Sir Peter MacCallum Department of Oncology - Research Publications

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    Patient-Reported Symptom Severity, Health- Related Quality of Life, and Emotional Distress Trajectories During and After Radiation Therapy for Human Papillomavirus-Associated Oropharyngeal Cancer: A TROG 12.01 Secondary Analysis
    Mcdowell, L ; Bressel, M ; King, MT ; Corry, J ; Kenny, L ; Porceddu, S ; Wratten, C ; Macann, A ; Jackson, JE ; Rischin, D (ELSEVIER SCIENCE INC, 2023-08-01)
    PURPOSE: This secondary analysis of clinical trial TROG 12.01, involving patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma, aimed to identify patient-reported outcome (PRO) trajectories before, during, and after chemoradiotherapy. METHODS AND MATERIALS: Head and neck cancer symptom severity (HNSS) and interference (HNSI), generic health-related quality of life (HRQL), and emotional distress were assessed with the MD Anderson Symptom Inventory-Head and Neck, Functional Assessment of Cancer Therapy-General, and Hospital Anxiety and Depression Scale questionnaires, respectively. Latent class growth mixture modeling (LCGMM) was used to identify distinct underlying trajectories. Baseline and treatment variables were compared between trajectory groups. RESULTS: The LCGMM identified latent trajectories for all PROs: HNSS, HNSI, HRQL, anxiety, and depression. Four HNSS trajectories (HNSS1-4) were identified, distinguished by differences in HNSS at baseline, during the peak of treatment symptoms, and during early and intermediate recovery. All trajectories were stable beyond 12 months. The reference trajectory (HNSS4, n = 74) score was 0.1 (95% confidence interval [CI], 0.1-0.2) at baseline, peaking at 4.6 (95% CI, 4.2-5.0), with rapid early recovery (1.1; 95% CI, 0.8-2.2) and gradual improvement to 12 months (0.6; 95% CI, 0.5-0.8). Patients in HNSS2 (high baseline, n = 30) reported higher baseline scores (1.4; 95% CI, 0.8-2.0) but were otherwise similar to HNSS4. Patients in HNSS3 (low acute, n = 53) reported reduced acute symptoms (2.5; 95% CI, 2.2-2.9) with stable scores beyond 9 weeks after chemoradiotherapy (1.1; 95% CI, 0.9-1.4). Patients in HNSS1 (slow recovery, n = 25) had slower recovery from an acute peak of 4.9 (95% CI, 4.3-5.6) to 0.9 (95% CI, 0.6-1.3) at 12 months. Age, performance status, education, receipt of cetuximab, and baseline anxiety varied between trajectories. The other PRO models demonstrated clinically relevant trajectories, with distinct associations with baseline factors. CONCLUSIONS: LCGMM identified distinct PRO trajectories during and after chemoradiotherapy. These and their associations with variations in the characteristics and treatment factors of patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma provide clinically relevant insights into identifying patients who may require increased support before, during, or after chemoradiotherapy.
