With improved outcomes associated with radiotherapy, radiation-induced sarcomas (RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stage-matched sarcomas that arise independent of irradiation and surgical resection with clear margins seems to offer the best chance for cure.

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In our cohort, PIS constituted 28% of head and neck sarcomas. Poorer prognosis traditionally associated with PIS compared with DN was not seen amongst patients treated with curative intent.

Purpose/Objective(s): Over the last 13 years at Washington University, we have developed three successive generations (G1-G3) of institutional therapy guidelines for the use of IMRT in the treatment of locally advanced HNSCC. We retrospectively analyzed spatial patterns of failure between these three generations. Materials/Methods: From 1997 to 2004, 256 patients were treated using G1 guidelines; from 2004 to 2007, 205 patients were treated using G2; and from 2007 to the present, 181 patients were treated using G3. Sites included oropharynx, hypopharynx, larynx, oral cavity, and unknown primary. 237 patients were treated with definitive IMRT, and 405 with postoperative IMRT. 52% of patients received chemotherapy. G1 treatments included upper head and neck IMRT with an AP low neck match, bilateral (BL) retropharyngeal (RTP) nodal coverage to the base of skull, BL high level II nodal coverage, and BL parotid gland sparing. In G2, all treatment was IMRT and high level II nodal coverage was eliminated in the N0 side of the neck, including the level IIa subdigastric lymph node as the superior-most target. G3 spared RTP nodes in the N0 side of the neck, which were contoured only up to the level were the posterior belly of the digastric crosses the internal jugular vein. Also in G3, for T1-4N0 patients with tumors of the oral cavity or larynx, BL RTP nodes and high level II nodes were spared. CTV1 was defined as the tumor bed plus any node positive region of the neck, and received 70 Gy in definitive RT patients and 60 to 66 Gy in postoperative RT patients all given at 2.0 Gy/fraction. CTV2 was defined as the N0 neck, and received 52 to 54 Gy (postoperative) and 56 Gy (definitive), given using 1.6 to 1.73 Gy/fraction. Results: Mean follow-up for living patients was 38 months and for G1, G2, and G3 was 64, 39 and 12 months, respectively. 114 patients had local regional recurrence (LRR) with 74 local failures, 74 regional failures and 93 distant metastases. There were 96 infield failures (IFF), 10 marginal failures (MF), 7 low neck match line failures (MLF) and 2 out of field failures (OOF). G1 had 29 IFF, 5 MF and 7 MLF. G2 had 40 IF and 2 MF. G3 had 27 IF, 3 MF and 2 OOF. For the entire cohort, mean survival was 75 months with a LRR free survival at 2 and 5 years of 83% and 80% respectively. Two year overall survival for G1, G2 and G3 was 71%, 70% and 76% respectively (p = 0.41). Conclusions: Through evolving IMRT guidelines we have achieved a marginal failure rate of approximately 1% while gradually limiting dose to important pharyngeal structures. Elimination of the low neck match and introduction of G2 and G3 reduced failure rates by 3% and increased IFF from 69% (G1) to 91% (G2+G3; p = 0.003). Comparison between generations shows no difference in OS or LRRFS. Infield failures constitute the predominate type of failure necessitating new strategies to further improve local control.

Brain metastases are the most common intracranial tumors in adults, accounting for more than 50% of all such cases. The approach to and management of brain metastases have evolved significantly in recent years due to several reasons. These include advances in neurosurgical and radiotherapeutic techniques, improved systemic therapy options offering better systemic and intracranial disease control and prolongation of survival as a result of these improvements, making side-effects of proposed therapies (e.g. neurocognitive decline from whole brain radiotherapy) an important consideration. In this article, we review the the primary therapeutic approaches to the management of brain metastases, namely, surgery, stereotactic radiosurgery, and whole brain radiation therapy and the primary factors dictating choice.