Radiotherapy For Oral Cancer Research Articles

Salivary Amylase as a Marker of Salivary Gland Function in Patients Undergoing Radiotherapy for Oral Cancer.

The aim of this study was to evaluate salivary amylase in patients with primary oral cancer undergoing radiotherapy as the main modality of treatment. The study was conducted on ten histologically proven cases of oral cancer undergoing radiotherapy. Stimulated whole saliva was collected at three stages of radiotherapy-0, 3, and 6 weeks. Salivary amylase was estimated using Henry-Chiamori method and comparison was made with appropriate age- and gender-matched controls. Salivary amylase levels showed significant decrease in healthy subjects when compared to oral cancer patients (P < 0.001). The latter group also showed changing trend with initial decrease from 0 to 3 weeks followed by increase from 3 to 6 weeks following radiotherapy (P < 0.0528). The trend in changes in the levels of salivary amylase could be used as a surrogate marker of salivary gland function in patients with oral cancer undergoing radiotherapy as primary treatment.

Outpatient intra-arterial chemotherapy without radiotherapy for oral cancer to reduce irradiation-related complications: A new treatment that improves the quality of life.

e17543Background: We developed a superselective intra-arterial chemotherapy (iaCT) approach with concurrent radiotherapy (RT) for treating oral cancer. This approach results in remarkable improveme...

Survivorship Challenges and Information Needs after Radiotherapy for Oral Cancer.

Oral cancer (OC) treatment can lead to considerable functional impairment, psychological distress, and decrements in quality of life. Given that limited information and support services are available for cancer survivors, many are turning to the Internet. However, little is known about the specific information and service needs of OC survivors. We conducted a descriptive study to (1) characterize the associations between OC survivor functional problems and distress and (2) describe the Internet use of OC survivors, their satisfaction with existing sources of information/support, and their unmet information and service needs. Ninety-three oral cancer survivors completed cross-sectional surveys within 1-year of completing radiotherapy. Clinical levels of distress were 10% for depression and 16% for anxiety. Dental health, smell, and range of motion problems were significant (p < .05) determinants of both depression and anxiety symptoms. Eighty-three percent of survivors used the Internet; most used it to obtain health-related information or support. Unmet information needs included how to live a healthy lifestyle after treatment (87%), strategies for dealing with eating and speaking problems (81%), and information about what to expect in terms of side effects after treatment (76%). Findings suggest that interventions that teach survivors coping and problem-solving skills to manage and cope with functional impairments may help to alleviate distress. Results of this study support the need for psychoeducational interventions for this population and showcase the potential of the Internet as a feasible mode for future dissemination.

Radiotherapy for oral cancer decreases the cutaneous expression of host defence peptides.

Bacterial resistance against antibiotics has become an increasing challenge in the treatment of cutaneous infections. Consequences can be severe, especially in infected wounds following previous local radiotherapy. Certain endogenous peptide antibiotics, the host defence peptides (HDPs), exhibit broad-spectrum antimicrobial activity and promote wound healing. Their use as supplements to conventional antibiotics is a current topic of discussion; however, knowledge of their quantities in healthy and compromised tissue is a prerequisite for such discussion. To date, no data concerning HDP quantities in irradiated skin are available. Expression profiles of the genes encoding HDPs, namely human beta-defensin-1 (DEFB1, hBD-1), beta-defensin-2 (DEFB4A, hBD-2), beta-defensin-3 (DEFB103, hBD-3) and S100A7, were assessed in samples of non-irradiated and irradiated neck. A reduction in the expression of all of the examined genes was observed in irradiated skin when compared with non-irradiated skin (statistically significant in the case of S100A7, P=0.013). Immunohistochemistry revealed differences in HDP distribution with respect to the epithelial layers. The study demonstrates a significant reduction in HDP gene expression in neck skin as a result of radiotherapy. These findings might represent a starting point for novel treatments of cutaneous infections in irradiated patients, such as topical supplementation of synthetic HDP.

Protocols for management of oral complications of chemotherapy and/or radiotherapy for oral cancer: Systematic review and meta-analysis current.

