Situational anxiety in head and neck cancer: Rates, patterns and clinical management interventions in a regional cancer setting.

INTRODUCTION: Research indicates that the immobilisation mask required for radiation therapy (RT) for head and neck cancers can provoke intense anxiety. However, little is known about the rates of this anxiety, whether it changes over a course of treatment and how it is managed in clinical practice. This study aimed to describe the rates and patterns of situational anxiety in patients undergoing RT for head and neck cancer and the use of anxiety management interventions in current clinical practice in a major regional cancer setting in New South Wales, Australia. METHODS: Situational anxiety rates and patterns were assessed at five time points using the State-Trait Anxiety Inventory prior to treatment planning (SIM), the first three treatment sessions (Tx 1, Tx 2 and Tx 3) and treatment 20 (Tx 20). Sessions were observed to record the use of general supportive interventions (music and support person) and anxiety-specific interventions (break from the mask, relaxation techniques and anxiolytic medication). Sociodemographic and clinical information was extracted from the medical record. RESULTS: One hundred and one patients were recruited. One-third had clinically significant anxiety at any of the first three time points (33.3-40%), and a quarter at Tx 3 (26.4%) and Tx 20 (23.4%). Of the sample, 55.4% had available data for categorisation into one of four pattern groups: 'No Anxiety' (46.4%); 'Decreasing Anxiety' (35.7%); 'Increasing Anxiety' (7.1%); and 'Stable High Anxiety' (10.7%). Most participants had social support present at SIM (53.5%) and listened to music during treatment (86.7-92.9%). Few participants received relaxation techniques alone (1.2-2.3%). Anxiolytic medication was provided for 10% of patients at some stage during the treatment journey and 5% required a break from the mask at SIM, with frequency decreasing throughout the treatment course. CONCLUSIONS: In this regional cancer setting, situational anxiety was common, but generally decreased throughout treatment. Some patients experience persistent or increasing anxiety, with up to 10% of patients receiving specific anxiety management interventions.

Biofeedback Enabled CALM (BeCALM)-the feasibility of biofeedback on procedural anxiety during radiation therapy: study protocol for a pilot randomised controlled trial.

INTRODUCTION: Patients undergoing treatment for cancer who require radiation therapy (RT) report anxiety specifically relating to the RT procedure. Procedural anxiety can be detrimental to treatment delivery, causing disruptions to treatment sessions, or treatment avoidance. Acute procedural anxiety is most commonly managed with anxiolytic medication. There is a need for effective, non-pharmacological interventions for patients not suitable for, or who prefer to avoid, anxiolytic medication. The primary objectives of this pilot trial are to evaluate the: (1) feasibility of conducting the Biofeedback Enabled CALM (BeCALM) intervention during RT treatment sessions; (2) acceptability of the BeCALM intervention among patients; and (3) acceptability of the BeCALM intervention among radiation therapists. The secondary objective of this pilot trial is to examine the potential effectiveness of the BeCALM intervention delivered by radiation therapists to reduce procedural anxiety during RT. METHODS AND ANALYSIS: This is a pilot randomised controlled trial. A researcher will recruit adult patients with cancer (3-month recruitment period) scheduled to undergo RT and meeting eligibility criteria for procedural anxiety at the Calvary Mater Hospital, Newcastle (NSW), Australia. Participants will be randomly assigned to receive treatment as usual or the BeCALM intervention (biofeedback plus brief breathing techniques). The primary outcomes are feasibility (measured by recruitment, retention rates and percentage of treatment sessions in which the intervention was successfully delivered); radiation therapists perceived feasibility and acceptability (survey responses); and patient perceived acceptability (survey responses). Secondary outcome is potential effectiveness of the intervention (as measured by the State Trait Anxiety Inventory-State subscale; the Distress Thermometer; and an analysis of treatment duration). ETHICS AND DISSEMINATION: The study protocol has received approval from Hunter New England Health Human Research Ethics Committee (2021/ETH11356). The results will be disseminated via peer-reviewed publications, as well as presentation at relevant conferences. TRIAL REGISTRATION NUMBER: ACTRN12621001742864.

Assessing the impact of magnetic resonance treatment simulation (MRSIM) on target volume delineation and dose to organs at risk for oropharyngeal radiotherapy.

