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What is the best approach to a solitary pulmonary nodule identified by chest x-ray?
Your initial risk assessment should include the patient’s smoking history, advancing age, cancer history, and chest radiography features (strength of recommendation [SOR]: A, based on a validated clinical decision rule). You’ll also need to review old chest radiographs (SOR: C, based on expert opinion). A solitary pulmonary nodule unchanged for >2 years on chest radiograph or containing benign central calcifications requires no further work-up (SOR: B, based on historical cohort studies).
While radiologists’ interpretations of a nodule’s calcification on chest radiograph and malignancy on computed tomography (CT) are incorrect in a substantial portion of cases (SOR: B, based on limited-quality diagnostic cohort studies), spiral CT with contrast is still diagnostically useful in making decisions regarding watchful waiting, needle biopsy, or surgery (SOR: B, based on a decision analysis study).
18-fluorodeoxyglucose positron emission tomography (FDG PET) is useful for assessing malignancy risk (SOR: B, based on decision analysis study), but not for solitary pulmonary nodules <1 cm (SOR: C, based on expert opinion).
Direct more costly, invasive tests to those with higher risk of malignancy
Parul Harsora, MD
Rhesa Sanni-Thomas, DO
UT Southwestern Medical Center, Dallas, Tex
Risk stratification of a solitary pulmonary nodule allows the clinician to direct more costly and invasive testing to patients with a higher probability of malignancy. Historical factors such as previous cancer, advanced age, and smoking increase suspicion for malignancy, but CT is generally warranted in all new solitary pulmonary nodules found on chest radiographs. It’s important to obtain a thorough history regarding symptoms (cough, night sweats, weight loss), occupational exposure (asbestos, bird droppings, decaying wood), travel, and comorbid conditions (especially immunocompromised states); this is likely to prove helpful in the workup.
Evidence summary
A solitary pulmonary nodule, or “coin lesion,” is an intraparenchymal finding on chest radiograph or CT that is less than 3 to 4 cm in diameter and not associated with atelectasis or adenopathy. Malignancy rates range from 15% to 75%, depending on the population studied.1 Although early detection of malignancy portends a major improvement in survival (up to 75% at 5 years following surgical resection of stage IA disease), most lung cancers progress asymptomatically until quite advanced.2
The presumed benign nature of lesions that are either unchanged over 2 years or have central calcifications is based on 3 retrospective studies from the 1950s.3-6 However, these should not be considered absolutes. A recent study revisiting the original data calculated the predictive value of benign nature based on no growth to be only 65% (95% confidence interval [CI], 47%–83%).7 Also, a study assessing the accuracy of radiologists’ assessment of calcification in solitary pulmonary nodules compared with thin-section CT found that 7% of “definitely calcified” nodules on chest radiograph lacked calcification on thin-section CT.8
Which clinical variables best predict malignancy?
The best available clinical decision rule was derived and validated from a single split population of patients with solitary pulmonary nodules.9 The outcome variable was defined as malignancy based on histologic tissue analysis or benignity by radiographic stability or resolution over 2 years. The authors did not report whether those determining outcomes and predictors were appropriately blinded.
The authors found that 3 clinical variables (age, smoking history, and cancer history) plus 3 radiographic variables (diameter, spiculation, and nodule location in the upper lobes) were independent predictors of malignancy. An online calculator using this prediction model is available at www.chestx-ray.com/SPN/ SPNProb.html.10
CT or PET?
Three comparative studies observed 8 to 12 radiologists’ readings of high-resolution CT images of 28 to 56 patients with solitary pulmonary nodules (established diagnoses by either histology or stability over time).11-13 Approximately half the nodules represented malignant lesions.
Radiologists assigned a level of confidence to their assessment of each case as benign or malignant. At a minimum, they were informed of each patient’s age and gender, and in 2 studies they also knew other information, such as the patient’s smoking and cancer histories. The study showed that the radiologists would have correctly diagnosed a pair of solitary pulmonary nodule cases, one malignant and one benign, between 75% and 83% of the time. Conversely, 17% to 25% of the time they would have diagnosed the case pair incorrectly.
A meta-analysis of 40 studies of FDG PET scanning for solitary pulmonary nodules yielded a maximum joint sensitivity and specificity of 90% (95% CI, 86.4%– 92.7%).14 The methodological quality of studies included in the meta-analysis was fair, with small sample sizes (inclusion criteria were for a minimum of 10 patients with pulmonary nodules and malignant prevalence of at least 0.5); masking was frequently incomplete.
Sensitivity of histologic/cytologic tests varies
A recent systematic review of studies evaluating patients with suspected lung cancer looked into the diagnostic sensitivity of various methods of histologic and cytologic tests.15 Researchers compared the evaluated test results to a reference standard of pathology/histology, definitive cytology, or at least 1-year radiographic follow-up.
Transbronchial needle aspiration showed a sensitivity of 67% (95% CI, 64%–70%) for peripheral lung malignancy of any size; however, only 5 studies met study criteria and their sample sizes varied greatly (n=20 to n=480). Eight studies looking at bronchoscopy (including brush or biopsy) for peripheral lung lesions <2 cm in diameter yielded a sensitivity of only 33% (95% CI, 28%–38%). In the same systematic review, 61 studies of transthoracic needle aspiration for localized pulmonary lesions of any size had a pooled sensitivity of 90% (95% CI, 88%–92%). The prevalence of malignancy in the studies ranged from 0.58 to 0.93.15 Factors affecting heterogeneity between studies included the wide range in study dates, imaging technology used, and study sizes.
What test is most cost-effective?
