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Waiting for Cancer Surgery
Waiting for Cancer Surgery
Length of Delay and Outcomes: Stage Distribution
Length of Delay and Outcomes: Stage Distribution
Type and Length of Delay
Type and Length of Delay
Longer Treatment Delays in SPN
Longer Treatment Delays in SPN
Longer Delays in Surgical Patients
Longer Delays in Surgical Patients
ROC Curve for Predictors of Rx Delay
ROC Curve for Predictors of Rx Delay
Effect of Delay on Survival
Effect of Delay on Survival
Effect of Delay on Survival
Effect of Delay on Survival
Stratification by SPN
Stratification by SPN
Stratification by SPN
Stratification by SPN
Stratification by Surgery
Stratification by Surgery
Stratification by Surgery
Stratification by Surgery
Effect of chemotherapy on survival Method Hazard Ratio Cox PH 0.81
Effect of chemotherapy on survival Method Hazard Ratio Cox PH 0.81
Stratification by Propensity
Stratification by Propensity
Stratification by Propensity
Stratification by Propensity
Hurry Up and Wait: The Effect of Delayed Diagnosis and Treatment on
Hurry Up and Wait: The Effect of Delayed Diagnosis and Treatment on
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Hurry Up and Wait: The Effect of Delayed Diagnosis and Treatment on Survival in Patients with Non-Small-Cell Lung Cancer

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1Hurry Up and Wait: The Effect of 24Chemotherapy. 40.2. No treatment. 19.7.
Delayed Diagnosis and Treatment on Admit within 7 days. 33.3.
Survival in Patients with Non-Small-Cell 25Type and Length of Delay. Length of
Lung Cancer. Michael K. Gould, MD, MS VA Delay (Days). 42d 11-117. 84d 38-153. 22d
Palo Alto Health Care System Stanford 8-41.
School of Medicine. 26Predictors of Delay <90 days. Tumor
2Lung Cancer. 175,000 new cases in U.S. size, cm*. Any symptom, %*. SPN, %*.
in 2004 160,000 deaths in U.S. in 2004 *p=0.001; † p=0.04. Characteristic.
More deaths than breast, prostate and Delay<90 d (n=67). Delay>90d (n=62).
colon cancer combined Jemal et al. CA Age (years). 66.5 ± 9.8. 67.9 ± 9.2.
Cancer J Clin 2004;54:8-29 Common in Gender (Male), %. 98.5. 96.9. White, %.
veterans 6,600 cases in 2003 (~20% of all 77.4. 87.8. 4.7 ± 2.8. 3.1 ± 1.8.
cancers) VA Central Cancer Registry: Adenocarcinoma, %. 57.4. 42.2. Squamous
http://www1.va.gov/cancer/index.cfm. cell, %. 25.0. 32.8. Central location, %.
3Lung Cancer Histology. SEER: 54.7. 56.5. 72.1. 43.8. Any CXR finding, %
http://seer.cancer.gov. †. 32.4. 17.2. 7.4. 29.7.
4Evaluation in Suspected Lung Cancer. 27Treatment and Delay. Surgery *. Admit
Diagnosis Imaging tests (e.g. CXR, chest within 7 days *. Characteristic. All, %
CT, PET) Biopsy (e.g. bronchoscopy, TTNA) (n=129). Delay<90 d, % (n=67).
Staging Imaging tests (e.g. brain CT or Delay>90d, % (n=62). 27.3. 13.2. 42.2.
MR) Biopsy (e.g. mediastinoscopy, adrenal Radiation. 35.6. 41.2. 29.7. Chemotherapy.
Bx) Pre-operative assessment (PFTs, 40.2. 45.6. 34.4. No treatment †. 19.7.
cardiac eval) Consultations Tumor Board. 26.5. 12.5. 33.3. 48.5. 17.2.
5Research Agenda: Lung Cancer. Defining *p<0.0001; † p=0.04.
Best Practices: Cost-effectiveness of 28Longer Treatment Delays in SPN. N=23
low-dose CT for lung cancer screening 222 days P=0.002. N=106 116 days.
Accuracy of FDG-PET for SPN diagnosis Cost 29Longer Delays in Surgical Patients.
of FDG-PET Cost-effectiveness of tests for N=36 208 days P<0.0001. N=93 106 days.
