Comparison of Skeletal Muscle Changes at Three Vertebral Levels Following Radiotherapy in Patients With Oropharyngeal Carcinoma.

Evaluation of skeletal muscle (SM) depletion, or sarcopenia, utilizes the cross-sectional area (CSA) of computed tomography (CT) scans at the lumbar level L3. However, alternate vertebral landmarks are used in patients with head and neck cancer due to scan unavailability. Muscle changes following radiotherapy at cervical (C3) and thoracic (T2) levels were compared to L3 in patients with oropharyngeal carcinoma. Muscle density data were derived retrospectively from diagnostic PET-CT scans at C3, T2 and L3 pretreatment, and up to six months post. CSA changes were compared to L3 in scans of 33 patients (88% male, mean age 61 (SD 8.5) years). On matched pair analysis; mean L3-CSA change -12.1 cm2 (SD 9.7, 95%CI -15.5 to -8.6, and p < 0.001), T2-CSA -30.5 cm2 (SD 34.8, 95%CI -42.8 to -18.1, and p < 0.001) and C3-CSA +2.1 cm2 (SD 4.1, 95%CI 0.63 to 3.5, and p < 0.00). No difference was found in the percentage change of T2-CSA with L3-CSA (mean -2.2%, SD 10.6, 95%CI -6.0 to 1.6, and p = 0.240), however, was significantly different to C3-CSA (mean 13.2%, SD 11.6, 95%CI 9.1 to 17.3, and p < 0.001). Results suggest SM at C3 does not change proportionately and may not be a reliable representation of whole-body SM change over time.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI), developing months or years following radiotherapy. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based on the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of complications following surgery and radiotherapy. OBJECTIVES: To evaluate the benefits and harms of hyperbaric oxygen therapy (HBOT) for treating or preventing late radiation tissue injury (LRTI) compared to regimens that excluded HBOT. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 24 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. survival from time of randomisation to death from any cause; 2. complete or substantial resolution of clinical problem; 3. site-specific outcomes; and 4. ADVERSE EVENTS: Our secondary outcomes were 5. resolution of pain; 6. improvement in quality of life, function, or both; and 7. site-specific outcomes. We used GRADE to assess certainty of evidence. MAIN RESULTS: Eighteen studies contributed to this review (1071 participants) with publications ranging from 1985 to 2022. We added four new studies to this updated review and evidence for the treatment of radiation proctitis, radiation cystitis, and the prevention and treatment of osteoradionecrosis (ORN). HBOT may not prevent death at one year (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.47 to 1.83; I2 = 0%; 3 RCTs, 166 participants; low-certainty evidence). There is some evidence that HBOT may result in complete resolution or provide significant improvement of LRTI (RR 1.39, 95% CI 1.02 to 1.89; I2 = 64%; 5 RCTs, 468 participants; low-certainty evidence) and HBOT may result in a large reduction in wound dehiscence following head and neck soft tissue surgery (RR 0.24, 95% CI 0.06 to 0.94; I2 = 70%; 2 RCTs, 264 participants; low-certainty evidence). In addition, pain scores in ORN improve slightly after HBOT at 12 months (mean difference (MD) -10.72, 95% CI -18.97 to -2.47; I2 = 40%; 2 RCTs, 157 participants; moderate-certainty evidence). Regarding adverse events, HBOT results in a higher risk of a reduction in visual acuity (RR 4.03, 95% CI 1.65 to 9.84; 5 RCTs, 438 participants; high-certainty evidence). There was a risk of ear barotrauma in people receiving HBOT when no sham pressurisation was used for the control group (RR 9.08, 95% CI 2.21 to 37.26; I2 = 0%; 4 RCTs, 357 participants; high-certainty evidence), but no such increase when a sham pressurisation was employed (RR 1.07, 95% CI 0.52 to 2.21; I2 = 74%; 2 RCTs, 158 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: These small studies suggest that for people with LRTI affecting tissues of the head, neck, bladder and rectum, HBOT may be associated with improved outcomes (low- to moderate-certainty evidence). HBOT may also result in a reduced risk of wound dehiscence and a modest reduction in pain following head and neck irradiation. However, HBOT is unlikely to influence the risk of death in the short term. HBOT also carries a risk of adverse events, including an increased risk of a reduction in visual acuity (usually temporary) and of ear barotrauma on compression. Hence, the application of HBOT to selected participants may be justified. The small number of studies and participants, and the methodological and reporting inadequacies of some of the primary studies included in this review demand a cautious interpretation. More information is required on the subset of disease severity and tissue type affected that is most likely to benefit from this therapy, the time for which we can expect any benefits to persist and the most appropriate oxygen dose. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should also be undertaken.