INTRODUCTION: Assessing the use of a radiation therapy (RT) planning MRI performed in the treatment position (pMRI) on target volume delineation and effect on organ at risk dose for oropharyngeal cancer patients planned with diagnostic MRI (dMRI) and CT scan. METHODS: Diagnostic MRI scans were acquired for 26 patients in a neutral patient position using a 3T scanner (dMRI). Subsequent pMRI scans were acquired on the same scanner with a flat couch top and the patient in their immobilisation mask. Each series was rigidly registered to the patients planning CT scan and volumes were first completed with the CT/dMRI. The pMRI was then made available for volume modification. For the group with revised volumes, two IMRT plans were developed to demonstrate the impact of the modification. Image and registration quality was also evaluated. RESULTS: The pMRI registration led to the modification of target volumes for 19 of 26 participants. The pMRI target volumes were larger in absolute volume resulting in reduced capacity for organ sparing. Predominantly, modifications occurred for the primary gross tumour volume (GTVp) with a mean Dice Similarity Coefficient (DSC) of 0.7 and the resulting high risk planning target volume, a mean DSC of 0.89. Both MRIs scored similarly for image quality, with the pMRI demonstrating improved registration quality and efficiency. CONCLUSIONS: A pMRI provides improvement in registration efficiency, quality and a higher degree of oncologist confidence in target delineation. These results have led to a practice change within our department, where a pMRI is acquired for all eligible oropharyngeal cancer patients.

Junior Doctor Evaluation of Radiation Oncology Education and Training in Medical Schools and Prevocational Training in Australia.

The purpose of this study is to evaluate radiation oncology (RO)-specific education, confidence and knowledge of junior doctors in Australian teaching hospitals. A 38-item web-based survey was emailed to prevocational junior doctors working in Australian hospitals in New South Wales (NSW), Australian Capital Territory (ACT) and Queensland (QLD) between November 2017 and January 2018. The survey evaluated RO educational and clinical exposure of participants during medical school, and prevocational training and their confidence and knowledge of the specialty. A total of 183 respondents across 17 Australian hospital networks completed the survey. During medical school, 53.4% had RO incorporated into their formal curriculum, 19.5% had no formal lectures and 51.7% had never visited a RO department. As a junior doctor, 73.8% of respondents did not receive any formal RO education. When compared with other oncology specialties, fewer junior doctors were confident in consulting the RO team (21.0%) compared with medical oncology (42.0%), palliative care (75.2%) and haematology (40.1%). Majority of respondents (61.6%) showed limited understanding of radiation safety. On multivariate sub-group analysis, both confidence and knowledge in RO improved when RO was incorporated into the formal medical school curriculum. This survey highlights the current low confidence and poor knowledge standard amongst Australian junior doctors on RO due to inadequate teaching during medical school and prevocational training and suggests improvement through standardisation of formal RO curriculum teaching within medical school and prevocational training.

Gastrostomy dependency trends over 15 years of patients at a large tertiary referral center following the insertion of a prophylactic gastrostomy for chemoradiation for mucosal head and neck cancer.

AIM: The routine use of prophylactic percutaneous endoscopic gastrostomy (PEG) tubes for nutrition support during radical chemoradiation for head and neck cancer has been suggested to result in PEG dependency. This research aimed to determine the rates of gastrostomy dependency at the Calvary Mater Newcastle (CMN) where PEGs are routinely used and to identify potentially modifiable risk factors. METHODS: All patients with head and neck cancer planned for curative chemoradiation with a prophylactic PEG inserted were included in this review. Medical records of 250 patients treated between 2000 and 2015 were examined. RESULTS: Overall, eight patients (3%) were unable to wean. At 12 months following treatment, 16 patients (6%) still required PEG tubes for feeding. A greater T extent (T4 or synchronous head and neck tumors) and number of days Nil By Mouth (NBM) remained as significant independent risk factors for PEG dependency at 12 months (Textent OR 6.96 P < .001; NBM OR 1.01 P = .004) and overall (Textent OR8.04 P = .02; NBM OR1.01 P = .001). Associations with NBM were investigated, which demonstrated that patients had less NBM days with intensity-modulated radiation therapy (IMRT) (ß-13.3, P = .007) and seeing a speech pathologist during treatment (ß-11.9, P = .026). More NBM days were associated with tumors with greater T extent (ß+22; P < .001). CONCLUSION: The routine use of prophylactic PEGs has not resulted in significant rates of PEG dependency at the CMN. Seeing a speech pathologist during treatment and IMRT may decrease time NBM, which was identified as a potentially modifiable risk factor for PEG dependency.

Oncology and Radiation Oncology Awareness in Final Year Medical Students in Australia and New Zealand.