Background and ObjectivesConsidering the high possibility of dentist consult a patient with oral complications of chemotherapy and/or radiotherapy for oral cancer because of the advances in this area, this study aims to systematically review the literature to identify and suggest effective and safe protocols for the managements of oral complications in oncology patients.Material and MethodsTThe systematic review was designed by PICO and PRISMA including eligibility and exclusion criteria; the source of information and search strategy in PubMed according MeSH: “Mouth Neoplasms and Radiotherapy” and “Mouth Neoplasms and Drug Therapy” the period from 2010 to 2015; selection and data collection of study was carried form blind and independently by two researchers; risk of bias and methodological quality: ensured by the PEDro scale; synthesis of data: of oral complications were evaluated by adapted version of associative direction classification proposed by Costigan and collaborators; and data analysis was performed by the meta-analysis of BioEstat program (5.0) in the included studies.Results2,700 articles found, 2,371 were selected after removal of duplicate and elected 40 full-text articles. Of these, only 06 articles were included in the systematic review with exclusion of others, per obtain punctuation ≥ 7 with high methodological quality for synthesis of the managements of oral complications. Since 05 articles were associated with low risk of bias composing the protocols suggestive for managements and the meta-analysis in odds ratio (0.916) to cure and relative risk (1.049) for the development of oral mucositis and pain.ConclusionsThe protocols suggestive for managements of oral mucositis and pain with MuGard - mucoadhesive hydrogel; PerioAid Tratamiento® antiseptic mouthrinse with chlorhexidine and cetylpyridinium chloride; Episil® plus benzydamine - bioadhesive oromucosal gel; 0,03% of Triclosan mouthwash Colgate Plax; and Diode Laser Therapy of low-level are safe for oncology patients applied according to adopted clinical parameters. Key words:Oral cancer, radiotherapy, chemotherapy,complications, management.

Osteoradionecrosis of the mandible: A case report

Osteoradionecrosis (ORN) of the jaws is a serious complication of radiotherapy of head and neck malignancies. Different assumptions about its occurring, risk factors and possible therapeutical modalities exist, but the clinical outcome of such patients is still not on the desired level. This article presents a clinical case of ORN of the mandible, occurring with exposed and infected bone, necrotic process that extended through all the mandible body, as well as cutaneous fistula. The first site of ORN was detected 2 years after radiotherapy for oral cancer, with the second one detected 3 and a half years after radiotherapy. In both, the reason for exposing the bone was local trauma due to tooth extraction. Due to the stage of the condition, a decision for surgical treatment accompanied with antibiotics was made. It is very important and critical for irradiated patients and patients with osteoradionecrosis to perform appropriate oral hygiene and frequent dental checks. Establishing protocols for prevention and treatment, but involving some new strategies regarding to this condition, are strongly recommended.

Effectiveness of transcutaneous electrical nerve stimulation on saliva production in post-radiated oral cancer patients

Aims and Objectives: To determine the effectiveness of transcutaneous electrical nerve stimulation (TENS) in stimulating salivary flow in post-radiated oral cancer patients, and to compare the salivary flow rate between unstimulated saliva and saliva stimulated with TENS in post-radiated oral cancer patients. Materials and Methods: In 30 patients who underwent radiotherapy for oral cancer, unstimulated saliva was collected every minute for 5 min in a graduated test tube. The TENS unit was activated and stimulated saliva was collected for 5 min in a separate graduated test tube, and the flow rate was compared with the unstimulated salivary flow rate. Results: A statistically significant improvement was seen in saliva production during stimulation (P < 0.001). In addition, statistically significant increase in TENS stimulated saliva was observed in patients aged ≥50 years compared to that in patients aged <50 years (P < 0.05). There was no significant difference in salivary flow rate between the two genders in both stimulated and unstimulated conditions, however, statistically significant increase in salivary flow rate was observed in males under stimulated condition (P < 0.01). Conclusion: TENS was highly effective in stimulating the whole salivary flow rate in post-radiated oral cancer patients. It is an effective supportive treatment modality in xerostomia patients caused by radiotherapy in oral cancer patients.

