1 Department of Radiation Oncology, U.T. M.D. Anderson Cancer Center, Houston, TX; 2 Departments of Radiation Oncology, Dana Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA; 3 Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
* Correspondence to: Dr P. Das, Department of Radiation Oncology, U.T. M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 97, Houston, TX 77 030, USA. Tel: +1-713-563-2300; Fax: +1-713-563-2366; Email: prajdas{at}mdanderson.org
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Abstract |
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Patients and methods:: Thirty-three patients treated for Hodgkin's disease at Harvard-affiliated hospitals subsequently developed small-cell lung carcinoma, non-small-cell lung carcinoma (NSCLC) or mesothelioma. Information was obtained from medical records about the initial treatment for Hodgkin's disease, any salvage therapy, smoking history, and the stage, histology, treatment and survival for thoracic cancers.
Results:: Of the 33 patients, 29 (88%) had a history of radiotherapy to the thorax, 17 (52%) had received alkylating chemotherapy, and 24 (73%) had a known history of smoking. The median time between diagnosis of Hodgkin's disease and diagnosis of thoracic cancer was 17.3 years (range 1.227.9 years). Among patients with NSCLC and a known stage, 85% presented with stage III or stage IV disease. Among patients whose treatment details were available, 40% underwent surgery, 40% received radiotherapy and 65% received chemotherapy. The median survival was 9 months (range 147 months).
Conclusions:: Most patients with thoracic cancers after Hodgkin's disease have a history of exposure to risk factors and present at an advanced stage. Patients with thoracic cancers after Hodgkin's disease have a poor survival.
Key words: Hodgkin's disease, lung cancer, risk factors, second malignancy, survival, thoracic neoplasm
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Introduction |
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Many studies have shown that lung cancer is one of the two most common solid tumors after Hodgkin's disease [1116
]. Prior radiation therapy, prior alkylating chemotherapy and smoking history increase the risk of developing lung cancer [17
21
]. Smoking appears to multiply the risks from treatment with radiotherapy or alkylating chemotherapy [21
]. In addition to lung cancers, malignant mesotheliomas have also been reported in Hodgkin's disease survivors [22
, 23
].
We investigated the clinical course of thoracic cancers in Hodgkin's disease survivors. Understanding the outcomes of thoracic cancers in these patients will help in ascertaining their prognosis. Furthermore, a knowledge of the stage distribution and clinical course in these patients will help determine whether these patients will benefit from early detection, such as through annual low-dose computed tomography (CT) screening [2426
]. Hence, we evaluated exposure to risk factors, stage distribution, treatment and survival from thoracic cancers in 33 patients who were treated for Hodgkin's disease at Harvard-affiliated hospitals.
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Patients and methods |
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Results |
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The median survival from diagnosis of thoracic cancer was 9 months (range 147 months). Figure 1 shows the KaplanMeier curve for survival from thoracic cancers.
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Discussion |
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Our findings are similar to those reported for 19 patients with non-small-cell lung carcinoma after Hodgkin's disease [28]. In that study, 14 of the 19 patients presented with stage III or IV disease, and the median survival was 5.1 months. Our study included a larger number of patients and different histologies, i.e. small-cell lung cancer, NSCLC and mesothelioma. We also found that most patients presented with an advanced stage and had poor survival.
There has been increasing interest in the role of screening in patients at high risk for lung cancers. Randomized studies have shown that screening with chest X-rays produces no differences in mortality compared with unscreened patients [29, 30
]. However, prospective studies on annual CT screening for lung cancer have shown early, promising results [24
26
]. We previously reported a decision-analytic model indicating that annual CT screening for lung cancer may increase survival and quality-adjusted survival among Hodgkin's disease survivors and that screening appears to be cost-effective, at least for smokers [31
]. A screening program can be successful only if unscreened patients present at advanced stages, and screening causes a stage-shift towards earlier stages. This study has shown that most patients with lung cancer after Hodgkin's disease present with advanced disease, while other studies have reported that CT screening causes a stage-shift towards earlier stages in subjects at high risk for lung cancer [24
26
]. Thus, the results of the present study help support the hypothesis that screening may help improve survival for lung cancer after Hodgkin's disease. Furthermore, in this study, thoracic cancers arose only in patients exposed to one or more risk factors and 82% of thoracic cancers arose in those exposed to at least two risk factors. This finding suggests that screening programs should be targeted towards those with multiple risk factors.
Many of the patients in this study were treated with extended-field radiation therapy or alkylating chemotherapy. The risk and natural history for thoracic cancers may be different for Hodgkin's disease patients treated in the current era with involved-field radiation therapy and non-alkylating chemotherapy regimens. Nevertheless, the results of this study are applicable to thoracic cancers in Hodgkin's disease patients who were first treated 1015 years ago. Since there is a long latency between Hodgkin's disease and thoracic cancers, the findings of this study are relevant for many thoracic cancers being diagnosed now in Hodgkin's disease survivors.
The patients in this study were all evaluated in the radiation oncology departments of Harvard-affiliated hospitals when they initially presented with Hodgkin's disease, and there may be a selection bias for patients being exposed to radiotherapy. However, the goal of this study was not to define risk factors, but to depict the clinical course of thoracic cancers after Hodgkin's disease. Other limitations of this study include incomplete information on the smoking history histology, stage and treatment in some patients. We were unable to obtain complete information on all patients since there was a long interval between Hodgkin's disease and thoracic cancers in many cases and since some patients were treated for thoracic cancers at other institutions.
Since thoracic malignancies are one of the most common secondary cancers after Hodgkin's disease, it is important to understand the risk factors, prognosis and treatment outcomes of thoracic cancers in Hodgkin's disease survivors. We found that patients with thoracic cancers after Hodgkin's disease had a history of exposure to risk factors, presented at advanced stages and had poor survival. Screening programs aimed at those with a history of risk factors may lead to the early detection of thoracic cancers and may improve survival in these patients.
Received for publication October 20, 2004. Revision received January 3, 2005. Accepted for publication January 5, 2005.
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