Abstract Aims To update previous meta-analyses of randomised palliative radiotherapy trials comparing single fractions versus multiple fractions. Materials and methods All published randomised controlled trials comparing single fraction versus multiple fraction schedules for the palliation of uncomplicated bone metastases were included in this analysis. Odds ratios and 95% confidence intervals were calculated for each trial. Forest plots were created using a random effects model and the Mantel–Haenszel statistic. Results In total, 25 randomised controlled trials were identified. For intention-to-treat patients, the overall response rate was similar in patients receiving single fractions (1696 of 2818; 60%) and multiple fractions (1711 of 2799; 61%). Complete response rates were 620 of 2641 (23%) in the single fraction arm and 634 of 2622 (24%) in the multiple fraction arm. No significant difference was seen in overall or complete response rates. Pathological fracture did not favour either arm, but spinal cord compression trended towards favouring multiple fractions; however, neither was statistically significant ( P = 0.72 and P = 0.13, respectively). Retreatment rates favoured patients in the multiple fraction arm, where the likelihood of requiring re-irradiation was 2.6-fold greater in the single fraction arm (95% confidence interval: 1.92–3.47; P < 0.00001). Repeated analyses excluding drop-out patients did not alter these findings. In general, no significant differences in acute toxicities were seen. Conclusion Overall and complete response rates were similar in both intention-to-treat and assessable patients. Single and multiple fraction regimens provided equal pain relief; however, significantly higher retreatment rates occurred in those receiving single fractions.
Abstract The Chernobyl Forum Report from the 20th anniversary of the Chernobyl nuclear power plant disaster concluded that mental health effects were the most significant public health consequence of the accident. This paper provides an updated review of research on the psychological impact of the accident during the 25 year period since the catastrophe began. First responders and clean-up workers had the greatest exposure to radiation. Recent studies show that their rates of depression and post-traumatic stress disorder remain elevated two decades later. Very young children and those in utero who lived near the plant when it exploded or in severely contaminated areas have been the subject of considerable research, but the findings are inconsistent. Recent studies of prenatally exposed children conducted in Kiev, Norway and Finland point to specific neuropsychological and psychological impairments associated with radiation exposure, whereas other studies found no significant cognitive or mental health effects in exposed children grown up. General population studies report increased rates of poor self-rated health as well as clinical and subclinical depression, anxiety, and post-traumatic stress disorder. Mothers of young children exposed to the disaster remain a high-risk group for these conditions, primarily due to lingering worries about the adverse health effects on their families. Thus, long-term mental health consequences continue to be a concern. The unmet need for mental health care in affected regions remains an important public health challenge 25 years later. Future research is needed that combines physical and mental health outcome measures to complete the clinical picture.
Abstract Twenty-five years have passed since radioactive releases from the Chernobyl nuclear accident led to the exposure of millions of people in Europe. Studies of affected populations have provided important new data on the links between radiation and cancer—particularly the risk of thyroid tumours from exposure to iodine isotopes—that are important not only for a fuller scientific understanding of radiation effects, but also for radiation protection. It is now well documented that children and adolescents exposed to radioiodines from Chernobyl fallout have a sizeable dose-related increase in thyroid cancer, with the risk greatest in those youngest at exposure and with a suggestion that deficiency in stable iodine may increase the risk. Data on thyroid cancer risks to other age groups are somewhat less definitive. In addition, there have been reported increases in incidence and mortality from non-thyroid cancers and non-cancer end points. Although some studies are difficult to interpret because of methodological limitations, recent investigations of Chernobyl clean-up workers (‘liquidators’) have provided evidence of increased risks of leukaemia and other haematological malignancies and of cataracts, and suggestions of an increase in the risk of cardiovascular diseases, following low doses and low dose rates of radiation. Further careful follow-up of these populations, including the establishment and long-term support of life-span study cohorts, could provide additional important information for the quantification of radiation risks and the protection of persons exposed to low doses of radiation.
