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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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Several reports have suggested that radiotherapy after reconstructive surgery for head and neck cancer (HNC), could have deleterious effects on the flaps with respect to functional outcomes. To predict and prevent toxicities, flap delineation should be accurate and reproducible. The objective of the present study was to evaluate the interobserver variability of frequent types of flaps used in HNC, based on the recent GORTEC atlas. Materials and methods: Each member of an international working group (WG) consisting of 14 experts delineated the flaps on a CT set from six patients. Each patient had one of the five most commonly used flaps in HNC: a regional pedicled pectoralis major myocutaneous flap, a local pedicled rotational soft tissue facial artery musculo-mucosal (FAMM) (2 patients), a fasciocutaneous radial forearm free flap, a soft tissue anterolateral thigh (ALT) free flap, or a fibular free flap. The WG's contours were compared to a reference contour, validated by a surgeon and a radiologist specializing in HNC. Contours were considered as reproducible if the median Dice Similarity Coefficient (DSC) was > 0.7. Results: The median volumes of the six flaps delineated by the WG were close to the reference contour value, with approximately 50 cc for the pectoral, fibula, and ALT flaps, 20 cc for the radial forearm, and up to 10 cc for the FAMM. The volumetric ratio was thus close to the optimal value of 100% for all flaps. The median DSC obtained by the WG compared to the reference for the pectoralis flap, the FAMM, the radial forearm flap, ALT flap, and the fibular flap were 0.82, 0.40, 0.76, 0.81, and 0.76, respectively. Conclusions: This study showed that the delineation of four main flaps used for HNC was reproducible. The delineation of the FAMM, however, requires close cooperation between radiologist, surgeon and radiation oncologist because of the poor visibility of this flap on CT and its small size.

Purpose: Target delineation in nasopharyngeal carcinoma (NPC) often proves challenging because of the notoriously narrow therapeutic margin. High doses are needed to achieve optimal levels of tumour control, and dosimetric inadequacy remains one of the most important independent factors affecting treatment outcome., Method: A review of the available literature addressing the natural behaviour of NPC and correlation between clinical and pathological aspects of the disease was conducted. Existing international guidelines as well as published protocols specified by clinical trials on contouring of clinical target volumes (CTV) were compared. This information was then summarized into a preliminary draft guideline which was then circulated to international experts in the field for exchange of opinions and subsequent voting on areas with the greatest controversies., Results: Common areas of uncertainty and variation in practices among experts experienced in radiation therapy for NPC were elucidated. Iterative revisions were made based on extensive discussion and final voting on controversial areas by the expert panel, to formulate the recommendations on contouring of CTV based on optimal geometric expansion and anatomical editing for those structures with substantial risk of microscopic infiltration., Conclusion: Through this comprehensive review of available evidence and best practices at major institutions, as well as interactive exchange of vast experience by international experts, this set of consensus guidelines has been developed to provide a practical reference for appropriate contouring to ensure optimal target coverage. However, the final decision on the treatment volumes should be based on full consideration of individual patients' factors and facilities of an individual centre (including the quality of imaging methods and the precision of treatment delivery)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To investigate the tolerability and feasibility of induction gemcitabine and carboplatin chemotherapy followed by radiotherapy with concurrent cisplatin in patients with locally advanced nasopharyngeal carcinoma., Patients and Methods: Twenty-eight patients with previously untreated non-keratinising nasopharyngeal carcinoma, with stage IIb to IV disease were enroled to receive three cycles of carboplatin AUC 5 and gemcitabine 1 g/m(2) day 1 and 8 every 21-days, followed by 70 Gy of radiotherapy with concurrent cisplatin 20 mg/m(2)/day for 5 days of weeks 1, 4 and 7., Results: 26/28 (93.0%) patients received all three cycles of induction chemotherapy. All 27 patients who commenced chemoradiotherapy received 70 Gy in 35 fractions of radiotherapy with at least two cycles of concurrent cisplatin. The three-year time to locoregional failure rate was 92.9% (95% CI: 75.5-98.2%) and the three-year overall survival rate was 89.3% (95% CI: 71.6-96.5%). Induction chemotherapy was well tolerated with 5/28 (17.9%) patients experiencing grade 3 non-haematological toxicities and no reported episodes of febrile neutropenia or grade 4 toxicity. For the 27 patients who received radiotherapy, no acute grade 4 radiation toxicities and only 2/27 (7.4%) late grade 4 radiation adverse events were observed., Conclusion: The use of induction carboplatin and gemcitabine followed by chemoradiotherapy is feasible, with acceptable toxicity, and is a promising regimen for the treatment of locally advanced nasopharyngeal carcinoma., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: The purpose of this study was to assess whether ethnicity is an independent prognostic factor in patients with World Health Organization (WHO) type 2 or 3 nasopharyngeal carcinoma (NPC). Specifically, we examined the patterns of relapse observed in patients classified as "Asian" (born in southern China or southeast Asia) or "non-Asian" (born in Australia, Europe, the Middle East, or the Pacific Islands)., Methods and Materials: All patients planned for radical treatment at the Peter MacCallum Cancer Centre from April 1985 to December 1999 were included in this study. Pathology was reviewed to confirm WHO type 2 or 3 NPC. Patients were staged using the 1997 International Union Against Cancer (UICC) criteria. Mean potential follow-up time was 9.6 years (range, 1.0-18.5 years), Results: There were 158 patients: 86 Asian and 72 non-Asian. Stage groupings were: I--12 patients; II--32 patients; III--59 patients; and IV--55 patients. A staging computerized tomography was performed in 121 patients, and 53 (34%) also had a staging magnetic resonance imaging (MRI). The Asian patients had significantly more women, more patients aged <45, and more with performance status 0 than the non-Asians. Other putative prognostic factors were not significantly different between the groups. The 5-year rates for freedom from local recurrence (FLR), failure-free survival (FFS), and overall survival (OS) for Asian and non-Asian patients were 74% vs. 82%, 61% vs. 55%, and 75% vs. 63%, respectively. Corresponding 10-year figures were: 62% vs. 82%, 43% vs. 48%, and 58% vs. 49%, respectively. Multifactor analysis showed stage and the use of MRI for staging to be significant prognostic factors for all three endpoints. Age was also significant for FFS and OS. There were no significant differences in FFS or OS between Asian and non-Asian patients. However, the FLR interval was significantly worse in the Asian group (hazard ratio [HR], 2.37; 95% confidence interval [CI], 1.11-5.06), whereas duration of freedom from distant metastasis tended to be better (HR, 0.71; 95% CI, 0.33-1.53)., Conclusions: Although this study provides no evidence that race is an independent prognostic factor for overall survival in patients with WHO 2/3 NPC, it does suggest that relapse patterns may vary, with a higher rate of late primary failures (offset by a lower rate of distant failure) in the Asian population. Further confirmatory studies with larger patient cohorts are indicated.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an uncommon malignancy associated with poor prognosis. The optimal treatment approach for SNUC has not been established was performed., Methods: A retrospective review of all patients with SNUC seen at the Peter MacCallum Cancer Centre over a 12-year period., Results: Ten patients with SNUC were identified, with nine having locally advanced disease (T4). Seven were treated with three cycles of platinum and 5-fluorouracil followed by radiation with two cycles of concurrent platinum. In these seven patients, the 2-year progress on-free survival was 43% (95% CI, 11% to 82%) and 2-year overall survival was 64% (95% CI, 23% to 91%). One patient with a T1N0 nasal cavity tumor treated with radiation alone has not relapsed. Two patients who were treated with initial surgical resection, prior to referral to our institution, received postoperative radiation, but they subsequently had relapses and died., Conclusion: Induction chemotherapy followed by concurrent chemoradiation is promising treatment strategy for SNUC., (Copyright 2004 Wiley Periodicals, Inc. Head Neck 26: 435-441, 2004.)

