Quality of life changes over time and predictors in a large head and neck patients' cohort: secondary analysis from an Italian multi-center longitudinal, prospective, observational study-a study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) head and neck working group.

PURPOSE: The present study examined the longitudinal trajectories, through hierarchical modeling, of quality of life among patients with head and neck cancer, specifically symptoms burden, during radiotherapy, and in the follow-up period (1, 3, 6, and 12 months after completion of radiotherapy), through the M.D. Anderson Symptom Inventory Head and Neck questionnaire, formed by three factors. Furthermore, analyses were conducted controlling for socio-demographic as well as clinical characteristics. METHODS: Multi-level mixed-effects linear regression was used to estimate the association between quality of life and time, age, gender, household, educational level, employment status, ECOG performance status, human papilloma virus (HPV) status, surgery, chemotherapy, alcohol intake, and smoking. RESULTS: Among the 166 participants, time resulted to be a predictor of all the three questionnaire factors, namely, general and specific related symptoms and interference with daily life. Moreover, regarding symptom interference with daily activities factor, HPV-positive status played a significant role. Considering only HPV-negative patients, only time predicted patients' quality of life. Differently, among HPV-positive patients, other variables, such as gender, educational level, alcohol use, surgery, age at diagnosis, employment status, and ECOG status, resulted significant. CONCLUSION: It was evident that quality of life of patients with head and neck cancer declined during RT, whereas it slowly improved after ending treatment. Our results clarified the role of some socio-demographic and clinical variables, for instance, HPV, which would allow to develop treatments tailored to each patient.

M. D. Anderson symptom inventory head neck (MDASI-HN) questionnaire: Italian language psychometric validation in head and neck cancer patients treated with radiotherapy ± systemic therapy - A study of the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

PURPOSE: Head and neck cancer (HNC) patients are likely to develop severe side effects, which may persist long after the end of treatment and may be responsible for decrease patient's quality of life. The M.D. Anderson Symptom Inventory- Head and Neck Module (MDASI-HN) is a questionnaire developed to detect patient's symptom burden. To conduct an Italian language psychometric validation of MDASI-HN among Italian HNC patients on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group. METHOD AND MATERIALS: To assess construct validity, it was performed a confirmatory factor analysis (CFA) with both a five-factor solution and three-factor solution, which were compared by a chi-square difference test. The concurrent validity was evaluated by the correlation with EORTC QLQ-C30 and HN35, and it was also assessed known-group validity. The internal consistency was tested using Cronbach's alpha coefficient. RESULTS: In total 166 patients (71.7% male) were included in the study, most of patients (56.2%) had an oropharynx cancer and received definitive chemoradiotherapy (51.2%). The chi-square difference test was significant and indicated that the five-factor solution fits the data better than the other one. Regarding CFA, all items had a significant saturation with their respective factors; besides, significant and strong correlations were found among factors. Most of the correlations between MDASI-HN factors and EORTC QLQ-C30 and HN35 were significant. It was found a good internal consistency. CONCLUSION: The MDASI-HN is a valid, short, and easy patient-reported outcome questionnaire which would be useful and efficient in clinical setting.

Clinical implication in the use of the AAA algorithm versus the AXB in nasopharyngeal carcinomas by comparison of TCP and NTCP values.

PURPOSE: Retrospective analysis of volumetric modulated arc therapy treatment plans to investigate qualitative, possible, clinical consequences of the use of AAA versus AXB in nasopharyngeal cancer (NPC) cases. METHODS: The dose distribution of 26 treatment plans, produced using RapidArc technique and AAA algorithm, were recalculated using AXB and the same number of monitor units provided by AAA and clinically delivered to each patient. The potential clinical effect of dosimetric differences in the planning target volume (PTV) and in organs at risk (OAR) were evaluated by comparing TCP and NTCP values. The Wilcoxon Signed Rank test was used for statistical comparison of all results obtained from the use of the two algorithms. RESULTS: The poorer coverage of the PTV, with higher prescribed dose, was reflected in the TCP, which was significantly lower when AXB was used, the median value was 81.55% (range: 74.90, 88.60%) and 84.10% (range: 77.70, 89.90%) for AAA (p < 0.001). OAR mean dose was lower in the AXB recalculated plan than the AAA plan and the difference was statistically significant for all the structures. The NTCP for developing mandible necrosis showed the largest median percentage difference between AAA and AXB (56.6%), the NTCP of risk for larynx edema of Grade ≥ 2 followed with 12.2%. CONCLUSIONS: Differences in dose distribution of NPC treatment plans recalculated with AXB are of clinical significance in those situations where the PTV and OAR involve air or bone, media in which AXB has been shown to more accurately represent the true dose distribution. The availability of AXB algorithm could improve patient dose estimation, increasing the data consistency of clinical trials.