Abstract Aims To analyse the outcomes and to evaluate the prognostic factors involved in the re-irradiation of locally recurrent nasopharyngeal carcinoma (NPC) using intensity-modulated radiotherapy (IMRT). Materials and methods A retrospective analysis of 239 NPC patients with local recurrence who were re-irradiated with IMRT between 2001 and 2008 was conducted. The distribution of disease re-staging was 5.4% for stage I, 18.4% for stage II, 29.7% for stage III and 46.4% for stage IV. Cisplatin-based chemotherapy was administered to 117 patients (49.0%) in addition to the IMRT. Results The mean D95 and the V95 of the gross tumour volume (GTV) were 66.78 Gy and 98.61%, respectively. The mean dose to the GTV was 70.04 Gy (61.73–77.54 Gy). The 5 year overall survival, local recurrence-free survival, distant metastasis-free survival and disease-free survival were 44.9, 85.8, 80.6 and 45.4%, respectively. In a univariate analysis, patient age, recurrent T (rT), recurrent N (rN), recurrent stage, tumour volume, mean dose and mean fractional dose of the GTV were significant prognostic factors for overall survival. In a multivariate analysis, only patient age, rN stage, recurrent stage, mean fractional dose and tumour volume remained significant for overall survival. Conclusions Re-irradiation using IMRT is available to improve local tumour control and to prolong patients’ survival. A smaller tumour volume, higher fractional dose, younger patient ages, lower rN0 stage and early recurrent stage are all independent prognostic factors for overall survival of recurrent NPC. It is of clinical importance to select the appropriate recurrent NPC cases for salvage re-irradiation by IMRT.
Abstract In 2008, the worldwide estimated age-standardised incidence rates for thyroid cancer incidence were 4.7 and 1.5 per 100 000 women and men, respectively. Thyroid cancer’s overall contribution to the worldwide cancer burden is relatively small, but incidence rates have increased over the last three decades throughout the world. This trend has been hypothesised to reflect a combination of technological advances enabling increased detection, but also changes in environmental factors, including population exposure to ionising radiation from fallout, diagnostic tests and treatment for benign and malignant conditions. Studies of the atomic bomb survivors and populations treated with radiotherapy have established radiation as a risk factor for thyroid cancer, particularly from early life exposure. About 0.62 mSv (20%) of the global annual per caput effective radiation dose comes from diagnostic medical and dental radiation for the period of 1997–2007, increased from 0.4 mSv for the years 1991–1996. This international trend of increasing population exposure to medical diagnostic sources of radiation, attributed in large part to the growing use of computed tomography scans, but also interventional radiology procedures, has raised concerns about exposure to radiosensitive organs such as the thyroid. Worldwide, medical and dental X-rays constitute the most common type of diagnostic medical exposures, but their contribution to the cumulative effective dose is relatively low, whereas computed tomography scans account for 7.9% of diagnostic radiology examinations but 47% of the collective effective dose from diagnostic radiation procedures in parts of the world. Although the radiation exposure from computed tomography scans is substantially lower than that from radiotherapy, multiple computed tomography scans could result in non-trivial cumulative doses to the thyroid. Studies are currently underway to assess the incidence of cancer in large cohorts of children who received computed tomography scans. National and international efforts have been developed to raise awareness and to standardise procedures for use of computed tomography and interventional radiology procedures in paediatric and general populations.
Abstract The triple-negative class (oestrogen receptor-negative, progesterone receptor-negative and human epidermal growth factor receptor 2 [HER2]-negative) comprises about 15% of breast cancer. It is associated with a poor prognosis compared with tumours that are positive for hormone receptors or HER2. Despite being sensitive to chemotherapy, many women with metastatic triple-negative breast cancer (TNBC) relapse quickly, and commonly develop visceral metastasis, including lung, liver and brain metastasis. TNBC has molecular features that overlap with breast cancer in BRCA1 germline mutation carriers and with those of the basal-like molecular class of tumours. Furthermore, tumours with the triple-negative phenotype have specific features and express markers that are potential therapeutic targets, for example an impaired DNA repair mechanism and increased expression of proliferation and basal-associated markers. The presence of these features has important implications for clinical practice and for the design of clinical trials looking at novel therapies. Targeted agents that are currently being investigated include poly (ADP-ribose) polymerase inhibitors, epidermal growth factor receptor inhibitors and anti-angiogenic compounds. Here we discuss the epidemiology, morphological and molecular spectrum of TNBC, the clinical significance of this important class of breast cancer and the current treatment options.