CT appears cost-effective when the pretest probability of malignancy is <90%; therefore, consider it on virtually all new cases of solitary pulmonary nodules.1 Also, when CT and pretest risk-assessments are discordant (eg, a patient has a low pretest probability of malignancy but his CT is suggestive of malignancy), the FDG PET scan is the most economically feasible at less than $20,000 per quality-adjusted life year.
Recommendations from others
The American College of Chest Physicians (ACCP)2 suggests pursuing no further evaluation if a nodule is unchanged for >2 years or has benign central calcifications. They recommend that physicians perform CT on every patient with a new nodule to characterize the nodule, its location, and the mediastinum. They do not recommend PET scans for nodules <1 cm. Patients who are marginal surgical candidates and have a negative PET scan should have a repeat CT scan in 3 months; serial CTs at 3, 6, 12, and 24 months are suggested, too, if prior chest radiographs are negative.
The ACCP states that transthoracic needle aspiration is not indicated in surgical candidates unless they decline surgery; then transthoracic needle aspiration or a transbronchial approach are the preferred procedure. Transthoracic needle aspiration may also be useful in establishing a diagnosis for patients who are not surgical candidates or who have a high surgical risk.
ACCP expert consensus favors the reference standard of video-assisted thoracoscopic surgery with wedge resection as the ideal method for obtaining tissue diagnosis in consenting, operable patients with solitary pulmonary nodules. Objective evidence is lacking on follow-up monitoring methods for patients with a nodule who do not have a tissue diagnosis and observation alone is chosen. ACCP expert consensus favors a 2-year follow-up with CT scanning at 3, 6, 12, and 24 months to monitor for nodule growth.2
1. Gould MK, Sanders GD, Barnett PG, et al. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138:724-735.
2. Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest 2003;123(1 suppl):89S-96S.
3. Hood RT, Good CA, Clagett OT, McDonald JR. Solitary circumscribed lesions of lung: study of 156 cases in which resection was performed. JAMA 1953;152:1175-1181.
4. Good CA, Hood RT, McDonald JR. Significance of solitary mass in lung. AJR Am J Roentgenol 1953;70:543-554.
5. Good CA. Management of patient with solitary mass in lung. Chic Med Soc Bull 1953;55:893-896.
6. Good CA, Wilson TW. The solitary circumscribed pulmonary nodule: study of 705 cases encountered roentgenologically in a period of three and one-half years. JAMA 1958;166:210-215.
7. Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am J Roentgenol 1997;168:325-328.
8. Berger WG, Erly WK, Krupinski EA, Standen JR, Stern RG. The solitary pulmonary nodule on chest radiography: can we really tell if the nodule is calcified? AJR Am J Roentgenol 2001;176:201-204.
9. Swensen SG, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules: application to small radiographically intermediate nodules. Arch Intern Med 1997;157:849-855.
10. Gurney JW. Probability of malignancy in SPN [Web page]. Available at: www.chestx-ray.com/SPN/ SPNProb.html. Accessed on September 7, 2007.
11. Li F, Aoyama M, Shiraishi J, et al. Radiologists’ performance for differentiating benign from malignant lung nodules on high-resolution CT using computer-estimated likelihood of malignancy. AJR Am J Roentgenol 2004;183:1209-1215.
12. Shah SK, McNitt-Gray MF, De Zoysa KR, et al. Solitary pulmonary nodule diagnosis on CT: results of an observer study. Acad Radiol 2005;12:496-501.
13. Matsuki Y, Nakamura K, Watanabe H, Aoki T, et al. Usefulness of an artificial neural network for differentiating benign from malignant pulmonary nodules on high-resolution CT: evaluation with receiver operating characteristic analysis. AJR Am J Roentgenol 2002;178:657-663.
14. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285:914-924.
15. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer. Chest 2003;123:115S-128S.
Your initial risk assessment should include the patient’s smoking history, advancing age, cancer history, and chest radiography features (strength of recommendation [SOR]: A, based on a validated clinical decision rule). You’ll also need to review old chest radiographs (SOR: C, based on expert opinion). A solitary pulmonary nodule unchanged for >2 years on chest radiograph or containing benign central calcifications requires no further work-up (SOR: B, based on historical cohort studies).
While radiologists’ interpretations of a nodule’s calcification on chest radiograph and malignancy on computed tomography (CT) are incorrect in a substantial portion of cases (SOR: B, based on limited-quality diagnostic cohort studies), spiral CT with contrast is still diagnostically useful in making decisions regarding watchful waiting, needle biopsy, or surgery (SOR: B, based on a decision analysis study).
18-fluorodeoxyglucose positron emission tomography (FDG PET) is useful for assessing malignancy risk (SOR: B, based on decision analysis study), but not for solitary pulmonary nodules <1 cm (SOR: C, based on expert opinion).
Direct more costly, invasive tests to those with higher risk of malignancy
Parul Harsora, MD
Rhesa Sanni-Thomas, DO
UT Southwestern Medical Center, Dallas, Tex
Risk stratification of a solitary pulmonary nodule allows the clinician to direct more costly and invasive testing to patients with a higher probability of malignancy. Historical factors such as previous cancer, advanced age, and smoking increase suspicion for malignancy, but CT is generally warranted in all new solitary pulmonary nodules found on chest radiographs. It’s important to obtain a thorough history regarding symptoms (cough, night sweats, weight loss), occupational exposure (asbestos, bird droppings, decaying wood), travel, and comorbid conditions (especially immunocompromised states); this is likely to prove helpful in the workup.