SPN management Predictors of mediastinal 30MV Predictors of Treatment Delay.
metastasis Accuracy of CT and FDG-PET for Predictor. OR. 95% CI. Admit within 7 days
staging in NSCLC Accuracy of TBNA for of 1st abnormal CXR. 6.0. 2.2 – 16.2.
staging in NSCLC Accuracy of Tumor Size > 3.0 cm. 5.4. 2.1 – 14.1.
mediastinoscopy for staging in NSCLC Any additional abnormality on CXR. 2.6.
Cost-effectiveness of tests for staging in 0.9 – 7.5. Any symptom. 2.5. 1.0 – 6.0.
NSCLC. Examining Current Practices: R2= 0.37; p= 0.82 for Hosmer-Lemeshow
Quality of practices for lung cancer test; all correlations< 0.35.
diagnosis and staging (with CanCORS) 31ROC Curve for Predictors of Rx Delay.
Aligning Current and Best Practices: AUC= 0.80; (0.73 to 0.87); P<0.0001.
Development, validation and evaluation of Model included admission within 7 days,
a computer-based decision support system presence of any symptom, presence of any
for managing SPN Eliciting preferences for additional CXR abnormality, tumor size,
shared decision making in patients with age, sex and race/ethnicity.
lung nodules. 32Predictors of Diagnostic Delay.
6CanCORS. NCI-funded collaboration Independent predictors of diagnosis within
Population based, prospective cohort study 42 days included hospitalization within 7
of practices and outcomes in patients with days (OR 10.3, 95% CI 3.5 to 30), tumor
lung and colorectal cancer in diverse size greater than 3 cm (OR 5.5, 95% CI 2.0
geographic regions of U.S. 8,000 lung to 15), and white race (OR 3.0, 95% CI 1.1
cancer patients, including 1,000 U.S. to 8.0).
veterans with lung cancer enrolled at 13 33Outcomes: Stage Distribution. Stage.
sites. All, % (n=129). Delay<90 d, % (n=67).
7Specific Aims: Wait Times. Describe Delay>90d, % (n=62). Stage I. 15.9.
variation in time to diagnosis and 9.7. 23.5. Stage II. 15.0. 11.3. 19.6.
treatment in U.S. veterans with non-small Stage III. 32.7. 29.0. 37.3. Stage IV.
cell lung cancer (NSCLC) Identify 36.3. 50.0. 19.6. P=0.006.
facilitators and barriers to timely 34Outcomes: Survival. Treatment within
diagnosis and treatment in VA Examine the 90 days of presentation associated with an
effect of delayed diagnosis and treatment increased risk of death RR=1.45 (95% CI
on stage distribution and survival. 79.4% vs. 54.7%) P=0.002.
8Why Measure Wait Times? Longer wait 35Effect of Delay on Survival. Med
times contribute to emotional distress of survival = 321 vs. 122 days, P=0.001. Med
patients and family members Longer wait survival = 570 vs. 161 days, P<0.0001.
times may lead to missed opportunities for 36Multivariable Predictors of Survival.
cure and/or effective palliation Longer In Cox proportional hazards models, TNM
wait times may (arguably) result in stage III (HR 11.4, P=0.01) and TNM stage
increased health care costs. IV (HR 24.0, P=0.001) were the only
9Guidelines for Wait Times. RAND statistically significant predictors of
Quality Indicators Diagnosis within 2 survival Trend towards worse survival in
months of presentation Treatment within 6 patients with symptoms (HR 3.1, P=0.08)
weeks of diagnosis and patients with shorter treatment delays
http://www.rand.org/publications/MR/MR1281 (HR 1.5, P=0.09) Age, ethnicity, tumor
BTS Referral & evaluation by size, histology not associated with
respiratory specialist within 2-7 days survival.
Results of diagnostic test communicated 37Longer Delay=Better Survival. After
within 2 weeks Thoracotomy within 8 weeks, adjusting for age, sex, stage &
palliative XRT within 4 weeks, radical XRT surgery, longer symptom delay (HR 0.79)
within 2 weeks, chemotherapy within 2 and hospital delay (HR 0.87) were
weeks Thorax 1998;53(Suppl 1):S1-8. ATS, associated with better survival. Myrdal et
ACCP, CCO: No recommendations. al. Thorax 2004;59:45-9. Symptom Delay.