This study aimed to determine final year students' core oncology and radiation oncology knowledge and attitudes about the quality of teaching in medical programmes delivered in Australia and New Zealand. Does the modern medical programme provide core oncology skills in this leading global cause of mortality and morbidity? An online survey was distributed between April and June 2018 and completed by 316 final year students across all 21 medical schools with final year cohorts in Australia and New Zealand. The survey examined teaching and clinical exposure, attitudes and core knowledge for oncology and radiation oncology. Several questions from a survey done of graduates in 2001 were repeated for comparison. We found that clinical exposure to oncology and its disciplines is low. Students rated oncology and haematology the worst taught medical specialties at medical school. Students reported the most confidence identifying when surgical management of cancer may be indicated and much lower levels of confidence identifying when systemic therapy and radiation therapy may be helpful. The majority of students had no formal course content on radiation therapy and more than one third of final year students erroneously believed that external beam radiation therapy turned patients radioactive. Exposure to oncology practice and the teaching of core oncology knowledge remains low for medical students in Australia and New Zealand. Many areas of oncology teaching and knowledge have worsened for medical students in Australia and New Zealand over the past 20 years. Well-established gaps in the core oncology knowledge of medical graduates must be urgently addressed given the increasing incidence of cancer and ongoing underutilisation of radiation therapy in particular.

The status of radiation oncology teaching in Australian and New Zealand medical schools.

INTRODUCTION: Radiation therapy is a core component of curative and palliative cancer treatment; however, its indications and benefits remain poorly understood across the medical profession. METHODS: An electronic survey focussing on curriculum content, teaching and assessment in radiation oncology and plans for curriculum change was developed. The Faculty of Radiation Oncology, Royal Australian and New Zealand College of Radiology (RANZCR) distributed the survey to all 24 Australian and New Zealand medical schools. The survey was conducted from November 2017 to January 2018 following ethics approval. RESULTS: Sixteen of the 24 (67%) medical Faculties in Australia and New Zealand responded. Ninety-four percent of Faculties had no formal radiation oncology curriculum. Most Faculties (87%) dedicated <15% of the total medical course to oncology, of which the majority (63%) dedicated <10% to radiation oncology. At least 50% of Faculties did not offer formal radiation oncology teaching to all students. When offered, students' exposure to radiation oncology was often <5 days over the entire course (44%). The majority of medical schools (73%) are planning curriculum changes in the next 5 years; however, most have no intention of changing radiation oncology teaching. CONCLUSION: Radiation oncology continues to be underrepresented in medical curricula throughout Australia and New Zealand with no plans for improvement by Faculties. This study supports the need for formal advocacy for improving radiation oncology education in medical schools and will form the basis of new national recommendations for radiation oncology curriculum development.

Neutrophil-lymphocyte ratio dynamics during concurrent chemo-radiotherapy for glioblastoma is an independent predictor for overall survival.

Elevated neutrophil-lymphocyte ratio (NLR) may predict worse outcomes in cancer, including glioblastoma (GBM). This study assessed whether change in NLR during focal radiotherapy and concomitant temozolomide (RT-TMZ) provides further prognostic information. This was a retrospective review of patients treated with RT-TMZ for histologically confirmed GBM from January 2004 to September 2010. Variables assessed included age, ECOG performance status (PS), dexamethasone use and extent of surgery. Hematological results were collected at baseline, during and 4 weeks post RT-TMZ. Kaplan-Meier method was used to calculate overall survival (OS). Multivariable analysis (MVA) assessed for joint effect of covariates on OS and Pearson Correlation Coefficients assessed for association between dexamethasone dose and NLR change. With a median age of 55 (range 18-70), 369 patients were included. Median follow up was 15.1 month (range 1.6-134.6). The OS was 66.1% (95% CI 61.2-70.6) and 31.4 (95% CI 26.8-36.1) at 1 and 2 years, respectively. On univariate analysis, both decrease in NLR post RT-TMZ (HR 0.641, p < 0.0001) and baseline NLR < 7.5 (HR 0.628, p < 0.0001) were associated with longer OS. On MVA decrease in NLR (HR 0.727, 95% CI 0.578-0.915), age (HR 1.025, 95% CI 1.012-1.038), baseline neutrophil (<8) (HR 0.689, 95% CI 0.532-0.891), total TMZ cycles (HR 0.89, 95% CI 0.867-0.913) and PS (HR 0.476, 95% CI 0.332-0.683) were independent predictors of OS. These findings suggest that a decrease in NLR during RT-TMZ, accounting for known prognostic factors, is an independent prognostic factor for survival in GBM.

