Psychological distress and coping in nasopharyngeal cancer: an explorative study in Western Europe.

Nasopharyngeal carcinoma (NPC) is the head and neck cancer with the greatest impact on patients' quality of life. The aim of this explorative study is to investigate the psychological distress, coping strategies and quality of life of NPC patients in the post-treatment observation period. Twenty-one patients disease-free for at least two years were assessed with a medical and a psycho-oncological evaluation. Clinically relevant depressive symptoms (CRD) were present in 23.8% of patients and 33.3% reported clinically relevant anxiety symptoms (CRA). Patients with CRD and CRA showed a significantly higher score in the use of hopelessness/helplessness and anxious preoccupation coping strategies and a worse quality of life. Even in the post-treatment period, about a quarter of patients showed CRD and CRA. Results showed that patients with high anxiety or depressive symptoms seem to use dysfunctional coping strategies, such as hopelessness and anxious preoccupation, more than patients with lower levels of anxiety and depression. The use of these styles of coping thus seems to be associated to a higher presence of CRA or CRD symptomatology and to a worse quality of life.

Late sensorial alterations in different radiotherapy techniques for nasopharyngeal cancer.

Intensity-modulated radiation therapy (IMRT) for nasopharyngeal cancer (NPC) allowed a better distribution of the dose to the tumor volume, sparing surrounding structures. Aim of the study is the objective evaluation of olfactory and gustatory impairments in patients who underwent chemo-radiotherapy for NPC. Correlation between smell and taste alterations, xerostomy, and radiation technique was investigated. Thirty healthy subjects and 30 patients treated with chemo-radiation therapy for NPC, with at least a 2-years follow-up period, were evaluated. All subjects underwent symptoms evaluation, endoscopic fiber optic nasal examination, taste strips, Sniffin' sticks tests, Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer late radiation morbidity scoring system. Patients were divided in 2 groups: 2-dimensional radiotherapy/conformal 3-dimensional radiotherapy and IMRT. A higher percentage of rhinorrhea, nasal obstruction, xerostomy, hyposmia, hypogeusia, mucosal hyperemia, and presence of nasopharyngeal secretions was found in irradiated subjects (P < 0.05). Concerning olfactory and gustatory scores, we demonstrated a statistically significant difference between healthy subjects and irradiated patients (P < 0.05), with lower gustatory total score in IMRT group (P < 0.01). In conclusion, chemo-radiotherapy for NPC induces long-term smell and taste impairments, which can compromise quality of life. Although based on small samples, it is also important to consider that IMRT can induce higher taste dysfunction compared with traditional techniques.

Conventional 2D (2DRT) and 3D conformal radiotherapy (3DCRT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer treatment.

PURPOSE: Nasopharyngeal carcinoma represents a distinct entity as compared to other head and neck tumours. Radio-chemotherapy is the treatment of first choice in non-metastatic disease. Intensity-modulated radiation therapy (IMRT) allows the sparing of parotid glands, improving the toxicity profile. The aim of this study was to compare the results obtained with IMRT with those obtained with conventional 2D (2DRT) and 3D conformal radiation therapy (3DCRT) in terms of tumour control, survival, acute and late toxicity. MATERIALS AND METHODS: We reviewed the clinical records of 52 patients with histologically proven carcinoma of the nasopharynx (stage I-IVB according to the 2002 American Joint Committee on Cancer staging system) treated with curative intent between January 2003 and August 2011: 26 patients were treated with 2D or 3D technique (arm A) and 26 with IMRT technique (arm B) with simultaneous integrated boost. Fifty patients (96 %) received chemotherapy. Local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), acute and late toxicity were retrospectively evaluated. RESULTS: After a median follow-up of 37.6 months (69 months in arm A and 23 months in arm B), 69 % of patients were alive and disease-free, 10 % were alive with disease and 21 % died of disease, with an OS of 81 % at 2 years and 79 % at 5 years, a LC rate of 88 % at 2 years and 78 % at 5 years, a LRC rate of 80 % at 2 years and 73 % at 5 years and a DFS of 74 % at 2 years and 65 % at 5 years, with no statistically significant differences between IMRT and 2DRT/3DCRT. In multivariate analysis, the TNM stage and the volume treated at high dose correlated with DFS. No factor was found to be related to OS. Chronic toxicity was not statistically different in the two study groups and in particular ≥ G2 xerostomia rates were 67 and 41 % in arm A and B, respectively (p = 0.10). CONCLUSIONS: The findings of this study confirm that IMRT associated with chemotherapy, even with moderately hypofractionated regimens, allows good disease control with better results in terms of late xerostomia, although without statistically significant differences compared to 2DRT and 3DCRT. The hypothesis of an impact of IMRT on survival has yet to be confirmed.

