Targeting head and neck tumoral stem cells： From biologicalaspects to therapeutic perspectives

Head and neck squamous cell cancer(HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells(CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self-renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities.

Targeting stem cells by radiation: From the biological angle to clinical aspects

Radiotherapy is a cornerstone of anticancer treatment. However in spite of technical evolutions, important rates of failure and of toxicity are still reported. Although numerous pre-clinical data have been published, we address the subject of radiotherapy-stem cells interaction from the clinical efficacy and toxicity perspective. On one side, cancer stem cells(CSCs) have been recently evidenced in most of solid tumor primary locations and are thought to drive radio-resistance phenomena. It is particularly suggested in glioblastoma, where CSCs were showed to be housed in the subventricular zone(SVZ). In recent retrospective studies, the radiation dose to SVZ was identified as an independent factor significantly influencing overall survival. On the other side, healthy tissue stem cells radio-destruction has been recently suggested to cause two of the most quality of life-impacting side effects of radiotherapy, namely memory disorders after brain radiotherapy, and xerostomia after head and neck radiotherapy. Recent publications studying the impact of a radiation dose decrease on healthy brain and salivary stem cells niches suggested significantly reduced long term toxicities. Stem cells comprehension should be a high priority for radiation oncologists, as this particular cell population seems able to widely modulate the efficacy/toxicity ratio of radiotherapy in real life patients.

Volumetric modulated arc radiotherapy for limited osteosclerotic myeloma

AIM:To assess the feasibility of volumetric intensity-modulated arc radiotherapy (VMAT) in patients with limited polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. METHODS:A 70-year-old male with histologically confirmed osteosclerotic myeloma was treated in our department in July 2010 with VMAT. Fourty-six Gray in 23 fractions were given on three bone lesions. Doses delivered to target volume and critical organs were compared with a tridimensional conformal radiotherapy (3D-RT) plan. Treatment was well tolerated without any side effects.RESULTS:VMAT improved dose homogeneity within the target volume, as compared to 3D-RT (standard deviations:2.9 Gy and 1.6 Gy for 3D and VMAT, respectively). VMAT resulted in a better sparing of critical organs. Dose delivered to 20% of organ volume (D20) was reduced from 22 Gy (3D-RT) to 15 Gy (VMAT) for small bowel, from 24 Gy (3D-RT) to 17 Gy (VMAT) for bladder and from 47 Gy (3D-RT) to 3 Gy (VMAT) for spinal cord. Volumes of critical organs that received at least 20 Gy (V20) were decreased by the use of VMAT, as compared to 3D-RT (V20 bladder:10% vs 99%; V20 small bowel:6% vs 21%). One year after treatment completion, no tumor progression has been reported. CONCLUSION:VMAT improved dose distribution as compared to 3D-RT for limited osteosclerotic myeloma, with better saving of critical organs.

Radiotherapy among nonagenarians with anal or rectal carcinoma: should we avoid or adapt treatment?

Dear editor,Radiotherapy is a cornerstone in the management of anal or rectal cancer. Because elderly patients are often excluded from clinical trials, little is known about radiotherapy’s therapeutic index (efficacy/toxicity ratio) in the geriatric population [1]. Still, the ageing of population imposes the challenge to treat older cancer patients and probably to adjust their treatment [2]. A few studies reported data on radiation-induced toxicities in nonagenarian patients, but data on efficacy are still scarce. For rectal cancer, preoperative radiotherapy programs were suggested to be feasible in elderly patients [3–5], with a preference for short protocols without chemotherapy [4]. For anal cancer, the safety of radiochemotherapy was only reported in limited sets of elderly patients [6]. The objective of the present study was to report efficacy and toxicity data on the radiotherapy treatment of nonagenarian patients with anal or rectal cancer.We analyzed the data of 34 nonagenarian patients with anal or rectal cancers: 27 (79.4%) with a rectal adenocarcinoma and 7 (20.6%) with an anal canal squamous cell carcinoma.