Evidence summary
A solitary pulmonary nodule, or “coin lesion,” is an intraparenchymal finding on chest radiograph or CT that is less than 3 to 4 cm in diameter and not associated with atelectasis or adenopathy. Malignancy rates range from 15% to 75%, depending on the population studied.1 Although early detection of malignancy portends a major improvement in survival (up to 75% at 5 years following surgical resection of stage IA disease), most lung cancers progress asymptomatically until quite advanced.2
The presumed benign nature of lesions that are either unchanged over 2 years or have central calcifications is based on 3 retrospective studies from the 1950s.3-6 However, these should not be considered absolutes. A recent study revisiting the original data calculated the predictive value of benign nature based on no growth to be only 65% (95% confidence interval [CI], 47%–83%).7 Also, a study assessing the accuracy of radiologists’ assessment of calcification in solitary pulmonary nodules compared with thin-section CT found that 7% of “definitely calcified” nodules on chest radiograph lacked calcification on thin-section CT.8
Which clinical variables best predict malignancy?
The best available clinical decision rule was derived and validated from a single split population of patients with solitary pulmonary nodules.9 The outcome variable was defined as malignancy based on histologic tissue analysis or benignity by radiographic stability or resolution over 2 years. The authors did not report whether those determining outcomes and predictors were appropriately blinded.
The authors found that 3 clinical variables (age, smoking history, and cancer history) plus 3 radiographic variables (diameter, spiculation, and nodule location in the upper lobes) were independent predictors of malignancy. An online calculator using this prediction model is available at www.chestx-ray.com/SPN/ SPNProb.html.10
CT or PET?
Three comparative studies observed 8 to 12 radiologists’ readings of high-resolution CT images of 28 to 56 patients with solitary pulmonary nodules (established diagnoses by either histology or stability over time).11-13 Approximately half the nodules represented malignant lesions.
Radiologists assigned a level of confidence to their assessment of each case as benign or malignant. At a minimum, they were informed of each patient’s age and gender, and in 2 studies they also knew other information, such as the patient’s smoking and cancer histories. The study showed that the radiologists would have correctly diagnosed a pair of solitary pulmonary nodule cases, one malignant and one benign, between 75% and 83% of the time. Conversely, 17% to 25% of the time they would have diagnosed the case pair incorrectly.
A meta-analysis of 40 studies of FDG PET scanning for solitary pulmonary nodules yielded a maximum joint sensitivity and specificity of 90% (95% CI, 86.4%– 92.7%).14 The methodological quality of studies included in the meta-analysis was fair, with small sample sizes (inclusion criteria were for a minimum of 10 patients with pulmonary nodules and malignant prevalence of at least 0.5); masking was frequently incomplete.
Sensitivity of histologic/cytologic tests varies
A recent systematic review of studies evaluating patients with suspected lung cancer looked into the diagnostic sensitivity of various methods of histologic and cytologic tests.15 Researchers compared the evaluated test results to a reference standard of pathology/histology, definitive cytology, or at least 1-year radiographic follow-up.
Transbronchial needle aspiration showed a sensitivity of 67% (95% CI, 64%–70%) for peripheral lung malignancy of any size; however, only 5 studies met study criteria and their sample sizes varied greatly (n=20 to n=480). Eight studies looking at bronchoscopy (including brush or biopsy) for peripheral lung lesions <2 cm in diameter yielded a sensitivity of only 33% (95% CI, 28%–38%). In the same systematic review, 61 studies of transthoracic needle aspiration for localized pulmonary lesions of any size had a pooled sensitivity of 90% (95% CI, 88%–92%). The prevalence of malignancy in the studies ranged from 0.58 to 0.93.15 Factors affecting heterogeneity between studies included the wide range in study dates, imaging technology used, and study sizes.
What test is most cost-effective?
CT appears cost-effective when the pretest probability of malignancy is <90%; therefore, consider it on virtually all new cases of solitary pulmonary nodules.1 Also, when CT and pretest risk-assessments are discordant (eg, a patient has a low pretest probability of malignancy but his CT is suggestive of malignancy), the FDG PET scan is the most economically feasible at less than $20,000 per quality-adjusted life year.
Recommendations from others
The American College of Chest Physicians (ACCP)2 suggests pursuing no further evaluation if a nodule is unchanged for >2 years or has benign central calcifications. They recommend that physicians perform CT on every patient with a new nodule to characterize the nodule, its location, and the mediastinum. They do not recommend PET scans for nodules <1 cm. Patients who are marginal surgical candidates and have a negative PET scan should have a repeat CT scan in 3 months; serial CTs at 3, 6, 12, and 24 months are suggested, too, if prior chest radiographs are negative.
The ACCP states that transthoracic needle aspiration is not indicated in surgical candidates unless they decline surgery; then transthoracic needle aspiration or a transbronchial approach are the preferred procedure. Transthoracic needle aspiration may also be useful in establishing a diagnosis for patients who are not surgical candidates or who have a high surgical risk.
ACCP expert consensus favors the reference standard of video-assisted thoracoscopic surgery with wedge resection as the ideal method for obtaining tissue diagnosis in consenting, operable patients with solitary pulmonary nodules. Objective evidence is lacking on follow-up monitoring methods for patients with a nodule who do not have a tissue diagnosis and observation alone is chosen. ACCP expert consensus favors a 2-year follow-up with CT scanning at 3, 6, 12, and 24 months to monitor for nodule growth.2
Your initial risk assessment should include the patient’s smoking history, advancing age, cancer history, and chest radiography features (strength of recommendation [SOR]: A, based on a validated clinical decision rule). You’ll also need to review old chest radiographs (SOR: C, based on expert opinion). A solitary pulmonary nodule unchanged for >2 years on chest radiograph or containing benign central calcifications requires no further work-up (SOR: B, based on historical cohort studies).