Current management of xerostomia in head and neck cancer patients.

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.

A prediction model for skeletal muscle evaluation and computed tomography-defined sarcopenia diagnosis in a predominantly overweight cohort of patients with head and neck cancer.

PURPOSE: This study investigates the feasibility of computed tomography (CT)-defined sarcopenia assessment using a prediction model for estimating the cross-sectional area (CSA) of skeletal muscle (SM) in CT scans at the third lumbar vertebra (L3), using measures at the third cervical level (C3) in a predominantly overweight population with head and neck cancer (HNC). METHODS: Analysis was conducted on adult patients with newly diagnosed HNC who had a diagnostic positron emission tomography-CT scan. CSA of SM in CT images was measured at L3 and C3 in each patient, and a predictive formula developed using fivefold cross-validation and linear regression modelling. Correlation and agreement between measured CSA at L3 and predicted values were evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plot. The model's ability to identify sarcopenia was investigated using Cohen's Kappa (k). RESULTS: A total of 109 patient scans were analysed, with 64% of the cohort being overweight or obese. The prediction model demonstrated high level of correlation between measured and predicted CSA measures (ICC 0.954, r = 0.916, p < 0.001), and skeletal muscle index (SMI) (ICC 0.939, r = 0.883, p < 0.001). Bland-Altman plot showed good agreement in SMI, with mean difference (bias) = 0.22% (SD 8.65, 95% CI - 3.35 to 3.79%), limits of agreement (- 16.74 to 17.17%). The model had a sensitivity of 80.0% and specificity of 85.0%, with moderate agreement on sarcopenia diagnosis (k = 0.565, p = 0.004). CONCLUSION: This model is effective in predicting lumbar SM CSA using measures at C3, and in identifying low SM in a predominately overweight group of patients with HNC.

Thoracic skeletal muscle index is effective for CT-defined sarcopenia evaluation in patients with head and neck cancer.

PURPOSE: Computed tomography (CT)-defined sarcopenia, as a measurement of low skeletal muscle (SM), is a poor prognostic indicator in patients with head and neck cancer (HNC), independent of weight or nutritional status. We used SM measures at the second thoracic vertebra (T2) to determine T2-SM index (SMI) thresholds for sarcopenia, and investigate the impact of low T2-SMI on overall survival (OS), and weight loss during radiotherapy (RT). METHODS: Adult patients with newly diagnosed HNC with a diagnostic PET-CT or RT planning CT scan were included. SM was analysed at T2 and a model applied to predict SM at L3. T2-SMI thresholds for sarcopenia were established with predicted measures, stratified by BMI and sex. Impact of sarcopenia and low T2-SMI on OS and weight loss during RT was investigated. RESULTS: A total of 361 scans were analysed (84% males, 54% oropharynx tumours). Sarcopenia was found in 49%, demonstrating worse OS (p = 0.037). T2-SMI cutoff values were: females-74 cm2/m2 [area under the curve (AUC): 0.89 (95%CI 0.80-0.98)], males (BMI < 25)-63 cm2/m2 [AUC 0.93 (95%CI 0.89-0.96)], males (BMI ≥ 25)-88cm2/m2 [AUC 0.86 (95%CI 0.78-0.93)]. No difference in OS with T2-SMI categories. Lowest T2-SMI quartile of < 63 cm2/m2 demonstrated worse OS (p = 0.017). Weight loss during RT was higher in patients; who were not sarcopenic (6.2% vs 4.9%, p = 0.023); with higher T2-SMI (6.3% vs 4.9%, p = 0.014) and; in the highest quartiles (3.6% vs 5.7% vs 7.2%, p < 0.001). CONCLUSIONS: These T2-SMI thresholds are effective in assessing CT-defined sarcopenia in HNC. Further assessment of clinical application is warranted.