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    Patient- and Clinician-Reported Outcomes in Human Papillomavirus-Associated Tonsillar Carcinoma Treated With Unilateral and Bilateral Intensity Modulated Radiation Therapy-A Substudy From TROG 12.01
    McDowell, L ; Rischin, D ; King, M ; Kenny, L ; Porceddu, S ; Wratten, C ; Macann, A ; Jackson, JE ; Bressel, M ; Fua, T ; Lin, C ; Liu, C ; Corry, J (ELSEVIER SCIENCE INC, 2023-01-01)
    PURPOSE: The aim of this TROG 12.01 substudy was to report longitudinal variations in patient- (PRO) and clinician-reported outcomes based on receipt of unilateral (URT) or bilateral radiation therapy (BRT). METHODS AND MATERIALS: Patients with lateralized T1-2 N1-2b human papillomavirus-associated tonsillar carcinoma (AJCC7) enrolled on TROG 12.01 were eligible. The primary endpoint was patient-reported radiation symptom severity score (MDASI-RSS) at 2 years, a composite of 9 MDASI-Head and Neck (HN) symptom items. Secondary endpoints included patient-reported symptom burden and interference (MDASI-HN), quality of life (FACT-HN), emotional distress (HADS), return to work (RTW), clinician-reported performance status scale (PSS-HN), and late adverse events (CTCAE). Mean MDASI-RSS, symptom severity (MDASI-SS), symptom interference (MDASI-SI) and selected single items were compared 1 week, 3 months, and 2 years post-RT. RESULTS: Seventy-four patients were eligible for analysis (26 URT, 48 BRT). Median follow-up was 3.7 years (1.8-5.2 years). Sociodemographic, staging, and treatment variables were mostly balanced, with larger primaries observed in the BRT group. Four regional failures were reported (3 URT, 1 BRT), including one isolated contralateral regional failure in the URT cohort. Mean MDASI-RSS scores did not differ at 2 years (URT vs BRT, 1.1 vs 1.3; difference 0.1 [95% CI: -0.7 to 0.9], P = .75) or at any other time points for the MDASI-RSS, MDASI-SS, and MDASI-SI scores, except for worse MDASI-SI 1 week after treatment in the BRT group (4.7 vs 5.6). Fatigue (6.6 vs 5.4) at 1 week and dry mouth (3.5 vs 2.0) at 2 years were also worse in the BRT group. FACT-HN, HADS, RTW, PSS-HN, and CTCAE results were similar across the follow-up period. CONCLUSIONS: In this favorable-risk cohort, treatment laterality resulted in fewer differences than anticipated in patient-reported or clinician-reported outcomes. Two years after treatment patients treated with BRT reported significantly worse dry mouth. Longer follow-up is needed to determine the impact of treatment laterality on late effects.
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    Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials
    Rischin, D ; Mehanna, H ; Young, RJ ; Bressel, M ; Dunn, J ; Corry, J ; Soni, P ; Fulton-Lieuw, T ; Iqbal, G ; Kenny, L ; Porceddu, S ; Wratten, C ; Robinson, M ; Solomon, BJ (ELSEVIER, 2022-08)
    BACKGROUND: High CD103+ intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis. PATIENTS AND METHODS: We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103+ ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial. RESULTS: Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103+ ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS. CONCLUSIONS: CD103+ ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials.
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    Individualised mindfulness-based stress reduction for head and neck cancer patients undergoing radiotherapy of curative intent: a descriptive pilot study
    Pollard, A ; Burchell, JL ; Castle, D ; Neilson, K ; Ftanou, M ; Corry, J ; Rischin, D ; Kissane, DW ; Krishnasamy, M ; Carlson, LE ; Couper, J (WILEY, 2017-03)
    People with head and neck cancer (HNC) experience elevated symptom toxicity and co-morbidity as a result of treatment, which is associated with poorer psychosocial and quality-of-life (QoL) outcomes. This Phase I study examined whether an individualised mindfulness-based stress reduction (IMBSR) programme could be successfully used with HNC patients undergoing curative treatment. Primary aims were to explore feasibility, compliance, acceptability and fidelity. Secondary aims were to determine whether (1) participation in the intervention was associated with changes in post-intervention mindfulness and (2) post-intervention mindfulness was associated with post-intervention distress and QoL. Nineteen HNC patients participated in a seven-session IMBSR programme with pre- and post-test outcome measures of psychological distress, depression, anxiety and QoL. Primary aims were assessed by therapists or participants. Mindfulness, distress and QoL were assessed using self-report questionnaires at pre- and post-intervention. Longer time spent meditating daily was associated with higher post-intervention mindfulness. After controlling for pre-intervention mindfulness, there was an association between higher post-intervention mindfulness and lower psychological distress and higher total, social and emotional QoL. This study offers important preliminary evidence than an IMBSR intervention can be administered to HNC patients during active cancer treatment. A randomised controlled trial is warranted to confirm these findings.