While radiologists’ interpretations of a nodule’s calcification on chest radiograph and malignancy on computed tomography (CT) are incorrect in a substantial portion of cases (SOR: B, based on limited-quality diagnostic cohort studies), spiral CT with contrast is still diagnostically useful in making decisions regarding watchful waiting, needle biopsy, or surgery (SOR: B, based on a decision analysis study).
18-fluorodeoxyglucose positron emission tomography (FDG PET) is useful for assessing malignancy risk (SOR: B, based on decision analysis study), but not for solitary pulmonary nodules <1 cm (SOR: C, based on expert opinion).
Direct more costly, invasive tests to those with higher risk of malignancy
Parul Harsora, MD
Rhesa Sanni-Thomas, DO
UT Southwestern Medical Center, Dallas, Tex
Risk stratification of a solitary pulmonary nodule allows the clinician to direct more costly and invasive testing to patients with a higher probability of malignancy. Historical factors such as previous cancer, advanced age, and smoking increase suspicion for malignancy, but CT is generally warranted in all new solitary pulmonary nodules found on chest radiographs. It’s important to obtain a thorough history regarding symptoms (cough, night sweats, weight loss), occupational exposure (asbestos, bird droppings, decaying wood), travel, and comorbid conditions (especially immunocompromised states); this is likely to prove helpful in the workup.
Evidence summary
A solitary pulmonary nodule, or “coin lesion,” is an intraparenchymal finding on chest radiograph or CT that is less than 3 to 4 cm in diameter and not associated with atelectasis or adenopathy. Malignancy rates range from 15% to 75%, depending on the population studied.1 Although early detection of malignancy portends a major improvement in survival (up to 75% at 5 years following surgical resection of stage IA disease), most lung cancers progress asymptomatically until quite advanced.2
The presumed benign nature of lesions that are either unchanged over 2 years or have central calcifications is based on 3 retrospective studies from the 1950s.3-6 However, these should not be considered absolutes. A recent study revisiting the original data calculated the predictive value of benign nature based on no growth to be only 65% (95% confidence interval [CI], 47%–83%).7 Also, a study assessing the accuracy of radiologists’ assessment of calcification in solitary pulmonary nodules compared with thin-section CT found that 7% of “definitely calcified” nodules on chest radiograph lacked calcification on thin-section CT.8
Which clinical variables best predict malignancy?
The best available clinical decision rule was derived and validated from a single split population of patients with solitary pulmonary nodules.9 The outcome variable was defined as malignancy based on histologic tissue analysis or benignity by radiographic stability or resolution over 2 years. The authors did not report whether those determining outcomes and predictors were appropriately blinded.
The authors found that 3 clinical variables (age, smoking history, and cancer history) plus 3 radiographic variables (diameter, spiculation, and nodule location in the upper lobes) were independent predictors of malignancy. An online calculator using this prediction model is available at www.chestx-ray.com/SPN/ SPNProb.html.10
CT or PET?
Three comparative studies observed 8 to 12 radiologists’ readings of high-resolution CT images of 28 to 56 patients with solitary pulmonary nodules (established diagnoses by either histology or stability over time).11-13 Approximately half the nodules represented malignant lesions.
Radiologists assigned a level of confidence to their assessment of each case as benign or malignant. At a minimum, they were informed of each patient’s age and gender, and in 2 studies they also knew other information, such as the patient’s smoking and cancer histories. The study showed that the radiologists would have correctly diagnosed a pair of solitary pulmonary nodule cases, one malignant and one benign, between 75% and 83% of the time. Conversely, 17% to 25% of the time they would have diagnosed the case pair incorrectly.
A meta-analysis of 40 studies of FDG PET scanning for solitary pulmonary nodules yielded a maximum joint sensitivity and specificity of 90% (95% CI, 86.4%– 92.7%).14 The methodological quality of studies included in the meta-analysis was fair, with small sample sizes (inclusion criteria were for a minimum of 10 patients with pulmonary nodules and malignant prevalence of at least 0.5); masking was frequently incomplete.
Sensitivity of histologic/cytologic tests varies
A recent systematic review of studies evaluating patients with suspected lung cancer looked into the diagnostic sensitivity of various methods of histologic and cytologic tests.15 Researchers compared the evaluated test results to a reference standard of pathology/histology, definitive cytology, or at least 1-year radiographic follow-up.
Transbronchial needle aspiration showed a sensitivity of 67% (95% CI, 64%–70%) for peripheral lung malignancy of any size; however, only 5 studies met study criteria and their sample sizes varied greatly (n=20 to n=480). Eight studies looking at bronchoscopy (including brush or biopsy) for peripheral lung lesions <2 cm in diameter yielded a sensitivity of only 33% (95% CI, 28%–38%). In the same systematic review, 61 studies of transthoracic needle aspiration for localized pulmonary lesions of any size had a pooled sensitivity of 90% (95% CI, 88%–92%). The prevalence of malignancy in the studies ranged from 0.58 to 0.93.15 Factors affecting heterogeneity between studies included the wide range in study dates, imaging technology used, and study sizes.
What test is most cost-effective?
CT appears cost-effective when the pretest probability of malignancy is <90%; therefore, consider it on virtually all new cases of solitary pulmonary nodules.1 Also, when CT and pretest risk-assessments are discordant (eg, a patient has a low pretest probability of malignancy but his CT is suggestive of malignancy), the FDG PET scan is the most economically feasible at less than $20,000 per quality-adjusted life year.
