- Email: [email protected]
Significant Response to Gemcitabine Monotherapy in Primary Pleural Epithelioid Angiosarcoma
Letters to the Editor
Thean H. Tan, MBBS, FRACP
Department of Medical Oncology Royal Adelaide Hospital Cancer Centre Adelaide, Australia
Glenice Cheetham, BSc
Molecular Pathology Directorate SA Pathology Adelaide, Australia
Hamish S. Scott, BSc (Hons), PhD, FFSc (RCPA) Molecular Pathology Directorate SA Pathology Adelaide, Australia School of Medicine University of Adelaide Adelaide, Australia
Michael P. Brown, MBBS (Hons), PhD, FRACP, FRCPA
Cancer Clinical Trials Unit Royal Adelaide Hospital Cancer Centre Adelaide, Australia School of Medicine University of Adelaide Adelaide, Australia
REFERENCES 1. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying respon siveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350: 2129–2139. 2. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73. 3. De Pas T, Toffalorio F, Manzotti M, et al. Activity of epidermal growth factor receptor-tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring rare epidermal growth factor receptor mutations. J Thorac Oncol 2011;6:1895–1901. 4. Wu JY, Yu CJ, Chang YC, Yang CH, Shih JY, Yang PC. Effectiveness of tyrosine kinase inhibitors on “uncommon” epi dermal growth factor receptor mutations of unknown clinical significance in nonsmall cell lung cancer. Clin Cancer Res 2011;17:3812–3821. 5. Kancha RK, von Bubnoff N, Peschel C, Duyster J. Functional analysis of epi dermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapy. Clin Cancer Res 2009;15:460–467. 6. Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med 2005;353:133–144. 7. Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2:e17.
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Journal of Thoracic Oncology • Volume 7, Number 5, May 2012
Significant Response to Gemcitabine Monotherapy in Primary Pleural Epithelioid Angiosarcoma To the Editor: Systemic chemotherapy is one treatment option for advanced epithelioid angiosarcoma, but no standard regimen has yet been established because of the rarity of the disease. We report a case of advanced epithelioid angiosarcoma showing marked response with gemcitabine monotherapy. A 72-year-old man presented with a 1-month history of dyspnea on exertion. Computed tomography revealed a left pleural tumor measuring 6.5 cm and bilateral pleural effusions. Histopathological examination of the pleural tumor obtained by biopsies under echographic guidance revealed neoplastic proliferation characterized by nests of highly atypical, large, and round to spindle-shaped epithelioid cells with abundant eosinophilic cytoplasm and hyperchromatic nuclei containing prominent nucleoli. Atypical epithelioid cells showed focal areas of vascular formation and intracellular lumina containing erythrocytes, and positive staining for CD31, a vascular marker. Advanced epithelioid angiosarcoma with bilateral malignant pleural effusions was diagnosed, and systemic chemotherapy was initiated. Despite treatment using four cycles of combination chemotherapy with ifosfamide and adriamycin, new evidence suggested skin and pulmonary metastases. After two cycles of secondline chemotherapy with carboplatin and etoposide, skin lesions enlarged. Disclosure: The authors declare no conflict of interest. Address for correspondence: Hiroshige Yoshioka, MD, Department of Respiratory Medicine, Kurashiki Central Hospital, 1-1-1, Miwa, Kurashiki, 710–8602, Japan. E-mail: hirotin@ kchnet.or.jp Copyright © 2012 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/12/942-943
Paclitaxel monotherapy (80 mg/m2 on days 1, 8, and 15 every 28 days) was administered as a third-line option, but cutaneous involvement progressed. As the patient suffered from severe cancer pain and bleeding from skin metastases after paclitaxel monotherapy, he received oral S-1 with concurrent palliative radiotherapy to the skin lesions, which also proved insufficient. Skin metastases progressed rapidly (Figs. 1 and 2A), and the patient underwent fifthline chemotherapy with gemcitabine (1000 mg/m2 on days 1 and 8, every 21 days). After six cycles of gemcitabine monotherapy, computed tomography revealed excellent response with marked reduction of skin lesions (Fig. 2B). As cancer pain and bleeding were markedly improved, the patient continued gemcitabine monotherapy for nine cycles over 30 weeks, with good quality of life. The patient died 2 years after initial diagnosis because of serious hemorrhage from the tumor. Epithelioid angiosarcomas are a subtype of soft-tissue sarcoma (STS) and are extremely rare aggressive malignancies of endothelial origin.1 The prognosis of unresectable angiosarcoma is typically poor. Penel et al.2 reported a median time to progression of 4 months, with median overall survival of 8 months. Patients with angiosarcoma display symptoms attributable to a hypocoagulable state.3 The present patient suffered bleeding from skin metastases. For advanced-stage disease, systemic chemotherapy is considered a treatment option. As a monotherapy, paclitaxel has shown effectiveness against advanced-stage angiosarcoma.2 Gemcitabine has been reported as inactive against advanced STS, providing a response rate of only 3.23%.4 However, Stacchiotti et al.5 recently reported the overall response rate of advanced angiosarcoma to gemcitabine was 68%, with acceptable levels of toxicity. This suggests that gemcitabine could represent a good option for unresectable angiosarcoma, if not other subtypes of STS. Although paclitaxel was ineffective in our case, gemcitabine led to good response with noted reduction of the skin mass. The patient’s overall condition also improved markedly. The favorable clinical outcome in this case suggests