The Utility of Oncology Information Systems for Prognostic Modelling in Head and Neck Cancer.

Cancer centres rely on electronic information in oncology information systems (OIS) to guide patient care. We investigated the completeness and accuracy of routinely collected head and neck cancer (HNC) data sourced from an OIS for suitability in prognostic modelling and other research. Three hundred and fifty-three adults diagnosed from 2000 to 2017 with head and neck squamous cell carcinoma, treated with radiotherapy, were eligible. Thirteen clinically relevant variables in HNC prognosis were extracted from a single-centre OIS and compared to that compiled separately in a research dataset. These two datasets were compared for agreement using Cohen's kappa coefficient for categorical variables, and intraclass correlation coefficients for continuous variables. Research data was 96% complete compared to 84% for OIS data. Agreement was perfect for gender (κ = 1.000), high for age (κ = 0.993), site (κ = 0.992), T (κ = 0.851) and N (κ = 0.812) stage, radiotherapy dose (κ = 0.889), fractions (κ = 0.856), and duration (κ = 0.818), and chemotherapy treatment (κ = 0.871), substantial for overall stage (κ = 0.791) and vital status (κ = 0.689), moderate for grade (κ = 0.547), and poor for performance status (κ = 0.110). Thirty-one other variables were poorly captured and could not be statistically compared. Documentation of clinical information within the OIS for HNC patients is routine practice; however, OIS data was less correct and complete than data collected for research purposes. Substandard collection of routine data may hinder advancements in patient care. Improved data entry, integration with clinical activities and workflows, system usability, data dictionaries, and training are necessary for OIS data to generate robust research. Data mining from clinical documents may supplement structured data collection.

The use of alternate vertebral levels to L3 in computed tomography scans for skeletal muscle mass evaluation and sarcopenia assessment in patients with cancer: a systematic review.

Body composition measurement using diagnostic computed tomography (CT) scans has emerged as a method to assess sarcopenia (low muscle mass) in oncology patients. Assessment of skeletal muscle mass (SMM) using the cross-sectional area of a single vertebral slice (at lumbar L3) in a CT scan is correlated with whole-body skeletal muscle volume. This method is used to assess CT-defined sarcopenia in patients with cancer, with low SMM effecting outcomes. However, as diagnostic scans are based on tumour location, not all include L3. We evaluated the evidence for the use of alternate vertebral CT slices for SMM evaluation when L3 is not available. Five electronic databases were searched from January 1996 to April 2020 for studies using CT scan vertebral slices above L3 for SM measurement in adults with cancer (solid tumours). Validation with whole-body SMM, rationale for the chosen slice and sarcopenia cut-off values were investigated. Thirty-two studies were included, all retrospective and cross-sectional in design. Cervical, thoracic and lumbar slices were used (from C3 to L1), with no validation of whole-body SMM using CT scans. Alternate slices were used in lung, and head and neck cancer patients. Sarcopenia cut-off values were reported in 75 % of studies, with differing methods, with or without sex-specific values, and a lack of consensus. Current evidence is inadequate to provide definitive recommendations for alternate vertebral slice use for SMM evaluation in cancer patients. Variation in sarcopenia cut-offs warrants more robust investigation, in order for risk stratification to be applied to all patients with cancer.

The Impact of Critical Weight Loss and Reactive Feeding Tubes on Cancer-Specific Survival in Head and Neck Cancer.