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    p16-positive lymph node metastases from cutaneous head and neck squamous cell carcinoma: No association with high-risk human papillomavirus or prognosis and implications for the workup of the unknown primary
    McDowell, LJ ; Young, RJ ; Johnston, ML ; Tan, T-J ; Kleid, S ; Liu, CS ; Bressel, M ; Estall, V ; Rischin, D ; Solomon, B ; Corry, J (WILEY-BLACKWELL, 2016-04-15)
    BACKGROUND: The incidence of p16 overexpression and the role of human papillomavirus (HPV) in cutaneous head and neck squamous cell carcinoma (cHNSCC) are unclear. METHODS: One hundred forty-three patients with cHNSCC lymph node metastases involving the parotid gland were evaluated for p16 expression by immunohistochemistry. The detection of 18 high-risk HPV subtypes was performed with HPV RNA in situ hybridization for a subset of 59 patients. The results were correlated with clinicopathological features and outcomes. RESULTS: The median follow-up time was 5.3 years. No differences were observed in clinicopathological factors with respect to the p16 status. p16 was positive, weak, and negative in 45 (31%), 21 (15%), and 77 cases (54%), respectively. No high-risk HPV subtypes were identified, regardless of the p16 status. The p16 status was not prognostic for overall (hazard ratio, 1.08; 95% confidence interval [CI], 0.85-1.36; P = .528), cancer-specific (hazard ratio, 1.12; 95% CI, 0.77-1.64; P = .542), or progression-free survival (hazard ratio, 1.03; 95% CI, 0.83-1.29; P = .783). Distant metastasis-free survival, freedom from locoregional failure, and freedom from local failure were also not significantly associated with the p16 status. CONCLUSIONS: p16 positivity is common but not prognostic in cHNSCC lymph node metastases. High-risk HPV subtypes are not associated with p16 positivity and do not appear to play a role in this disease. HPV testing, in addition to the p16 status in the unknown primary setting, may provide additional information for determining a putative primary site.
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    Unilateral Radiotherapy Treatment for p16/Human Papillomavirus-Positive Squamous Cell Carcinoma of Unknown Primary in the Head and Neck
    Tiong, A ; Rischin, D ; Young, RJ ; Herschtal, A ; Solomon, B ; D'Costa, I ; Fua, T ; Liu, C ; Coleman, A ; Kleid, S ; Dixon, BJ ; Corry, J (WILEY, 2018-09)
    OBJECTIVES/HYPOTHESIS: The outcomes of unilateral radiotherapy treatment for patients with p16/HPV-positive squamous cell carcinomas of unknown primary (SCCUP) affecting cervical lymph nodes are under-reported. Compared to radiating large volumes of the pharyngeal axis (the more common approach), this is potentially a much less toxic treatment for a good prognosis group. STUDY DESIGN: Retrospective cohort study. METHODS: We identified patients with SCCUP who were treated radically at our center and did not have parotid or isolated level IV or V nodal involvement. Failure-free and overall survivals were calculated using Kaplan-Meier methods. RESULTS: From 2004 to 2012, there were 49 radically treated patients with SCCUP. Fourteen patients had bilateral neck treatment (they had bilateral nodal disease or suspected lesions in the base of tongue, though not proven with biopsy), two had surgery alone, whereas 33 had unilateral radiotherapy (after neck dissection, excisional biopsy, or definitively with concurrent chemotherapy). Of the 33 patients, 21 tested positive to p16/HPV and had median follow-up of 57 months. In this group, no isolated contralateral neck failures or putative primaries emerged. There was 1/21 (4.3%) ipsilateral neck failure, 1/21 (4.3%) concurrent contralateral neck and distant failure, and 1/21 (4.3%) patient with distant failure. The 5-year freedom from failure was 78% (95% confidence interval [CI]: 56%-100%) and overall survival was 90% (95% CI: 79%-100%). CONCLUSIONS: With no emergence of putative primaries and no isolated contralateral neck failures, this single-institution experience in p16/HPV-positive SCCUP patients suggests that unilateral radiotherapy may be an underutilized management strategy. LEVELS OF EVIDENCE: 4 Laryngoscope, 128:2076-2083, 2018.
