ABSTRACT
GOAL OF WORK: The aim of this study was to investigate the expression of pro-apoptotic protein p53 and anti-apoptotic proteins BCl-2 and MCl-1, as well as the expression of pro-inflammatory cytokines tumor necrosis factor (TNF) and interleukin-1beta (IL-1beta) in patients developing mucositis during radiotherapy for head and neck cancer. MATERIALS AND METHODS: Thirty-five patients receiving radiotherapy for head/neck cancer were included in this study. Patients were examined before radiotherapy. Oral mucositis was recorded weekly during radiotherapy. Cytologic smears from the oral cavity were taken with a brush. Immunocytochemical staining was performed by the use of p53, BCl-2, MCl-1 TNF and IL-1beta monoclonal antibodies. MAIN RESULTS: P53 was expressed in 1 of 15 smears before the initiation of radiotherapy (6.5%) compared to 3 of 7 smears from patients with grade III mucositis (43%) during radiotherapy. BCl-2 was expressed in 15 of 15 smears before radiotherapy (100%) and in three of seven patients with grade III mucositis (43%) during radiotherapy. MCl-1 was expressed in 10 of 14 samples before radiotherapy (71.5%) and in two of seven patients with grade III (28.5%) mucositis during radiotherapy. TNF was expressed in 9 of 14 patients before radiotherapy (64%) and in six of seven patients with grade III mucositis during radiotherapy (86%). IL-1beta was detected in 7 of 14 patients before radiotherapy (50%) compared to 6 of 7 patients with grade III mucositis during radiotherapy (86%). CONCLUSION: Our preliminary results indicate an induction of apoptosis and inflammation in the oral mucosa in patients developing mucositis during radiotherapy for head/neck cancer.
Subject(s)
Apoptosis , Biomarkers, Tumor/analysis , Head and Neck Neoplasms/chemistry , Head and Neck Neoplasms/radiotherapy , Inflammation/physiopathology , Stomatitis/etiology , Stomatitis/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Interleukin-1beta/analysis , Karnofsky Performance Status , Male , Middle Aged , Myeloid Cell Leukemia Sequence 1 Protein , Pilot Projects , Proto-Oncogene Proteins c-bcl-2/analysis , Radiotherapy/adverse effects , Risk Factors , Severity of Illness Index , Tumor Necrosis Factor-alpha/analysisABSTRACT
GOAL OF WORK: The aim of the study was to investigate the incidence of herpes simplex virus-1 (HSV-1) infection in mucositis during head and neck cancer radiotherapy. PATIENTS AND METHODS: Sixty patients with malignant head and neck tumor, eligible to receive radiotherapy, who were referred to the Dental Oncology Unit, entered the study. Sixteen patients (26.6%) received concomitant chemotherapy. Mucositis was recorded weekly. Smears taken from the ulcers of mucositis grade 2, or 3, or 4 were stained with Papanicolaou and alkaline phosphatase/antialkaline phosphatase immunocytochemical method to identify HSV-1. MAIN RESULTS: Forty-eight of all 60 patients developed ulcerative mucositis. Smear was available from 29 of 48 patients with ulcerations. HSV-1 infection was identified in 14 of 29 smears available (48.2%). Mucositis healed or was reduced after 1 week of antiviral treatment in 11 of those 14 HSV-1-positive patients; 3 patients responded to 1 g/day of valacyclovir, 7-2 g/day, and 1 patient responded to i.v. acyclovir. Ulcerations recurred after quitting antivirals. Three patients did not respond to 1 g/day of valacyclovir. No HSV-1-negative patient responded to acyclovir (P = 0.000). CONCLUSION: HSV-1 was isolated from 14 of 29 available smears taken from 48 patients with ulcerative mucositis. The incidence of HSV-1 infection during radiotherapy was estimated as being 14 of all 48 patients at risk (29.1%). Healing or reduction in the grade of mucositis after antivirals in HSV-1 positive patients, combined with the negative response to antivirals in HSV-1 negative patients, denoted that HSV-1 infection was a component of ulcerative radiation mucositis in those HSV-1-positive patients.