Critical weight loss (CWL) continues to be a major issue in head and neck cancer (HNC) and many patients require tube feeding. We investigated the use of reactive feeding tubes (RFTs), associated CWL, and the impact on cancer-specific survival (CSS). A single-institution, retrospective audit was conducted on 460 adult HNC patients who received radiotherapy ± chemotherapy between 2005 and 2017. CSS in patients with CWL and RFTs was compared to those with no tube. Prediction analysis for RFT insertion was also performed. CWL occurred in 53% of patients, and in 88% of those with a RFT (p < 0.001). In patients with CWL, those with a RFT had worse 5 and 10-year CSS compared to those with no tube (68% and 65% vs 83% and 80% respectively, p = 0.040) in multivariate Cox regression analysis. Concurrent chemoradiotherapy combined with CWL was the strongest predictor for RFT insertion (p = 0.003). CWL, combined with having a RFT, impacts negatively on CSS. CWL may be one of the triggers for RFT insertion, however those with no tube have better CSS. This may be due to higher weight loss levels seen in those who have a RFT, and earlier insertion to prevent such losses seems indicated.

Content analysis of rehabilitation goals for patients following non-surgical head and neck cancer treatment.

PURPOSE: Following head and neck cancer (HNC) treatment, individuals experience an array of side effects which can impact on physical, emotional, and practical aspects of their lives. Responsive, supportive rehabilitation services are therefore essential to address ongoing survivorship needs. This study examined the nature of patient-reported goals from acute to long-term post-treatment, to inform design/delivery of future rehabilitation services. METHODS: Using a cross-sectional cohort design, 91 patients between 2 weeks and 5 years of post non-surgical HNC treatment (acute n = 29; sub-acute n = 28; long-term n = 34), provided their top four rehabilitation goals considering any aspect of their lives. Content analysis was used to categorise responses at each time point. RESULTS: Three core categories of patient goals were identified relating to: (1) treatment side effects (TSE), (2) overall health (OH), and (3) living life (LL). TSE goals were a priority during the acute and sub-acute phases, with less focus long-term. LL goals were prevalent across all time points, though increased in the long-term. Approximately a third of all goals at each time point related to OH. CONCLUSIONS: A variety of rehabilitation goals were identified, and the focus shifted over time. These data highlight the importance of changing the focus of rehabilitation as patients' priorities vary over time. Early multidisciplinary care from allied health services is crucial to provide support with managing side effects and returning to daily activities. In the long-term, greater input from services to address health, nutrition, leisure, and fitness goals may be more beneficial.

Optimising Radiation Therapy Dose to the Swallowing Organs at Risk: An In Silico Study of feasibility for Patients with Oropharyngeal Tumours.

Recent evidence suggests that reducing radiotherapy dose delivered to specific anatomical swallowing structures [Swallowing Organs at Risk (SWOARs)] may improve swallowing outcomes post-treatment for patients with head and neck cancer. However, for those patients with tumours of the oropharynx, which typically directly overlap the SWOARs, reducing dose to these structures may be unachievable without compromising on the treatment of the disease. To assess the feasibility of dose reduction in this cohort, standard IMRT plans (ST-IMRT) and plans with reduced dose to the SWOARs (SW-IMRT) were generated for 25 oropharyngeal cancer patients (Brouwer et al. in Radiother Oncol 117(1):83-90, https://doi.org/10.1016/j.radonc.2015.07.041 , 2015; Christianen et al. in Radiother Oncol 101(3):394-402, https://doi.org/10.1016/j.radonc.2011.05.015 , 2011). ST-IMRT and SW-IMRT plans were compared for: mean dose to the SWOARs, volume of pharynx and larynx receiving 50 Gy and 60 Gy (V50 and V60 respectively) and overlap between the tumour volume and the SWOARs. Additionally, two different SWOARs delineation guidelines (Brouwer et al. in Radiother Oncol 117(1):83-90, https://doi.org/10.1016/j.radonc.2015.07.041 , 2015; Christianen et al. in Radiother Oncol 101(3):394-402, https://doi.org/10.1016/j.radonc.2011.05.015 , 2011) were used to highlight differences in calculated volumes between existing contouring guidelines. Agreement in SWOARs volumes between the two guidelines was calculated using a concordance index (CI). Despite a large overlap between the tumour and SWOARs, significant (p < 0.05) reductions in mean dose to 4 of the 5 SWOARs, and V50/V60 for the pharynx and larynx were achieved with SW-IMRT plans. Low CIs per structure (0.15-0.45) were found between the two guidelines highlighting issues comparing data between studies when different guidelines have been used (Hawkins et al. in Semin Radiat Oncol 28(1):46-52, https://doi.org/10.1016/j.semradonc.2017.08.002 , 2018; Brodin et al. in Int J Radiat Oncol Biol Phys 100(2):391-407, https://doi.org/10.1016/j.ijrobp.2017.09.041 , 2018). This study found reducing dose to the SWOARs is a feasible practice for patients with oropharyngeal cancer. However, future prospective research is needed to determine if the extent of dose reduction achieved equates to clinical benefits.