Copyright © 2012 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology • Volume 7, Number 5, May 2012
Letters to the Editor
Low-Dose Computed Tomography
Could It be Applied for Secondary Prevention in Patients Undergoing Resection for Lung Cancer?
FIGURE 1. Multiple skin lesions occurring on right lower quadrant of the abdomen. Some tumors have undergone self-destruction and fusion.
FIGURE 2. A, Abdominal CT showing multiple skin lesions in the right lower quadrant of the abdomen and tumor infiltration to subcutaneous tissue. B, CT after six cycles of gemcitabine, revealing significant reductions to tumors. CT, computed tomography.
gemcitabine monotherapy as a promising therapeutic option for patients with unresectable epithelioid angiosarcoma. Kazuya Tsubouchi, MD Hiroshige Yoshioka, MD Tadashi Ishida, MD, PhD Department of Respiratory Medicine Kurashiki Central Hospital Kurashiki, Japan REFERENCES 1. Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol 2010;11:983–991.
2. Penel N, Bui BN, Bay JO, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol 2008;26:5269–5274. 3. Hart J, Mandavilli S. Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis. Arch Pathol Lab Med 2011;135:268–272. 4. Svancárová L, Blay JY, Judson IR, et al. Gemcitabine in advanced adult soft-tissue sarcomas. A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2002;38:556–559. 5. Stacchiotti S, Palassini E, Sanfilippo R, et al. Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network. Ann Oncol 2012;23:501–508.
Copyright © 2012 by the International Association for the Study of Lung Cancer
To the Editor: In the January issue of Journal of Thoracic Oncology, Field et al.1 reemphasize the recently published results of the National Lung Screening Trial (NLST) regarding the role of lowdose spiral computed tomography (CT) as a screening modality in heavy smokers. The Strategic CT Screening Advisory Committee is currently engaging professional societies to focus on delivering clear guidelines and recommendations in this regard. Notably, NLST showed that primary prevention with low-dose CT in heavy smokers led to 20% fewer deaths from non–small-cell lung cancer (NSCLC) when compared with screening via old-fashioned chest radiographs.2 There is no doubt that recent technical developments have revolutionized CT capabilities and, as a result, its clinical applications. However, costeffectiveness of this screening modality and the amount of overdiagnosis in the NLST remains to be clarified before recommending it for general practice.1,2 Confounding comorbidities and practical hurdles may further reduce this screening’s efficacy, as 89% of smokers will never develop lung cancer. Conversely, it is known that 20% of completely resected Stage I NSCLC patients do develop recurrent lung cancer, most commonly to the thorax and usually within the first years postoperatively.3 The recurrence rate more than doubles for the Disclosure: The authors declare no conflicts of interest. Address for correspondence: Constantin A. Dasanu, MD, PhD, Medical Oncology and Blood Disorders Gothic Park, 43 Woodland Street, Suite G-80, Hartford, CT 06105. E-mail: [email protected] Copyright © 2012 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/12/943-944
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Thean H. Tan, MBBS, FRACP
Department of Medical Oncology Royal Adelaide Hospital Cancer Centre Adelaide, Australia
Glenice Cheetham, BSc
Molecular Pathology Directorate SA Pathology Adelaide, Australia
Hamish S. Scott, BSc (Hons), PhD, FFSc (RCPA) Molecular Pathology Directorate SA Pathology Adelaide, Australia School of Medicine University of Adelaide Adelaide, Australia
Michael P. Brown, MBBS (Hons), PhD, FRACP, FRCPA
Cancer Clinical Trials Unit Royal Adelaide Hospital Cancer Centre Adelaide, Australia School of Medicine University of Adelaide Adelaide, Australia