Recommendations from others
The American College of Chest Physicians (ACCP)2 suggests pursuing no further evaluation if a nodule is unchanged for >2 years or has benign central calcifications. They recommend that physicians perform CT on every patient with a new nodule to characterize the nodule, its location, and the mediastinum. They do not recommend PET scans for nodules <1 cm. Patients who are marginal surgical candidates and have a negative PET scan should have a repeat CT scan in 3 months; serial CTs at 3, 6, 12, and 24 months are suggested, too, if prior chest radiographs are negative.
The ACCP states that transthoracic needle aspiration is not indicated in surgical candidates unless they decline surgery; then transthoracic needle aspiration or a transbronchial approach are the preferred procedure. Transthoracic needle aspiration may also be useful in establishing a diagnosis for patients who are not surgical candidates or who have a high surgical risk.
ACCP expert consensus favors the reference standard of video-assisted thoracoscopic surgery with wedge resection as the ideal method for obtaining tissue diagnosis in consenting, operable patients with solitary pulmonary nodules. Objective evidence is lacking on follow-up monitoring methods for patients with a nodule who do not have a tissue diagnosis and observation alone is chosen. ACCP expert consensus favors a 2-year follow-up with CT scanning at 3, 6, 12, and 24 months to monitor for nodule growth.2
1. Gould MK, Sanders GD, Barnett PG, et al. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138:724-735.
2. Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest 2003;123(1 suppl):89S-96S.
3. Hood RT, Good CA, Clagett OT, McDonald JR. Solitary circumscribed lesions of lung: study of 156 cases in which resection was performed. JAMA 1953;152:1175-1181.
4. Good CA, Hood RT, McDonald JR. Significance of solitary mass in lung. AJR Am J Roentgenol 1953;70:543-554.
5. Good CA. Management of patient with solitary mass in lung. Chic Med Soc Bull 1953;55:893-896.
6. Good CA, Wilson TW. The solitary circumscribed pulmonary nodule: study of 705 cases encountered roentgenologically in a period of three and one-half years. JAMA 1958;166:210-215.
7. Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am J Roentgenol 1997;168:325-328.
8. Berger WG, Erly WK, Krupinski EA, Standen JR, Stern RG. The solitary pulmonary nodule on chest radiography: can we really tell if the nodule is calcified? AJR Am J Roentgenol 2001;176:201-204.
9. Swensen SG, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules: application to small radiographically intermediate nodules. Arch Intern Med 1997;157:849-855.
10. Gurney JW. Probability of malignancy in SPN [Web page]. Available at: www.chestx-ray.com/SPN/ SPNProb.html. Accessed on September 7, 2007.
11. Li F, Aoyama M, Shiraishi J, et al. Radiologists’ performance for differentiating benign from malignant lung nodules on high-resolution CT using computer-estimated likelihood of malignancy. AJR Am J Roentgenol 2004;183:1209-1215.
12. Shah SK, McNitt-Gray MF, De Zoysa KR, et al. Solitary pulmonary nodule diagnosis on CT: results of an observer study. Acad Radiol 2005;12:496-501.
13. Matsuki Y, Nakamura K, Watanabe H, Aoki T, et al. Usefulness of an artificial neural network for differentiating benign from malignant pulmonary nodules on high-resolution CT: evaluation with receiver operating characteristic analysis. AJR Am J Roentgenol 2002;178:657-663.
14. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285:914-924.
15. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer. Chest 2003;123:115S-128S.
1. Gould MK, Sanders GD, Barnett PG, et al. Cost-effectiveness of alternative management strategies for patients with solitary pulmonary nodules. Ann Intern Med 2003;138:724-735.
2. Tan BB, Flaherty KR, Kazerooni EA, Iannettoni MD. The solitary pulmonary nodule. Chest 2003;123(1 suppl):89S-96S.
3. Hood RT, Good CA, Clagett OT, McDonald JR. Solitary circumscribed lesions of lung: study of 156 cases in which resection was performed. JAMA 1953;152:1175-1181.
4. Good CA, Hood RT, McDonald JR. Significance of solitary mass in lung. AJR Am J Roentgenol 1953;70:543-554.
5. Good CA. Management of patient with solitary mass in lung. Chic Med Soc Bull 1953;55:893-896.
6. Good CA, Wilson TW. The solitary circumscribed pulmonary nodule: study of 705 cases encountered roentgenologically in a period of three and one-half years. JAMA 1958;166:210-215.
7. Yankelevitz DF, Henschke CI. Does 2-year stability imply that pulmonary nodules are benign? AJR Am J Roentgenol 1997;168:325-328.
8. Berger WG, Erly WK, Krupinski EA, Standen JR, Stern RG. The solitary pulmonary nodule on chest radiography: can we really tell if the nodule is calcified? AJR Am J Roentgenol 2001;176:201-204.
9. Swensen SG, Silverstein MD, Ilstrup DM, Schleck CD, Edell ES. The probability of malignancy in solitary pulmonary nodules: application to small radiographically intermediate nodules. Arch Intern Med 1997;157:849-855.
10. Gurney JW. Probability of malignancy in SPN [Web page]. Available at: www.chestx-ray.com/SPN/ SPNProb.html. Accessed on September 7, 2007.
11. Li F, Aoyama M, Shiraishi J, et al. Radiologists’ performance for differentiating benign from malignant lung nodules on high-resolution CT using computer-estimated likelihood of malignancy. AJR Am J Roentgenol 2004;183:1209-1215.
12. Shah SK, McNitt-Gray MF, De Zoysa KR, et al. Solitary pulmonary nodule diagnosis on CT: results of an observer study. Acad Radiol 2005;12:496-501.
