Randomized Clinical Trial on Reduction of Radiotherapy Dose to the Elective Neck in Head and Neck Squamous Cell Carcinoma: Results on the Quality of Life.

PURPOSE: A randomized trial was initiated to investigate whether a reduction of the dose to the elective nodal sites would result in less toxicity and improvement in Quality of Life (QoL) without compromising tumor control. This paper aimed to compare QoL in both treatment arms. METHODS: Two-hundred head and neck cancer patients treated with radiotherapy (RT) or chemo-RT were randomized (all stages, mean age: 60 years, M/F: 82%/18%). The elective nodal volumes of patients randomized in the experimental arm were treated up to a 40 Gy equivalent dose. In the standard arm, the elective nodal volumes were treated up to a 50 Gy equivalent dose. The QoL data were collected using The European Organization for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and the EORTC Head and Neck Cancer module (H&N35). RESULTS: A trend toward less decline in QoL during treatment was observed in the 40 Gy arm compared to the 50 Gy arm. Statistically significant differences for global health status, physical functioning, emotional functioning, speech problems, and trouble with social eating in favor of the 40 Gy arm were observed. A clinically relevant better outcome in the 40 Gy arm was found for physical functioning at the end of therapy. CONCLUSION: QoL during RT for head and neck cancer tends to be less impaired in the 40 Gy arm. However, reducing the dose only on the elective neck does not result in clinically relevant improvement of QoL. Therefore, additional treatment strategies must be examined to further improve the QoL of HNSCC patients.

Correlation of Patient- and Physician-Scored Dysphagia with Videofluoroscopies in Patients Treated with Radiotherapy for Head and Neck Cancer.

The aim of this study was to investigate the correlation between patient-scored dysphagia and physician-scored dysphagia in head and neck cancer patients treated with radiotherapy. Furthermore, we wanted to compare both patient- and physician-scored dysphagia with dysphagia evaluated on swallowing videofluoroscopies. Sixty-three patients from two different centers treated with radiotherapy for head and neck cancer were evaluated in the current study. Swallowing videofluoroscopies at baseline, 6, and 12 months following radiotherapy were evaluated by 2 observers using the Penetration Aspiration Scale (PAS) and Swallowing Performance Status Scale (SPS) and correlated with patient and physician scored dysphagia. We observed a significant association between physician and patient scored dysphagia (p < 0.01), pre-treatment and post-treatment. Furthermore, the risk of observing dysphagia on videofluoroscopies increased significantly with increasing scores of both physician as well as patient scored dysphagia, and this at all assessed time-points. Patient-scored dysphagia correlates better with dysphagia evaluated by the PAS. Physician-scored dysphagia, however, correlates better with dysphagia as evaluated using the SPS. Both physician- and patient-scored dysphagia correlate well with dysphagia evaluated on videofluoroscopies. Since patient-scored dysphagia correlates better with PAS and changes in the PAS score, and physician-scored dysphagia correlates better with SPS, we advocate to use both patient- and physician-scored dysphagia in future trials.

The incidence of hypothyroidism after radiotherapy for head and neck cancer.

The incidence of hypothyroidism after radiotherapy for head and neck cancer. OBJECTIVES: To identify the incidence of radiation-induced hypothyroidism (HT) after head and neck radiotherapy.Furthermore, we wanted to correlate patient and treatment characteristics with the incidence of HT in order to identify predictive factors for radiation-induced HT. METHODOLOGY: We examined the values of thyrotropin, i.e., the thyroid-stimulating hormone (TSH), in head and neck cancer patients who received a combination treatment of radiotherapy and chemotherapy between 2005 and 2012. HT was defined as having a TSH value of > 10 mIU/L or whenever the patient started to take substitution therapy after treatment. We correlated the radiotherapy mean dose to the thyroid gland (Dmean), the pretreatment volume of the thyroid gland, sex, age, type of concomitant treatment, tumour localization, and T and N classification with the incidence of HT. RESULTS: We were able to obtain data from 72 patients. From these 72 patients, 48 (66%) had a normal thyroid function and 25 (34%) had developed HT. The mean follow-up for these patients was 55 months (range: 21 to 103 months). Out of the 25 patients with HT, 8 (32%) were diagnosed within the first year of follow-up. Increasing Dmean is a significant risk factor for developing HT. Increasing thyroid volume, on the other hand, was correlated with less HT in our patient cohort. CONCLUSIONS: In our study, the incidence of HT is 34%. We also noticed that HT can even develop shortly after treatment. Patients with a higher Dmean to the thyroid gland and lower pretreatment thyroid gland volumes are more at risk.

