- Email: [email protected]
Effectiveness of a noninvasive digital infrared thermal imaging system in the detection of breast cancer
with the assessment of residual cancer burden based on pathologic examination, but with the advantage of in vivo clinical examination. These results may also be used to decide whether additional therapy should be given to the patient before surgery to further enhance the possibility of achieving a pCR. Another technical aspect that warrants further investigation is the reliability of the 3D volumetric measurement, especially given the limited capability
of MRI to detect minimal residual disease presenting as scattered cells and cell clusters.
Effectiveness of a noninvasive digital infrared thermal imaging system in the detection of breast cancer
to be associated with malignancy (30% vs 90%, P < .03). Conclusion.—DITI is a valuable adjunct to mammography and ultrasound, especially in women with dense breast parenchyma.
Arora N, Martins D, Ruggerio D, et al (New York Presbyterian Hosp–Cornell) Am J Surg 196:523-526, 2008
Background.—Digital infrared thermal imaging (DITI) has resurfaced in this era of modernized computer technology. Its role in the detection of breast cancer is evaluated. Methods.—In this prospective clinical trial, 92 patients for whom a breast biopsy was recommended based on prior mammogram or ultrasound underwent DITI. Three scores were generated: an overall risk score in the screening mode, a clinical score based on patient information, and a third assessment by artificial neural network. Results.—Sixty of 94 biopsies were malignant and 34 were benign. DITI identified 58 of 60 malignancies, with 97% sensitivity, 44% specificity, and 82% negative predictive value depending on the mode used. Compared to an overall risk score of 0, a score of 3 or greater was significantly more likely
268
M.-Y. L. Su, PhD
References 1. Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after
The abstract of this article could potentially mislead the reader, as it mentions only the best results rather than the full range of observed results and then does not substantiate the proposed conclusion. This article provides an excellent example of why readers need to critically evaluate an entire article instead of relying on the summary information provided in the abstract. This study by Arora and colleagues is described in the Introduction as a double-blinded trial but is, in fact, a pilot study that provides a preliminary assessment of the performance of a new breast thermography device. The patient population included women who already had lesions recommended for biopsy based on prior mammography and/or ultrasonography. No data were provided to indicate the degree to which the patient population was
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 3 2009
neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414-4422. 2. Partridge SC, Gibbs JE, Lu Y, et al. MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival. AJR Am J Roentgenol. 2005;184:1774-1781. 3. Chen JH, Feig BA, Hsiang DJ, et al. Impact of MRI-evaluated neoadjuvant chemotherapy response on change of surgical recommendation in breast cancer. Ann Surg. 2009;249:448-454.
symptomatic, but the high (64%) frequency of cancer in this population suggests that relatively few patients were screening patients. The thermography application was evaluated in 3 modes (screening, clinical, and artificial neural network), producing 3 independent cancer risk scores. However, the authors did not describe in sufficient detail for the reader how these modes differ, which could lead to a misunderstanding of how the results were different for the 3 modes. There is a minor problem with the methodology of this study. The authors considered lobular carcinoma in situ (LCIS) to represent cancer, citing the tumor-node-metastasis (TNM) definition of LCIS as stage 0 cancer. However, thermography here is being used as a breast imaging application, and the standard breast imaging definition of cancer considers LCIS to be benign, albeit a marker of high risk for cancer.1 Since only 2 of the 94 lesions studied were LCIS, it is unlikely that the misclassification of LCIS as cancer had a substantial effect on reported outcomes. On the other hand, such an error in classification suggests that both
the authors (all surgeons) and the peer reviewers (for a surgical journal) may lack expertise in breast imaging. The conclusion of this study stated that the observed results indicate clinical utility for the thermography application as ‘‘a valuable adjunct to mammography and ultrasound examination, especially in women with dense breast parenchyma.’’ However, I could not find any data on breast parenchymal density, so the second part of this conclusion appears to be unsubstantiated. Concerning the first part of the conclusion on adjunctive efficacy, the only potential clinical utility that could be evaluated, given the study population of lesions already recommended for biopsy, would be to demonstrate a negative predictive value (NPV) equal to or greater than that of tissue diagnosis, such that biopsy could be averted with
a negative test result. However, the observed NPVs of 67%, 71%, and 82% for the 3 modes of analysis are smaller than the approximately 99% NPV observed for either percutaneous core biopsy or surgical excision. Therefore, it seems that the reported data are insufficient to demonstrate clinical utility. Instead, the data indicate that this thermography application is capable of identifying already suspicious lesions in a study population heavily weighted with patients who have breast cancer. The authors also suggest that ‘‘ultimately, evaluating a screening population [with the thermography application] will give clinicians and patients more information so as to determine who will necessitate a biopsy and who can be followed clinically where mammography or ultrasound is inconclusive.’’ This suggestion could be confusing
because use of this thermography application in a screening population would indicate only who should or should not be recalled for additional imaging (not which detected lesions should undergo biopsy vs follow-up). I also believe that the authors’ suggestion is premature, as they have not studied a screening population or a population of women in whom mammography or ultrasonography is inconclusive.