10Prior Research. Type and length of Hospital Delay.
delay n=17 studies between 1989 to 2004 38Sources of Bias and Variation. Sources
Heterogeneous patient populations Most of Bias Selection bias Confounding by
studies from Europe, 3 from North America, severity of disease Lead-time bias Sources
1 from Japan Effect of delay on lung of Variation Heterogeneous patient
cancer outcomes n=11 studies between 1993 populations Heterogeneous health care
and 2004 4 studies of surgical patients (1 systems.
from U.S.) 2 studies of delays following 39Strategies for Dealing with Selection
screen-detection of lung cancer in Japan 1 Bias. Stratification Should be performed
European study of patients referred for according to baseline characteristics
curative XRT. Propensity score methods Adjust, match or
11Prior Research: Length of Delay. stratify by propensity or likelihood of
Interval. # of Studies. Median Time. receiving intervention/exposure Connors et
Symptom to first contact. 5. ~3 weeks. al. JAMA 1996;276:889-97. Instrumental
First contact to diagnosis. 6. 2-6 weeks ( variable methods Newhouse & McClellan.
1 study >12 weeks). First contact to Ann Rev Pub Health 1998;19:17-34.
treatment. 5. ~3 months. Diagnosis to McClellan et al. JAMA 1994;272:859-866.
radiation. 2. 5 to 6 weeks. Diagnosis to 40Stratification by SPN. Med survival =
surgery. 1. 7 weeks. 467 vs. 142 days, P=0.001. P=0.19.
12Waiting for Cancer Surgery. Simunovic 41Stratification by Surgery. Med
et al. CMAJ 2001;165:421-5. survival =478 vs. 142 days, P=0.001.
13Waiting for Cancer Surgery. One U.S. P=0.08.
study from SFVA (retrospective) 83 42Propensity Scores. Used to control for
veterans with stage I or II lung cancer selection bias in observational studies of
Underwent surgical resection between valve surgery for endocarditis,
1989-99 Median time from initial contact chemotherapy for advanced lung cancer,
to resection was 82 days. Quarterman et coronary angiography following acute
al. J Thorac Cardiovasc Surg myocardial infarction and right heart
2003;125:108-14. catheterization for critical illness
14Median Wait Times for Radiation and Controls for observed differences between
Chemotherapy. Ontario, Canada 1 to 4.1 groups Typically use logistic regression
weeks from referral to radiation 1.9 to to predict use of intervention Adjust,
6.3 weeks from referral to chemotherapy match or stratify by propensity to receive
http://www.cancercare.on.ca/access_waitTim intervention/exposure 5 strata usually
s.htm No data from U.S. sufficient to remove over 90% of bias due
15Predictors of Delay. Longer symptom to selection.
delay in patients <45 years old Bourke 43Effect of chemotherapy on survival
et al. Chest 1992;102:1723-9. Age not Method Hazard Ratio Cox PH 0.81 Propensity
related to diagnostic or treatment delay score 1st 0.78 2nd 0.81 3rd 0.85 4th 0.80
Deegan et al. J Royal Coll Phys London 5th 0.78. Earle et al. J Clin Oncol 2001;
1998;32:339-43. Simunovic et al. CMAJ 19:1064-1070.
2001;165:421-5. Pita-Fernandez et al. J 44Stratification by Propensity. P=0.06.
Clin Epidemiol 2003;56:820-5. Kanashiki et P=0.43.
al. Onc Reports 2003;10:649-52. Gender not 45Improving Propensity Model in CanCORS.
related to symptom or treatment delay Patient characteristics Age, sex,
Pita-Fernandez et al. J Clin Epidemiol race/ethnicity, education, marital status,
2003;56:820-5. Kanashiki et al. Onc SES Measures of disease severity, sypmtoms
Reports 2003;10:649-52. No data for and co-morbidity Institutional
race/ethnicity, SES, education, physician characteristics Lung cancer volume;
or institutional factors. frequency of thoracic tumor board meetings
16Length of Delay and Outcomes. Delays Presence of dedicated thoracic surgeon,
of 18 to 131 days between diagnostic CT number of other specialists Availability
and XRT planning CT associated with 19% of PET scanner, number of CT scanners
increase in tumor X-sectional area (range Availability of OR time for thoracic
0% to 373%) 6/29 patients (21%) progressed surgeons Other non-clinical factors
to incurable disease while waiting Distance of residence to VA Means test
O’Rourke & Edwards. Clin Oncol category Other insurance.