HPV-positive head and neck tumours, a distinct clinical entity.

A worldwide rise in the incidence of oropharyngeal squamous cell cancer has been recorded over the past decade. This rise has been attributed to an increase in oncogenic human papilloma virus (HPV) infections. The biology of HPV-positive oropharyngeal cancer is distinct; it includes p53 degradation, retinoblastoma pathway inactivation, and p16 upregulation. The best method for detecting HPV in tumour material is controversial; both in-situ hybridisation and PCR are commonly used. However, p16 can serve as a potential surrogate marker, and therefore, p16 immunohistochemistry is widely used in clinical practice. Compared to HPV-negative cancers, HPV-positive oropharyngeal cancer appears to be more responsive to chemotherapy and radiotherapy. Thus, p16 can serve as a prognostic marker for enhanced overall survival and disease-free survival. In this review, we aimed to highlight the current understanding of the epidemiology, biology, detection, and management of HPV-related oropharyngeal head and neck squamous cell carcinoma.

HPV-related oropharyngeal cancers in Flanders (Belgium): a multicenter study.

INTRODUCTION: Human papilloma virus (HPV) was recently reported to play a major role in oropharyngeal carcinoma. Large geographical differences in the disease prevalence have been described. Until now, no data have been reported for Flanders (Belgium). METHODS: A multicenter cooperative study was undertaken at the radiation-oncology departments of Flemish universities. Tumor blocks from patients diagnosed with oropharyngeal carcinoma between 2000 and 2010 were tested for HPV at a single center. Patients' characteristics, treatments, and follow-up data were recorded from medical files. Age standardized incidence rates of oropharyngeal carcinoma were collected from the Belgian Cancer Registry. RESULTS AND CONCLUSIONS: The incidence of oropharyngeal carcinoma has increased in males and females. Tissues were collected from 264 patients and the HPV status could be defined in 249 of them. The prevalence of HPV(+) oropharyngeal carcinoma was 24.78% (19.93-30.36%). In our cohort, HPV(+) tumors occurred in patients with more advanced tumor stages (p < 0.05), who smoked less (p < 0.05), consumed less alcohol (p < 0.05), had a tonsillar/base of tongue sublocalization (p < 0.05), and were older (p < 0.05). After radiotherapy, locoregional control and disease free survival were significantly better for patients with HPV(+) status (p < 0.05) in univariate analysis. HPV status remained a strong predictor of better locoregional control after multivariate analysis. We found that concurrent chemotherapy had an equal benefit for locoregional control in both HPV(+) and HPV(-) patients.

Intensity-modulated radiotherapy vs. parotid-sparing 3D conformal radiotherapy. Effect on outcome and toxicity in locally advanced head and neck cancer.

BACKGROUND AND PURPOSE: Intensity-modulated radiotherapy (IMRT) has rapidly become standard of care in the management of locally advanced head and neck squamous cell carcinoma (HNSCC). In this study, our aim was to retrospectively investigate the effect of the introducing IMRT on outcome and treatment-related toxicity compared to parotid-sparing 3D conformal radiotherapy (3DCRT). MATERIAL AND METHODS: A total of 245 patients with stage III and IV HNSCC treated with primary radiotherapy between January 2003 and December 2010 were included in this analysis: 135 patients were treated with 3DCRT, 110 patients with IMRT. Groups were compared for acute and late toxicity, locoregional control (LRC), and overall survival (OS). Oncologic outcomes were estimated using Kaplan-Meier analysis and compared using a log-rank test. Acute toxicity was analyzed according to the Common Terminology Criteria for Adverse Events v3.0 and late toxicity was scored using the RTOG/EORTC late toxicity scoring system. RESULTS: Median follow-up was 35 months in the IMRT group and 68 months in the 3DCRT group. No significant differences were found in 3-year LRC and OS rates between the IMRT group and 3DCRT group. Significantly less acute mucositis ≥ grade 3 was observed in the IMRT group (32% vs. 44%, p = 0.03). There was significantly less late xerostomia ≥ grade 2 in the IMRT group than in the 3DCRT group (23% vs. 68%, p < 0.001). After 24 months, there was less dysphagia ≥ grade 2 in the IMRT group although differences failed to reach statistical significance. CONCLUSION: The introduction of IMRT in the radiotherapeutic management of locally advanced head and neck cancer significantly improved late toxicity without compromising tumor control compared to a parotid-sparing 3D conformal radiotherapy technique.

