Journal of Thoracic Oncology ® • Volume 9, Number 11, November 2014
How to Minimize Harms of Lung Cancer Screening To the Editor: I appreciated the recent editorial of Menezes and Roberts on the harms of lung cancer screening.1 I also appreciated their comments on our paper published in the same issue.2 I agree that we need to identify strategies to mitigate the negative physical and psychological consequences of screening. I would like to underline, however, that their comments focused only on one of the less important features of our diagnostic protocol: we considered false positive (FP) cases as those found benign after surgical biopsy, instead of adopting the more usual FP definition as nodules identified on screening CT but nonprogressive over the long term. Menezes and Roberts commented that this definition change did not decrease harms to the screened individuals. We agree. They did not mention, however, that the main findings of our study were that a low number of subjects with benign nodules underwent surgery, and that the recall rate was low, both thanks to the adoption of a noninvasive nodule work-up protocol. Thus our recall rate of 10% was considerably lower than the 27% of the NLST.3 Our figure of 14% undergoing “useless surgery” compared well with the 29% of the NLST, where no diagnostic protocol was suggested to participating centers. The main message of our paper was that the physical harms of screening can be limited when a (noninvasive) diagnostic protocol is adopted, when PET-CT and VDT are used routinely instead of lung biopsy, when a 5-mm instead of 4-mm threshold is
Disclosure: The authors declare no conflict of interest. Address for correspondence: Giulia Veronesi, Division of Thoracic Surgery, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. E-mail: [email protected] DOI: 10.1097/JTO.0000000000000329 Copyright © 2014 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/14/0911-0e83
adopted for investigating noncalcified nodules,2,4 and when positive cases are routinely discussed at multidisciplinary meetings. Our change in FP definition may be important because the low specificity characteristic of the old FP definition may adversely affect the perception of the public and health policy-makers regarding the risks and benefits of lung cancer screening. Giulia Veronesi, MD Division of Thoracic Surgery European Institute of Oncology Milan, Italy REFERENCES 1. Menezes R, Roberts H. Lung cancer screening using low-dose computed tomography— keeping participants out of harm’s way. J Thorac Oncol 2014;9:912–913. 2. Veronesi G, Maisonneuve P, Spaggiari L, et al. Diagnostic performance of low-dose computed tomography screening for lung cancer over five years. J Thorac Oncol 2014;9:935–939. 3. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395–409. 4. Bellomi M, Veronesi G, Rampinelli C, Ferretti S, De Fiori E, Maisonneuve P. Evolution of lung nodules < or =5 mm detected with lowdose CT in asymptomatic smokers. Br J Radiol 2007;80:708–712.
Letters to the Editor
mediastinum, bilateral pulmonary nodules, and mediastinal lymphadenopathy (Fig. 1). Lung biopsy and positron emission tomography scan confirmed stage IV (T4N2M1a) squamous cell carcinoma of the lung. Tumor tissue samples analyzed locally using Multiplex polymerase chain reaction/mass spectroscopy did not reveal activating mutations in the panel of genes tested (Table 1). Because of the contraindication of DNA cross-linking agents in the setting of FA, the patient initially received reduced doses of gemcitabine and vinorelbine achieving a good response to therapy lasting approximately 1 year. Subsequently, he received two cycles of paclitaxel with rapid progression of the disease. At this point, his original tissue samples were sent to an outside laboratory for further mutation testing by Next Generation Sequencing which revealed EGFR (P733T) and TP53 (A159P) gene mutations (Table 1). He was treated with erlotinib achieving disease stabilization lasting for 4 months. He then participated in a phase II trial of an experimental heat shock protein inhibitor (HSP90). Unfortunately, after a month of experimental therapy, his disease progressed and he withdrew from the trial. The patient died in 2014, 29 months after his initial diagnosis.