18F-FDG PET-CT performed before and during radiation therapy of head and neck squamous cell carcinoma: Are they independent or complementary to each other?

INTRODUCTION: The aims of this study are to evaluate the prognostic value of metabolic parameters derived from (18) F-FDG PET-CT performed before definitive radiation therapy (RT) (prePET) in patients with mucosal primary head and neck squamous cell carcinoma (MPHNSCC) and to assess the additive prognostic values of FDG PET-CT performed during RT (iPET). METHODS: One hundred patients with MPHNSCC treated with radical RT underwent staging prePET and iPET performed during the third week of treatment. The maximum standardized uptake value (SUVmax ), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary tumour were analysed for both prePET and iPET, and results were correlated with loco-regional recurrence-free survival (LRFS), disease-free survival (DFS), metastatic failure-free survival (MFFS) and overall survival (OS), using Kaplan-Meier analysis. Optimal cut-offs (OC) for prePET and iPET were derived from Receiver Operating Characteristic curves. Patients with metabolic parameters above/below the individual OC of prePET as well as iPET (i.e. combined prePET and iPET (comPET)) were evaluated against their outcomes. RESULTS: Median age was 61 years (range 39-81), median follow-up of 20 months (range 4-70, mean 27), and AJCC 7th Edition clinical stage II, III and IV were 8, 24 and 68 patients respectively. Metabolic values below individual OC in comPET were found to be associated with statistically significant improvements (P < 0.05) in DFS, LRFS and OS. In addition, patients with SUVmax above the OC in comPET were associated with worse MFFS (P = 0.011) and confirmed on both univariate (P = 0.019) and multivariate analyses (P = 0.04). CONCLUSION: Addition of iPET significantly improves the prognostic values of all three metabolic parameters and can potentially be used in future adaptive local and systemic therapy trials.

Prognostic role of metabolic parameters of (18)F-FDG PET-CT scan performed during radiation therapy in locally advanced head and neck squamous cell carcinoma.

PURPOSE: To evaluate the prognostic value of (18)F-FDG PET-CT performed in the third week (iPET) of definitive radiation therapy (RT) in patients with newly diagnosed locally advanced mucosal primary head and neck squamous-cell-carcinoma (MPHNSCC). METHODOLOGY: Seventy-two patients with MPHNSCC treated with radical RT underwent staging PET-CT and iPET. The maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesional glycolysis (TLG) of primary tumour (PT) and index node (IN) [defined as lymph node(s) with highest TLG] were analysed, and results were correlated with loco-regional recurrence-free survival (LRFS), disease-free survival (DFS), metastatic failure-free survival(MFFS) and overall survival (OS), using Kaplan-Meier analysis. RESULTS: Optimal cutoffs (OC) were derived from receiver operating characteristic curves: SUVmax-PT = 4.25 g/mL, MTVPT = 3.3 cm(3), TLGPT = 9.4 g, for PT, and SUVmax-IN = 4.05 g/mL, MTVIN = 1.85 cm(3) and TLGIN = 7.95 g for IN. Low metabolic values in iPET for PT below OC were associated with statistically significant better LRFS and DFS. TLG was the best predictor of outcome with 2-year LRFS of 92.7 % vs. 71.1% [p = 0.005, compared with SUVmax (p = 0.03) and MTV (p = 0.022)], DFS of 85.9% vs. 60.8% [p = 0.005, compared with SUVmax (p = 0.025) and MTV (p = 0.018)], MFFS of 85.9% vs. 83.7% [p = 0.488, compared with SUVmax (p = 0.52) and MTV (p = 0.436)], and OS of 81.1% vs. 75.0% [p = 0.279, compared with SUVmax (p = 0.345) and MTV (p = 0.512)]. There were no significant associations between the percentage reduction of primary tumour metabolic parameters and outcomes. In patients with nodal disease, metabolic parameters below OC (for both PT and IN) were significantly associated with all oncological outcomes, while TLG was again the best predictor: LRFS of 84.0% vs. 55.3% (p = 0.017), DFS of 79.4% vs. 38.6% (p = 0.001), MFFS 86.4% vs. 68.2% (p = 0.034) and OS 80.4% vs. 55.7% (p = 0.045). CONCLUSION: The metabolic parameters of iPET can be useful predictors of patient outcome and potentially have a role in adaptive therapy for MPHNSCC. Among the three parameters, TLG was found to be the best prognostic indicator of oncological outcomes.

Impact of glycemia on survival of glioblastoma patients treated with radiation and temozolomide.