REFERENCES 1. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying respon siveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004;350: 2129–2139. 2. Pao W, Miller VA, Politi KA, et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med 2005;2:e73. 3. De Pas T, Toffalorio F, Manzotti M, et al. Activity of epidermal growth factor receptor-tyrosine kinase inhibitors in patients with non-small cell lung cancer harboring rare epidermal growth factor receptor mutations. J Thorac Oncol 2011;6:1895–1901. 4. Wu JY, Yu CJ, Chang YC, Yang CH, Shih JY, Yang PC. Effectiveness of tyrosine kinase inhibitors on “uncommon” epi dermal growth factor receptor mutations of unknown clinical significance in nonsmall cell lung cancer. Clin Cancer Res 2011;17:3812–3821. 5. Kancha RK, von Bubnoff N, Peschel C, Duyster J. Functional analysis of epi dermal growth factor receptor (EGFR) mutations and potential implications for EGFR targeted therapy. Clin Cancer Res 2009;15:460–467. 6. Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer - molecular and clinical predictors of outcome. N Engl J Med 2005;353:133–144. 7. Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med 2005;2:e17.
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Journal of Thoracic Oncology • Volume 7, Number 5, May 2012
Significant Response to Gemcitabine Monotherapy in Primary Pleural Epithelioid Angiosarcoma To the Editor: Systemic chemotherapy is one treatment option for advanced epithelioid angiosarcoma, but no standard regimen has yet been established because of the rarity of the disease. We report a case of advanced epithelioid angiosarcoma showing marked response with gemcitabine monotherapy. A 72-year-old man presented with a 1-month history of dyspnea on exertion. Computed tomography revealed a left pleural tumor measuring 6.5 cm and bilateral pleural effusions. Histopathological examination of the pleural tumor obtained by biopsies under echographic guidance revealed neoplastic proliferation characterized by nests of highly atypical, large, and round to spindle-shaped epithelioid cells with abundant eosinophilic cytoplasm and hyperchromatic nuclei containing prominent nucleoli. Atypical epithelioid cells showed focal areas of vascular formation and intracellular lumina containing erythrocytes, and positive staining for CD31, a vascular marker. Advanced epithelioid angiosarcoma with bilateral malignant pleural effusions was diagnosed, and systemic chemotherapy was initiated. Despite treatment using four cycles of combination chemotherapy with ifosfamide and adriamycin, new evidence suggested skin and pulmonary metastases. After two cycles of secondline chemotherapy with carboplatin and etoposide, skin lesions enlarged. Disclosure: The authors declare no conflict of interest. Address for correspondence: Hiroshige Yoshioka, MD, Department of Respiratory Medicine, Kurashiki Central Hospital, 1-1-1, Miwa, Kurashiki, 710–8602, Japan. E-mail: hirotin@ kchnet.or.jp Copyright © 2012 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/12/942-943
Paclitaxel monotherapy (80 mg/m2 on days 1, 8, and 15 every 28 days) was administered as a third-line option, but cutaneous involvement progressed. As the patient suffered from severe cancer pain and bleeding from skin metastases after paclitaxel monotherapy, he received oral S-1 with concurrent palliative radiotherapy to the skin lesions, which also proved insufficient. Skin metastases progressed rapidly (Figs. 1 and 2A), and the patient underwent fifthline chemotherapy with gemcitabine (1000 mg/m2 on days 1 and 8, every 21 days). After six cycles of gemcitabine monotherapy, computed tomography revealed excellent response with marked reduction of skin lesions (Fig. 2B). As cancer pain and bleeding were markedly improved, the patient continued gemcitabine monotherapy for nine cycles over 30 weeks, with good quality of life. The patient died 2 years after initial diagnosis because of serious hemorrhage from the tumor. Epithelioid angiosarcomas are a subtype of soft-tissue sarcoma (STS) and are extremely rare aggressive malignancies of endothelial origin.1 The prognosis of unresectable angiosarcoma is typically poor. Penel et al.2 reported a median time to progression of 4 months, with median overall survival of 8 months. Patients with angiosarcoma display symptoms attributable to a hypocoagulable state.3 The present patient suffered bleeding from skin metastases. For advanced-stage disease, systemic chemotherapy is considered a treatment option. As a monotherapy, paclitaxel has shown effectiveness against advanced-stage angiosarcoma.2 Gemcitabine has been reported as inactive against advanced STS, providing a response rate of only 3.23%.4 However, Stacchiotti et al.5 recently reported the overall response rate of advanced angiosarcoma to gemcitabine was 68%, with acceptable levels of toxicity. This suggests that gemcitabine could represent a good option for unresectable angiosarcoma, if not other subtypes of STS. Although paclitaxel was ineffective in our case, gemcitabine led to good response with noted reduction of the skin mass. The patient’s overall condition also improved markedly. The favorable clinical outcome in this case suggests
Copyright © 2012 by the International Association for the Study of Lung Cancer
Journal of Thoracic Oncology • Volume 7, Number 5, May 2012
Letters to the Editor
Low-Dose Computed Tomography
Could It be Applied for Secondary Prevention in Patients Undergoing Resection for Lung Cancer?