13. Matsuki Y, Nakamura K, Watanabe H, Aoki T, et al. Usefulness of an artificial neural network for differentiating benign from malignant pulmonary nodules on high-resolution CT: evaluation with receiver operating characteristic analysis. AJR Am J Roentgenol 2002;178:657-663.
14. Gould MK, Maclean CC, Kuschner WG, Rydzak CE, Owens DK. Accuracy of positron emission tomography for diagnosis of pulmonary nodules and mass lesions: a meta-analysis. JAMA 2001;285:914-924.
15. Schreiber G, McCrory DC. Performance characteristics of different modalities for diagnosis of suspected lung cancer. Chest 2003;123:115S-128S.
Evidence-based answers from the Family Physicians Inquiries Network
Is methylphenidate useful for treating adolescents with ADHD?
Methylphenidate (Ritalin) is effective in the short-term treatment of attention deficit/hyperactivity disorder (ADHD) (strength of recommendation [SOR]: A, multiple randomized control trials).
Though the immediate-release preparation is the best studied of methylphenidate formulations, extended-release methylphenidate (Concerta) has similar benefits, with a dosing regimen that may better suit an adolescent lifestyle (SOR: B, based on extrapolation of 1 randomized controlled trial and expert opinion).
Evidence Summary
The subjects of most ADHD medication studies have been school-age children. Most children with ADHD will have symptoms persisting into teenage years, and methylphenidate has been increasingly prescribed for them.1,2 Various systematic reviews and meta-analyses have demonstrated the effectiveness of short-term methylphenidate in the treatment of adolescents with ADHD.3-5 Most participants in these studies are males aged <13 years. Therefore, any conclusions about the effectiveness of methylphenidate in older adolescents must be inferred.
The most comprehensive systematic review found 8 well-controlled crossover trials with an average sample size of 24.8 (range, 9–48).6 The average duration of the studies was 6 weeks. The majority of the participants were white males with a mean age of 13 years. Each study showed statistically significant improvement from treatment with methylphenidate. Average effect sizes were calculated for 3 domains: ADHD symptoms (0.94), social behavior (1.06), and academic performance (1.25). Effect sizes were calculated using a modified Cohen’s d, which is the difference between the treated and untreated means divided by the standard deviation in the untreated condition. It is difficult to translate these changes in effect size into clinically meaningful outcome measures, although one rule of thumb estimates an effect size of 0.8 is moderate to large.
Of the 3 studies that reported the proportion of subjects with clinically significant improvement, the modal result was about one half showings improvement with methylphenidate. Of trials assessing dosing levels, <50% found significant differences between “low” and “high” doses. However, the researchers did not give their definition of low and high doses. Also, diminishing clinical improvement was noted with higher methylphenidate doses.
A single study on the once-daily stimulant preparation, extended-release methylphenidate, shows statistically significant improvement in adolescent ADHD.7 In this multicenter, randomized, double-blind, placebo-controlled trial of 177 adolescents, subjects were given placebo (n=87) or extended-release methylphenidate (n=90) at titrated doses from 18 mg/d to 72 mg/d. Following a subsequent 2-week randomization phase, clinical investigators found extended-release methylphenidate significantly superior to placebo (P=.001) on the ADHD scale. Subjects also rated it significantly superior to placebo (P=.001) on the Conners-Wells’ Self-Report Scale. Mean dose and average age were not reported. This study has been presented as an abstract and is not yet published.
Recommendations from others
The American Academy of Child and Adolescent Psychiatry (AACAP) supports the prescribing of methylphenidate in adolescents with ADHD.8 Given the unique psychosocial, environmental, and scheduling challenges of adolescence, the AACAP mentions extended-release methylphenidate as “well-suited for treatment of adolescents.”
Patients with childhood ADHD usually benefit from continuing their medication
Lisa Johnson, MD
Providence St. Peter’s Family Practice Residency, Olympia, Wash
Adolescents must face the challenge of becoming more organized and independent to be successful in middle school and high school. Those with childhood ADHD may have a particularly difficult transition, and will usually benefit from continuing to take their stimulants. Some adolescents, who were not previously identified as having ADHD, may declare themselves at this age due to school performance issues. Careful evaluation and treatment of these patients will contribute to their success.
Physicians should use the lowest effective dose of methylphenidate, as the studies seem to indicate that higher dosages do not improve performance in adolescents. Teens often prefer long-acting preparations, which obviate the need to take medication at school. The studies reviewed do not define long-term academic or vocational success, which is a more important outcome than symptom control for adolescents.
1. Safer DJ, Zito JM, Fine EM. Increased methylphenidate usage for attention deficit disorder in the 1990s. Pediatrics 1996;98:1084-1088.
2. Fischer M, Barkley RA, Edelbrock CS, Smallish L. The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status. J Consult Clin Psychol 1990;58:580-588.
3. Klassen A, Miller A, Raina P, Lee SK, Olsen L. Attention-deficit hyperactivity disorder in children and youth: a quantitative systematic review of the efficacy of different management strategies. Can J Psychiatry 1999;44:1007-1016.
4. Schachar R, Jadad AR, Gauld M, et al. Attention-deficit hyperactivity disorder: critical appraisal of extended treatment studies. Can J Psychiatry 2002;47:337-348.
5. Schachter HM, Pham B, King J, Langford S, Moher D. How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis. CMAJ 2001;165:1475-1488.
6. Smith BH, Waschbusch DA, Willoughby MT, Evans S. The efficacy, safety, and practicality of treatments for adolescents with attention-deficit/hyperactivity disorder (ADHD). Clin Child Fam Psychol Rev 2000;3:243-267.
