Palifermin reduced the occurrence of severe oral mucositis in patients with head and neck cancer undergoing postoperative radiochemotherapy. Additional clinical exploration of palifermin with postoperative radiochemotherapy would be useful.

Radiation-induced bystander effects are defined as biological effects expressed after irradiation by cells whose nuclei have not been directly irradiated. These effects include DNA damage, chromosomal instability, mutation, and apoptosis. There is considerable evidence that ionizing radiation affects cells located near the site of irradiation, which respond individually and collectively as part of a large interconnected web. These bystander signals can alter the dynamic equilibrium between proliferation, apoptosis, quiescence or differentiation. The aim of this review is to examine the most important biological effects of this phenomenon with regard to areas of major interest in radiotherapy. Such aspects include radiation-induced bystander effects during the cell cycle under hypoxic conditions when administering fractionated modalities or combined radio-chemotherapy. Other relevant aspects include individual variation and genetics in toxicity of bystander factors and normal tissue collateral damage. In advanced radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), the high degree of dose conformity to the target volume reduces the dose and, therefore, the risk of complications, to normal tissues. However, significant doses can accumulate out-of-field due to photon scattering and this may impact cellular response in these regions. Protons may offer a solution to reduce out-of-field doses. The bystander effect has numerous associated phenomena, including adaptive response, genomic instability, and abscopal effects. Also, the bystander effect can influence radiation protection and oxidative stress. It is essential that we understand the mechanisms underlying the bystander effect in order to more accurately assess radiation risk and to evaluate protocols for cancer radiotherapy.

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A multivariate analysis was carried out in 492 patients with metastatic neck disease from squamous cell carcinoma to determine the influence of clinical and therapeutic factors on survival, local and regional control, and distant metastases. After radiation treatment with radical intent, recurrence at the primary site was the most frequent site of treatment failure (20% of cases), followed by distant metastases (14% of the cases), whereas isolated neck recurrences occurred in only 7% of the patients. The most significant factors influencing survival were primary tumor site, node fixation, N-stage, T-stage, and number of lymphatic chains. The most significant factors influencing local control were primary site, T-stage, and node fixation. Significant factors influencing regional control were radiation therapy volume, primary tumor site, node fixation, and node location (upper and lower neck). Significant factors influencing distant control were N-stage, number of nodes, and number of involved lymphatic chains. Cancer 1992; 69:1224-1234.In head and neck cancer the presence of clinically involved lymph nodes (Stages I11 and IV) seems to be a major determinant of patient outcome.'-3 Despite the advances of surgery and radiation therapy, tumor control and survival remain disappointing, and a multidisciplinary approach often has been a d~o c a t e d .~,~ Some studies have analyzed the patterns of failure in this group of patients, either considering a specific tumor site6-8 or head and neck tumors in These generally have shown that the recurrence at the primary site is the main cause of tumor failure. In addition, some major prognostic factors have been previously defined mainly based on information from the neck d i s~e c t i o n .~~'~~'~ The effect on prognosis is less clear for other clinical parameters, which might be useful in determining the likelihood of eradicating the cancer with locoregional treatment or might indicate the need for additional systemic therapy. This study attempts to identify, by means of a multivariate analysis, the clinical and treatment factors most significantly associated with survival, local and regional recurrences, and distant metastases in a large series of patients with squamous cell carcinoma of the head and neck (SCCHN) and clinically positive neck nodes.. Patients and Methods PatientsWe have retrospectively reviewed 492 patients with previously untreated SCCHN and clinically positive neck nodes at diagnosis who where treated with radical radiation therapy at the Clinica Puerta de Hierro, Madrid, Spain, between 1965 and. The Department of Radiation Oncology receives patients from the Surgery Department of this hospital and other hospitals in the country with ap indication of radiation therapy. Patients with histology other than squamous cell carcinoma with previous cancer, distant metastases at presentation, those who had primary surgical treatment other than a biopsy, and those who did not finish a radical course of radiation were excluded from the analysis.The median age was 53 ...

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The management of patients with cervical lymph node metastases from an unknown primary cancer (CUP) remains a matter of controversy. Although new advanced diagnostic tools, such as positron emission tomography, have recently been introduced in oncology, the frequency of this tumour entity in clinical practice means it is still relevant. Recently introduced molecular profiling platforms may provide biological classification for the primary tissue of origin as well as insights into the pathophysiology of this clinical entity, including the characterisation of the Epstein-Barr virus and human papilloma virus genomas in the metastatic cervical nodes. Due to the lack of randomised trials, a standard therapy has not been identified yet. Although neck dissection followed by post-operative radiotherapy is the most generally accepted approach, there are other curative options that can be used in some patients: neck dissection alone, nodal excision followed by post-operative radiotherapy or radiotherapy alone. A major controversy remains in the target radiation volumes that range from ipsilateral neck irradiation to prophylactic irradiation of all potential mucosal sites and both sides of the neck. Finally, the administration of concurrent chemotherapy is currently being advised for patients with adverse prognostic factors.

Purpose: To analyze the prognostic value of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in patients with locally advanced rectal cancer treated with preoperative radiotherapy. Methods: Eighty-one patients with locally advanced rectal cancer were studied. All patients received preoperative pelvic radiotherapy. Forty-seven patients received concomitant chemotherapy. Surgical resection was performed 4–8 weeks later in all patients. Immunohistochemical examination of COX-2 and VEGF was performed on the preirradiation diagnostic biopsies. An immunohistochemical score established from the extension and intensity of the markers was used for analysis. The log-rank test and proportional hazards regression analysis were used to calculate the probability that the biomarkers were associated with patient outcome. Results: COX-2 expression was positive in 38 tumors (51%) while VEGF expression was positive in 43 (57%). The only clinicopathological parameter significantly associated with COX-2 or VEGF expression was performance status. None of the 2 markers were found to predict treatment response. There was no statistically significant correlation between COX-2 and VEGF. Univariate analysis identified pathological stage (pT, pN) as prognostic for disease-free survival. When VEGF expression was analyzed, disease-free survival was reduced among patients with VEGF-positive tumors (p = 0.047). This was specifically related to metastases-free survival (p = 0.016). These results were not observed for COX-2. After multivariate analysis, the pT and pN stage remained as independent prognostic factors. Conclusions: VEGF-positive expression is an indicator of poor disease-free survival, specifically linked to distant metastasis. More aggressive treatment strategies are warranted in pT3–4 and pN1–2 rectal cancer patients.

Background: In head and neck cancer, bilateral neck irradiation is the standard approach for many tumor locations and stages. Increasing knowledge on the pattern of nodal invasion leads to more precise targeting and normal tissue sparing. The aim of the present study was to evaluate the morbidity and tumor control for patients with well lateralized squamous cell carcinomas of the oral cavity and oropharynx treated with ipsilateral radiotherapy.