Irradiation of Large Lung Tumors or Two or More Lung Metastases Simultaneously

A phase I/II multicenter trial will be conducted in patients with medically inoperable with
peripheral non small cell lung cancer (NSCLC) > 5 cm without lymph node involvement (group A)
or medically with ≥ 2 or more lung metastases (group B). Radiation pneumonitis is expected to
be dose-limiting in these patients and there is evidence that the incidence is predicted by
the mean lung dose (MLD). The MLD escalation will be performed separately in both patient
groups, using a time-to-event continual reassessment method (TITE-CRM). All patients will
receive 3-5 fractions SBRT to the lung tumor(s), with a minimum mean PTV dose ≥ 42 Gy.
Fraction size may be downscaled based on the MLD constraint.

Inclusion Criteria for group A and B:

- Weight loss < 10% in the last three months.

- WHO-performance status ≤ 2

- Medical inoperable patients or patients refusing surgery.

- Chemotherapy is allowed in neoadjuvant and adjuvant setting, with exclusion of the
period 4 weeks pre-SBRT and 6 weeks post-SBRT.

- Before patient registration, written informed consent must be given according to
ICH/GCP, national and local regulations.

Risk group A specification:

- NSCLC (Cytological or histological proven) patients with peripheral tumors >5 cm with
tumor staging cT2bN0M0 or cT3N0M0 (chest wall infiltration is no exclusion criteria,
as long as the tumor diameter is > 5 cm).

- Single peripheral lung metastasis in inoperable patients with a diameter of > 5 cm. In
case of first presentation of metastatic disease, cytological or histological proof is
obligated.

- In patients without cytological or histological confirmation of NSCLC, a growing
FDG-PET positive lesion (SUV >5) is accepted if a contra-indication for invasive
diagnostic examination (or refusal) is present.

Risk group B specification:

- Patients with ≥ 2 simultaneous peripheral lung metastases ≤ 5 cm of any origin at any
location in the lung.

- In case of first presentation of metastatic disease, cytological or histological proof
is obligated. This is not necessary in case of a history of an already proven
disseminated disease.

- Patients having ≥ 2 peripheral lung metastases without unacceptable dose overlap.

Exclusion Criteria:

- Patients with central tumors

- Pancoast tumors

- Prior radiotherapy treatment to the thorax

- Patients receiving any systemic treatment during SBRT

- Pregnant patients

- Patients previously treated with adriamycin agents in case of heart involvement within
the treatment field.