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.

Radiotherapy alone or with concomitant daily low-dose carboplatin in locally advanced, unresectable head and neck cancer: definitive results of a phase III study with a follow-up period of up to ten years.

AIM AND BACKGROUND: Radiotherapy is the conventional treatment for locally advanced inoperable head and neck squamous cell carcinoma. However, the poor therapeutic results justify the development of radiochemotherapy combinations. In an attempt to improve local control and survival in patients with stage III and IV unresectable head and neck squamous cell carcinoma and based on the results of our previous dose escalation study, we undertook a prospective multicentric randomized trial. MATERIALS AND METHODS: From November 1992 through December 1995, a total of 164 patients were randomized to receive radiotherapy alone (arm I) or combined (arm II) with daily low-dose carboplatin. RESULTS: The 3, 5 and 10-year local-regional recurrence-free survival rates were better in arm II (21.7%, 15.1% and 15.1%, respectively) than in arm I (15%, 10.7% and 10.7%), but without statistical significance (P = 0.11). The 3, 5 and 10-year disease-free survival rates showed the same positive trend for arm II (16%, 6.8% and 6.8% vs. 9%, 5.5% and 5.5%, in arm I, respectively), again without statistical significance (P = 0.09). Instead, a statistical advantage was found in overall survival rates at 3, 5 and 10-years (28.9%, 9% and 5.5% in arm II and 11.1%, 6.9% and 6.9% in arm I, respectively) (P = 0.02). The 3, 5 and 10-year local-regional recurrence-free survival rates in stage IV disease were statistically better in arm II (21.5%, 15.9% and 15.9%) than in arm I (12.8%, 7.7% and 7.7%, respectively) (P = 0.04). CONCLUSIONS: Long-term results in both treatment arms of the trial appear less positive than most published series. However, our findings do not exclude that carboplatin may be beneficial, but the benefit in local control must be lower than the 15% assumed to dimension the trial.

Prospective assessment of taste impairment and nausea during radiotherapy for head and neck cancer.

Dysgeusia and nausea are common side effects observed in head and neck cancer patients treated with either exclusive radiotherapy or combined modality treatment. The aim of the present study was to prospectively evaluate dysgeusia, during treatment and follow-up, using the chemotherapy-induced taste alteration scale (CiTAS), a metrics based on 18-items exploring three dimensions (quantitative and qualitative changes in taste perception, and diet-related issues) identified through a four-factor analysis: decline in basic taste, discomfort, phantogeusia-parageusia, and general taste alterations. Moreover, we scored, according to Common Toxicity Criteria Adverse Events, nausea and other treatment-related toxicities. Since, ginger is traditionally used to prevent and/or treat nausea and vomiting, we prophylactically employed a ginger-based supplement named Naumix/Naugin (Gamfarma, Milan, Italy), to potentially mitigate both nausea and taste impairment. Using the CiTAS scale, we highlighted a progressive increase in all dysgeusia dimensions, peaking at the VII week of treatment and a subsequent partial late recovery. In particular, we observed a recovery for discomfort, phantogeusia-parageusia, and general taste alterations at 6 months. Grade 2 nausea, observed to be as low as 12.9% potentially due to the use of ginger, peaked at the III week of treatment. Finally, for patients experiencing nausea, the dysgeusia dimension of discomfort was also relevant.

Management of acute skin toxicity with Hypericum perforatum and neem oil during platinum-based concurrent chemo-radiation in head and neck cancer patients.