Dynamic Contrast-Enhanced MRI for Prediction of Breast Cancer Response to Neoadjuvant Chemotherapy: Initial Results
Multivariate analysis with crossvalidation was performed on MRI features describing kinetics and morphology of contrast uptake in the early and late phases of enhancement. Receiver operating characteristic (ROC) analysis was used to develop a guideline that switches patients at high risk for incomplete remission to a different chemotherapy regimen while maintaining first-line therapy in 95% of patients who are not at risk (i.e., high specificity). Results.—Change in largest diameter of late enhancement during chemotherapy was the single most predictive MRI characteristic for tumor response in multivariate analysis (Az [area under the ROC curve] ¼ 0.73, p < 0.00001). Insufficient (< 25%) decrease in largest diameter of late enhancement during chemotherapy
was most indicative of residual tumor at final pathology. Using this criterion, the fraction of unfavorable responders indicated by MRI was 41% (22/54). Approximately half (44%, 14/32) of the patients who showed favorable response at MRI achieved complete remission at pathology. Conversely, 95% (21/22) of patients who showed unfavorable response at MRI had residual tumor at pathology. Conclusion.—Reduction of less than 25% in largest diameter of late enhancement during neoadjuvant chemotherapy shows the potential to predict residual tumor after therapy with high specificity.
Loo CE, Teertstra HJ, Rodenhuis S, et al (Netherlands Cancer Inst, Amsterdam) AJR Am J Roentgenol 191:1331-1338, 2008
Objective.—The aim of this study was to establish changes in contrastenhanced MRI of breast cancer during neoadjuvant chemotherapy that are indicative of pathology outcome. Materials and Methods.—In 54 patients with breast cancer, dynamic contrast-enhanced MRI was performed before chemotherapy and after two chemotherapy cycles. Imaging was correlated with final histopathology.
E. A. Sickles, MD
Reference 1. American College of Radiology. Breast Imaging Reporting and Data System. ed 4. Reston, VA: American College of Radiology; 2003;229-252.
Loo and colleagues reported the results of a retrospective analysis of 54 patients with breast cancer who were treated with neoadjuvant
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 3 2009
269
of MRI to detect minimal residual disease presenting as scattered cells and cell clusters.
Effectiveness of a noninvasive digital infrared thermal imaging system in the detection of breast cancer
to be associated with malignancy (30% vs 90%, P < .03). Conclusion.—DITI is a valuable adjunct to mammography and ultrasound, especially in women with dense breast parenchyma.
Arora N, Martins D, Ruggerio D, et al (New York Presbyterian Hosp–Cornell) Am J Surg 196:523-526, 2008
Background.—Digital infrared thermal imaging (DITI) has resurfaced in this era of modernized computer technology. Its role in the detection of breast cancer is evaluated. Methods.—In this prospective clinical trial, 92 patients for whom a breast biopsy was recommended based on prior mammogram or ultrasound underwent DITI. Three scores were generated: an overall risk score in the screening mode, a clinical score based on patient information, and a third assessment by artificial neural network. Results.—Sixty of 94 biopsies were malignant and 34 were benign. DITI identified 58 of 60 malignancies, with 97% sensitivity, 44% specificity, and 82% negative predictive value depending on the mode used. Compared to an overall risk score of 0, a score of 3 or greater was significantly more likely
268
M.-Y. L. Su, PhD
References 1. Symmans WF, Peintinger F, Hatzis C, et al. Measurement of residual breast cancer burden to predict survival after
The abstract of this article could potentially mislead the reader, as it mentions only the best results rather than the full range of observed results and then does not substantiate the proposed conclusion. This article provides an excellent example of why readers need to critically evaluate an entire article instead of relying on the summary information provided in the abstract. This study by Arora and colleagues is described in the Introduction as a double-blinded trial but is, in fact, a pilot study that provides a preliminary assessment of the performance of a new breast thermography device. The patient population included women who already had lesions recommended for biopsy based on prior mammography and/or ultrasonography. No data were provided to indicate the degree to which the patient population was
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 3 2009
neoadjuvant chemotherapy. J Clin Oncol. 2007;25:4414-4422. 2. Partridge SC, Gibbs JE, Lu Y, et al. MRI measurements of breast tumor volume predict response to neoadjuvant chemotherapy and recurrence-free survival. AJR Am J Roentgenol. 2005;184:1774-1781. 3. Chen JH, Feig BA, Hsiang DJ, et al. Impact of MRI-evaluated neoadjuvant chemotherapy response on change of surgical recommendation in breast cancer. Ann Surg. 2009;249:448-454.
