Purpose To report the results of the Trans Tasman Radiation Oncology Group randomized phase III trial designed to determine whether the addition of concurrent chemotherapy to postoperative ...radiotherapy (CRT) improved locoregional control in patients with high-risk cutaneous squamous cell carcinoma of the head and neck. Patients and Methods The primary objective was to determine whether there was a difference in freedom from locoregional relapse (FFLRR) between 60 or 66 Gy (6 to 6.5 weeks) with or without weekly carboplatin (area under the curve 2) after resection of gross disease. Secondary efficacy objectives were to compare disease-free survival and overall survival. Results Three hundred twenty-one patients were randomly assigned, with 310 patients commencing allocated treatment (radiotherapy RT alone, n = 157; CRT, n = 153). Two hundred thirty-eight patients (77%) had high-risk nodal disease, 59 (19%) had high-risk primary or in-transit disease, and 13 (4%) had both. Median follow-up was 60 months. Median RT dose was 60 Gy, with 84% of patients randomly assigned to CRT completing six cycles of carboplatin. The 2- and 5-year FFLRR rates were 88% (95% CI, 83% to 93%) and 83% (95% CI, 77% to 90%), respectively, for RT and 89% (95% CI, 84% to 94%) and 87% (95% CI, 81% to 93%; hazard ratio, 0.84; 95% CI, 0.46 to 1.55; P = .58), respectively, for CRT. There were no significant differences in disease-free or overall survival. Locoregional failure was the most common site of first treatment failure, with isolated distant metastases as the first site of failure seen in 7% of both arms. Treatment was well tolerated in both arms, with no observed enhancement of RT toxicity with carboplatin. Grade 3 or 4 late toxicities were infrequent. Conclusion Although surgery and postoperative RT provided excellent FFLRR, there was no observed benefit with the addition of weekly carboplatin.
In regard to Duchesne et al Le, Hien V; Penniment, Michael G
International journal of radiation oncology, biology, physics,
2015-Jan-01, Letnik:
91, Številka:
1
Journal Article
To select one of two chemoradiotherapy regimens for locally advanced squamous cell carcinoma (SCC) of the head and neck as the experimental arm for the next Trans-Tasman Radiation Oncology Group ...phase III trial.
One hundred twenty-two previously untreated patients with stage III/IV SCC of the head and neck were randomized to receive definitive radiotherapy (70 Gy in 7 weeks) concurrently with either cisplatin (75 mg/m(2)) plus tirapazamine (290 mg/m(2)/d) on day 2 of weeks 1, 4, and 7, and tirapazamine alone (160 mg/m(2)/d) on days 1, 3, and 5 of weeks 2 and 3 (TPZ/CIS), or cisplatin (50 mg/m(2)) on day 1 and infusional fluorouracil (360 mg/m(2)/d) on days 1 through 5 of weeks 6 and 7 (chemoboost).
Three-year failure-free survival rates were 55% with TPZ/CIS (95% CI, 39% to 70%) and 44% with chemoboost (95% CI, 30% to 60%; log-rank P = .16). Three-year locoregional failure-free rates were 84% in the TPZ/CIS arm (95% CI, 71% to 92%) and 66% in the chemoboost arm (95% CI, 51% to 79%; P = .069). More febrile neutropenia and grade 3 or 4 late mucous membrane toxicity were observed with TPZ/CIS, while acute skin radiation reaction was more severe and prolonged with chemoboost. Compliance with protocol treatment was satisfactory on both arms.
Both regimens are feasible and are associated with significant but acceptable toxicity profiles in the cooperative group setting. Based on the promising efficacy seen in this trial, TPZ/CIS is being evaluated in a large phase III trial.
Abstract Background and purpose To investigate the hypothesis that primary tumor volume is prognostic independent of T and N stages in patients with non-small cell lung cancer (NSCLC) treated by ...definitive radiotherapy. Materials and methods Multicenter prospective observational study. Patient eligibility: pathologically proven stage I–III non-small cell lung cancer planned for definitive radiotherapy (minimum 50 Gy in 20 fractions) using CT-based contouring. Volumes of the primary tumor and enlarged nodes were measured according to a standardized protocol. Survival was adjusted for the effect of T and N stage. Results There were 509 eligible patients. Five-year survival rates for tumor volume grouped by quartiles were, for increasing tumor volume, 22%, 14%, 15% and 21%. Larger primary tumor volume was associated with shorter survival (HR = 1.060 (per doubling); 95% CI 1.01–1.12; P = 0.029). However, after adjusting for the effects of T and N stage, there was no evidence for an association (HR = 1.029, 95% CI, 0.96–1.10, P = 0.39). There was evidence, however, that larger primary tumor volume was associated with an increased risk of dying, independently of T and N stage, in the first 18 months but not beyond. Conclusions In patients treated by non-surgical means we were unable to show that lung tumor volume, overall, provides additional prognostic information beyond the T and N stage (TNM, 6th edition). There is evidence, however, that larger primary tumor volume adversely affects outcome only within the first 18 months. Larger tumor size alone should not by itself exclude patients from curative (chemo)radiotherapy.