Abstract 3314: DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer and its implication in treatment and outcome prediction

Abstract Radioresistance is still an emerging problem for radiotherapy of oral cancer. Aberrant epigenetic alterations play an important role in cancer development, yet the role of such alterations in radioresistance of oral cancer is not fully explored. Using Illumina 27K methylation BeadChip microarray, we identified promoter hypermethylation of FHIT (fragile histidine triad) in radioresistant OML1-R cells, established from hypo-fractionated irradiation (5-Gy by 10 fractions) of parental OML1 radiosensitive oral cancer cells. Further analysis confirmed that transcriptional repression of FHIT was due to promoter hypermethylation and H3K27me3 as demonstrated by MBDcap-PCR, bisulfite pyrosequencing and ChIP-PCR. These phenomenon were partially attributed to overexpression of EZH2 and DNMT3a, 3b in OML1-R cells. In consistent with these observations, treatment of 5-azaDC, EZH2 inhibitor (GSK343) or depletion of EZH2 by lentiviral knockdown restored FHIT expression in OML1-R cells. Interestingly, knockdown of EZH2 also reversed histone modifications (increased of H3K4me3 and decreased of H3K27me3) and reduced promoter methylation of FHIT thus suggesting that H3K27me3 linked to DNA methylation in this loci. We also analyzed the expression of FHIT in primary human oral keratinocyte (HOK) and four other oral cancer cell lines (OCSL, SCC25, SAS, and SCC4). FHIT expression demonstrated a tight inverse relationship with its promoter methylation. Ectopic expression of FHIT restored radiosensitivity (single fraction, 10-Gy) in OML1-R cells and oral cancer cells (SAS, SCC25) showing epigenetic silencing of FHIT. These phenomenon may be due to restoration of Chk2 phosphorylation, induction of apoptosis and G2/M check point. Reciprocal experiments also showed that depletion of FHIT in OSCL cells, which highly express FHIT, slightly enhanced radioresistance. Clinically, bisulfite pyrosequencing and iummnohistochemistry revealed that promoter hypermethylation of FHIT inversely correlated with its expression. Patients with higher FHIT methylation (methylation&amp;gt;10%, n = 22) are associated with lower locoregional control (P&amp;lt;0.05) and overall survival rate (P&amp;lt;0.05) than patients with lower FHIT methylation (n = 18). For patients treated with post-operative radiotherapy alone (n = 19), sub-group analysis also found that patients with higher FHIT methylation tend to have a 2-fold lower locoregional control rate (P = 0.0998). Further in vivo therapeutic experiments confirmed that treatment of 5-azaDC significantly resensitized radioresistant oral cancer cell xenograft tumors. These results show that epigenetic silencing of FHIT contributes partially to radioresistance and predicts clinical outcomes in irradiated oral cancer. The radiosensitizing effect of epigenetic interventions warrants further clinical investigation. Citation Format: Hon-Yi Lin, Shih-Kai Hung, Moon-Sing Lee, Wen-Yen Chiou, Tze-Ta Huang, Chih-En Tseng, Liang-Yu Shih, Ru-Inn Lin, Jora Lin, Yi-Hui Lai, Chia-Bin Chang, Feng-Chun Hsu, Liang-Cheng Chen, Shiang-Jiun Tsai, Yu-Chieh Su, Szu-Chi Li, Hung-Chih Lai, Wen-Lin Hsu, Dai-Wei Liu, Chien-Kuo Tai, Shu-Fen Wu, Michael W. Chan. DNA methylome analysis identifies epigenetic silencing of FHIT as a determining factor for radiosensitivity in oral cancer and its implication in treatment and outcome prediction. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3314. doi:10.1158/1538-7445.AM2015-3314

OP0008 Conventional radiotherapy versus altered fractionation for patients receiving radical radiotherapy for oral cancer: A randomised phase 2b trial