Radiotherapy for parapharyngeal space tumors.

A wide variety of tumors, both benign and malignant, occur in the parapharyngeal space. Depending on histology and extent, treatment may include surgery and/or radiotherapy (RT). Herein we discuss the role of RT in the management of some of the more commonly encountered neoplasms, including salivary gland tumors, paragangliomas, schwannomas, and soft-tissue sarcomas.

Radiation-induced carotid artery lesions.

PURPOSE: To review the current aspects of knowledge related to the risk of cerebrovascular events in patients receiving head and neck radiotherapy. METHODS: A literature search was performed in PubMed. Papers meeting selection criteria were reviewed. RESULTS: We provide an update on the problem by identifying key studies that have contributed to our current understanding of the epidemiology, radiologic features, pathogenesis, and treatment of the disease. The incidence of carotid artery stenosis ranged from 18 to 38% in patients who underwent radiotherapy for head and neck cancer versus from 0 to 9.2% among the nonirradiated patients. Neck irradiation increases the intima-media thickness of the carotid artery wall. These changes are the earliest visible alteration in the carotid wall and are also detected with color Doppler ultrasonography. Endovascular treatment with a carotid angioplasty and stenting is the first-line treatment for most symptomatic patients. CONCLUSIONS: Radiation-induced atherosclerosis is a different and accelerated form of atherosclerosis, which implies a more aggressive disease with a different biologic behavior. The disease is characterized by a high rate of carotid artery stenosis compared to those observed in nonirradiated control group patients. To prevent the risk of stroke, surveillance and imaging with ultrasonography should enable detection of severe stenosis. Endovascular treatment with a carotid angioplasty and stenting has been proposed as an attractive and minimally invasive alternative for some radiation-induced stenoses.

Treatment toxicities and their impact on oral intake following non-surgical management for head and neck cancer: a 3-year longitudinal study.

PURPOSE: Patients who receive (chemo)radiotherapy [(C)RT] for head and neck cancer (HNC) experience multiple treatment effects. However, the presence and recovery of treatment toxicities and how these impact on oral intake over time post-treatment are not fully understood. The primary aim of this study was to examine patient perceptions of the toxicities present and which are barriers to oral intake, up to 3 years post (C)RT. The secondary aim was to identify mealtime strategies used to optimise oral intake. METHODS: A prospective cohort of 96 patients after completion of (C)RT for HNC reported the presence of toxicities, if they were barriers to oral intake, and use of any mealtime strategies at the end of treatment (EoT), and at 3, 6, 12, 24, and 36 months post-treatment. RESULTS: All toxicities and reported barriers changed over time (p < 0.05) except trismus. Odynophagia, reduced appetite, and fatigue improved (p < 0.05) by 3 months. Significantly less patients reported xerostomia and dysgeusia as barriers to oral intake at 3 months despite no improvement in their presence. No change in the presence of any toxicity or its impact on oral intake occurred from 12 to 36 months, with exception of dentition problems which significantly increased at 36 months. Alternating food/fluids was the most frequently used mealtime swallowing strategy at all time points beyond the EoT. CONCLUSIONS: The dysphagia and associated toxicities HNC patients experience are chronic in nature. Rehabilitation should include mealtime strategies and support with adjusting to the changing presence and impact of toxicities on oral intake.

Hyperbaric oxygenation for tumour sensitisation to radiotherapy.

