The goal of modern cancer therapy is to achieve optimal tumor control with as few side effects as possible. The STRIPE trial demonstrated excellent tumor control and quality of life after stereotactic radiotherapy of small lung tumors in elderly, inoperable patients. In view of the high tumor control in this situation, radiotherapy could possibly also be a perfectly justifiable and “gentler” alternative to surgery in younger patients. Another strategy to reduce side effects while maintaining efficacy is to reduce the target volume by 18F-FDG PET/CT-based “involved field” irradiation in advanced NSCLC.
Lung cancer is one of the most common causes of cancer-related deaths in Europe. In about one in four patients, the tumor is inoperable even at an early stage. Without local treatment, however, only one in three patients survives more than five years. Very good cure rates can be achieved with high-precision irradiation, also called stereotactic irradiation or SBRT. SBRT offers an important treatment alternative to many of even the most inoperable patients because, unlike surgery, it can be performed without anesthesia/non-invasively.
In the STRIPE study, 100 patients with small lung tumors were treated with high-precision radiation in the Department of Radiation Oncology at the University Medical Center Freiburg under the direction of Prof. Dr. Anca-Ligia Grosu from 2011 to 2014, for whom surgery was not considered the most oncologically appropriate therapy in interdisciplinary tumor conferences due to old age or massive concomitant diseases, or who rejected surgery. Treatment outcomes and side effects were systematically recorded over 2 years. A local healing rate of 91.8% percent was achieved, which is comparable to rates described after surgical procedures. At the same time, the treatment is well tolerated even by old and very sick patients. In the STRIPE study, all patients were also interviewed about their quality of life using standardized questionnaires before treatment, as well as 2 and 7 weeks after radiation, then 3 monthly until about 2 years after treatment completion. It was shown that the overall quality of life remains stable after treatment, and the patients’ view of the questioned symptoms is that there is hardly any relevant increase over 2 years. However, if we look only at those patients who had rated their quality of life as very poor before treatment, it is interesting to note that it was precisely these patients who benefited relevantly in terms of their quality of life. In contrast, there are data on quality of life after surgery for small lung tumors, which show a severe and sometimes long-lasting deterioration of physical functions, especially patients with concomitant diseases and poor general condition were affected.
Overall, the STRIPE study confirms the good efficacy and tolerability of SBRT even for elderly and very sick patients, contributing to a broadly based data set for this therapeutic option. The STRIPE study is the first prospective study to show that patients with initially poor quality of life benefit from SBRT of small lung tumors in terms of quality of life. Prof. Dr. Anca-Ligia Grosu, Director of the Department of Radiation Oncology at Freiburg University Hospital and Congress President of the 27th Annual Meeting of the German Society of Radiation Oncology, also takes the study data as an opportunity to rethink the standard therapy for younger patients who can still be operated on: “SBRT is an elegant method that leads to excellent tumor control without relevant losses in terms of quality of life. It is true that in young patients, ‘by tradition’, one first tries to treat with steel instead of beam, but in view of the good therapeutic results, this should be questioned. The study suggests that in this situation radiotherapy could be a perfectly acceptable alternative to surgery.”
With the use of positron emission tomography (FDG-PET), the target volume of irradiation can be reduced while delivering more effective radiation doses with “pinpoint accuracy.” An international study led by Germany showed that this resulted in a better therapeutic outcome in patients with inoperable non-small cell lung cancer (NSCLC): There was almost a halving of the local relapse rate. For inoperable non-small cell lung cancer, the combination of radiotherapy and chemotherapy is the standard of care. If lymph nodes are affected but no metastases have formed, a cure is also possible with this combination therapy. In order to be able to help as many patients as possible, the search for ways to optimize therapy continues.
An international study group led by Prof. Dr. Ursula Nestle (Freiburg and Mönchengladbach, Germany) investigated whether the use of positron emission tomography (FDG-PET) to reduce target volume provides benefits to treated patients. Twenty-four centers in Germany, Austria, and Switzerland participated in the randomized study. Two groups of patients were compared in whom radiotherapy was performed either according to conventional standards or innovatively with restriction to areas conspicuous on FDG-PET. The results of the PET-Plan study [1] were published in the Lancet Oncology – and they are a milestone in the success story of radiation oncology: PET-assisted radiation planning reduced the occurrence of new tumor growth in the originally affected region to almost half (local recurrence rate of 0.39 vs. 0.2 after two years, HR: 0.57). There were no differences between the study arms with regard to side effects. The most common acute adverse events, esophagitis and dysphagia, occurred at a higher intensity (grade 3 ) in both study groups in only 16% of treated patients.
A recent re-evaluation of the study results was presented by PD Dr. Eleni Gkika from Freiburg at the DEGRO Annual Meeting 2021 (see highlight DEGRO 2021). Dr. Gkika showed that deviation from specified radiotherapy quality parameters is associated with an unfavorable prognosis. The results underscore the importance of quality assurance measures in radiotherapy.
The study has shown that the irradiated areas can be limited to the tumor region detected by imaging without the need for precautionary irradiation of other regions. This even results in the chance of a better effect of the treatment without risking more side effects,” explained Prof. Nestle. Exactly how this positive effect comes about is the subject of further research. Higher radiation doses could be given after image-guided radiation planning without more side effects. In addition, less healthy, non-tumor tissue was irradiated, which is not only more favorable for the tolerability of the treatment, but possibly also for the immune system. DEGRO President Prof. Rainer Fietkau, Erlangen, said, “This is an increasingly important aspect, as radiochemotherapy is now also combined with immunotherapy in patients with non-small cell lung cancer.” Various studies have shown that in these patients, the combination of targeted radiotherapy and immunotherapy can further improve treatment success. “Therefore, in order to take full advantage of the therapeutic spectrum, radiotherapeutic procedures that affect the immune system as little as possible are preferable.”
Literature
1st Nestle U, Adebahr S, Kaier K, Gkika E, Schimek-Jasch T, Hechtner M, Momm F, Gaertner J, Becker G, Grosu AL. Quality of life after pulmonary stereotactic fractionated radiotherapy (SBRT): Results of the phase II STRIPE trial. Radiother Oncol. 2020 Jul;148:82-88.
2. Ursula Nestle, Tanja Schimek-Jasch, Stephanie Kremp, Andrea Schaefer-Schuler, Michael Mix, Andreas Küsters, Marco Tosch, Thomas Hehr, Susanne Martina Eschmann, Yves-Pierre Bultel, Peter Hass, Jochen Flecken-stein, Alexander Thieme, Marcus Stockinger, Karin Dieckmann, Matthias Miederer, Gabriele Holl, Christian Rischke, Eleni Gkika, Sonja Adebahr, Jochem König, Anca-Ligia Grosu, for the PET-Plan study group. Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): a multicentre, open-label, randomised, controlled trial. The Lancet Oncology 2020. Published:March 12, 2020. https://doi.org/10.1016/S1470-2045(20)30013-9
Source: German Society for Radiation Oncology e. V.