Abstract The accident at the Chernobyl nuclear power plant was the worst industrial accident of the last century that involved radiation. The unprecedented release of multiple different radioisotopes led to radioactive contamination of large areas surrounding the accident site. The exposure of the residents of these areas was varied and therefore the consequences for health and radioecology could not be reliably estimated quickly. Even though some studies have now been ongoing for 25 years and have provided a better understanding of the situation, these are yet neither complete nor comprehensive enough to determine the long-term risk. A true assessment can only be provided after following the observed population for their natural lifespan. Here we review the technical aspects of the accident and provide relevant information on radioactive releases that resulted in exposure of this large population to radiation. A number of different groups of people were exposed to radiation: workers involved in the initial clean-up response, and members of the general population who were either evacuated from the settlements in the Chernobyl nuclear power plant vicinity shortly after the accident, or continued to live in the affected territories of Belarus, Russia and Ukraine. Through domestic efforts and extensive international co-operation, essential information on radiation dose and health status for this population has been collected. This has permitted the identification of high-risk groups and the use of more specialised means of collecting information, diagnosis, treatment and follow-up. Because radiation-associated thyroid cancer is one of the major health consequences of the Chernobyl accident, a particular emphasis is placed on this malignancy. The initial epidemiological studies are reviewed, as are the most significant studies and/or aid programmes in the three affected countries.
Abstract Aims A variety of dosimetric parameters have been shown to influence the incidence of late radiation toxicity. The effect of other treatment- and patient-related factors is less well established. The aim of this study was to elucidate the influence of such factors in the development of late symptoms after radical radiotherapy to the prostate. Materials and methods Patient- and treatment-related factors that are thought to influence the development of late toxicity were analysed in 788 patients who had received radical radiotherapy to the prostate in the Medical Research Council RT01 trial. Late toxicity data were recorded using the Radiation Therapy Oncology Group, Late Effects of Normal Tissues/Subjective, Objective, Management, Analytic, Royal Marsden Hospital and the University of California, Los Angeles, Prostate Cancer Index. Acute toxicity was measured using the Radiation Therapy Oncology Group grading system. Results On multivariate analysis, acute bowel toxicity was statistically significantly associated with increased proctitis (hazard ratio = 1.63, 95% confidence interval 1.18, 2.24; P = 0.003) and increased stool frequency (hazard ratio = 1.77, 95% confidence interval 1.27, 2.46; P = 0.001). Hypertension was strongly associated with a decreased risk of poor urinary stream (hazard ratio = 0.25, 95% confidence interval 0.09, 0.71; P = 0.009). There was an increased risk of rectal bleeding with increased age (hazard ratio = 1.04 per year of age, 95% confidence interval 1.01, 1.08; P = 0.009). As expected, a higher prescribed dose increased the risk of several late toxicity end points. Although acute bladder toxicity was associated with the presence of bladder symptoms at 5 years, the effect disappeared for all symptoms except increased urinary frequency and haematuria when a change in bladder function from baseline was calculated. Patients with any pretreatment bladder symptoms were more likely to report increased urinary frequency (hazard ratio = 2.09, 95% confidence interval 1.48, 2.95; P < 0.0005), increased urinary incontinence (hazard ratio = 4.22, 95% confidence interval 2.13, 8.35; P < 0.0005) and decreased stream (hazard ratio = 2.64, 95% confidence interval 1.62, 4.31; P < 0.0005), after treatment and before the most recent follow-up assessment. Conclusions In this study, increased acute gastrointestinal and bladder symptoms and prescribed dose were associated with increased late radiation toxicity. The presence of hypertension seemed to be protective for the development of late effects. Baseline symptoms should be taken into account when radiation toxicity is analysed.
Abstract Aims A retrospective analysis was carried out of 291 cases of oesophageal cancer treated with definitive chemoradiotherapy (dCRT) at a single UK cancer centre between 1995 and 2009. Our protocol consisted of two cycles of neoadjuvant platinum-based chemotherapy followed by two further cycles given concurrently with 50 Gy of external beam radiotherapy delivered in 25 fractions over 5 weeks. Materials and methods Demographic, patient and outcome data were recorded prospectively through an electronic health record and retrospectively analysed, using appropriate statistical tools. Results Data on 266 patients were available for analysis. The median age was 66.6 years, 53% were adenocarcinomas. dCRT was used instead of surgery because of age/co-morbidity in 44% and disease extent in 39%. Ninety-three per cent of patients completed treatment according to protocol. Grade 3 and 4 toxicities were seen in 42 and 7%, respectively. Median survival was 20.6 months; 2, 3 and 5 year survival rates were 43.6, 32.9 and 19.5%, respectively. Advanced disease was associated with a worse outcome. Shorter disease length was associated with a better median survival, but some patients with disease >10 cm had long-term disease control. The effect of other patient- and disease-related factors was also analysed. Conclusion We present data showing that dCRT is well tolerated and should be considered as an alternative to surgery for all patients with locally advanced oesophageal cancer, not only those with co-morbidity. Furthermore, the benefits of dCRT are not confined to carcinomas with squamous histology.
