Ongoing studies within the Nordic SBRT-study group

Here is a description of the ongoing studies within the Nordic SBRT study group

ANDROMEDA

Addition of hypofractionated high dose radiation in oligometastatic disease - An open label randomized phase III trial comparing up-front radiation in oligometastatic non-small cell lung cancer (NSCLC) and systemic treatment with systemic treatment alone

Summary: This is a 2:1 randomized multicentre open label phase III study of radiation combined with standard systemic treatment compared with systemic treatment alone in oligometastatic (≤5 metastases) NSCLC. Stratification factors: performance status, gender and systemic strategy. The systemic treatment consists of chemotherapy/chemoimmunotherapy or immunotherapy and is given according to local practice. During the first 3 months of systemic treatment, aiming to start around the 2^nd cycle is radiotherapy delivered to all known lesions. Preferably with SBRT /SRT/SRS but conventional radiotherapy may also be used. After the first three cycles of systemic treatment, the patients are assessed, and after four cycles, they are continuing maintenance therapy if indicated. The patients are followed with radiology every three months.

Type of cancer and stage: NSCLC, stage IV with limited metastatic burden (oligometastatic disease)

Principal investigator: Andreas Hallqvist, Sahlgrenska University Hospital, Gothenburg, Sweden

Results: Patient recruitment ongoing

Participating sites: Umeå, Gävle, Uppsala, Stockholm, Linköping, Jönköping, Karlstad, Lund, Gothenburg

Support/grants: The study is supported by the Swedish Cancer Society special investment in radiation therapy.

ASAB-study

Alectinib followed by consolidation SBRT or hypofractionated radiotherapy in stage IV NSCLC with ALK-rearrangement

Summary: the last years´ rapid development in precision cancer medicine has enabled the delivery of highly effective targeted therapy for some patients. A clinical problem is however, that resistance to the drug develops and the tumour lesions grow. In this study, want to integrate SBRT with the medical treatment to eradicate resistant tumour cell clones and thereby increase the usage time of the drug and prolong survival of the patients. The ASAB-study is a clinical phase II study where we combine SBRT with medical targeted therapy for stage IV NSCLC harbouring ALK-rerrangements. Here, we use SBRT after medical induction therapy to eradicate residual tumour. In conjunction to this clinical study, we will also perform blood sampling to analyse blood and tumour tissue biomarkers to understand how the treatment works and why some tumours do not respond.

Principal investigator: Karin Lindberg MD, PhD

Results: Patient recruitment ongoing.

Participating sites

Karolinska University Hospital, Stockholm, Sweden
Sahlgrenska University Hospital, Gothenburg, Sweden

Grants:

The Swedish Cancer Socitey
The Stockholm County Council (ALF-funds)
Svenska läkaresällskapet??
Karolinska Institutet Funds

ASTEROID

Ablative STEreotactic RadiOtherapy wIth Durvalumab (MEDI4736). An open label randomized phase II trial with durvalumab following Stereotactic Body radiotherapy (SBRT) in patients with T_1-2N0M0 Non-small Cell Lung Cancer (NSCLC)

Summary: Patients with early stage NSCLC treated with SBRT develop relapse in approximately 35 % with distant metastases being the major problem. This patient group may benefit from a systemic treatment approach but is seldom given adjuvant chemotherapy and there are no data on adjuvant therapy after SBRT. Immunotherapy is a very interesting alternative as the toxicity is less than with chemotherapy and in addition immunotherapy has efficacious advantages in combination with radiotherapy. Design: Randomized multicentre open label phase II study of Durvalumab following SBRT in patients with T_1-2N0M0 NSCLC. Patients will be randomized 1:1 to follow up (arm A) or receiving Durvalumab every 4th week for 12 months (arm B)

Type of cancer and stage: T_1-2N0M0 NSCLC

Principal investigator: Andreas Hallqvist, Sahlgrenska University Hospital, Gothenburg, Sweden

Results: Patient recruitment ongoing. Presented ELCC 2021: Safety Analysis Shows that Durvalumab Treatment After SBRT (esmo.org)

Participating sites: Sweden: Umeå, Luleå, Gävle, Stockholm, Linköping, Lund, Gothenburg. Norway: Ålesund, Trondheim, Tromsö, Oslo. Finland: Åbo, Helsingfors, Tammerfors, Wasa

Support/grants: The study is supported by the Swedish Cancer Society special investment in radiation therapy.

The HILUS-studies

Treatment with stereotactic body radiation therapy (SBRT) of ultracentral pulmonary tumours (i. e tumours close to the bronchi and central organs of the thorax) is challenging. A suboptimal treatment may lead to local failure, while at the same time, too high doses to the normal tissue nearby might result in serious side effects. Within this project, patients who have received SBRT with 7 Gy x 8 for a central lung tumour (about 230 patients) are analyzed with respect to tumour effects and effects on the normal tissue. All organ at risk have been unanimously delineated. We are performing several analyses to understand the clinical effect of the treatment and the risk factors for high grade toxic effects. The aim is to deepen our understanding of the bronchial tolerance to high doses per fraction.