The point of pain in head and neck cancer.

Head and neck cancer (HNC) can have a devastating impact on patient's lives as both disease and treatment may affect the ability to speak, swallow and breathe. These conditions limit the oral intake of food and drugs, reduce social functioning and impact on patient's quality of life. Up to 80% of patients suffering from HNC have pain due to the spread of the primary tumor, because of consequences of surgery, or by developing oral mucositis, dysphagia or neuropathy as toxic side effects of radiotherapy, chemotherapy or both. All healthcare professionals caring for HNC patients should assess palliative and supportive care needs in initial treatment planning and throughout the disease, with awareness when specialist palliative care expertise is needed. This paper focuses on assessment, characterizations and clinical management of pain in advanced HNC patients undergoing surgery, chemotherapy and radiotherapy, also underlining the importance of symptom assessment in HNC survivors and the need of clinical research in this field.

Lactobacillus brevis CD2 for Prevention of Oral Mucositis in Patients With Head and Neck Tumors: A Multicentric Randomized Study.

BACKGROUND: Oropharyngeal mucositis occurs in virtually all patients with head and neck cancer receiving radiochemotherapy. The manipulation of the oral cavity microbiota represents an intriguing and challenging target. PATIENTS AND METHODS: A total of 75 patients were enrolled to receive Lactobacillus brevis CD2 lozenges or oral care regimen with sodium bicarbonate mouthwashes. The primary endpoint was the incidence of grade 3 or 4 oropharyngeal mucositis during radiotherapy treatment. RESULTS: There was no statistical difference in the incidence of grade 3-4 oropharyngeal mucositis between the intervention and control groups (40.6% vs. 41.6% respectively, p=0.974). The incidence of pain, dysphagia, body weight loss and quality of life were not different between the experimental and standard arm. CONCLUSION: Our study was not able to demonstrate the efficacy of L. brevis CD2 lozenges in preventing radiation-induced mucositis in patients with head and neck cancer. Although modulating homeostasis of the salivary microbiota in the oral cavity seems attractive, it clearly needs further study.

Dysphagia in head and neck cancer patients treated with radiotherapy and systemic therapies: Literature review and consensus.

BACKGROUND: Head and neck cancer (HNC) and its therapy are associated with acute and late swallowing dysfunction. Consensus guidelines regarding evaluation and management are lacking. To address this gap, a multidisciplinary team of experts (oncologists, practitioners, deglutologists, etc.) met in Milan 17-18 February 2013 with the aim of reaching a consensus on the management of swallowing difficulties in HNC patients treated with radiotherapy with or without systemic therapies (such as chemotherapy and targeted agents). The consensus was focused particularly on those statements with limited evidence. The results of the literature review and the statements that obtained a consensus are reported and discussed in this paper. MATERIALS AND METHODS: The Delphi Appropriateness Method was used for this consensus. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. RESULTS: This paper contains 6 clusters of statements about the management of swallowing problems in radio-treated HNC patients and a review of the recent literature on these topics. CONCLUSIONS: Dysphagia assessment and its management are difficult and require a multi-team cooperation (ENT specialists, radiation and medical oncologists, deglutologists, etc.).

Predictive Role of ERCC1 Expression in Head and Neck Squamous Cell Carcinoma Patients Treated with Surgery and Adjuvant Cisplatin-Based Chemoradiation.

OBJECTIVE: ERCC1 (excision repair cross-complementation group 1) expression predicts survival in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with chemoradiation. In order to evaluate the predictive role in the adjuvant setting, we investigated ERCC1 expression in radically resected HNSCC patients who underwent surgery and cisplatin chemoradiation. METHODS: ERCC1 expression levels were determined by immunohistochemistry in primary tumor tissues from 48 patients with stage III-IV cancers. The median follow-up was 38.5 months (range: 5-121). RESULTS: High ERCC1 expression was observed in 36 (75%) patients. Univariate analysis showed that patients with high levels of ERCC1 had significantly worse disease-free survival and overall survival (OS) than patients with low levels (HR = 7.15; 95% CI, 1.68-30.35; p = 0.008 and HR = 9.90; 95% CI, 1.33-73.96; p = 0.025, respectively). In the multivariate analysis, high ERCC1 expression (HR = 7.36; 95% CI, 1.72-31.4; p = 0.007) together with high-risk category (HR = 2.69; 95% CI, 1.01-7.18; p = 0.048) were the best predictors for relapse. High ERCC1 expression was the only unfavorable independent determinant for OS (HR = 9.53; 95% CI, 1.27-71.35; p = 0.028). CONCLUSIONS: This investigation suggests that ERCC1 expression might be useful to predict prognosis in radically resected HNSCC patients treated with surgery and chemoradiation.