Acute skin toxicity is a frequent finding during combined radiotherapy and chemotherapy in head and neck cancer patients. Its timely and appropriate management is crucial for both oncological results and patient's global quality of life. We herein report clinical data on the use of Hypericum perforatum and neem oil in the treatment of acute skin toxicity during concurrent chemo-radiation for head and neck cancer. A consecutive series of 50 head and neck cancer patients undergoing concomitant radio-chemotherapy with weekly cisplatin was analyzed. Treatment with Hypericum perforatum and neem oil was started in case of G2 acute skin toxicity according to the RTOG/EORTC scoring scale and continued during the whole treatment course and thereafter until complete recovery. The maximum detected acute skin toxicity included Grade 2 events in 62% of cases and G3 in 32% during treatment and G2 and G3 scores in 52 and 8%, respectively, at the end of chemo-radiation. Grade 2 toxicity was mainly observed during weeks 4-5, while G3 during weeks 5-6. Median times spent with G2 or G3 toxicity were 23.5 and 14 days. Patients with G3 toxicity were reconverted to a G2 profile in 80% of cases, while those with a G2 score had a decrease to G1 in 58% of cases. Time between maximum acute skin toxicity and complete skin recovery was 30 days. Mean worst pain score evaluated with the Numerical Rating Scale-11 was 6.9 during treatment and 4.5 at the end of chemo-radiotherapy. Hypericum perforatum and neem oil proved to be a safe and effective option in the management of acute skin toxicity in head and neck cancer patients submitted to chemo-radiation with weekly cisplatin. Further studies with a control group and patient-reported outcomes are needed to confirm this hypothesis.

Prospective assessment of oral mucositis and its impact on quality of life and patient-reported outcomes during radiotherapy for head and neck cancer.

Oral mucositis (OM) is a common acute side effect during radiotherapy treatments for head and neck cancer (HNC), with a potential impact on patient's compliance to therapy, quality of life (QoL) and clinical outcomes. Its timely and appropriate management is of paramount importance. Several quantitative scoring scales are available to properly assess OM and its influence on patient-reported outcomes (PROs) and QoL. We prospectively assessed OM in a cohort of HNC patients submitted to radiation using the Oral Mucositis Assessment Scale (OMAS), while its impact on PROs and QoL was evaluated employing the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer (OMWQ-HN) and the Functional Assessment of Cancer Therapy-Head and Neck Cancer (FACT-HN). Evaluation of OMAS scores highlighted a progressive increase in OM during treatment and a partial recovery after the end of radiation. These trends were correlated to PROs and QoL as evaluated with OMWQ-HN and FACT-HN questionnaires. In the present study, we provided a quantitative assessment of OM, PROs and QoL in HNC patient undergoing radiotherapy, potentially useful for future comparison.

Clinicopathological parameters and outcome of 245 patients operated for oral squamous cell carcinoma.

INTRODUCTION: This report analysed the outcome of patients undergoing surgery for oral squamous cell carcinoma in order to identify the prognostic value of several factors. PATIENTS: A total of 245 patients were studied who had undergone surgery for oral squamous cell carcinoma between 1989 and 2002, of whom 109 had received postoperative radiation therapy. METHODS: For each patient, personal data, alcohol and tobacco consumption, symptoms, histological findings, treatment, and outcome were recorded and analysed statistically. Survival curves were calculated using the Kaplan-Meier algorithm, and the difference in survival among subgroups was examined. RESULTS: The overall 5-year survival rate in the 245 patients was 63% (72.5% at 3 years). The differences in the 5-year survival were significant (p<0.05) for the site of origin, N and pN status, TNM stage, grading, status of the resection margins, osseous infiltration, and perineural invasion. Vascular involvement as a discriminator was not statistically significant. In patients undergoing radiation therapy, only perineural invasion negatively influenced the 5-year survival prognosis (p<0.01). CONCLUSION: The overall survival rate was within the (previously) reported range. The prognostic value of many parameters is widely recognized; the combined evaluation of 'composite factors' is promising.