2000;12:141-4. Delays in patients with 46Instrumental Variables. Can control
screen-detected lung cancer associated for unobserved characteristics Instrument”
with 2-fold reduction in survival time should be associated with use of
Kanashiki et al. Onc Reports intervention, but not with health status
2003;10:649-52. Kashiwabara et al. Lung or outcome Example: Heart catheterization
Cancer 2003;40:67-72. following acute MI—differential distance
17Length of Delay and Outcomes. No from home to hospital with/without cardiac
association between different types of catheterization lab.
delay and survival in 4 studies of 47Strengths & Limitations. Strengths
surgical patients Quarterman et al. J Study sample captured full spectrum of
Thorac Cardiovasc Surg 2003;125:108-14. NSCLC Objective measurement of time
Pita-Fernandez et al. J Clin Epidemiol intervals avoided faulty recall
2003;56:820-5. Aragoneses et al. Lung Measurement of survival from time of 1st
Cancer 2002;36:59-63. Billing and Wells. abnormal CXR minimized lead time bias
Thorax 1996;51:903-6. Limitations Small sample size
18Length of Delay and Outcomes: Stage Stratification limited statistical power
Distribution. Christensen et al. Eur J further Single center limited variability
Cardio-thorac Surg 1997;12:880-4. N=103. in practices Retrospective design—unable
N=103. N=69. N=69. to assess symptom delay Not able to fully
19Research Methods. Retrospective cohort control for severity at presentation.
study 129 U.S. veterans with NSCLC 48Conclusions. Important biases
Consecutive patients diagnosed and treated complicate the interpretation of previous
at VAPAHCS between 1/1/02 and 12/31/03 studies of delayed treatment in NSCLC
Median follow-up: 270 days from 1st x-ray Delays in diagnosis and treatment are
abnormality 194 days from histologic longer than is currently recommended
diagnosis 147 days from treatment. Patients with aggressive tumors tend to
20Statistical Methods. Associations experience the shortest delays Reducing
between length of delay and potential delays in patients with malignant SPNs and
predictors of delay Non-parametric other potentially resectable tumors may
correlations for continuous predictors yield greatest benefits Future studies
Pearson chi-square for categorical should be large & prospective, avoid
predictors Multiple logistic regression selection & lead time biases, and use
Associations between length of delay and sophisticated methods to account for
survival Kaplan-Meier, Cox proportional confounding by severity of disease at
hazards. presentation.
21Patient Characteristics. 49
Characteristic. n=129. Age (years). 67.2 ± 50Acknowledgements. Funding Advanced
9.5. Gender (Male), %. 97.7. White, %. RCDA, VA HSR&D Service Collaborators
82.4. Tumor size, cm. 3.9 ± 2.4. David Au, MD, MS Dawn Provenzale, MD, MS
Adenocarcinoma, %. 50.0. Squamous cell, %. Sharfun Ghaus CanCORS Ancillary Study
28.8. Central location, %. 55.6. Any Investigators Jay Bhattacharya, PhD Todd
symptom, %. 58.3. Any CXR finding, %. Wagner, PhD Doug Owens, MD, MS.
25.0. SPN, %. 18.2. 51
22Pre-treatment Imaging Tests. N % >1 52Specific Aims: Staging Practices.
test X-ray chest 128 99 30% CT chest 126 Describe variation in use of FDG-PET
98 11% PET 107 83 3% CT abdomen/pelvis 51 imaging and invasive mediastinal biopsy
40 CT brain/spinal cord 29 22 MRI head 23 procedures for staging in U.S. veterans
18 X-ray bone 19 15 MRI spinal cord 15 12 with NSCLC Examine the effect of PET
MRI chest 10 8. PET imaging more common in imaging and mediastinal biopsy on survival
patients without symptoms (p=0.02), and and rate of thoracotomy without cure in VA
those with centrally located tumors Measure pre-treatment resource utilization
(p=0.02) or malignant solitary nodules and evaluate the cost-effectiveness of
(p=0.07). selected imaging tests and biopsy
23Pre-treatment Staging Procedures. N % procedures for lung cancer staging.
>1 test Bronchoscopy/TBNA 15 12 4% 53Correlations. Age not correlated with
Mediastinoscopy 7 5 Endoscopic ultrasound time to treatment Spearman’s rho= 0.10,
1 1. Mediastinal biopsy more common in P=0.26 Tumor size negatively correlated
patients with primary tumors that were with time to treatment Spearman’s rho=
centrally located (p=0.02) or spiculated -0.32, P<0.0001.
(p<0.05). 54Effect of Delay on Survival. Med
24Treatment Received. Characteristic. %, survival = 321 vs. 122 days, P=0.001. Med
n=129. Surgery. 27.3. Radiation. 35.6. survival = 570 vs. 161 days, P<0.0001.
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