Subject(s)
Abnormalities, Radiation-Induced/etiology , Head and Neck Neoplasms/radiotherapy , Herpes Simplex/virology , Herpesvirus 1, Human , Oral Ulcer/etiology , Stomatitis/etiology , Abnormalities, Radiation-Induced/drug therapy , Abnormalities, Radiation-Induced/virology , Acyclovir/analogs & derivatives , Acyclovir/therapeutic use , Adult , Aged , Aged, 80 and over , Antiviral Agents/therapeutic use , Candidiasis, Oral/etiology , Dose-Response Relationship, Radiation , Female , Herpes Simplex/drug therapy , Herpesvirus 1, Human/isolation & purification , Humans , Incidence , Male , Middle Aged , Oral Ulcer/drug therapy , Oral Ulcer/epidemiology , Radiotherapy/adverse effects , Recurrence , Stomatitis/drug therapy , Stomatitis/virology , Treatment Outcome , Valacyclovir , Valine/analogs & derivatives , Valine/therapeutic useABSTRACT
GOAL OF WORK: The aim of the study is to evaluate the effect of fluconazole antifungal prophylaxis on the severity of mucositis in head and neck cancer patients receiving radiotherapy. PATIENTS AND METHODS: Sixty-three patients, with malignant head and neck tumor, eligible to receive radiotherapy, entered the study. Thirty-four patients (group A) received 100 mg/day of fluconazole prophylaxis during radiotherapy and were compared with 29 patients, who received radiotherapy alone (group B). The two groups were similar in terms of patients and radiotherapy characteristics. Smear to test for Candida carriage was taken before and after radiotherapy. Oral candidiasis was diagnosed using the criteria described before. Oral mucositis was recorded according to EORTC/RTOG criteria. MAIN RESULTS: A significant reduction of severe mucositis at the end of radiotherapy (14.7 vs 44.8%, p=0.018) and of interruptions (0 vs 17.2%, p=0.017) was observed in group A. Candidiasis was prevented (0 vs 34.5%, p=0.001), with a significant reduction of Candida carriage of 40.7% (p=0.001). CONCLUSION: Fluconazole prophylaxis showed a significant beneficial impact on the severity of mucositis and on radiotherapy interruptions in this group of patients. The current study provides data on the build of a randomized controlled trial on the effect of fluconazole prophylaxis on treatment schedule and quality of life of the patients during head and neck radiotherapy.
Subject(s)
Antifungal Agents/therapeutic use , Fluconazole/therapeutic use , Head and Neck Neoplasms/radiotherapy , Radiation Injuries/prevention & control , Stomatitis/etiology , Stomatitis/prevention & control , Adult , Aged , Aged, 80 and over , Candidiasis, Oral/etiology , Candidiasis, Oral/prevention & control , Drug Resistance, Fungal , Female , Humans , Incidence , Male , Middle Aged , Radiation Injuries/etiology , Radiation Injuries/pathology , Radiotherapy/adverse effects , Severity of Illness Index , Stomatitis/pathology , Treatment OutcomeABSTRACT
This controlled study assessed the incidence of oral candidiasis, a xerostomia-related complication, in head and neck cancer patients receiving radiotherapy, with amifostine cytoprotection. Thirty-eight patients received 500 mg amifostine i.v., prior to each radiotherapy fraction, while 16 patients received radiotherapy alone. Oral candidiasis was diagnosed according to the criteria described before. Subjective xerostomia scales were completed by all patients. Mucositis was evaluated using the RTOG criteria. Oral candidiasis was diagnosed in 11/38 amifostine patients and in 9/16 controls (P = 0.07). Severe xerostomia was reported by 4/38 amifostine patients and by 7/16 controls. Oral candidiasis was reduced with amifostine cytoprotection. Oral candidiasis is suggested as an objective, early, though indirect, endpoint for amifostine's radioprotective effect on salivary glands.