One of the largest change operations to take place in South Australia was the moving of the Royal Adelaide Hospital (RAH) to its new site in 2017. Change can influence workplace effectiveness and ...staff satisfaction and morale. Understanding the stages of change, staff experience and carefully managing the process is important. This paper aims to describe the successful move of the radiation therapy department at the RAH to its new site, focusing on the staff experience and management strategies to ensure the success of the move. A four‐stage model of change was used to guide understand, manage and reflect upon the transition of the RAH radiation therapy department to a new site. Key change events and management strategies are described and aligned with the four stages of change. The move to the new site was a great success with a transition period working across two sites enabling a slower ramp up of activity at the new site supporting staff and patients in adjusting to the new environment. The four‐stage model of change assisted in the smooth implementation of a transition plan for radiation oncology. At the RAH, innovation and development are encouraged, along with management having a comprehensive understanding of organisational change enabling the radiation oncology department to successfully navigate rapid change.
One of the largest change operations to take place in South Australia was the moving of the Royal Adelaide Hospital (RAH) to its new site in 2017. Change can influence workplace effectiveness and staff satisfaction and morale. Understanding the stages of change staff experience and carefully managing the process is important. This paper aims to describe a change operation of moving a radiation therapy department to a new site with a focus on the change experience for staff.
A short course of radiotherapy is commonly prescribed for palliative relief of malignant dysphagia in patients with incurable oesophageal cancer. We compared chemoradiotherapy with radiotherapy alone ...for dysphagia relief in the palliative setting.
This multicentre randomised controlled trial included patients with advanced or metastatic oesophageal cancer who were randomly assigned (1:1) through a computer-generated adaptive biased coin design to either palliative chemoradiotherapy or radiotherapy alone for treatment of malignant dysphagia at 22 hospitals in Australia, Canada, New Zealand, and the UK. Eligible patients had biopsy-proven oesophageal cancer that was unsuitable for curative treatment, symptomatic dysphagia, Eastern Cooperative Oncology Group performance status 0-2, and adequate haematological and renal function. Patients were stratified by hospital, dysphagia score (Mellow scale 1-4), and presence of metastases. The radiotherapy dose was 35 Gy in 15 fractions over 3 weeks for patients in Australia and New Zealand and 30 Gy in ten fractions over 2 weeks for patients in Canada and the UK. Chemotherapy consisted of one cycle of intravenous cisplatin (either 80 mg/m
on day 1 or 20 mg/m
per day on days 1-4 of radiotherapy at clinician's discretion) and intravenous fluorouracil 800 mg/m
per day on days 1-4 of radiotherapy in week 1. Patients were assessed weekly during treatment. The primary endpoint was dysphagia relief (defined as ≥1 point reduction on the Mellow scale at 9 weeks and maintained 4 weeks later), and key secondary endpoints were dysphagia progression-free survival (defined as a worsening of at least 1 point on the Mellow scale from baseline or best response) and overall survival. These endpoints were analysed in the intention-to-treat population. This study is registered at ClinicalTrials.gov, number NCT00193882. This trial is closed.
Between July 7, 2003, and March 21, 2012, 111 patients were randomly assigned to chemoradiotherapy and 109 patients to radiotherapy. One patient in the chemoradiotherapy group was omitted from analysis because of ineligibility. 50 (45%, 95% CI 36-55) patients in the chemoradiotherapy group and 38 (35%, 26-44) in the radiotherapy group obtained dysphagia relief (difference 10·6%, 95% CI -2 to 23; p=0·13). Median dysphagia progression-free survival was 4·1 months (95% CI 3·5-4·8) versus 3·4 months (3·1-4·3) in the chemoradiotherapy and radiotherapy groups, respectively (p=0·58), and median overall survival was 6·9 months (95% CI 5·1-8·3) versus 6·7 months (4·9-8·0), respectively (p=0·88). Of the 211 patients who commenced radiotherapy, grade 3-4 acute toxicity occurred in 38 (36%) patients in the chemoradiotherapy group and in 17 (16%) patients in the radiotherapy group (p=0·0017). Anaemia, thrombocytopenia, neutropenia, oesophagitis, diarrhoea, nausea and vomiting, and mucositis were significantly worse in patients who had chemoradiotherapy than in patients who had radiotherapy.