Medullary thyroid cancer: prognostic factors for survival and recurrence, recommendations for the extent of lymph node dissection and for surgical therapy in recurrent disease.

BACKGROUND: We reviewed our experience with MTC (medullary thyroid cancer), focusing on recurrence and survival, recommendations for the extent of lymph node (LN) dissection and surgery for recurrent disease. METHODS: Of 51 MTC patients treated between 1988 and 2008 at the University Hospitals Leuven, 38 previously untreated patients were analysed. RESULTS: Overall and disease-specific (DSS) five-year survival rates were 75% and 82%. Variables univariately associated with DSS were age, pN, stage, vascular invasion, pre-operative recurrent laryngeal nerve function and last calcitonin level. Recurrence occurred in 10 patients (26%). For recurrence, age was no longer a prognostic factor and post-operative calcitonin, number of positive LN and of positive compartments proved to be prognostic factors. Of 21 clinical NO patients, 2 out of 6 (33%) undergoing a prophylactic central neck dissection (ND) based on per-operative palpatory suspicion proved pN+, and 2 out of 9 patients (22%) undergoing a prophylactic lateral ND were pN+. Five patients surgically treated for recurrence did not achieve long-term normalisation of calcitonin, but remained alive with locoregional control. CONCLUSION: Overall survival and DSS rates are within the range reported in the literature. The results confirm that (1) total thyroidectomy and central compartment dissection is the treatment of choice in the cN0 patients, (2) additional ipsilateral lateral ND is needed for cN+ disease in the ipsilateral lateral compartment, and (3) in the clinically uninvolved contralateral lateral neck, per-operative inspection should serve as a basis for a decision about further ND. Locoregional control and prolonged survival is achieved in surgically treated locoregionally recurrent MTC.

Malignant ectomesenchymoma of the paranasal sinuses with proptosis.

PROBLEM: A 36-year-old woman presented with a feeling of pressure in the right orbit and proptosis of the right eye after a "common cold". METHODOLOGY: Computed tomography (CT) of the maxillofacial region revealed, and endoscopy confirmed, a mass in the right ethmoid sinus, eroding the lamina papyracea and extending into the orbit. Pathology of multiple biopsies revealed a nasal neoplasm composed of neuroectodermal and mesenchymal neoplastic elements, suggestive of a malignant ectomesenchymoma (MEM). Magnetic resonance imaging was used for MEM staging. Computed tomography of the chest and abdomen show no evidence of distant metastases. RESULTS: Due to the intracranial and intraorbital extension of the tumour, radical surgery was not an option. Appropriate chemotherapy (6 cycles of vincristine/ifosfamide/adriamycin and 2 cycles of vincristine/ifosfamide/cisplatin) and intensity-modulated radiation therapy were administered. CONCLUSION: Twenty-eight months after treatment, there was no evidence of residual or metastatic disease.

Cyclophosphamide, doxorubicin, and cisplatin in advanced salivary gland cancer.

OBJECTIVES: Advanced salivary gland cancer is a rare disease that comprises different histopathological tumour types; correspondingly, data on palliative systemic treatment are scarce. Combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) has been reported to induce a reasonable response rate, although fewer than 100 cases have been described. We conducted a retrospective review of advanced salivary gland cancer patients treated with CAP. METHODOLOGY: Fifteen consecutive patients with recurrent, locally advanced, or metastatic progressive salivary gland cancer treated with CAP were identified over a five-year period. The mean age at start of treatment was 53.5 years, and the male/female ratio was 11/4. The most common histological subtypes were adenoid cystic carcinoma and adenocarcinoma not otherwise specified (NOS), with the parotid gland as the most frequently affected anatomical site. RESULTS: A response rate of 60% was achieved, with one complete and eight partial responses and six stable diseases according to RECIST criteria. No patient progressed under treatment. An average of 5.4 treatment cycles were administered; median time to progression after ending CAP was 6.6 months, and median overall survival was 15.1 months. Patients with adenocarcinoma NOS appeared to benefit more than patients with adenoid cystic carcinoma, but had a shorter time to progression. Except for neutropenia with neutropenic fever and alopecia, no NCI-CTC grade III or IV toxicity was observed. CONCLUSION: This retrospective study confirms the clinically meaningful efficacy of CAP in advanced adenocarcinomas NOS of the salivary gland in routine practice, with acceptable safety levels.