Background Radical radiotherapy with 66–70 Gy in 33–35 fractions is the standard radiotherapy schedule in head and neck squamous cell carcinoma. Altered fractionation improves the therapeutic ratio compared to conventional radiotherapy. We did a phase 2b randomised trial to compare two radiotherapy schedules in patients undergoing radical radiotherapy in oral cancer. Methods This study was conducted in Thiruvananthapuram, India, from May 2013 to December 2014. 76 patients with squamous cell carcinoma of oral cavity intended to be treated with radical radiotherapy were randomised either to receive conventional radiotherapy (70 Gy in 35 fractions) or altered fractionation (52.5 Gy in 15 fractions). The primary endpoints were acute toxicity and response rate. Acute toxicity was evaluated weekly during treatment using RTOG toxicity criteria. Findings 38 patients were randomly assigned to each group. Two patients from the conventional group and four patients from the altered fractionation group were excluded from final analysis. Acute grade 2 skin toxicity was significantly more common in the conventional radiotherapy group than in the altered fractionation group (80.5% versus 2.9%; p = 0.0001). World Health Organisation (WHO) step III analgesics usage was significantly higher in the conventional group than in the altered fractionation group (52.7% versus 14.7%; p = 0.004). Complete response at 6 months was more common in the altered fractionation group than in the conventional group (91% versus 63.8%; p = 0.01). One-year disease free survival was higher in the altered fractionation group than in the conventional group (76.9% versus 54.7%; p = 0.0107). Overall survival data are pending. Interpretation Results favoured altered fractionation radiotherapy. Longer follow-up is needed to assess late toxicity and overall survival. A phase 3 trial is warranted.

Professional oral health care reduces oral mucositis pain in patients treated by superselective intra-arterial chemotherapy concurrent with radiotherapy for oral cancer.

Oral mucositis (OM) is a painful complication of radiation therapy (RT) for head and neck cancer. OM can compromise nutrition, require opioid analgesics and hospitalization for pain control, and lead to interruption of treatment. Severe oral mucositis appears inevitable in superselective intra-arterial chemotherapy concurrent with radiotherapy (SSIACRT), requiring management of OM for the patient. The objective of this study was to assess the utility of professional oral health care (POHC) for the management of OM in patients undergoing SSIACRT. Thirty-three patients were enrolled in this study. The first 17 patients underwent SSIACRT before we created an oral management team, and thus did not receive POHC. The remaining 16 patients received POHC. Fever duration, duration of oral feeding difficulty, opioid usage, duration of opioid administration, duration of hospitalization, and number of hospital days from the end of irradiation to discharge were compared between these two groups. Median total dose of morphine during SSIACRT, median number of hospital days from end of irradiation to discharge, and duration of hospitalization all differed significantly between groups (P < 0.05). Duration of opioid administration, fever duration, and duration of oral feeding difficulty did not differ significantly between groups. These findings indicate that POHC may reduce opioid use and shorten the hospital stay. Such results might be obtained through infection control by POHC. This report appears to be the first study to evaluate the efficiency of POHC in SSIACRT for oral cancer from the perspective of mucositis pain and opioid use.

Radiotherapy effect on nano-mechanical properties and chemical composition of enamel and dentine

ObjectiveTo understand radiotherapy-induced dental lesions characterized by enamel loss or delamination near the dentine–enamel junction (DEJ), this study evaluated enamel and dentine nano-mechanical properties and chemical composition before and after simulated oral cancer radiotherapy. DesignSections from seven non-carious third molars were exposed to 2Gy fractions, 5 days/week for 7 weeks for a total of 70Gy. Nanoindentation was used to evaluate Young's modulus, while Raman microspectroscopy was used to measure protein/mineral ratios, carbonate/phosphate ratios, and phosphate peak width. All measures were completed prior to and following radiation at the same four buccal and lingual sites 500 and 30μm from the DEJ in enamel and dentine (E-500, E-30, D-30 and D-500). ResultsThe elastic modulus of enamel and dentine was significantly increased (P≤0.05) following radiation. Based on Raman spectroscopic analysis, there was a significant decrease in the protein to mineral ratio (2931/430cm−1) following radiation at all sites tested except at D-500, while the carbonate to phosphate ratio (1070/960cm−1) increased at E-30 and decreased at D-500. Finally, phosphate peak width as measured by FWHM at 960cm−1 significantly decreased at both D-30 and D-500 following radiation. ConclusionsSimulated radiotherapy produced an increase in the stiffness of enamel and dentine near the DEJ. Increased stiffness is speculated to be the result of the radiation-induced decrease in the protein content, with the percent reduction much greater in the enamel sites. Such changes in mechanical properties and chemical composition could potentially contribute to DEJ biomechanical failure leading to enamel delamination that occurs post-radiotherapy. However, other analyses are required for a better understanding of radiotherapy-induced effects on tooth structure to improve preventive and restorative treatments for oral cancer patients.