Palliative chemoradiotherapy showed a modest, but not statistically significant, increase in dysphagia relief compared with radiotherapy alone, with minimal improvement in dysphagia progression-free survival and overall survival with chemoradiotherapy but at a cost of increased toxicity. A short course of radiotherapy alone should be considered a safe and well tolerated treatment for malignant dysphagia in the palliative setting.
National Health and Medical Research Council, Canadian Cancer Society Research Institute, Canadian Cancer Trials Group, Trans Tasman Radiation Oncology Group, and Cancer Australia.
To assess the impact of domicile-based humidification on symptom burden during radiation therapy (RT) for head-and-neck (H&N) cancer.
From June 2007 through June 2011, 210 patients with H&N cancer ...receiving RT were randomized to either a control arm or to receive humidification using the Fisher & Paykel Healthcare MR880 humidifier. Humidification commenced on day 1 of RT and continued until Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, clinical mucositis (CMuc) grade ≤1 occurred. Forty-three patients (42%) met a defined benchmark for humidification compliance and contributed to per protocol (PP) analysis. Acute toxicities, hospitalizations, and feeding tube events were recorded prospectively. The McMaster University Head and Neck Radiotherapy Questionnaire (HNRQ) was used for patient-reported outcomes. The primary endpoint was area under the curve (AUC) for CMuc grade ≥2.
There were no significant differences in AUC for CMuc ≥2 between the 2 arms. Humidification patients had significantly fewer days in hospital (P=.017). In compliant PP patients, the AUC for CTCAE functional mucositis score (FMuc) ≥2 was significantly reduced (P=.009), and the proportion who never required a feeding tube was significantly greater (P=.04). HNRQ PP analysis estimates also in the direction favoring humidification with less symptom severity, although differences at most time points did not reach significance.
TROG 07.03 has provided efficacy signals consistent with a role for humidification in reducing symptom burden from mucositis, but the influence of humidification compliance on the results moderates recommendations regarding its practical utility.
Purpose: We performed a randomized trial to compare the GI and urogenital toxicity of radiotherapy (RT) for localized (confined to the organ), early-stage (T1-T2N0M0, TNM classification) carcinoma of ...the prostate, using a conventional (64 Gy in 32 fractions within 6.5 weeks) vs. a hypofractionated (55 Gy in 20 fractions within 4 weeks) schedule and to determine the efficacy of the respective treatment schedules.
Methods and Materials: This report is based on an interim analysis of the first 120 consecutive patients in this Phase III trial after a median follow-up of 43.5 months (range 23–62). RT planning was based on two-dimensional CT data, and the treatment was delivered using a three- or four-field 6–23-MV photon technique. GI and urogenital toxicity (symptom questionnaires incorporating the subjective elements of the late effects of normal tissues—subjective, objective, management, analytic classification of late effects and the European Organization for Research and Treatment of Cancer sexual function questionnaire) were evaluated before RT and 1 month, 1 year, and 2 years after RT completion. The efficacy of RT was assessed clinically (digital rectal examination and radiologic imaging) and biochemically (prostate-specific antigen assay) at baseline, and every 3 months for 2 years after RT and every 6 months subsequently.
