- Email: [email protected]
Evidenced-based medicine in glioma: molecular biology is only part of the story
Correspondence
Evidence-based management of adult patients with diffuse glioma Recently, Weller and colleagues1 proposed the new European Association for Neuro-Oncology (EANO) guidelines for adult gliomas. They have to be congratulated for their efforts in building recommendations based on the 2016 revision of the WHO classification, translating the integrated histomolecular diagnosis into algorithmic decision making. They confirm that maximal safe surgical resection in high-volume specialist centres has to be proposed whenever feasible, independent of the grade of malignancy and the histomolecular profile. However, several important concepts that are disregarded in this paper would deserve further comment. First, there is no reference to radiological growth rate, which has been shown to be an independent prognostic factor of overall survival for diffuse low-grade gliomas, regardless of the molecular status (IDH mutation, 1p19q codeletion).2,3 Second, the role of surgery is presented in an ambiguous manner. The authors claim that “a large residual tumour volume after surgery is a negative prognostic factor, but it remains uncertain whether extent of resection truly matters, or whether resectable tumours have a different biology associated with a less aggressive course of disease.” Considering the recent evidence about the survival benefit of increased extent of resection, this statement, which is in itself inconsistent, cannot be defended in this era. For example, in diffuse low-grade gliomas, two have randomised-like studies4,5 provided indisputable conclusions about the relationship between improved survival and extent of resection. Moreover, this survival www.thelancet.com/oncology Vol 18 August 2017
benefit still persists after adjusting for molecular markers.4 Last but not least, although it is stated that “quality of life is a high priority to patients and carers”, there is no mention of cognitive and quality of life assessments as a general recommendation. Glioma progression, seizures, antiepileptic medication, and oncological adjuvant treatments directly affect patients’ cognition, which in turn affects their quality of life. Clinicians in charge of patients with glioma should always keep in mind oncological and functional aspects—two intricate but distinct facets of this disease. These guidelines appear to focus exclusively on survival curves, whereas “survival with preserved quality of life” appears to be of greater importance.6 Clinicians are treating individual patients each with specific expec tations about cognitive abilities. In other words, decision making should be based on continual updates of personalised weighting of each treatment modality to achieve the optimal oncofunctional balance. In the era of integrated diagnosis, therapeutic strategies cannot rely solely on molecular profiling, but should also focus on radiological growth rates, seizure activity, cognitive status, and the patient’s own wishes.
4
5
6
Jakola AS, Skjulsvik AJ, Myrmel KS, et al. Surgical resection versus watchful waiting in low-grade gliomas. Ann Oncol 2017; published online May 5. DOI:10.1093/annonc/mdx230. Roelz R, Strohmaier D, Jabbarli R, et al. Residual tumor volume as best outcome predictor in low grade glioma—a nine-years nearrandomized survey of surgery vs. biopsy. Sci Rep 2016; 6: 32286. Mandonnet E, Duffau H, Bauchet L. A new tool for grade II glioma studies: plotting cumulative time with quality of life versus time to malignant transformation. J Neurooncol 2012; 106: 213–15.
We declare no competing interests.
The European Low-Grade Glioma Network (see appendix for full list of contributors)
See Online for appendix
[email protected] 1
2
3
Weller M, van den Bent M, Tonn JC, et al, for the European Association for NeuroOncology (EANO) Task Force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017; 18: e315–29. Gozé C, Blonski M, Le Maistre G, et al. Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas. Neuro Oncol 2014; 16: 1100–09. Pallud J, Blonski M, Mandonnet E, et al. Velocity of tumor spontaneous expansion predicts long-term outcomes for diffuse low-grade gliomas. Neuro Oncol 2013; 15: 595–606.
e429
Evidence-based management of adult patients with diffuse glioma Recently, Weller and colleagues1 proposed the new European Association for Neuro-Oncology (EANO) guidelines for adult gliomas. They have to be congratulated for their efforts in building recommendations based on the 2016 revision of the WHO classification, translating the integrated histomolecular diagnosis into algorithmic decision making. They confirm that maximal safe surgical resection in high-volume specialist centres has to be proposed whenever feasible, independent of the grade of malignancy and the histomolecular profile. However, several important concepts that are disregarded in this paper would deserve further comment. First, there is no reference to radiological growth rate, which has been shown to be an independent prognostic factor of overall survival for diffuse low-grade gliomas, regardless of the molecular status (IDH mutation, 1p19q codeletion).2,3 Second, the role of surgery is presented in an ambiguous manner. The authors claim that “a large residual tumour volume after surgery is a negative prognostic factor, but it remains uncertain whether extent of resection truly matters, or whether resectable tumours have a different biology associated with a less aggressive course of disease.” Considering the recent evidence about the survival benefit of increased extent of resection, this statement, which is in itself inconsistent, cannot be defended in this era. For example, in diffuse low-grade gliomas, two have randomised-like studies4,5 provided indisputable conclusions about the relationship between improved survival and extent of resection. Moreover, this survival www.thelancet.com/oncology Vol 18 August 2017
benefit still persists after adjusting for molecular markers.4 Last but not least, although it is stated that “quality of life is a high priority to patients and carers”, there is no mention of cognitive and quality of life assessments as a general recommendation. Glioma progression, seizures, antiepileptic medication, and oncological adjuvant treatments directly affect patients’ cognition, which in turn affects their quality of life. Clinicians in charge of patients with glioma should always keep in mind oncological and functional aspects—two intricate but distinct facets of this disease. These guidelines appear to focus exclusively on survival curves, whereas “survival with preserved quality of life” appears to be of greater importance.6 Clinicians are treating individual patients each with specific expec tations about cognitive abilities. In other words, decision making should be based on continual updates of personalised weighting of each treatment modality to achieve the optimal oncofunctional balance. In the era of integrated diagnosis, therapeutic strategies cannot rely solely on molecular profiling, but should also focus on radiological growth rates, seizure activity, cognitive status, and the patient’s own wishes.
4
5
6
Jakola AS, Skjulsvik AJ, Myrmel KS, et al. Surgical resection versus watchful waiting in low-grade gliomas. Ann Oncol 2017; published online May 5. DOI:10.1093/annonc/mdx230. Roelz R, Strohmaier D, Jabbarli R, et al. Residual tumor volume as best outcome predictor in low grade glioma—a nine-years nearrandomized survey of surgery vs. biopsy. Sci Rep 2016; 6: 32286. Mandonnet E, Duffau H, Bauchet L. A new tool for grade II glioma studies: plotting cumulative time with quality of life versus time to malignant transformation. J Neurooncol 2012; 106: 213–15.
We declare no competing interests.
The European Low-Grade Glioma Network (see appendix for full list of contributors)
See Online for appendix
[email protected] 1
2
3
Weller M, van den Bent M, Tonn JC, et al, for the European Association for NeuroOncology (EANO) Task Force on Gliomas. European Association for Neuro-Oncology (EANO) guideline on the diagnosis and treatment of adult astrocytic and oligodendroglial gliomas. Lancet Oncol 2017; 18: e315–29. Gozé C, Blonski M, Le Maistre G, et al. Imaging growth and isocitrate dehydrogenase 1 mutation are independent predictors for diffuse low-grade gliomas. Neuro Oncol 2014; 16: 1100–09. Pallud J, Blonski M, Mandonnet E, et al. Velocity of tumor spontaneous expansion predicts long-term outcomes for diffuse low-grade gliomas. Neuro Oncol 2013; 15: 595–606.
e429