Interobserver variability in organ at risk delineation in head and neck cancer.

BACKGROUND: In radiotherapy inaccuracy in organ at risk (OAR) delineation can impact treatment plan optimisation and treatment plan evaluation. Brouwer et al. showed significant interobserver variability (IOV) in OAR delineation in head and neck cancer (HNC) and published international consensus guidelines (ICG) for OAR delineation in 2015. The aim of our study was to evaluate IOV in the presence of these guidelines. METHODS: HNC radiation oncologists (RO) from each Belgian radiotherapy centre were invited to complete a survey and submit contours for 5 HNC cases. Reference contours (OARref) were obtained by a clinically validated artificial intelligence-tool trained using ICG. Dice similarity coefficients (DSC), mean surface distance (MSD) and 95% Hausdorff distances (HD95) were used for comparison. RESULTS: Fourteen of twenty-two RO (64%) completed the survey and submitted delineations. Thirteen (93%) confirmed the use of delineation guidelines, of which six (43%) used the ICG. The OARs whose delineations agreed best with the OARref were mandible [median DSC 0.9, range (0.8-0.9); median MSD 1.1 mm, range (0.8-8.3), median HD95 3.4 mm, range (1.5-38.7)], brainstem [median DSC 0.9 (0.6-0.9); median MSD 1.5 mm (1.1-4.0), median HD95 4.0 mm (2.3-15.0)], submandibular glands [median DSC 0.8 (0.5-0.9); median MSD 1.2 mm (0.9-2.5), median HD95 3.1 mm (1.8-12.2)] and parotids [median DSC 0.9 (0.6-0.9); median MSD 1.9 mm (1.2-4.2), median HD95 5.1 mm (3.1-19.2)]. Oral cavity, cochleas, PCMs, supraglottic larynx and glottic area showed more variation. RO who used the consensus guidelines showed significantly less IOV (p = 0.008). CONCLUSIONS: Although ICG for delineation of OARs in HNC exist, they are only implemented by about half of RO participating in this study, which partly explains the delineation variability. However, this study highlights that guidelines alone do not suffice to eliminate IOV and that more effort needs to be done to accomplish further treatment standardisation, for example with artificial intelligence.

Deep learning for elective neck delineation: More consistent and time efficient.

BACKGROUND/PURPOSE: Delineation of the lymph node levels of the neck for irradiation of the elective clinical target volume in head and neck cancer (HNC) patients is time consuming and prone to interobserver variability (IOV), although international consensus guidelines exist. The aim of this study was to develop and validate a 3D convolutional neural network (CNN) for semi-automated delineation of all nodal neck levels, focussing on delineation accuracy, efficiency and consistency compared to manual delineation. MATERIAL/METHODS: The CNN was trained on a clinical dataset of 69 HNC patients. For validation, 17 lymph node levels were manually delineated in 16 new patients by two observers, independently, using international consensus guidelines. Automated delineations were generated by applying the CNN and were subsequently corrected by both observers separately as needed for clinical acceptance. Both delineations were performed two weeks apart and blinded to each other. IOV was quantified using Dice similarity coefficient (DSC), mean surface distance (MSD) and Hausdorff distance (HD). To assess automated delineation accuracy, agreement between automated and corrected delineations were evaluated using the same measures. To assess efficiency, the time taken for manual and corrected delineations were compared. In a second step, only the clinically relevant neck levels were selected and delineated, once again manually and by applying and correcting the network. RESULTS: When all lymph node levels were delineated, time taken for correcting automated delineations compared to manual delineations was significantly shorter for both observers (mean: 35 vs 52 min, p < 10-5). Based on DSC, automated delineation agreed best with corrected delineation for lymph node levels Ib, II-IVa, VIa, VIb, VIIa, VIIb (DSC >85%). Manual corrections necessary for clinical acceptance were 1.4 mm MSD on average and were especially low (<1mm) for levels II-IVa, VIa, VIIa and VIIb. IOV was significantly smaller with automated compared to manual delineations (MSD: 1.4 mm vs 2.5 mm, p < 10-11). When delineating only the clinically relevant neck levels, the correction time was also significantly shorter (mean: 8 vs 15 min, p < 10-5). Based on DSC, automated delineation agreed very well with corrected delineation (DSC > 87%). Manual corrections necessary for clinical acceptance were 1.3 mm MSD on average. IOV was significantly smaller with automated compared to manual delineations (MSD: 0.8 mm vs 2.3 mm, p < 10-3). CONCLUSION: The CNN developed for automated delineation of the elective lymph node levels in the neck in HNC was shown to be more efficient and consistent compared to manual delineation, which justifies its implementation in clinical practice.