7. Greenhill LL. Safety and Efficacy of OROS MPH in Adolescents with ADHD. Program and Abstracts of the American Psychiatric Association, 156th Annual Meeting; Scientific and Clinical Reports. May 17-22, 2003; San Francisco, Calif. Abstract S&CR12-37.
8. Greenhill LL, Pliszka S, Dulcan MK, et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 2002;41(2 Suppl):26S-49S.
Methylphenidate (Ritalin) is effective in the short-term treatment of attention deficit/hyperactivity disorder (ADHD) (strength of recommendation [SOR]: A, multiple randomized control trials).
Though the immediate-release preparation is the best studied of methylphenidate formulations, extended-release methylphenidate (Concerta) has similar benefits, with a dosing regimen that may better suit an adolescent lifestyle (SOR: B, based on extrapolation of 1 randomized controlled trial and expert opinion).
Evidence Summary
The subjects of most ADHD medication studies have been school-age children. Most children with ADHD will have symptoms persisting into teenage years, and methylphenidate has been increasingly prescribed for them.1,2 Various systematic reviews and meta-analyses have demonstrated the effectiveness of short-term methylphenidate in the treatment of adolescents with ADHD.3-5 Most participants in these studies are males aged <13 years. Therefore, any conclusions about the effectiveness of methylphenidate in older adolescents must be inferred.
The most comprehensive systematic review found 8 well-controlled crossover trials with an average sample size of 24.8 (range, 9–48).6 The average duration of the studies was 6 weeks. The majority of the participants were white males with a mean age of 13 years. Each study showed statistically significant improvement from treatment with methylphenidate. Average effect sizes were calculated for 3 domains: ADHD symptoms (0.94), social behavior (1.06), and academic performance (1.25). Effect sizes were calculated using a modified Cohen’s d, which is the difference between the treated and untreated means divided by the standard deviation in the untreated condition. It is difficult to translate these changes in effect size into clinically meaningful outcome measures, although one rule of thumb estimates an effect size of 0.8 is moderate to large.
Of the 3 studies that reported the proportion of subjects with clinically significant improvement, the modal result was about one half showings improvement with methylphenidate. Of trials assessing dosing levels, <50% found significant differences between “low” and “high” doses. However, the researchers did not give their definition of low and high doses. Also, diminishing clinical improvement was noted with higher methylphenidate doses.
A single study on the once-daily stimulant preparation, extended-release methylphenidate, shows statistically significant improvement in adolescent ADHD.7 In this multicenter, randomized, double-blind, placebo-controlled trial of 177 adolescents, subjects were given placebo (n=87) or extended-release methylphenidate (n=90) at titrated doses from 18 mg/d to 72 mg/d. Following a subsequent 2-week randomization phase, clinical investigators found extended-release methylphenidate significantly superior to placebo (P=.001) on the ADHD scale. Subjects also rated it significantly superior to placebo (P=.001) on the Conners-Wells’ Self-Report Scale. Mean dose and average age were not reported. This study has been presented as an abstract and is not yet published.
Recommendations from others
The American Academy of Child and Adolescent Psychiatry (AACAP) supports the prescribing of methylphenidate in adolescents with ADHD.8 Given the unique psychosocial, environmental, and scheduling challenges of adolescence, the AACAP mentions extended-release methylphenidate as “well-suited for treatment of adolescents.”
Patients with childhood ADHD usually benefit from continuing their medication
Lisa Johnson, MD
Providence St. Peter’s Family Practice Residency, Olympia, Wash
Adolescents must face the challenge of becoming more organized and independent to be successful in middle school and high school. Those with childhood ADHD may have a particularly difficult transition, and will usually benefit from continuing to take their stimulants. Some adolescents, who were not previously identified as having ADHD, may declare themselves at this age due to school performance issues. Careful evaluation and treatment of these patients will contribute to their success.
Physicians should use the lowest effective dose of methylphenidate, as the studies seem to indicate that higher dosages do not improve performance in adolescents. Teens often prefer long-acting preparations, which obviate the need to take medication at school. The studies reviewed do not define long-term academic or vocational success, which is a more important outcome than symptom control for adolescents.
Methylphenidate (Ritalin) is effective in the short-term treatment of attention deficit/hyperactivity disorder (ADHD) (strength of recommendation [SOR]: A, multiple randomized control trials).
Though the immediate-release preparation is the best studied of methylphenidate formulations, extended-release methylphenidate (Concerta) has similar benefits, with a dosing regimen that may better suit an adolescent lifestyle (SOR: B, based on extrapolation of 1 randomized controlled trial and expert opinion).
Evidence Summary
The subjects of most ADHD medication studies have been school-age children. Most children with ADHD will have symptoms persisting into teenage years, and methylphenidate has been increasingly prescribed for them.1,2 Various systematic reviews and meta-analyses have demonstrated the effectiveness of short-term methylphenidate in the treatment of adolescents with ADHD.3-5 Most participants in these studies are males aged <13 years. Therefore, any conclusions about the effectiveness of methylphenidate in older adolescents must be inferred.
The most comprehensive systematic review found 8 well-controlled crossover trials with an average sample size of 24.8 (range, 9–48).6 The average duration of the studies was 6 weeks. The majority of the participants were white males with a mean age of 13 years. Each study showed statistically significant improvement from treatment with methylphenidate. Average effect sizes were calculated for 3 domains: ADHD symptoms (0.94), social behavior (1.06), and academic performance (1.25). Effect sizes were calculated using a modified Cohen’s d, which is the difference between the treated and untreated means divided by the standard deviation in the untreated condition. It is difficult to translate these changes in effect size into clinically meaningful outcome measures, although one rule of thumb estimates an effect size of 0.8 is moderate to large.