Background: The purpose of this study was to evaluate the local control, pattern of recurrence, overall survival, and prognostic factors of patients with squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma of the paranasal sinuses (PNS) and nasal cavity (NC) presenting to our center for curative treatment over a 10-year period., Methods: Between 1991 and 2000, 60 patients with SCC (n = 32), adenocarcinoma (n = 25), and undifferentiated carcinoma (n = 3) of the PNS or NC were identified. Forty patients received surgery and postoperative radiotherapy, four surgery alone; 11, radiotherapy alone; three radical radiotherapy after surgical recurrence; one, chemoradiotherapy and surgery; and one, induction chemotherapy followed by radiotherapy., Results: Forty-seven patients (78%) were seen with T3-4 disease; however, most (92%) were node negative on initial assessment. The predominant failure pattern was local disease persistence or recurrence. The estimated 2- and 5-year local control rates were 63% and 49%, respectively. Orbital and neural invasion significantly affected local control. The estimated 2- and 5 year overall survival rates were 57% and 40%, respectively., Conclusions: Local failure remains the dominant cause for poor outcome in this group of patients. Because of the proximity of critical normal structures, the ability to perform adequate surgery and to deliver effective radiotherapy is limited in many cases. The use of postoperative concurrent chemoradiotherapy warrants further investigation., (Copyright 2004 Wiley Periodicals, Inc.)

Intensity-modulated radiotherapy (IMRT) has been available at Peter MaCallum Cancer Centre (PMCC) since November 2000. The present report illustrates two cases of our early experience with IMRT. Case 1 is a 66-year-old man with a T(1)N(2)M(0) nasopharyngeal carcinoma treated with chemo-radiotherapy using parotid-sparing IMRT. Fourteen months following treatment he remains in complete remission, with salivary function assessed using a xerostomia-specific quality of life questionnaire, having returned to near pretreatment levels by 12 months. Case 2 is a 70-year-old man with a T(4)N(0)M(0) base of tongue squamous cell carcinoma treated with chemo-radiotherapy after refusing radical surgery. He had received subtotal nodal irradiation to 36 Gy in 1994 for Hodgkins disease stage IIA. A radical dose was still achievable despite previous irradiation without exceeding unacceptable spinal cord dose with IMRT. He remains in complete remission 14 months from his initial presentation without evidence of neurological toxicity. Intensity-modulated radiotherapy allows sparing of critical normal structures in the head and neck without compromising dose to the tumour. It is, therefore, desirable for several clinical applications and essential in some, if unacceptable compromises are not to be made.

The purpose of this dosimetric study was to evaluate the effect of beam number and arrangement on the dose distribution with intensity-modulated radiation therapy in patients with nasopharyngeal cancer. Computed tomography data sets of seven patients who were treated for nasopharyngeal carcinoma at the Peter MacCallum Cancer Centre were used for the present dosimetric study. The dose planned was 70 Gy in 7 weeks for the gross nasopharyngeal and nodal disease and the biological equivalents of 60 Gy in 6 weeks for the high-risk and 50 Gy in 5 weeks for the low-risk nodal disease. A plan using seven fields was compared to that using nine fields in all patients. Plans were assessed on the dose to the planning target volume (PTV) and the degree of parotid sparing achieved by evaluating both dose-volume histograms (DVH) and axial slices. Seven fields (three anterior and four posterior) provide good PTV coverage and satisfactory parotid sparing in patients with localized nasopharyngeal lesions. Nine fields appear to be better for tumours with significant posterolateral parapharyngeal extension. Parotid sparing is consistently better with nine fields. Both DVH and axial slices need to be evaluated before accepting any plan.