Dynamic contrast-enhanced and diffusion-weighted MRI for early detection of tumoral changes in single-dose and fractionated radiotherapy: evaluation in a rat rhabdomyosarcoma model.

We aimed to examine different intratumoral changes after single-dose and fractionated radiotherapy, using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in a rat rhabdomyosarcoma model. Four WAG/Rij rats with rhabdomyosarcomas in the flanks received single-dose radiotherapy of 8 Gy, and four others underwent fractionated radiotherapy (five times 3 Gy). In rats receiving single-dose radiotherapy, a significant perfusion decrease was found in the first 2 days post-treatment, with slow recuperation afterwards. No substantial diffusion changes could be seen; tumor growth delay was 12 days. The rats undergoing fractionated radiotherapy showed a similar perfusion decrease early after the treatment. However, a very strong increase in apparent diffusion coefficient occurred in the first 10 days; growth delay was 18 days. DW-MRI and DCE-MRI can be used to show early tumoral changes induced by radiotherapy. Single-dose and fractionated radiotherapy induce an immediate perfusion effect, while the latter induces more intratumoral necrosis.

Promoter methylation of TIMP3 and CDH1 predicts better outcome in head and neck squamous cell carcinoma treated by radiotherapy only.

As with other solid tumor types, head and neck squamous cell carcinoma (HNSCC) has been identified as an epigenetic, as well as genetic, disease. Consequently, promoter hypermethylation, being the most important aberrant epigenetic characteristic, has been intensively investigated for its biomarker potential in this cancer type. As many of these evaluations are obscured by a heterogeneity of treatments, the current study aimed to evaluate the incidence and prognostic value of the promoter hypermethylation of TIMP3, CDH1, DAPK, RASSF1A, p16INK4A and MGMT in HNSCC treated solely by radiotherapy. In 46 patients with advanced HNSCC treated with a hybrid accelerated fractionation radiotherapy schedule, DNA extracted from pretreatment paraffin-embedded tumor biopsies was used to determine the methylation status of the genes of interest by methylation-specific PCR (MSP). The detected epigenetic silencing was related with outcome in terms of locoregional control (LRC), and overall (OS), disease-free (DFS) and disease-specific survival (DSS). Tumor biopsies revealed the epigenetic silencing of MGMT in 42.5% (17 of 40) of patients and of TIMP3 in 40.5% (17 of 42) of cases. For the remaining investigated genes, a lower methylation percentage was detected: 13.2% (5 of 38) for CDH1, 11.4% (4 of 44) for DAPK, 4.8% (2 of 42) for p16INK4A and 2.4% (1 of 41) for RASSF1A. The promoter hypermethylation of TIMP3 and CDH1 was significantly related with better LRC (p=0.009 and p=0.02, respectively), OS (p=0.005 and p=0.002, respectively), DFS (p=0.02 and p=0.004, respectively) and DSS (p=0.12 and p=0.007, respectively). In conclusion, in this representative group of 46 patients with advanced HNSCC treated by radiotherapy only, the epigenetic silencing of TIMP3 and CDH1 predicted a better outcome.

Does intensity-modulated radiation therapy lower the risk of osteoradionecrosis of the jaw? A long-term comparative analysis.