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    Suboptimal health literacy in patients with lung cancer or head and neck cancer
    Koay, K ; Schofield, P ; Gough, K ; Buchbinder, R ; Rischin, D ; Ball, D ; Corry, J ; Osborne, RH ; Jefford, M (SPRINGER, 2013-08)
    BACKGROUND: Health literacy is the capacity to seek, understand and utilise health information to make informed health decisions. Suboptimal health literacy has been linked to poor health outcomes. This study assessed health literacy in patients treated for head and neck or lung cancer and associations between health literacy and demographic factors and distress levels. METHODS: Consecutive English-speaking patients were approached at Peter MacCallum Cancer Centre. Face-to-face interviews were conducted. Health literacy was assessed using the Shortened Test of Functional Health Literacy in Adults (S-TOFHLA) and Health Literacy Management Scale (HeLMS). Distress was assessed by the Distress Thermometer. RESULTS: Response rate was 73 % (n = 93). Using S-TOFHLA, prevalence of inadequate and marginal health literacy was 5.4 and 6.5 % respectively, and both groups were associated with older age (p = 0.043) and low education level (p = 0.009). Specific assessment of S-TOFHLA revealed that 70 % could not interpret prescription labels. HeLMS reported that 17 % had health literacy difficulties. Low scores on domains of HeLMS were associated with lower education level (p < 0.05) but younger age (p < 0.05). Distress was not associated with S-TOFHLA scores but related to low scores in two domains of HeLMS (p < 0.05). CONCLUSION: Using two different measures, a substantial proportion of patients have poor health literacy abilities and may experience difficulties in accessing health services.
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    Quality of Life, Toxicity and Unmet Needs in Nasopharyngeal Cancer Survivors
    McDowell, L ; Corry, J ; Ringash, J ; Rischin, D (FRONTIERS MEDIA SA, 2020-06-12)
    Concerted research efforts over the last three decades have resulted in improved survival and outcomes for patients diagnosed with nasopharyngeal carcinoma (NPC). The evolution of radiotherapy techniques has facilitated improved dose delivery to target volumes while reducing dose to the surrounding normal tissue, improving both disease control and quality of life (QoL). In parallel, clinical trials focusing on determining the optimal systemic therapy to use in conjunction with radiotherapy have been largely successful, resulting in improved locoregional, and distant control. As a consequence, neoadjuvant chemotherapy (NACT) prior to definitive chemoradiotherapy has recently emerged as the preferred standard for patients with locally advanced NPC. Two of the major challenges in interpreting toxicity and QoL data from the published literature have been the reliance on: (1) clinician rather than patient reported outcomes; and (2) reporting statistical rather than clinical meaningful differences in measures. Despite the lower rates of toxicity that have been achieved with highly conformal radiotherapy techniques, survivors remain at moderate risk of persistent and long-lasting treatment effects, and the development of late radiation toxicities such as hearing loss, cranial neuropathies and cognitive impairment many years after successful treatment can herald a significant decline in QoL. Future approaches to reduce long-term toxicity will rely on: (1) identifying individual patients most likely to benefit from NACT; (2) development of response-adapted radiation strategies following NACT; and (3) anticipated further dose reductions to organs at risk with proton and particle therapy. With increasing numbers of survivors, many in the prime of their adult life, research to identify, and strategies to address the unmet needs of NPC survivors are required. This contemporary review will summarize our current knowledge of long-term toxicity, QoL and unmet needs of this survivorship group.
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    Frequency of Fibroblast Growth Factor Receptor 1 gene amplification in oral tongue squamous cell carcinomas and associations with clinical features and patient outcome
    YOUNG, RICHARD ; LIM, ANNETTE ; ANGEL, CHRISTOPHER ; COLLINS, MARNIE ; DEB, SIDDHARTHA ; CORRY, JUNE ; WIESENFELD, DAVID ; KLEID, STEPHEN ; SIGSTON, ELIZABETH ; SOLOMON, BENJAMIN ; RISCHIN, DANNY ; FOX, STEPHEN ; MCARTHUR, GRANT ; WRIGHT, GAVIN ; RUSSELL, PRUDENCE ; LYONS, BERNARD ( 2013)