Results: RT, whether conventional or hypofractionated, resulted in an increase in all six symptom categories used to characterize GI toxicity and in four of five symptom categories used to document urinary morbidity 1 month after therapy completion. Sexual dysfunction (based on limited data), which existed in more than one-third of patients before RT, also increased to just more than one-half of patients 1 month after RT. The increase in urinary toxicity after RT was not sustained (diurnal urinary frequency had decreased significantly at 2 years). In contrast, all six symptom categories of GI toxicity remained increased 1 year after RT. Four of the six GI symptom categories (rectal pain, mucous discharge, urgency of defecation, and rectal bleeding) were still increased at 2 years compared with baseline. Except for a slightly greater percentage of patients experiencing mild rectal bleeding at 2 years among those who received hypofractionated RT, no differences were noted in toxicity between the conventional and hypofractionated RT schedule. The mean prostate-specific antigen level was 14.0 ± 1.0 ng/mL at baseline and declined to a nadir of 1.3 ± 0.2 ng/mL at a median of 16.8 months (range 0.8–28.3) after RT completion. However, it then rose in 17 patients (8 in the hypofractionated and 9 in the conventional treatment group). Only 8 of these 17 patients were found to have signs of clinical relapse (5 local, 1 regional lymph node, and 2 systemic bony metastases) after histopathologic and radiologic reassessment). The remaining 9 patients had biochemical relapse only (defined as three consecutive rises in prostate-specific antigen after nadir). The 4-year biochemical relapse-free survival rate was 85.8% for all patients and did not differ significantly between the two radiation dose schedules (86.2% for the hypofractionated and 85.5% for the conventional fractionation group).
Conclusion: RT for prostate carcinoma, using a three- or four-field 6–23-MV photon technique without posterior shielding of the lateral fields, is an underestimated cause of persistent GI morbidity. The incidence of clinically significant GI and urogenital toxicity after conventional and hypofractionated RT appears to be similar. Hypofractionated RT for carcinoma of the prostate seems just as effective as conventional RT after a median follow-up approaching 4 years.
Abstract only
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Background: RT relieves dysphagia of advanced oesophageal cancer, without data from randomised phase III trials determining response, toxicity, or role of palliative CRT. Aims (1) to ...establish effective and least toxic treatment for symptom relief (2) determine effects of common cancer treatments on QoL (3) establish an evidence base for patient decision making. Methods: 220 patients were randomised to receive a course of palliative RT 35 Gy in 15 fractions, (n=115) or 30 Gy in 10 fractions (n=105) in Canada and UK, or concomitant CRT with Cisplatin and 5FU (D1-4) (n=111). Dysphagia measured using the Mellow score, toxicity using CTCAE v2, and QoL using EORTC QLQ30, oesophagus module (OES-18). The primary end point was proportion of patients with improved dysphagia measured at week 9 maintained until week 13. Results: Radiotherapy alone showed a dysphagia response (at any point) of 68% compared to CMT 74%, not a significant difference (p=0.343). the primary endpoint of maintained swallowing improvement was achieved in 41% with RT, 47% CMT again not statistically significant(p=0.4163).There was increased toxicity in patients receiving CRT, (nausea (p=0.0019) and vomiting (p=0.0072)). Median survival was 210 days for CRT, 203 days for RT. Although the results of the trial showed equally poor survival prognosis in both arms, there were some patients (n=21) still alive at 2 years post treatment.Quality of life analysis showed no statistical difference between arms. 17 patients in the RT alone arm ultimately received chemotherapy for specific palliative endpoints, thus 92 patients did not require chemotherapy. Conclusions: Although the CRT group had slightly better dysphagia response and median survival, the bowel toxicity was worse. Nearly 10% of patients were alive at 2 years indicating this is a group of patients who should not be denied active cancer treatment, but it should be tailored to offer maximum symptom relief minimising treatment toxicity. This multicentre trial, conducted in the UK, Canada, Australia, and New Zealand reflects practice in several countries. Clinical trial information: ACTRN12606000526572.
Introduction
There is a perception that Indigenous patients are less likely to attend radiotherapy treatment. This study sought to determine if a difference in radiotherapy treatment compliance rates ...exists between Indigenous and non‐Indigenous patients. Secondly, we aimed to ascertain which patient, disease and treatment factors affect compliance in Indigenous patients.
Methods
All patients treated with radiotherapy at the Alan Walker Cancer Care Centre between March and October 2010 were analysed. Data regarding compliance rates (defined as those who chose and completed the recommended course of treatment), patient, disease and treatment factors were collected, and chi‐squared and Fisher's exact tests were applied.
Results
A total of 41 courses were delivered to Indigenous patients and 224 courses delivered to non‐Indigenous patients in this period. There was no difference in compliance between Indigenous and non‐Indigenous patients (83% vs. 81%, P = 0.75). Of the factors assessed, it was found that there was an association between toxicity grade and compliance (P = 0.048).
Conclusions
From this cohort, we cannot support the perception that Indigenous patients have overall poorer compliance with recommended radiation treatment courses. In this study, the only factor which correlated significantly with compliance was toxicity grade. It is felt that a number of factors, which negatively impact on compliance, can potentially be counteracted by a culturally sensitive model of care.
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