Abstract Aims To correlate the pre-treatment plasma Epstein–Barr virus (EBV) DNA with tumour burden and to explore the prognostic implications of pre- and post-treatment plasma EBV DNA load in nasopharyngeal carcinoma patients treated with radiotherapy. Materials and methods Plasma EBV DNA load was measured using a real-time quantitative polymerase chain reaction assay in 69 patients with nasopharyngeal carcinoma before and after radiation treatment and correlated with tumour volume and treatment outcome. Tumour volume was calculated by multiplying the sum of the areas of gross extent of the primary tumour and regional lymph nodes shown by computed tomography images and/or magnetic resonance imaging. Prognostic models for distant metastasis and overall survival were constructed using a multivariable fractional polynomial algorithm. Results The pre-treatment plasma EBV DNA concentration was significantly associated with tumour volume (Spearman correlation coefficient, 0.61; P < 0.001). The multivariable fractional polynomial algorithm selected post-treatment EBV DNA and administration of chemotherapy as prognostic factors for distant metastasis ( P < 0.001, P = 0.021, respectively), as well as for overall survival ( P < 0.001, P = 0.018, respectively). Conclusions Pre- and post-treatment plasma EBV DNA load have important clinical significance. Pre-treatment plasma EBV DNA concentration reflects tumour burden, whereas clearance of circulating plasma EBV DNA after treatment predicts the risk of distant metastasis and overall survival.
Abstract Aims To compare the performance of volumetric-modulated arc radiotherapy (VMAT) by dual arc with fixed beam intensity-modulated radiotherapies (IMRTs) and single arc VMAT on nasopharyngeal carcinomas (NPC). Materials and methods Twenty NPC cases were re-planned using the planning system of the Pinnacle3® SmartArc (SA) module to compare the performance of the following four techniques: seven-field (7F) and 18-field (18F) fixed beam IMRT, and single (SA1 ) and dual arc VMAT (SA2 ). The plan was delivered on an Elekta Synergy™ Linac equipped with an 80-leaf 1 cm multileaf collimator. Three dose levels of planning target volumes (PTVs) with 70/59.4/54.0 Gy in 33 fractions were prescribed and delivered as a simultaneous integrated boost. The conformity index and homogeneity index of the PTVs, the comprehensive quality index (CQI), the normal tissue complication probability for the organs at risk (OARs), and the planning time, delivery efficiency and accuracy were analysed. Results A significantly inferior conformity index at the three dose levels of PTV and homogeneity index of PTV70 were observed in SA1 compared with the other techniques. Comparable conformity index and homogeneity index of the PTV were observed among 7F/18F IMRT and SA2 . Based on the CQI of the 11 OARs, the most efficient dose reduction was observed in 18F IMRT followed in order by SA2 , 7F IMRT and SA1 . The planning time was on average 13.2/24.9/40.1/42.8 min for 7F/18F IMRT/SA1 /SA2 , respectively. With regards to the delivery efficiency compared with 7F IMRT, a 51 and 41% reduction in delivery time was achieved by SA1 and SA2 , respectively. All techniques presented a high quality assurance pass rate (>98%) of the Γ3mm,3% criterion. Conclusion In NPC cases, SA2 gave superior results in terms of PTV coverage and OAR sparing compared with SA1 and approached the performance achieved by 18F IMRT, but without sacrificing the delivery efficiency.