BACKGROUND: Cancer is a common disease and radiotherapy is one well-established treatment for some solid tumours. Hyperbaric oxygenation therapy (HBOT) may improve the ability of radiotherapy to kill hypoxic cancer cells, so the administration of radiotherapy while breathing hyperbaric oxygen may result in a reduction in mortality and recurrence. OBJECTIVES: To assess the benefits and harms of administering radiotherapy for the treatment of malignant tumours while breathing HBO. SEARCH METHODS: In September 2017 we searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library Issue 8, 2017, MEDLINE, Embase, and the Database of Randomised Trials in Hyperbaric Medicine using the same strategies used in 2011 and 2015, and examined the reference lists of included articles. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing the outcome of malignant tumours following radiation therapy while breathing HBO versus air or an alternative sensitising agent. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of and extracted data from the included trials. MAIN RESULTS: We included 19 trials in this review (2286 participants: 1103 allocated to HBOT and 1153 to control).For head and neck cancer, there was an overall reduction in the risk of dying at both one year and five years after therapy (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98, number needed to treat for an additional beneficial outcome (NNTB) = 11 and RR 0.82, 95% CI 0.69 to 0.98, high-quality evidence), and some evidence of improved local tumour control immediately following irradiation (RR with HBOT 0.58, 95% CI 0.39 to 0.85, moderate-quality evidence due to imprecision). There was a lower incidence of local recurrence of tumour when using HBOT at both one and five years (RR at one year 0.66, 95% CI 0.56 to 0.78, high-quality evidence; RR at five years 0.77, 95% CI 0.62 to 0.95, moderate-quality evidence due to inconsistency between trials). There was also some evidence with regard to the chance of metastasis at five years (RR with HBOT 0.45 95% CI 0.09 to 2.30, single trial moderate quality evidence imprecision). No trials reported a quality of life assessment. Any benefits come at the cost of an increased risk of severe local radiation reactions with HBOT (severe radiation reaction RR 2.64, 95% CI 1.65 to 4.23, high-quality evidence). However, the available evidence failed to clearly demonstrate an increased risk of seizures from acute oxygen toxicity (RR 4.3, 95% CI 0.47 to 39.6, moderate-quality evidence).For carcinoma of the uterine cervix, there was no clear benefit in terms of mortality at either one year or five years (RR with HBOT at one year 0.88, 95% CI 0.69 to 1.11, high-quality evidence; RR at five years 0.95, 95% CI 0.80 to 1.14, moderate-quality evidence due to inconsistency between trials). Similarly, there was no clear evidence of a benefit of HBOT in the reported rate of local recurrence (RR with HBOT at one year 0.82, 95% CI 0.63 to 1.06, high-quality evidence; RR at five years 0.85, 95% CI 0.65 to 1.13, moderate-quality evidence due to inconsistency between trials). We also found no clear evidence for any effect of HBOT on the rate of development of metastases at both two years and five years (two years RR with HBOT 1.05, 95% CI 0.84 to 1.31, high quality evidence; five years RR 0.79, 95% CI 0.50 to 1.26, moderate-quality evidence due to inconsistency). There were, however, increased adverse effects with HBOT. The risk of a severe radiation injury at the time of treatment with HBOT was 2.05, 95% CI 1.22 to 3.46, high-quality evidence. No trials reported any failure of local tumour control, quality of life assessments, or the risk of seizures during treatment.With regard to the treatment of urinary bladder cancer, there was no clear evidence of a benefit in terms of mortality from HBOT at one year (RR 0.97, 95% CI 0.74 to 1.27, high-quality evidence), nor any benefit in the risk of developing metastases at two years (RR 2.0, 95% CI 0.58 to 6.91, moderate-quality evidence due to imprecision). No trial reported on failure of local control, local recurrence, quality of life, or adverse effects.When all cancer types were combined, there was evidence for an increased risk of severe radiation tissue injury during the course of radiotherapy with HBOT (RR 2.35, 95% CI 1.66 to 3.33, high-quality evidence) and of oxygen toxic seizures during treatment (RR with HBOT 6.76, 96% CI 1.16 to 39.31, moderate-quality evidence due to imprecision). AUTHORS' CONCLUSIONS: We found evidence that HBOT improves local tumour control, mortality, and local tumour recurrence for cancers of the head and neck. These benefits may only occur with unusual fractionation schemes. Hyperbaric oxygenation therapy is associated with severe tissue radiation injury. Given the methodological and reporting inadequacies of the included studies, our results demand a cautious interpretation. More research is needed for head and neck cancer, but is probably not justified for uterine cervical or bladder cancer. There is little evidence available concerning malignancies at other anatomical sites.