Exclusive Radiotherapy for Early-stage Glottic Cancer: A Single-institution Retrospective Analysis with a Focus on Voice Quality.

AIM: To report on clinical outcomes of patients with early-stage glottic cancer treated with exclusive radiotherapy with specific analysis of voice quality. PATIENTS AND METHODS: A consecutive cohort of 55 patients with early glottic cancer was retrospectively analyzed. Patients were treated with exclusive radiation up to a conventionally fractionated total dose of 66-70 Gy with a 3-dimensional conformal technique. Oncological outcomes and toxicity profiles were investigated. A sub-sample of this cohort was also analyzed in terms of voice quality employing subjective and objective tools such as the Voice Handicap Index-10 (VHI-10) and the Multidimensional Voice Program (MDVP™) software and was compared to a group of similar patients treated with CO2 laser cordectomy. RESULTS: after a median observation time of 74.5 months, 5- and 10-year local control was 89% [95% confidence interval (CI)=70.7-93.1%] and 86% (95% CI=68.7-89.6%), respectively. Larynx-preservation rate was 91.8% (95% CI=82.4%-94.9%) at 10 years. Five- and 10-year actuarial overall survival was 72% (95% CI=50.4-79.2%) and 56% (95% CI=48.7-64.3%). Maximum detected acute toxicity included G3 dermatitis (5.4%) and G4 dyspnea (1.8%). Late toxicity profile was mild. VHI-10 scores showed a mild voice disability in both groups, with no statistically significant difference (p=0.12), even when investigating different domains. Patients treated with radiation had a lower deterioration rate in all parameters excluding low voice, interruptions of sound and diplophony. CONCLUSION: Exclusive radiation proved an effective treatment for patients with early glottic cancer in terms of both oncological outcome and voice quality.

Nasal cytological changes as late effects of radiotherapy for nasopharyngeal cancer.

BACKGROUND: Radiation therapy is a cornerstone in nasopharyngeal cancer treatment. However, it can induce acute and long-term adverse effects, such as acute mucositis and late submucosal fibrosis. Late toxicities could not only affect submucosa but also mucosal cells, determining long-term cytological changes. OBJECTIVE: Evaluation of delayed nasal cytological alterations in patients who underwent radiation therapy for nasopharyngeal carcinoma (NPC). METHODS: In this case-control study, we analyzed 30 healthy subjects and 30 patients treated with chemotherapy and radiotherapy for NPC between 2003 and 2011, with a median follow-up of 59 months. All subjects underwent symptoms anamnestic evaluation (rhinorrea, nasal obstruction), endoscopic fiber optic nasal examination, skin-prick tests, and nasal scraping for cytological exam. RESULTS: A higher percentage of rhinorrhea, nasal obstruction, mucosal hyperemia, and presence of nasopharyngeal secretions at fiber optic endoscopic exam was found in radiated subjects (p < 0.05). Nasal cytology analysis demonstrated a higher percentage of neutrophilic inflammation and squamous cell metaplasia and mucous cell metaplasia in treated patients (p < 0.05). No cytological atypia was seen. No statistically significant correlation between nasal cytological changes and objective findings, patients' age, tobacco smoking, and gastroesophageal reflux has been found in the radiotherapy group (p > 0.05). CONCLUSION: Radiation therapy induces late nasal mucosal changes, which may be related to clinical consequences, such as abundant mucus production and its consequent endonasal stagnation. In the future, detailed knowledge of cytological changes in patients' nasal mucosa could represent a key prerequisite for the choice of effective interventions for late radiation-induced rhinitis.

Induction Chemotherapy and Sequential Concomitant Chemo-radiation in Locally Advanced Head and Neck Cancers: How Induction-phase Intensity and Treatment Breaks May Impact on Clinical Outcomes.