Neck muscle atrophy and soft-tissue fibrosis after neck dissection and postoperative radiotherapy for oral cancer.

Late complications of head and neck cancer survivors include neck muscle atrophy and soft-tissue fibrosis. We present an autopsy case of neck muscle atrophy and soft-tissue fibrosis (sternocleidomastoid, omohyoid, digastric, sternohyoid, sternothyroid, and platysma muscles) within the radiation field after modified radical neck dissection type I and postoperative radiotherapy for floor of mouth cancer. A 70-year-old man underwent primary tumor resection of the left floor of mouth, left marginal mandibulectomy, left modified radical neck dissection type I, and reconstruction with a radial forearm free flap. The patient received adjuvant radiotherapy. The dose to the primary tumor bed and involved neck nodes was 63 Gy in 35 fractions over 7 weeks. Areas of subclinical disease (left lower neck) received 50 Gy in 25 fractions over 5 weeks. Adjuvant chemotherapy was not administered.

Mucoadhesive Propolis Gel for Prevention of Radiation-Induced Oral Mucositis

The objective of this phase II study was to determine the effectiveness of a mucoadhesive propolis gel in the prevention of radiation-induced oral mucositis. Twenty-four patients who were selected to undergo radiation therapy for oral cancer were included in this open-label trial. They were advised to use a mucoadhesive gel containing propolis 5,0% w/v three times a day starting one day before the course of radiation therapy and concluding after 2 weeks of radiation therapy. A weekly follow-up for evaluation of food intake, pain and grading of mucositis was performed. In order to confirm the absence of Candida-related mucositis in patients who developed mucositis, it was performed exfoliative cytology of buccal mucosa, palate and tongue and the material for Candifast(®) Candida species identification. At the end of the study was made the compliance of patients, quality, appreciation and acceptance of product evaluation. Twenty patients did not develop mucositis, two patients developed grade 1 mucositis and two patients developed grade 2 mucositis. None of the patients discontinued food intake and no pain was observed during the study. Candidosis was not detected in any patient. Mucoadhesive propolis gel could be considered as a potential topical medication for preventing radiation-induced oral mucositis. However, comparative phase III study with larger number of patients should be done for confirmation of the efficacy of the product.

Type IV Collagen is a Novel DEJ Biomarker that is Reduced by Radiotherapy

The dental basement membrane (BM) is composed of collagen types IV, VI, VII, and XVII, fibronectin, and laminin and plays an inductive role in epithelial-mesenchymal interactions during tooth development. The BM is degraded and removed during later-stage tooth morphogenesis; however, its original position defines the location of the dentin-enamel junction (DEJ) in mature teeth. We recently demonstrated that type VII collagen is a novel component of the inner enamel organic matrix layer contiguous with the DEJ. Since it is frequently co-expressed with and forms functional complexes with type VII collagen, we hypothesized that type IV collagen should also be localized to the DEJ in mature human teeth. To identify collagen IV, we first evaluated defect-free erupted teeth from various donors. To investigate a possible stabilizing role, we also evaluated extracted teeth exposed to high-dose radiotherapy – teeth that manifest post-radiotherapy DEJ instability. We now show that type IV collagen is a component within the morphological DEJ of posterior and anterior teeth from individuals aged 18 to 80 yr. Confocal microscopy revealed that immunostained type IV collagen was restricted to the 5- to 10-µm-wide optical DEJ, while collagenase treatment or previous in vivo tooth-level exposure to > 60 Gray irradiation severely reduced immunoreactivity. This assignment was confirmed by Western blotting with whole-tooth crown and enamel extracts. Without reduction, type IV collagen contained macromolecular α-chains of 225 and 250 kDa. Compositionally, our results identify type IV collagen as the first macromolecular biomarker of the morphological DEJ of mature teeth. Given its network structure and propensity to stabilize the dermal-epidermal junction, we propose that a collagen-IV-enriched DEJ may, in part, explain its well-known fracture toughness, crack propagation resistance, and stability. In contrast, loss of type IV collagen may represent a biochemical rationale for the DEJ instability observed following oral cancer radiotherapy.