Principal investigator: Karin Lindberg MD, PhD / Rolf Lewensohn MD, PhD

Results: The results of the HILUS-studies have been published in internationally recognized medical journals with focus in radiation therapy and lung cancer and have been presented in national and international meetings.

Participating sites

Aarhus University Hospital, Aarhus, Denmark
Centralsjukhuset Karlstad, Karlstad, Sweden
Karolinska University Hospital, Stockholm, Sweden
Skåne University Hospital, Lund, Sweden
Norrland University Hospital, Umeå, Sweden
Odense University Hospital, Odense, Denmark
Rigshospitalet, Copenhagen, Denmark
Sahlgrenska University Hospital, Gothenburg, Sweden
Oslo University Hospital, Oslo, Norway

Grants:

The Swedish Cancer Socitey
Nordforsk
The Stockholm County Council (ALF-funds)

KSAB

Sotorasib followed by SBRT to 1-3 lesions in advanced NSCLC with KRAS G12c mutation

Summary: The rapid development of precision cancer medicine in recent years has enabled targeted therapy for some patients. However, a clinical problem concerns the development of acquired resistance to the drug, resulting in tumour growth. Our aim is to integrated radiation therapy with medical treatment to eradicate resistant clones of the tumour, thereby prolonging the active use of the drug and increasing patient survival. Patients with lung cancer who have a specific type of the so called KRAS-mutation (KRASG12C) may now be treated with the drug Sotorasib® which is a specific KRAS-inhibitor. However, it is unclear how Sotorasib® interacts with radiotherapy. This is a phase I study in which patients are treated with Sotorasib® with the addition of radiation therapy. The aim of the study is to examine the tolerability of the treatment and to evaluate if we can prolong the sensitivity of the drug. In conjunction with this clinical study, we will also perform repeated blood sampling to analyse factors in the blood and in the tumour tissue to understand the effect of the treatment and why some tumours do not respond. The trial is an academic investigator-initiated trial financed by Amgen.

Principal investigator: Karin Lindberg, MD, PhD

Results: Patient recruitment ongoing.

Participating sites

Karolinska University Hospital, Stockholm, Sverige
Sahlgrenska University Hospital, Gotenburg, Sverige

Funding

Amgen
The Swedish Cancer Society

OLIGO-DK

A national, longitudinal, observational cohort study with embedded trials - Metastases-directed local ablative therapy in oligometastatic disease (OLIGO-DK)

Summary: The OLIGO-DK is a Danish national, longitudinal cohort study with embedded trials. It will include patients across cancer diagnoses, metastatic sites, and local treatment modalities, and follow them prospectively through these complex disease courses. The primary endpoint is to evaluate the overall effect of the local ablative therapy strategy, secondary endpoints include progression free survival, overall survival, time to change of systemic treatment, as well as pro-spective data on complications/side effects after local treatments and longitudinal quality of life data. All prospective data will be collected by a centralized study unit through phone calls and electronic questionnaires, while the remaining follow-up with evaluation scans and blood tests will be managed by the local department according to clinical guidelines.

Within OLIGO-DK, trials can be embedded, such as translational studies, randomized trials with local treatments, or cancer-specific trials. These embedded trials can benefit from the infrastructure of the cohort, such as identification and recruitment of patients and central-ized data collection. OLIGO-DK aims to shed light on these complex disease trajectories for patients with oli-gometastatic disease and generate evidence to be utilized in national guidelines.

Principal investigator Michael Ruben Teindl Laursen & Gitte Fredberg Persson

Results: Currently recruiting

Participating sites: Department of Oncology, Herlev Department of Oncology, Hillerød Department of Thoracic Surgery, Rigshospitalet Department of Surgical Gastroenterology, Rigshospitalet. Expected: All Danish departments of oncology and surgical oncology

Grants: Danish Cancer Society (grant no. R325-A18958), Independent Research Fund Denmark (grant no. 3165-00242B), Danish Comprehensive Cancer Center, Research Council of Herlev and Gentofte Hospital

PTV-margin project

Margins in stereotactic radiotherapy of tumours in the thorax, abdomen, pelvis and skeleton

Summary: In radiotherapy, there are a number of different uncertainties in the planning and treatment process to consider, such as tumour definition, patient positioning at treatment, tumour and patient movements during treatment, machine uncertainties, etc. With technological advances, including improved use of imaging modalities and adjusted patient immobilization equipment, as well as new tumour locations being referred for stereotactic radiation therapy (SBRT), the geometrical safety margins need to be reviewed. The purpose of this study is to develop updated, individually adapted CTV-PTV margins during SBRT for different tumour locations in the thorax, abdomen, pelvis and skeleton. Uncertainties such as intra-fractional tumour motion will be evaluated from CBCT taken before and after each treatment fraction, and uncertainties in online matching with CBCT will be investigated with offline review. In addition, the patients will be followed regarding toxicities and local control, to investigate whether there is any correlation to individual uncertainties.