Sepsis in head and neck cancer patients treated with chemotherapy and radiation: Literature review and consensus.

The reporting of infection/sepsis in chemo/radiation-treated head and neck cancer patients is sparse and the problem is underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of infections and sepsis. The Delphi appropriateness method was used for this consensus. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. The paper contains seven clusters of statements about the clinical definition and management of infections and sepsis in head and neck cancer patients, which had a consensus. Furthermore, it offers a review of recent literature in these topics.

Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology - head and neck working group.

Performing intensity-modulated radiotherapy (IMRT) on head and neck cancer patients (HNCPs) requires robust training and experience. Thus, in 2011, the Head and Neck Cancer Working Group (HNCWG) of the Italian Association of Radiation Oncology (AIRO) organized a study group with the aim to run a literature review to outline clinical practice recommendations, to suggest technical solutions and to advise target volumes and doses selection for head and neck cancer IMRT. The main purpose was therefore to standardize the technical approach of radiation oncologists in this context. The following paper describes the results of this working group. Volumes, techniques/strategies and dosage were summarized for each head-and-neck site and subsite according to international guidelines or after reaching a consensus in case of weak literature evidence.

Contouring of the Pharyngeal Superior Constrictor Muscle (PSCM). A cooperative study of the Italian Association of Radiation Oncology (AIRO) Head and Neck Group.

BACKGROUND AND PURPOSE: Irradiation of the Pharyngeal Superior Constrictor Muscle (PSCM) seems to play a crucial role in radiation-related swallowing dysfunctions. Purpose of our study was to quantify operator-related variability in the contouring of PSCM on Computed Tomography (CT) scans and adherence with contours derived from MR images. MATERIALS AND METHODS: Three sets of treatment planning CT and their corresponding MR images were selected. Contouring of the PSCM was performed using both a literature-based method, derived from literature review, and an optimized method, derived from Magnetic Resonance (MR) images thus obtaining "literature-based" and "optimized" contours. Each operator contoured the PSCM on CT scans according to both methods for three times in three different days. Inter- and intra-operator variability and adherence to a contour obtained from MR images (named "MR-derived" contour) were analyzed. RESULTS: Thirty-four operators participated and 612 contours were obtained. Both intra- and inter-operator variability and adherence to the "MR-derived" contour were significantly different between the two methods (p⩽0.05). The "optimized" method showed a lower intra- and inter-operator variability and a higher adherence to the "MR-derived" contour. CONCLUSIONS: The "optimized" method ameliorates both operator-related variability and adherence with MR images.

Patterns of postoperative radiotherapy for head and neck cancer in Italy: a prospective, observational study by the head and neck group of the Italian Association for Radiation Oncology (AIRO).

AIMS AND BACKGROUND: Our previous survey showed that the patterns of postoperative radiotherapy (PORT) for head and neck cancer (HNC) in Italy might be suboptimal. A prospective observational study was therefore designed to evaluate this issue in greater detail. METHODS: All radiotherapy centers involved in the HNC Working Group of the Italian Radiation Oncology Association were asked to enter into the study all patients treated with PORT during a 6-month period. RESULTS: A total of 200 patients were accrued by 24 centers from December 2008 to May 2009. Larynx (38%) and oral cavity (34%) were the most common primary sites. The median time between surgery and the start of radiotherapy was 69 days (range, 25-215 days). Seventy-nine percent of cases with no evidence of risk factors for local recurrence were treated with high-dose radiotherapy to the primary site. In about 75% of cases the pN0 neck was included in the target volume. Concomitant chemotherapy was delivered to about 60% of patients with major risk factors and 21% of patients with no risk factors. CONCLUSIONS: Three issues emerged from our study as potential targets for future investigations: the impact on clinical outcome of the interval between surgery and the start of PORT; factors driving radiation oncologists to overtreat volumes at low risk of recurrence; and problems associated with the delivery of concomitant chemotherapy.