The combined effects of irradiation and herpes simplex virus type 1 infection on an immortal gingival cell line.

BackgroundOral mucosa is frequently exposed to Herpes simplex virus type 1 (HSV-1) infection and irradiation due to dental radiography. During radiotherapy for oral cancer, the surrounding clinically normal tissues are also irradiated. This prompted us to study the effects of HSV-1 infection and irradiation on viability and apoptosis of oral epithelial cells.MethodsImmortal gingival keratinocyte (HMK) cells were infected with HSV-1 at a low multiplicity of infection (MOI) and irradiated with 2 Gy 24 hours post infection. The cells were then harvested at 24, 72 and 144 hours post irradiation for viability assays and qRT-PCR analyses for the apoptosis-related genes caspases 3, 8, and 9, bcl-2, NFκB1, and viral gene VP16. Mann–Whitney U-test was used for statistical calculations.ResultsIrradiation improved the cell viability at 144 hours post irradiation (P = 0.05), which was further improved by HSV-1 infection at MOI of 0.00001 (P = 0.05). Simultaneously, the combined effects of infection at MOI of 0.0001 and irradiation resulted in upregulation in NFκB1 (P = 0.05). The combined effects of irradiation and HSV infection also significantly downregulated the expression of caspases 3, 8, and 9 at 144 hours (P = 0.05) whereas caspase 3 and 8 significantly upregulated in non-irradiated, HSV-infected cells as compared to uninfected controls (P = 0.05). Infection with 0.0001 MOI downregulated bcl-2 in non-irradiated cells but was upregulated by 27% after irradiation when compared to non-irradiated infected cells (P = 0.05). Irradiation had no effect on HSV-1 shedding or HSV gene expression at 144 hours.ConclusionsHSV-1 infection may improve the viability of immortal cells after irradiation. The effect might be related to inhibition of apoptosis.

Extracts of irradiated mature human tooth crowns contain MMP-20 protein and activity

ObjectivesWe recently demonstrated a significant correlation between enamel delamination and tooth-level radiation dose in oral cancer patients. Since radiation can induce the synthesis and activation of matrix metalloproteinases, we hypothesized that irradiated teeth may contain active matrix metalloproteinases. Materials and methodsExtracted teeth from oral cancer patients treated with radiotherapy and from healthy subjects were compared. Extracted mature third molars from healthy subjects were irradiated in vitro and/or incubated for 0–6 months at 37°C. All teeth were then pulverized, extracted, and extracts subjected to proteomic and enzymatic analyses. ResultsScreening of irradiated crown extracts using mass spectrometry identified MMP-20 (enamelysin) which is expressed developmentally in dentine and enamel but believed to be removed prior to tooth eruption. MMP-20 was composed of catalytically active forms at Mr=43, 41, 24 and 22kDa and was immunolocalized predominantly to the morphological dentine enamel junction. The proportion of different sized MMP-20 forms changed with incubation and irradiation. While the pattern was not altered directly by irradiation of healthy teeth with 70Gy, subsequent incubation at 37°C for 3–6 months with or without prior irradiation caused the proportion of Mr=24–22kDa MMP-20 bands to increase dramatically. Extracts of teeth from oral cancer patients who received >70Gy radiation also contained relatively more 24 and 22kDa MMP-20 than those of healthy age-related teeth. ConclusionMMP-20 is a radiation-resistant component of mature tooth crowns enriched in the dentine–enamel. We speculate that MMP-20 catalyzed degradation of organic matrix at this site could lead to enamel delamination associated with oral cancer radiotherapy.