AIM: The purpose of the study was to assess outcomes of locally advanced head and neck (LAHNC) treated with induction chemotherapy (ICT) and subsequent concurrent chemo-radiation. PATIENTS AND METHODS: A total of 71 LAHNC patients were treated with 2-3 cycles of docetaxel, cisplatin and 5-fluorouracil as induction chemotherapy and subsequent concurrent chemoradiation with weekly cisplatin or carboplatin. Definitive radiotherapy was delivered with intensity-modulated radiation and a simultaneous integrated boost approach up to a total dose of 70 Gy in 35 fractions to the macroscopic primary and nodal disease. RESULTS: Actuarial 2-year OS, CSS, DFS, MFS, LC were 55.3% (95%CI=39.3-68.6), 58.6% (95%CI=41.9-72), 60.5% (95%CI=47.3-71.4), 87.3% (95%CI=76.2-93.5) and 74.7% (95%CI=61.5-83.9), respectively. On multivariate analysis undergoing to 3 vs. 2 cycles of TPF (HR=22.31; 95%CI=2.68-185.66; p=0.004) and radiotherapy treatment break >4 days (HR=1.28; 95%CI=1.06-1.55; p=0.01) negatively affected cancer-specific survival (CSS) with statistical significance. Achieving complete remission after ICT had a statistically significant impact on CSS (HR=0.9; 95%CI=0.01-0.54; p=0.009). Patients undergoing ICT with 3 cycles had more frequently treatment breaks compared to those submitted to 2 cycles (HR=1.36; 95%CI=1.06-1.73; p=0.01), and had statistically significant longer treatment break time (5.9+1.8 vs. 3+0.36; p=0.02). CONCLUSION: A shorter ICT phase may be a better option enhancing patients' tolerance during concurrent chemoradiation and affecting clinical outcomes.

Acute skin toxicity management in head and neck cancer patients treated with radiotherapy and chemotherapy or EGFR inhibitors: Literature review and consensus.

The adverse effects of radiation therapy, often integrated with chemotherapy and/or targeted therapies, on the skin include severe acute and chronic dermatitis associated with pain, discomfort, itching, and burning, and may heavily affect patients' quality of life. The management of these skin adverse effects in head and neck cancer patients (HNCPs) are very heterogeneous due to the lack of shared rigorous classification systems and evidence based treatments. 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 dermatitis in HNCPs treated with radiotherapy with or without systemic therapies in order to improve skin toxicity management. The Delphi Appropriateness Method was used. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. This paper offers contains seven clusters of statements about the management of dermatitis in HNCPs and a review of recent literature on these topics.

Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study.

BACKGROUND: Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. METHODS: A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery. RESULTS: The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days. CONCLUSIONS: Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic effect in the prevention of moist desquamation may be hypothesized for hypericum and neem oil and need to be tested within a prospective controlled study.

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.

Total skin electron beam therapy in mycosis fungoides. Our experience from 1985 to 1999.

PURPOSE: The specific goal of this retrospective study is to evaluate the role of total skin electron beam therapy (TSEBT) in the treatment of Mycosis Fungoides (MF) and to assess the most significant prognostic factors in univariate and multivariate analyses. MATERIAL AND METHODS: From January 1985 to December 1999, 92 TSEBT (Stanford Standing technique) were performed on a total of 86 patients (63 with Mycosis Fungoides, 6 with Sezary Syndrome and 17 with Cutaneous Lymphomas). This study considers only the Mycosis Fungoides group, which consisted of 60 cases evaluable for response, survival and toxicity. The distribution of patients by stage (MFCG Staging Classification, 1991) was 21, 5, 12, 22 for stages I, II, III and IV, respectively. RESULTS: The overall response rate was 96.6% (58/60) with complete response (CR) in 50/60 patients (83.3%) and partial response (PR) in 8 cases (13.3%). The five-year and ten-year actuarial overall survival (OS) was 50% and 45%, respectively. Local control, intended as control of the disease in the skin, was 35% at five years and 20% at ten years, and was correlated with skin involvement. The prognostic factors confirmed by the multivariate analysis for both overall survival and local control were: T (p<0.001) and response after TSEBT (p<0.001). The treatment was very well tolerated. CONCLUSIONS: Our study showed good results in terms of response and survival with a long follow-up time (mean value 40 months). We confirm that TSEBT yields very good results in early-stage MF; additional trials of combined modality and investigational therapies are needed to improve the outcome for advanced-stage disease.