Critical Weight Loss in Patients With Oropharynx Cancer During Radiotherapy (± Chemotherapy).

Critical weight loss (CWL) defined as ≥5% in one month, is common in patients with oropharynx cancer and identification of patients at risk is challenging. We aimed to investigate if predictors of CWL in this population exist to guide nutritional intervention. Data were collected retrospectively on 134 patients who had radiotherapy (RT) ± concurrent chemotherapy (CRT) ± surgery. Body weights were collected pre-RT and during RT, with percentage weight change measured against baseline. Logistic regression was used to analyze chosen predictors. The incidence of CWL was 67% (26% of these patients experiencing ≥10% loss). Patients who had CRT experienced significantly higher weight loss (7.1% versus 4.7%; p = 0.001). Tube feeding was used in 64% of patients with CWL, the majority of tubes inserted reactively. These patients had a mean weight change of -8.8% (versus -7.1% in those with no tube) (p = 0.004). Multivariate models identified increased risk of CWL in tonsil origin tumors (p < 0.05), with CRT being the only predictor of weight loss ≥10% (p < 0.05). These patients are particularly vulnerable to CWL and the majority experience significant nutritional issues during RT, regardless of nutritional status at diagnosis. Nutritional intervention should be targeted accordingly.

Metastatic basal cell carcinoma: case series and review of the literature.

Metastatic basal cell carcinoma is exceedingly uncommon, with a poorly defined natural history, and its incidence, risk factors, patterns of spread, prognosis and potential treatment options are not well understood. This retrospective single institution case series aims to shed light on these issues. Aggressive local management in patients with locoregional disease may result in long-term survivors.

Clinical predictors for reactive tube feeding in patients with advanced oropharynx cancer receiving radiotherapy ± chemotherapy.

Enteral feeding is often required for nutrition support in head and neck cancer patients when oral intake is inadequate. When to initiate the insertion of a feeding tube continues to be a debated issue in our institution. We investigated the use of reactive feeding tubes (RFTs) in patients with advanced stage oropharynx cancer (OPC). Data were retrospectively collected on 131 patients who had radiotherapy (RT) ± chemotherapy from 2005 to 2015. Predictors for RFT insertion were investigated. Weight loss during RT was compared between those with RFT versus prophylactic tubes (PFTs) versus no tube, and survival outcomes evaluated. RFTs were more likely to be needed in patients who had bilateral neck node irradiation (p = 0.001) and concurrent chemoradiotherapy (CRT) (p = 0.038). Patients with RFTs had significantly higher mean percentage weight loss during RT (9.5 ± 3.4%) (p < 0.001) when compared to those with a PFT (5.2 ± 4.7%) and those with no tube (5.4 ± 3.1%). No difference was seen in 5-year survival rates in patients who did not have a feeding tube to those who required a RFT. RFT use is frequent in OPC, although difficult to predict. CRT and bilateral neck node irradiation were found to be associated with the need for the insertion of a feeding tube during RT. These patients also experience significantly higher weight loss, therefore, prophylactic tubes may need to be considered more often in this population.

Pretreatment factors associated with functional oral intake and feeding tube use at 1 and 6 months post-radiotherapy (+/- chemotherapy) for head and neck cancer.