Dental status, dental rehabilitation procedures, demographic and oncological data as potential risk factors for infected osteoradionecrosis of the lower jaw after radiotherapy for oral neoplasms: a retrospective evaluation

PurposeRetrospective evaluation of the dental status of patients with oral cancer before radiotherapy, the extent of dental rehabilitation procedures, demographic and radiotherapy data as potential risk factors for development of infected osteoradionecrosis of the lower jaw.MethodsA total of 90 patients who had undergone radiotherapy for oral cancer were included into this retrospective evaluation. None of them had distant metastases. After tumour surgery the patients were referred to an oral and maxillofacial surgeon for dental examination and the necessary dental rehabilitation procedures inclusive potential tooth extraction combined with primary soft tissue closure. Adjuvant radiotherapy was started after complete healing of the gingiva (> 7 days after potential extraction). The majority of patients (n = 74) was treated with conventionally fractionated radiotherapy with total doses ranging from 50-70Gy whereas further 16 patients received hyperfractionated radiotherapy up to 72Gy. The records of the clinical data were reviewed. Furthermore, questionnaires were mailed to the patients’ general practitioners and dentists in order to get more data concerning tumour status and osteoradionecrosis during follow-up.ResultsThe patients’ dental status before radiotherapy was generally poor. On average 10 teeth were present, six of them were regarded to remain conservable. Extensive dental rehabilitation procedures included a mean of 3.7 tooth extractions. Chronic periodontitis with severe attachment loss was found in 40%, dental biofilm in 56%. An infected osteoradionecrosis (IORN) grade II according to (Schwartz et al., Am J Clin Oncol 25:168-171, 2002) was diagnosed in 11 of the 90 patients (12%), mostly within the first 4 years after radiotherapy. We could not find significant prognostic factors for the occurrence of IORN, but a trendwise correlation with impaired dental status, rehabilitation procedures, fraction size and tumour outcome.ConclusionThe occurrence of IORN is an important long-term side effect of radiotherapy for oral cancers. From this data we only can conclude that a poor dental status, conventional fractionation and local tumour progression may enhance the risk of IORN which is in concordance with the literature.

A national survey of supportive practices for patients undergoing radiotherapy for oral cancers

PurposeXerostomia and mucositis are two of the main radiation induced toxicities experienced by patients undergoing radiotherapy to the oral cavity. These toxicities can lead to significant weight loss with the potential to cause complications with radiotherapy treatment. Literature has shown that nutritional intervention can help to minimise these side effects. The aim of the survey was to explore current practice across the UK in nutritional intervention for these patients. MethodPostal questionnaires were sent to all 63 radiotherapy departments in the UK in November 2009. Results29 responses (43%) were received. 90% (n = 26) of the departments used 3D-Conformal radiotherapy (3D-CRT) as the main technique for treatment of these patients, with 48% (n = 14) of departments having implemented Intensity modulated radiotherapy (IMRT). All departments referred their patients to a dietician. 93% (n = 27) of departments placed percutaneous endoscopic gastrostomy or radiologically-inserted gastrostomy tubes. 55% (n = 16) departments administered nasogastric tubes. ConclusionThis survey verified many common practices regarding dietary care and advice, some variation was evident in the use of feeding tubes. All responding centres referred patients to a dietician with the aim to maintain nutritional status and prevent weight loss that could contribute to uncertainty in treatment setup.This survey also demonstrated that since Macknelly and Day's (2009) study, a greater number of centres have implemented IMRT for patients undergoing radiotherapy to the head and neck. Although IMRT has been shown to reduce xerostomia, this audit found no changes in the dietary care and advice given to these patients.

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer

Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers. The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed. Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years. Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5-10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.

Radiation-Induced Carotid Artery Stenosis in a Patient with Carcinoma of the Oral Floor

Radiation-induced carotid artery stenosis (RI-CS), a life-threatening condition, can occur after external radiation for head and neck cancer. We here describe a case of asymptomatic RI-CS in a 73-year-old patient treated with chemoradiotherapy and radical neck dissection for a basaloid squamous cell carcinoma of the oral floor. Stenosis of the left carotid artery, diagnosed as RI-CS, showed on an MRI performed 1.5 years after radiotherapy. Blood from the left side of the anterior cerebral artery and the middle anterior artery was flowing to the brain through the anterior and posterior communicating arteries, so no stent surgery or other treatment was necessary. The cancer has not recurred during approximately 5 years of followup after radiotherapy, and the patient has had no adverse effects from the RI-CS since it was diagnosed 3.5 years ago. This case emphasizes the necessity of early scrutiny for RI-CS in patients given radiotherapy for oral cancer.