Evidence suggests hyperglycemia is associated with worse outcomes in glioblastoma (GB). This study aims to confirm the association between glycemia during radiotherapy (RT) and temozolomide (TMZ) treatment and overall survival (OS) in patients with newly diagnosed GB. This retrospective study included GB patients treated with RT and TMZ from 2004 to 2011, randomly divided into independent derivation and validation datasets. Time-weighted mean (TWM) glucose and dexamethasone dose were collected from start of RT to 4 weeks after RT. Univariate (UVA) and multivariable (MVA) analyses investigated the association of TWM glucose and other prognostic factors with overall survival (OS). In total, 393 patients with median follow-up of 14 months were analyzed. In the derivation set (n = 196) the median OS was 15 months and median TWM glucose was 6.3 mmol/L. For patients with a TWM glucose ≤6.3 and >6.3 mmol/L, median OS was 16 and 13 months, respectively (p = 0.03). On UVA, TWM glucose, TWM dexamethasone, age, extent of surgery, and performance status were associated with OS. On MVA, TWM glucose remained an independent predictor of OS (p = 0.03) along with TWM dexamethasone, age, and surgery. The validation set (n = 197), with similar baseline characteristics, confirmed that TWM glucose ≤6.3 mmol/L was independently associated with longer OS (p = 0.005). This study demonstrates and validates that glycemia is an independent predictor for survival in GB patients treated with RT and TMZ.

Breast cancer detection among young survivors of pediatric Hodgkin lymphoma with screening magnetic resonance imaging.

BACKGROUND: Female survivors of pediatric Hodgkin lymphoma (HL) who have received chest radiotherapy are at increased risk of breast cancer. Guidelines for early breast cancer screening among these survivors are based on little data regarding clinical outcomes. This study reports outcomes of breast cancer screening with MRI and mammography (MMG) after childhood HL. METHODS: We evaluated the results of breast MRI and MMG screening among 96 female survivors of childhood HL treated with chest radiotherapy. Outcomes measured included imaging sensitivity and specificity, breast cancer characteristics, and incidence of additional imaging and breast biopsy. RESULTS: Median age at first screening was 30 years, and the median number of MRI screening rounds was 3. Ten breast cancers were detected in 9 women at a median age of 39 years (range, 24-43 years). Half were invasive and half were preinvasive. The median size of invasive tumors was 8 mm (range, 3-15 mm), and none had lymph node involvement. Sensitivity and specificity of the screening modalities were as follows: for MRI alone, 80% and 93.5%, respectively; MMG alone, 70% and 95%, respectively; both modalities combined, 100% and 88.6%, respectively. All invasive tumors were detected by MRI. Additional investigations were required in 52 patients, (54%), and 26 patients (27%) required breast biopsy, with 10 patients requiring more than 1 biopsy. CONCLUSIONS: Screening including breast MRI with MMG has high sensitivity and specificity in pediatric HL survivors, with breast cancers detected at an early stage, although it is associated with a substantial rate of additional investigations.

The effect of adjuvant postmastectomy radiotherapy bolus technique on local recurrence.

PURPOSE: Postmastectomy radiotherapy bolus is heterogenous, with little evidence to guide clinical practise. This study explores the effect of chest wall bolus technique on chest wall recurrence. METHODS AND MATERIALS: This was a retrospective cohort study of 254 patients treated with adjuvant postmastectomy radiotherapy between 1993 and 2003. Patient and treatment characteristics including bolus details were extracted. Outcomes considered were treatment toxicities, treatment delivery, and local recurrence. RESULTS: In all, 143 patients received radiotherapy with whole chest wall bolus, 88 patients with parascar bolus, and 23 with no bolus. Twenty patients did not complete radiotherapy because of acute skin toxicity: 17 in the whole chest wall bolus group, 2 in the parascar bolus group, and 1 in the group not treated with bolus. On multivariate analysis, whole chest wall bolus and chemotherapy were found to be significant predictors for early cessation of radiotherapy resulting from acute skin toxicity. There were 19 chest wall failures: 13 in the whole chest wall bolus group, 4 in the parascar bolus group, and 2 in the no-bolus group. On multivariate analysis, lymphovascular invasion and failure to complete radiotherapy because of acute skin toxicity were associated with chest wall recurrence. CONCLUSIONS: From our results, parascar bolus and no bolus performed no worse than did whole chest wall bolus with regard to chest wall recurrence. However, bolus may have an impact on early cessation of radiotherapy caused by skin toxicity, which then may influence chest wall recurrence.