiotherapy decreased (34, 25, 22%), P < 0.001. There was substantial regional variation in the proportion of cases undergoing radiotherapy (range 16-51%). Five year cancer-specific survival (CSS) and overall survival were 40 and 36% for surgical cases and 35 and 26% for radiotherapy cases (P < 0.001). In multivariate Cox model and propensity score analyses, there was no significant difference in CSS between surgery and radiotherapy (hazard ratio 0.99, 95% confidence interval 0.91-1.08); radiotherapy was associated with slightly inferior overall survival (hazard ratio 1.08, 95% confidence interval 1.00-1.16). CONCLUSION Utilisation of cystectomy for bladder cancer in routine practice has increased over time with no evidence of a significant difference in CSS between radiotherapy and cystectomy.

The use of palliative radiotherapy for bone metastasis.

BACKGROUND The value of palliative radiotherapy (PRT) for bone metastases is well established, but little is known about its use in the general population. PURPOSE To describe the use of PRT for bone metastases in Ontario. MATERIALS AND METHODS This was a retrospective cohort study. Treatment records from all Ontario RT departments were linked to a population-based cancer registry to describe the use of PRT. RESULTS 12.2% of the 434,241 patients, who died of cancer in Ontario between 1984 and 2004, received at least one course of PRT for bone metastases in the last 2 years of life. The rate of use of PRT varied across the province (inter-county range, 8.2-18.6%). Older patients and residents of poorer areas were less likely to receive PRT (p<0.0001). Patients diagnosed with cancer in a hospital with a radiotherapy facility and those who lived closer to a radiotherapy centre were more likely to receive PRT (p<0.0001). Over the study period, the use of PRT decreased in breast cancer and myeloma, but increased in prostate cancer (p<0.0001). CONCLUSIONS Access to PRT appears to be inequitable. More effort is required to make this useful treatment available to all those who would benefit from it.