Principal investigator: Kristin Karlsson, PhD & Mattias Hedman, MD, PhD

Results: Patient recruitment ongoing

Participating sites: Karolinska University Hospital

RealMove

RealMove (lung): assessing tumour motion with dynamic MRI

Summary: The study aims to develop an improved method to tailor the geometric safety margin when treating with stereotactic body radiotherapy (SBRT), to avoid tumour cells being missed during irradiation and to limit the exposure of normal tissues as much as possible. Dynamic magnetic resonance imaging (MRI) is assumed to represent the tumour motion during the respiratory cycle more realistically, compared to 4-dimensional computed tomography (4D CT), thanks to its high temporal resolution and the possibility to image the motion over a longer period of time. Patients receiving SBRT for a pulmonary target located below the level of the carina are included in the study, and the hypothesis will be tested through a comparison of the tumour amplitude measured with each modality. Furthermore, the predictive value of the image series acquired at treatment planning, for the motion patterns observed at each treatment fraction, will be evaluated through repeated 4D CBCT acquisitions.

Principal investigator: Eva Onjukka, MSc, PhD, Karolinska University Hospital, Stockholm, Sweden

Results: Pilot study completed, main study recruiting

Participating sites

Karolinska University Hospital (Stockholm, Sweden)
Uppsala University Hospital (Uppsala, Sweden)

Grants

Partially funded by the ASSIST grant (VINNOVA)

STRICT

A Multicenter Phase II Study of Stereotactic Radiotherapy for Centrally Located Lung Tumors (STRICT-LUNG STUDY) and Ultra-centrally Located Lung Tumors (STAR-LUNG STUDY). (STRICTSTARLUNG): NCT05354596

Summary: This is an open-label phase II study, investigating toxicity, treatment efficacy and the local tumor control rate in 69 patients with centrally located tumors and in 69 patients with ultra-centrally located tumors in the lung. Treatment and patient outcomes will be recorded. Centrally located tumors are treated on standard-linacs with daily CBCT image-guidance and plan adaptation. Ultra-centrally tumors are treated on MR-linacs with daily MR-guided plan-adaptation. Ablative dose delivery is limited by tolerance of the nearby organs-at-risk (OAR) for tumors located centrally and ultra-centrally in the lung. The safety of delivering SBRT in unresectable centrally and ultra-centrally located tumors will be investigated in this prospective study. Enrolment in both trial categories may continue until the required numbers in both groups have been reached

Type of cancer and stage: early stage central lung tumors and solitary lung metastases from other solid tumors

Principal investigator: Mette Pøhl, MD, PhD and Lone Hoffmann, Associate professor, MSc, PhD

Results: Currently recruiting

Publications:

Hoffmann L, Persson GF, Nygård L, Nielsen TB, Borrisova S, Gaard-Petersen F, Josipovic M, Khalil AA, Kjeldsen R, Knap MM, Kristiansen C, Møller DS, Ottosson W, Sand H, Thing R, Pøhl M, Schytte T. Thorough design and pre-trial quality assurance (QA) decrease dosimetric impact of delineation and dose planning variability in the STRICTLUNG and STARLUNG trials for stereotactic body radiotherapy (SBRT) of central and ultra-central lung tumours. Oncol. 2022 Jun;171:53-61. doi: 10.1016/j.radonc.2022.04.005. Epub 2022 Apr 11. PMID: 35421513.

Abstract conferences

ESTRO2022: Pre-study QA reduces delineation errors and minimize dose to OAR in a central lung tumour SBRT trial. Hoffmann L, Persson GF, Nygård L, Nielsen TB, Borrisova S, Gaard-Petersen F, Josipovic M, Khalil AA, Kjeldsen R, Knap MM, Kristiansen C, Møller DS, Ottosson W, Sand H, Thing R, Pøhl M & Schytte T

Participating sites: All Danish RT clinics

STAR

Cancer type and stage: Early stage central lung tumors and solitary lung metastases from other solid tumors

Principal investigator :Mette Pøhl, MD, PhD and Lone Hoffmann, Associate professor, MSc, PhD

Results: Currently recruiting

Publications:

Conference abstracts:

ESTRO2024: Daily adaptive MR-guided SBRT of ultra-central lung tumors (NCT05354596) – first dosimetric results. Susanne Nørring Bekke, Susan Blak Nyrup Biancardo, Kristian Boye, Cécile Peucelle, Anders Smedegaard Bertelsen, Lone Hoffmann, Tine Schytte, Mette Pøhl, Gitte Persson

Participating sites: All Danish RT clinics