symptomatic, but the high (64%) frequency of cancer in this population suggests that relatively few patients were screening patients. The thermography application was evaluated in 3 modes (screening, clinical, and artificial neural network), producing 3 independent cancer risk scores. However, the authors did not describe in sufficient detail for the reader how these modes differ, which could lead to a misunderstanding of how the results were different for the 3 modes. There is a minor problem with the methodology of this study. The authors considered lobular carcinoma in situ (LCIS) to represent cancer, citing the tumor-node-metastasis (TNM) definition of LCIS as stage 0 cancer. However, thermography here is being used as a breast imaging application, and the standard breast imaging definition of cancer considers LCIS to be benign, albeit a marker of high risk for cancer.1 Since only 2 of the 94 lesions studied were LCIS, it is unlikely that the misclassification of LCIS as cancer had a substantial effect on reported outcomes. On the other hand, such an error in classification suggests that both
the authors (all surgeons) and the peer reviewers (for a surgical journal) may lack expertise in breast imaging. The conclusion of this study stated that the observed results indicate clinical utility for the thermography application as ‘‘a valuable adjunct to mammography and ultrasound examination, especially in women with dense breast parenchyma.’’ However, I could not find any data on breast parenchymal density, so the second part of this conclusion appears to be unsubstantiated. Concerning the first part of the conclusion on adjunctive efficacy, the only potential clinical utility that could be evaluated, given the study population of lesions already recommended for biopsy, would be to demonstrate a negative predictive value (NPV) equal to or greater than that of tissue diagnosis, such that biopsy could be averted with
a negative test result. However, the observed NPVs of 67%, 71%, and 82% for the 3 modes of analysis are smaller than the approximately 99% NPV observed for either percutaneous core biopsy or surgical excision. Therefore, it seems that the reported data are insufficient to demonstrate clinical utility. Instead, the data indicate that this thermography application is capable of identifying already suspicious lesions in a study population heavily weighted with patients who have breast cancer. The authors also suggest that ‘‘ultimately, evaluating a screening population [with the thermography application] will give clinicians and patients more information so as to determine who will necessitate a biopsy and who can be followed clinically where mammography or ultrasound is inconclusive.’’ This suggestion could be confusing
because use of this thermography application in a screening population would indicate only who should or should not be recalled for additional imaging (not which detected lesions should undergo biopsy vs follow-up). I also believe that the authors’ suggestion is premature, as they have not studied a screening population or a population of women in whom mammography or ultrasonography is inconclusive.
Dynamic Contrast-Enhanced MRI for Prediction of Breast Cancer Response to Neoadjuvant Chemotherapy: Initial Results
Multivariate analysis with crossvalidation was performed on MRI features describing kinetics and morphology of contrast uptake in the early and late phases of enhancement. Receiver operating characteristic (ROC) analysis was used to develop a guideline that switches patients at high risk for incomplete remission to a different chemotherapy regimen while maintaining first-line therapy in 95% of patients who are not at risk (i.e., high specificity). Results.—Change in largest diameter of late enhancement during chemotherapy was the single most predictive MRI characteristic for tumor response in multivariate analysis (Az [area under the ROC curve] ¼ 0.73, p < 0.00001). Insufficient (< 25%) decrease in largest diameter of late enhancement during chemotherapy
was most indicative of residual tumor at final pathology. Using this criterion, the fraction of unfavorable responders indicated by MRI was 41% (22/54). Approximately half (44%, 14/32) of the patients who showed favorable response at MRI achieved complete remission at pathology. Conversely, 95% (21/22) of patients who showed unfavorable response at MRI had residual tumor at pathology. Conclusion.—Reduction of less than 25% in largest diameter of late enhancement during neoadjuvant chemotherapy shows the potential to predict residual tumor after therapy with high specificity.
Loo CE, Teertstra HJ, Rodenhuis S, et al (Netherlands Cancer Inst, Amsterdam) AJR Am J Roentgenol 191:1331-1338, 2008
Objective.—The aim of this study was to establish changes in contrastenhanced MRI of breast cancer during neoadjuvant chemotherapy that are indicative of pathology outcome. Materials and Methods.—In 54 patients with breast cancer, dynamic contrast-enhanced MRI was performed before chemotherapy and after two chemotherapy cycles. Imaging was correlated with final histopathology.
E. A. Sickles, MD
Reference 1. American College of Radiology. Breast Imaging Reporting and Data System. ed 4. Reston, VA: American College of Radiology; 2003;229-252.
Loo and colleagues reported the results of a retrospective analysis of 54 patients with breast cancer who were treated with neoadjuvant
Breast Diseases: A Year BookÒ Quarterly Vol 20 No 3 2009
269