Of the 3 studies that reported the proportion of subjects with clinically significant improvement, the modal result was about one half showings improvement with methylphenidate. Of trials assessing dosing levels, <50% found significant differences between “low” and “high” doses. However, the researchers did not give their definition of low and high doses. Also, diminishing clinical improvement was noted with higher methylphenidate doses.
A single study on the once-daily stimulant preparation, extended-release methylphenidate, shows statistically significant improvement in adolescent ADHD.7 In this multicenter, randomized, double-blind, placebo-controlled trial of 177 adolescents, subjects were given placebo (n=87) or extended-release methylphenidate (n=90) at titrated doses from 18 mg/d to 72 mg/d. Following a subsequent 2-week randomization phase, clinical investigators found extended-release methylphenidate significantly superior to placebo (P=.001) on the ADHD scale. Subjects also rated it significantly superior to placebo (P=.001) on the Conners-Wells’ Self-Report Scale. Mean dose and average age were not reported. This study has been presented as an abstract and is not yet published.
Recommendations from others
The American Academy of Child and Adolescent Psychiatry (AACAP) supports the prescribing of methylphenidate in adolescents with ADHD.8 Given the unique psychosocial, environmental, and scheduling challenges of adolescence, the AACAP mentions extended-release methylphenidate as “well-suited for treatment of adolescents.”
Patients with childhood ADHD usually benefit from continuing their medication
Lisa Johnson, MD
Providence St. Peter’s Family Practice Residency, Olympia, Wash
Adolescents must face the challenge of becoming more organized and independent to be successful in middle school and high school. Those with childhood ADHD may have a particularly difficult transition, and will usually benefit from continuing to take their stimulants. Some adolescents, who were not previously identified as having ADHD, may declare themselves at this age due to school performance issues. Careful evaluation and treatment of these patients will contribute to their success.
Physicians should use the lowest effective dose of methylphenidate, as the studies seem to indicate that higher dosages do not improve performance in adolescents. Teens often prefer long-acting preparations, which obviate the need to take medication at school. The studies reviewed do not define long-term academic or vocational success, which is a more important outcome than symptom control for adolescents.
1. Safer DJ, Zito JM, Fine EM. Increased methylphenidate usage for attention deficit disorder in the 1990s. Pediatrics 1996;98:1084-1088.
2. Fischer M, Barkley RA, Edelbrock CS, Smallish L. The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status. J Consult Clin Psychol 1990;58:580-588.
3. Klassen A, Miller A, Raina P, Lee SK, Olsen L. Attention-deficit hyperactivity disorder in children and youth: a quantitative systematic review of the efficacy of different management strategies. Can J Psychiatry 1999;44:1007-1016.
4. Schachar R, Jadad AR, Gauld M, et al. Attention-deficit hyperactivity disorder: critical appraisal of extended treatment studies. Can J Psychiatry 2002;47:337-348.
5. Schachter HM, Pham B, King J, Langford S, Moher D. How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis. CMAJ 2001;165:1475-1488.
6. Smith BH, Waschbusch DA, Willoughby MT, Evans S. The efficacy, safety, and practicality of treatments for adolescents with attention-deficit/hyperactivity disorder (ADHD). Clin Child Fam Psychol Rev 2000;3:243-267.
7. Greenhill LL. Safety and Efficacy of OROS MPH in Adolescents with ADHD. Program and Abstracts of the American Psychiatric Association, 156th Annual Meeting; Scientific and Clinical Reports. May 17-22, 2003; San Francisco, Calif. Abstract S&CR12-37.
8. Greenhill LL, Pliszka S, Dulcan MK, et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 2002;41(2 Suppl):26S-49S.
1. Safer DJ, Zito JM, Fine EM. Increased methylphenidate usage for attention deficit disorder in the 1990s. Pediatrics 1996;98:1084-1088.
2. Fischer M, Barkley RA, Edelbrock CS, Smallish L. The adolescent outcome of hyperactive children diagnosed by research criteria: II. Academic, attentional, and neuropsychological status. J Consult Clin Psychol 1990;58:580-588.
3. Klassen A, Miller A, Raina P, Lee SK, Olsen L. Attention-deficit hyperactivity disorder in children and youth: a quantitative systematic review of the efficacy of different management strategies. Can J Psychiatry 1999;44:1007-1016.
4. Schachar R, Jadad AR, Gauld M, et al. Attention-deficit hyperactivity disorder: critical appraisal of extended treatment studies. Can J Psychiatry 2002;47:337-348.
5. Schachter HM, Pham B, King J, Langford S, Moher D. How efficacious and safe is short-acting methylphenidate for the treatment of attention-deficit disorder in children and adolescents? A meta-analysis. CMAJ 2001;165:1475-1488.
6. Smith BH, Waschbusch DA, Willoughby MT, Evans S. The efficacy, safety, and practicality of treatments for adolescents with attention-deficit/hyperactivity disorder (ADHD). Clin Child Fam Psychol Rev 2000;3:243-267.
7. Greenhill LL. Safety and Efficacy of OROS MPH in Adolescents with ADHD. Program and Abstracts of the American Psychiatric Association, 156th Annual Meeting; Scientific and Clinical Reports. May 17-22, 2003; San Francisco, Calif. Abstract S&CR12-37.
8. Greenhill LL, Pliszka S, Dulcan MK, et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents, and adults. J Am Acad Child Adolesc Psychiatry 2002;41(2 Suppl):26S-49S.
Evidence-based answers from the Family Physicians Inquiries Network