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Fattori determinanti della sopravvivenza nel mesotelioma maligno

Determinants of Survival in Malignant Pleural Mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) Study of 14,228 Patients

Emanuela Taioli,
Andrea S. Wolf,
Marlene Camacho-Rivera,
Andrew Kaufman,
Dong-Seok Lee,
Daniel Nicastri,
Kenneth Rosenzweig,
Raja M. Flores

PLOS
  • Published: December 14, 2015
  • DOI: 10.1371/journal.pone.0145039

Abstract

Introduction

Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Data Availability: Data are available on the SEER database,http://seer.cancer.gov/data/.
Funding: The authors have no support or funding to report.
Competing interests: The authors have declared that no competing interests exist.
1]. The diagnosis of mesothelioma often occurs when the disease is already at an advanced stage, and life expectancy is usually limited to few months. In recent years, several therapeutic approaches have been attempted with the hope to extend survival, including surgery, radiation, surgery combined with radiation, chemotherapy in various combinations with radiotherapy and surgery. A recent meta-analysis comparing survival after extra-pleural pneumonectomy and pleurectomy decortication [2] suggests that less invasive surgical approaches, such as pleurectomy/decortication are associated with prolonged survival. A randomized controlled trial conducted in the UK to assess survival, complications, and quality of life after extra-pleural pneumonectomy [3] suggested that the extensive surgical approach did not offer any survival advantage over chemotherapy alone.
Table 1. The majority of the patients were white, and roughly three quarters of the cases were males; median age at diagnosis was 62 years. More than half of the cases were diagnosed with distant metastases. Only 23% of the cases received cancer-directed surgery, and 13% received radiation therapy. Localized cases are more likely to be treated with radiation only, while regional cases with surgery only or in combination with chemotherapy. Distant cases are less likely to receive surgery or radiotherapy; probably other palliative care is used, which is not collected by SEER. The median overall survival was 7 months,; the large part of the patients (91%) was deceased at the end of follow-up.thumbnailDownload:Table 1. Patient, Disease, and Treatment Characteristics (n = 14228), SEER (Surveillance, Epidemiology, and End Results).
doi:10.1371/journal.pone.0145039.t001
Fig 1). At multivariate analysis (Table 2), independent significant predictors of survival were: being female [adjusted Hazard Ratio (adjHR): 0.79 (95% CI: 0.75–0.82)], disease stage [adjHR for distant versus local disease: 1.4 (95% CI: 1.31–1.49)], and age [adjHR: 1.02 (95% CI: 1.02–1.02) with increasing age]. Survival was also improved in the most recent calendar year of diagnosis (adjHR: 0.81 (95%CI: 0.77–0.86) for patients diagnosed in 2005–2009 versus patients diagnosed in 1973–1989). Epithelial histology was associated with best survival in comparison to the other histologic types.thumbnailDownload:Fig 1. Survival according to type of treatment (SEER database).
doi:10.1371/journal.pone.0145039.g001
thumbnailDownload:Table 2. Association between Patient and Disease Characteristics and Survival.
doi:10.1371/journal.pone.0145039.t002
Table 3). In patients diagnosed between 1973 and 1999, the adj HR for radiation was 1.14 (95% CI: 1.05–1.23), for surgery 0.63 (95% CI: 0.59–0.68), for surgery plus radiation 0.75 (95% CI: 0.66–0.84); similar results were obtained in patients diagnosed between 2000 and 2009.thumbnailDownload:Table 3. Effect of therapy on survival according to period of diagnosis.
doi:10.1371/journal.pone.0145039.t003
4]. One aspect that needs to be considered is that the SEER program includes data from both general hospitals and highly specialized cancer centers, and the surgical techniques used may greatly differ between these two hospital settings. centers. However, the improved survival with multi-modal therapy reported here confirms results of individual studies conducted in Europe [4] or in the US [5] on smaller series. Bovolato et al showed a statistically significant improvement in patients who underwent a surgical approach versus those who were non-surgically treated [4]. Kapeles et al [5]suggests that patients treated with trimodality therapy have a significantly improved survival, but the result is not confirmed by others [6]. The Kapeles study however does not disentangle the effects of each individual procedure (surgery versus radiation versus chemotherapy); other predictors of survival were gender and age, similar to what we report here.7] suggesting that such approach should be conducted by experts in the field. Results from our study indicate that surgery is the main determinant of survival, alone or in combination with radiation.8] on a smaller sample of patients (n = 5937), on the predictors of undergoing surgery. The study found that age, race and stage were main factors associated with the surgical approach, and provided the first evidence that surgery was associated with improved survival. However, the paper did not compare survival according to the different treatment approaches as we have done here.9]. A previously published study [4] suggests that MPM surgical approach improves survival over non-surgical approach (including radiation and chemotherapy).10]. In these patients, MPM seems to progress very slowly and surgery might be particularly indicated as main treatment. Further research on the impact of adjuvant treatment, and of new approaches such as gene therapy and immunotherapy, alone or in combination with surgery, is necessary to improve prognosis in this challenging disease [11].
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