DISCUSSION
Young Male with Fanconi Anemia and EGFR-Mutant Non–Small-Cell Lung Cancer
To our knowledge, this is the first case report detailing the molecular profile of lung cancer in a patient with FA and the clinical course of a patient with the EGFR P733T mutation. It is well known that patients with FA living into adulthood are prone to develop hematologic malignancies and solid tumors.1 In fact, if the risks of aplastic anemia and leukemia are removed, 75% of patients with FA will develop a solid tumor by the age of 45 years.2 The most common nonhematological tumors are squamous
To the Editor: A 32-year-old male with a 10-packyear smoking history and Fanconi anemia (FA) with somatic mosaicism presented to the emergency department in 2011 with a right-sided pneumothorax. A computed tomography scan of the chest revealed a 4.4 × 3.8 cm mass in the left lung apex extending into the
Address for correspondence: Ariel Lopez-Chavez, MD, MS, Department of Hematology and Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center, 1120 NW 14th Street, CRB 610H, Miami, FL 33156. E-mail: [email protected] DOI: 10.1097/JTO.0000000000000351 Copyright © 2014 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/14/0911-0e83
Copyright © 2014 by the International Association for the Study of Lung Cancer
e83
How to Minimize Harms of Lung Cancer Screening To the Editor: I appreciated the recent editorial of Menezes and Roberts on the harms of lung cancer screening.1 I also appreciated their comments on our paper published in the same issue.2 I agree that we need to identify strategies to mitigate the negative physical and psychological consequences of screening. I would like to underline, however, that their comments focused only on one of the less important features of our diagnostic protocol: we considered false positive (FP) cases as those found benign after surgical biopsy, instead of adopting the more usual FP definition as nodules identified on screening CT but nonprogressive over the long term. Menezes and Roberts commented that this definition change did not decrease harms to the screened individuals. We agree. They did not mention, however, that the main findings of our study were that a low number of subjects with benign nodules underwent surgery, and that the recall rate was low, both thanks to the adoption of a noninvasive nodule work-up protocol. Thus our recall rate of 10% was considerably lower than the 27% of the NLST.3 Our figure of 14% undergoing “useless surgery” compared well with the 29% of the NLST, where no diagnostic protocol was suggested to participating centers. The main message of our paper was that the physical harms of screening can be limited when a (noninvasive) diagnostic protocol is adopted, when PET-CT and VDT are used routinely instead of lung biopsy, when a 5-mm instead of 4-mm threshold is
Disclosure: The authors declare no conflict of interest. Address for correspondence: Giulia Veronesi, Division of Thoracic Surgery, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy. E-mail: [email protected] DOI: 10.1097/JTO.0000000000000329 Copyright © 2014 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/14/0911-0e83
adopted for investigating noncalcified nodules,2,4 and when positive cases are routinely discussed at multidisciplinary meetings. Our change in FP definition may be important because the low specificity characteristic of the old FP definition may adversely affect the perception of the public and health policy-makers regarding the risks and benefits of lung cancer screening. Giulia Veronesi, MD Division of Thoracic Surgery European Institute of Oncology Milan, Italy REFERENCES 1. Menezes R, Roberts H. Lung cancer screening using low-dose computed tomography— keeping participants out of harm’s way. J Thorac Oncol 2014;9:912–913. 2. Veronesi G, Maisonneuve P, Spaggiari L, et al. Diagnostic performance of low-dose computed tomography screening for lung cancer over five years. J Thorac Oncol 2014;9:935–939. 3. National Lung Screening Trial Research Team, Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395–409. 4. Bellomi M, Veronesi G, Rampinelli C, Ferretti S, De Fiori E, Maisonneuve P. Evolution of lung nodules < or =5 mm detected with lowdose CT in asymptomatic smokers. Br J Radiol 2007;80:708–712.
Letters to the Editor
mediastinum, bilateral pulmonary nodules, and mediastinal lymphadenopathy (Fig. 1). Lung biopsy and positron emission tomography scan confirmed stage IV (T4N2M1a) squamous cell carcinoma of the lung. Tumor tissue samples analyzed locally using Multiplex polymerase chain reaction/mass spectroscopy did not reveal activating mutations in the panel of genes tested (Table 1). Because of the contraindication of DNA cross-linking agents in the setting of FA, the patient initially received reduced doses of gemcitabine and vinorelbine achieving a good response to therapy lasting approximately 1 year. Subsequently, he received two cycles of paclitaxel with rapid progression of the disease. At this point, his original tissue samples were sent to an outside laboratory for further mutation testing by Next Generation Sequencing which revealed EGFR (P733T) and TP53 (A159P) gene mutations (Table 1). He was treated with erlotinib achieving disease stabilization lasting for 4 months. He then participated in a phase II trial of an experimental heat shock protein inhibitor (HSP90). Unfortunately, after a month of experimental therapy, his disease progressed and he withdrew from the trial. The patient died in 2014, 29 months after his initial diagnosis.
DISCUSSION
Young Male with Fanconi Anemia and EGFR-Mutant Non–Small-Cell Lung Cancer
To our knowledge, this is the first case report detailing the molecular profile of lung cancer in a patient with FA and the clinical course of a patient with the EGFR P733T mutation. It is well known that patients with FA living into adulthood are prone to develop hematologic malignancies and solid tumors.1 In fact, if the risks of aplastic anemia and leukemia are removed, 75% of patients with FA will develop a solid tumor by the age of 45 years.2 The most common nonhematological tumors are squamous
To the Editor: A 32-year-old male with a 10-packyear smoking history and Fanconi anemia (FA) with somatic mosaicism presented to the emergency department in 2011 with a right-sided pneumothorax. A computed tomography scan of the chest revealed a 4.4 × 3.8 cm mass in the left lung apex extending into the
Address for correspondence: Ariel Lopez-Chavez, MD, MS, Department of Hematology and Medical Oncology, University of Miami Sylvester Comprehensive Cancer Center, 1120 NW 14th Street, CRB 610H, Miami, FL 33156. E-mail: [email protected] DOI: 10.1097/JTO.0000000000000351 Copyright © 2014 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/14/0911-0e83
Copyright © 2014 by the International Association for the Study of Lung Cancer
e83