A proportion of patients with head and neck cancer (HNC) experience significant swallowing difficulty during and post-radiotherapy/chemoradiotherapy (RT/CRT). Identifying patients during the pretreatment period who are anticipated to have compromised oral intake would allow for early and accurate patient education, and prioritisation of their management. Ascertaining a clear set of pretreatment predictors from the literature is challenging due to heterogeneity in study designs and patient cohorts, with minimal prospective data available (especially at 1-month post-treatment). The objectives of this study were to investigate which pretreatment factors predicted compromised oral intake and feeding tube use at 1 and 6 months post-RT/CRT. Prospective data were collected on 80 consecutive HNC patients receiving RT/CRT from 2011 to 2014. The primary outcome was to identify predictors of a modified diet at 1 and 6 months post-RT/CRT. Secondary outcomes were to identify predictors of feeding tube use at these time intervals, and <6 vs. >6 week duration of feeding tube use. Multivariate analysis revealed bilateral neck radiotherapy treatment was a strong predictor of modified diets at 1 month (p < 0.001), and T-stages T3/T4 a predictor of modified diets at 6 months (p = 0.03). Patients treated with concurrent CRT (p = 0.02) and bilateral neck treatment (p = 0.02) predicted feeding tube use at 1 month, and concurrent CRT predicted feeding tube use for >6 weeks (p = 0.04). Therefore, patients receiving bilateral neck treatment and/or CRT are at greatest risk of requiring modified diets and feeding tube use early post-treatment, and should be prioritised for intervention and ongoing support.

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of people having radiotherapy will be long-term survivors. Some will experience late radiation tissue injury (LRTI) developing months or years later. Hyperbaric oxygen therapy (HBOT) has been suggested as a treatment for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery. OBJECTIVES: To assess the benefits and harms of HBOT for treating or preventing LRTI. SEARCH METHODS: We updated the searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 11), MEDLINE, EMBASE, DORCTIHM and reference lists of articles in December 2015. We also searched for ongoing trials at clinicaltrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: Three review authors independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook for Systematic Reviews of Interventions and extracted the data from the included trials. MAIN RESULTS: Fourteen trials contributed to this review (753 participants). There was some moderate quality evidence that HBOT was more likely to achieve mucosal coverage with osteoradionecrosis (ORN) (risk ratio (RR) 1.3; 95% confidence interval (CI) 1.1 to 1.6, P value = 0.003, number needed to treat for an additional beneficial outcome (NNTB) 5; 246 participants, 3 studies). There was also moderate quality evidence of a significantly improved chance of wound breakdown without HBOT following operative treatment for ORN (RR 4.2; 95% CI 1.1 to 16.8, P value = 0.04, NNTB 4; 264 participants, 2 studies). From single studies there was a significantly increased chance of improvement or cure following HBOT for radiation proctitis (RR 1.72; 95% CI 1.0 to 2.9, P value = 0.04, NNTB 5), and following both surgical flaps (RR 8.7; 95% CI 2.7 to 27.5, P value = 0.0002, NNTB 4) and hemimandibulectomy (RR 1.4; 95% CI 1.1 to 1.8, P value = 0.001, NNTB 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4; 95% CI 1.1 to 1.7, P value = 0.009, NNTB 4).There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no randomised data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse events. AUTHORS' CONCLUSIONS: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.

Should patients with laryngeal small cell neuroendocrine carcinoma receive prophylactic cranial irradiation?

While small cell neuroendocrine carcinomas (SCNCs) most often arise in the lung, extrapulmonary SCNCs arise in a variety of locations-including the head and neck region. In particular, laryngeal SCNCs-while rare tumors-are nevertheless recognized as distinct lesions. The rarity of laryngeal SCNC gives rise to two distinct difficulties: first (particularly with small biopsy specimens), laryngeal SCNC can be difficult to diagnose by routine light microscopy; second, limited experience with these tumors can make the crafting of a treatment plan for individual patients difficult. As regards the first problem, pathologic diagnosis is greatly enhanced by the application of immunohistochemistry. The second problem-crafting a successful treatment strategy-presents a much larger difficulty. It is tempting to extrapolate from experience with the (more common) pulmonary SCNC in search of a strategy applicable to laryngeal SCNC; such an extrapolation, however, may not be uniformly successful. In particular, while a combination of radiation therapy and chemotherapy appears to be as valuable in the treatment of extrapulmonary as it is in the treatment of pulmonary SCNC, prophylactic cranial irradiation (PCI)-which has enjoyed some success in the treatment of some patients with pulmonary SCNC-does not appear to have similar utility in patients with laryngeal SCNC. Accordingly, the use of PCI does not appear to have a role to play at this point in time in the treatment of patients with laryngeal SCNC.