Table 1 Rationales to combine PARP inhibitors with radical (chemo-)radiotherapy

Locoregional recurrence rate despite primary curative (concurrent chemo-) radiotherapy

± 30% after platinum-based CCRT [33,34,35]

After combination of systemic treatment, surgery and radiotherapy:

- 19–28% in high risk locally advanced breast cancer [36, 37]

- 20% in inflammatory breast cancer, and up to 38% in triple negative inflammatory breast cancer [38, 39]

± 20–50% after platinum-based or cetuximab based CCRT [40,41,42]

Clinical evidence of benefit of DNA damaging radiosensitisers

Absolute benefits of platinum-based CCRT versus SCRT in meta-analysis [33]:

- 5-year OS + 4.5%

- 5-year LR control + 6.1%

N.A.

Absolute benefits of CCRT versus RT alone in meta-analysis [43]:

- 5-year OS + 6.5%

- 5-year LR control + 13.5%

for 5-FU/platinum-based CCRT

Frequency of HR deficiency

- Somatic mutations in BRCA1/BRCA2 (±8%) and ATM genes (±5%) [44, 45] (biomarkers with clinical evidence of PARP inhibitor efficacy in other tumour types [46,47,48,49])

- Alterations in other FA genes (±6%) and other HR genes (±16%) [50] (biomarkers with in vitro evidence of PARP inhibitor efficacy [51, 52])

See Additional file 2: Table S1.

- 5% of all breast cancer patients with germline BRCA 1 or BRCA2 mutations [53] (biomarkers with clinical proof of benefit of olaparib and talazoparib monotherapy in phase 3 double blind randomized control trials [54, 55]

- Up to 20–25% of all breast cancer patients (40–70% in triple negative breast cancer subtype) with HR deficient / BRCA-like tumours^# (biomarkers with clinical evidence of benefit of treatment with PARP inhibitors and/or DSB inducing agents^#)

See Additional file 2: Table S2.

19–25% of all HNSCC patients with FA/HR gene alterations [50, 56, 57] (biomarkers with in vitro evidence of PARP inhibitor efficacy [51, 52] and limited evidence of clinical benefit of high cumulative cisplatin dose in CCRT [56])

See Additional file 2: Table S3.

Clinical benefit of hypoxia modifying strategies

N.A.

N.A.

In meta-analysis LR control + 8% versus RT alone, with a number needed to treat of 13 [58]