The aim of this study was to analyze the impact of different radiation techniques on the long-term incidence of osteoradionecrosis in head and neck cancer. Risk factors and the occurrence of osteoradionecrosis were analyzed in a retrospective, comparative, observational study. Medical files and radiological images of 109 patients treated with primary intensity-modulated radiation therapy (IMRT) and 129 patients treated with primary three-dimensional conformal radiotherapy (3D-CRT) were evaluated. Proportional hazards models were used to analyse the effects of the radiation modality and patient characteristics on the necrosis risk. Twenty-two patients developed osteoradionecrosis (9.2%) during a mean follow-up of 4.3 years. A numerical difference was observed, with more osteoradionecrosis after 3D-CRT (n=18) than after IMRT (n=4). After correction for group differences and confounders, no statistical difference in risk was observed between the two treatment groups (P=0.37). Multivariate analysis showed evidence of a higher osteoradionecrosis risk for patients with a tumour of the oropharynx and for patients with tooth extraction after radiation therapy. Although the incidence of osteoradionecrosis tended to be lower after IMRT, due to the multifactorial aetiology it remains a severe problem and cannot be prevented by new radiotherapy techniques. Continuous efforts are necessary to control additional risk factors and avoid osteoradionecrosis.

Benefits of deep learning for delineation of organs at risk in head and neck cancer.

PURPOSE/OBJECTIVE: Precise delineation of organs at risk (OARs) in head and neck cancer (HNC) is necessary for accurate radiotherapy. Although guidelines exist, significant interobserver variability (IOV) remains. The aim was to validate a 3D convolutional neural network (CNN) for semi-automated delineation of OARs with respect to delineation accuracy, efficiency and consistency compared to manual delineation. MATERIAL/METHODS: 16 OARs were manually delineated in 15 new HNC patients by two trained radiation oncologists (RO) independently, using international consensus guidelines. OARs were also automatically delineated by applying the CNN and corrected as needed by both ROs separately. Both delineations were performed two weeks apart and blinded to each other. IOV between both ROs was quantified using Dice similarity coefficient (DSC) and average symmetric surface distance (ASSD). To objectify network accuracy, differences between automated and corrected delineations were calculated using the same similarity measures. RESULTS: Average correction time of the automated delineation was 33% shorter than manual delineation (23 vs 34 minutes) (p < 10-6). IOV improved significantly with network initialisation for nearly all OARs (p < 0.05), resulting in decreased ASSD averaged over all OARs from 1.9 to 1.2 mm. The network achieved an accuracy of 90% and 84% DSC averaged over all OARs for RO1 and RO2 respectively, with an ASSD of 0.7 and 1.5 mm, which was in 93% and 73% of the cases lower than the IOV. CONCLUSION: The CNN developed for automated OAR delineation in HNC was shown to be more efficient and consistent compared to manual delineation, which justify its implementation in clinical practice.

Basal oxidative stress ratio of head and neck squamous cell carcinomas correlates with nodal metastatic spread in patients under therapy.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that is strongly associated with oxidative damage and oxidative stress. Tobacco and alcohol - sources of massive quantities of reactive oxygen species (ROS) - have been clearly identified as etiologic factors that contribute to these malignancies. Considering the role of glutathione (GSH) in ROS detoxification, we hypothesized that potential biological markers can be found in addition to the parameters of oxidative stress. In line with previous studies that emphasized the accumulation of GSH in tumor cells, in this study, we have reported a lower ratio of oxidized versus reduced GSH in head and neck tumors. OBJECTIVE: The aim of the paper was to evaluate the prognostic and clinical significance of the ratio of oxidized versus reduced GSH in patients with head and neck cancers. METHODS: Thirty-six patients with HNSCC were included in this study. The tumoral redox status was determined by measuring the ratio of oxidized/reduced GSH (GSSG/GSH) by capillary electrophoresis. Statistical analysis was performed to assess the correlation between patient, clinical factors and the redox status. RESULTS: The results showed a low tumoral ratio of GSSG/GSH and a better locoregional control. Moreover, a significant correlation between the tumoral redox status ratio (GSSG/GSH) and nodal stage (N0 versus N1, N2 and N3) was also observed. A higher tumoral redox status ratio was found to be associated with the presence of lymph node metastasis (N1, N2 and N3). CONCLUSION: A strong correlation was observed between the oxidative status and locoregional control of the tumors. Moreover, a higher basal tumoral redox status ratio was found to be correlated with the presence of lymph node metastasis.