FIGURE 1. Multiple skin lesions occurring on right lower quadrant of the abdomen. Some tumors have undergone self-destruction and fusion.
FIGURE 2. A, Abdominal CT showing multiple skin lesions in the right lower quadrant of the abdomen and tumor infiltration to subcutaneous tissue. B, CT after six cycles of gemcitabine, revealing significant reductions to tumors. CT, computed tomography.
gemcitabine monotherapy as a promising therapeutic option for patients with unresectable epithelioid angiosarcoma. Kazuya Tsubouchi, MD Hiroshige Yoshioka, MD Tadashi Ishida, MD, PhD Department of Respiratory Medicine Kurashiki Central Hospital Kurashiki, Japan REFERENCES 1. Young RJ, Brown NJ, Reed MW, Hughes D, Woll PJ. Angiosarcoma. Lancet Oncol 2010;11:983–991.
2. Penel N, Bui BN, Bay JO, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX Study. J Clin Oncol 2008;26:5269–5274. 3. Hart J, Mandavilli S. Epithelioid angiosarcoma: a brief diagnostic review and differential diagnosis. Arch Pathol Lab Med 2011;135:268–272. 4. Svancárová L, Blay JY, Judson IR, et al. Gemcitabine in advanced adult soft-tissue sarcomas. A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2002;38:556–559. 5. Stacchiotti S, Palassini E, Sanfilippo R, et al. Gemcitabine in advanced angiosarcoma: a retrospective case series analysis from the Italian Rare Cancer Network. Ann Oncol 2012;23:501–508.
Copyright © 2012 by the International Association for the Study of Lung Cancer
To the Editor: In the January issue of Journal of Thoracic Oncology, Field et al.1 reemphasize the recently published results of the National Lung Screening Trial (NLST) regarding the role of lowdose spiral computed tomography (CT) as a screening modality in heavy smokers. The Strategic CT Screening Advisory Committee is currently engaging professional societies to focus on delivering clear guidelines and recommendations in this regard. Notably, NLST showed that primary prevention with low-dose CT in heavy smokers led to 20% fewer deaths from non–small-cell lung cancer (NSCLC) when compared with screening via old-fashioned chest radiographs.2 There is no doubt that recent technical developments have revolutionized CT capabilities and, as a result, its clinical applications. However, costeffectiveness of this screening modality and the amount of overdiagnosis in the NLST remains to be clarified before recommending it for general practice.1,2 Confounding comorbidities and practical hurdles may further reduce this screening’s efficacy, as 89% of smokers will never develop lung cancer. Conversely, it is known that 20% of completely resected Stage I NSCLC patients do develop recurrent lung cancer, most commonly to the thorax and usually within the first years postoperatively.3 The recurrence rate more than doubles for the Disclosure: The authors declare no conflicts of interest. Address for correspondence: Constantin A. Dasanu, MD, PhD, Medical Oncology and Blood Disorders Gothic Park, 43 Woodland Street, Suite G-80, Hartford, CT 06105. E-mail: [email protected] Copyright © 2012 by the International Association for the Study of Lung Cancer ISSN: 1556-0864/12/943-944
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