Salvage Transoral Laser Microsurgery for Radiorecurrent Laryngeal Cancer: Indications, Limits, and Outcomes.

PURPOSE OF REVIEW: The aim of this report is to identify relevant literature reports on salvage transoral laser microsurgery (TLM); to consider its oncologic and functional outcomes, as well as reported complications; and to address indications and limitations of salvage TLM. FINDINGS: The weighted average of local control after first salvage TLM was 57%. Repeated TLM procedures for second or third recurrences were required in up to 41% of cases, resulting in a weighted average of local control with TLM alone of 67%. The rate of definite laryngeal preservation was 73%. The ultimate local control rate, including cases that required total laryngectomy, was 90%. The overall complication rate after salvage TLM was 14%. SUMMARY: Salvage TLM of radiorecurrent laryngeal cancer yields excellent oncologic outcomes. Serious complications are scarce, hospitalization times are short, and functional outcomes in terms of voice and swallowing are favorable when compared to open conservation laryngeal surgery. The key to success is an optimal patient selection.

Elevated carcinoembryonic antigen tumour marker caused by head and neck cancer: a case report and literature study.

Carcinoembryonic antigen is a tumour marker commonly increased in gastrointestinal and pulmonary cancers. We report a case of a 46-year-old man with a mucoepidermoid carcinoma of the base of tongue with an elevated and traceable serum carcinoembryonic antigen level. This antigen proved to be a valuable marker in the treatment follow-up. When a raised carcinoembryonic antigen level is found, salivary gland malignancies should be taken into the differential diagnosis and clinical examination of the head and neck region should not be overlooked.

Specific targeting of cytosine deaminase to solid tumors by engineered Clostridium acetobutylicum.

The presence of severe hypoxia and necrosis in solid tumors offers the potential to apply an anaerobic bacterial enzyme/prodrug approach in cancer treatment. In this context the apathogenic C. acetobutylicum was genetically engineered to express and secrete E. coli cytosine deaminase (CDase). Considerable levels of functional cytosine deaminase were detected in lysates and supernatants of recombinant C acetobutylicum cultures. After administration of the recombinant Clostridium to rhabdomyosarcoma bearing rats used as a model, cytosine deaminase could be detected at the tumor site. Moreover, following administration of the vascular targeting agent combretastatin A-4 phosphate significantly increased levels of cytosine deaminase were detected at the tumor site as a consequence of enlarged tumor necrosis and subsequently improved growth of C. acetobutylicum. The results provide evidence for the potential application of Clostrisdium-based therapeutic protein transfer to tumors in anticancer therapy.

Tumor-specific gene delivery using genetically engineered bacteria.

The loco-regional control of cancer remains a major contributor to the treatment outcome for many cancer patients prescribed conventional radiotherapy or chemotherapy. Failure of treatment coupled with the realisation that cancer is essentially a genetic disease has led to development of many clinical protocols based on gene therapy. In this review, we will describe an alternative gene delivery system based on the use of non-pathogenic bacteria. Tumor regressions have been reported long ago in patients with bacterially infected tumors, suggesting that bacteria could target tumors and have local anti-tumor effects. The basis of this phenomenon is attributable to the unique properties of the tumor micro-environment. The presence of hypoxic and/or necrotic areas provides a haven for a number of anaerobic bacteria and over the past 60 years, several strains of anaerobic bacteria have been shown to localise within and cause cell lysis of experimental animal tumors. One of the most important strains in that context is Clostridium. Other bacteria have also been implicated in experimental anti-cancer settings. Of these, attenuated Salmonella strains capable of both selective amplification within tumors and expression of effector genes encoding therapeutic proteins are probably the most promising. We will discuss the potential advantages and the pitfalls of this alternative delivery approach. We will emphasize the importance of hypoxia in solid tumors and discuss the potential of radiation-inducible promoters and combined treatment modalities, involving vascular targeting and radiotherapy. We believe that this approach will act in a complementary way to current radiotherapy and chemotherapy treatments of solid tumors.