Abstract Neuroendocrine tumours (NETs) are a genetically diverse group of malignancies that sometimes produce peptides causing characteristic hormonal syndromes. NETs can be clinically symptomatic (functioning) or silent (non-functioning); both types frequently synthesise more than one peptide, although often these are not associated with specific syndromes. Based on data from various sources, the incidence and prevalence of NETs is increasing. The primary treatment goal for patients with NETs is curative, with symptom control and the limitation of tumour progression as secondary goals. Surgery is the only possible curative approach and so represents the traditional first-line therapy. However, as most patients with NETs are diagnosed once metastases have occurred, curative surgery is generally not possible. Patients therefore require chronic postoperative medical management with the aim of relieving symptoms and, in recent years, suppressing tumour growth and spread. Somatostatin analogues, such as octreotide long-acting repeatable (LAR), can improve the symptoms of carcinoid syndrome and stabilise tumour growth in many patients. Results from the PROMID study show that octreotide LAR 30 mg is an effective antiproliferative treatment in patients with newly diagnosed, functionally active or inactive, well-differentiated metastatic midgut NETs. An antiproliferative effect can also be achieved with everolimus, and combination therapy with octreotide LAR has shown synergistic antiproliferative activity. In the future, pasireotide, the multi-receptor targeted somatostatin analogue, has the potential to be an effective therapy for de novo or octreotide-refractory carcinoid syndrome and for inhibiting tumour cell proliferation. Peptide receptor radiotherapy with yttrium-DOTATOC or lutetium-DOTATE is also a new interesting treatment option for NETs.
Abstract High-intensity focused ultrasound (HIFU) has recently been promoted as a non-invasive treatment option for prostate cancer. This systematic review sought to evaluate the evidence comparing it with standard treatment in patients with localised prostate cancer. The literature review included searches of MEDLINE, EMBASE, the Cochrane Library, annual meetings’ abstracts and websites of evidence-based practice guideline producers. Studies were included if they were randomised controlled trials comparing HIFU with current management approaches, or were meta-analyses, systematic reviews or practice guidelines addressing HIFU. No randomised controlled trials or meta-analyses were identified. Seven systematic reviews and two practice guidelines were identified; neither contained randomised controlled trials. Adjusting the selection criteria to include case series found 34 clinical studies of HIFU. Twenty-nine evaluated HIFU as the primary treatment and five examined HIFU as salvage treatment for recurrence after radiotherapy. In most studies the outcomes used to determine efficacy were negative biopsy rates or prostate-specific antigen (PSA) levels. Among the 29 studies of HIFU as the primary treatment, negative biopsy rates ranged from 35 to 95% in 21 studies, a PSA nadir of ≤0.5 ng/ml ranged from 55 to 91% in 10 studies and mean PSA nadirs ranged from 0 to 1.9 ng/ml in 17 studies. Five studies reported 5-year disease-free survival rates ranging from 55 to 95%. Among five studies of HIFU as salvage treatment, negative biopsy rates ranged from 73 to 84% in four studies, a PSA nadir of ≤0.5 ng/ml ranged from 57 to 66% in three studies and mean PSA nadirs were 1.97 and 2.38 ng/ml in two studies, respectively. Current evidence on HIFU use in prostate cancer patients is of low quality, rendering it difficult to draw conclusions about its efficacy. Until results from case series are confirmed in prospective studies, the widespread use of HIFU is not supported.
Abstract The purpose of this systematic review was to investigate the effects of therapeutic radiopharmaceuticals in patients with different types of advanced neuroendocrine tumour (NETs). A literature search was carried out in MEDLINE and EMBASE from January 1998 to November 2010. The Cochrane Library (to Issue 10, 2010) and the Standards and Guidelines Evidence Inventory of Cancer Guidelines, including over 1100 English-language cancer guidelines from January 2003 to June 2010, were also checked. No existing systematic reviews or clinical practice guidelines based on a systematic review or randomised controlled trials focusing on this topic were found. Twenty-four fully published articles were abstracted and summarised: 16 articles focused on five peptide receptor radionuclide therapy (111 In-DTPAOC,90 Y-DOTALAN,90 Y-DOTATOC,90 Y-DOTATATE, and177 Lu-DOTATATE) and eight focused on131 I-MIBG treatment. Limited evidence from a historical comparison of studies in one centre supported that177 Lu-DOTATATE might be associated with greater clinical outcomes compared with90 Y-DOTATOC or111 In-DTPAOC. The severe toxicities for177 Lu-DOTATATE included hepatic insufficiency in 0.6%, myelodysplastic syndrome in 0.8% and renal insufficiency in 0.4% of patients in this study. Insufficient evidence suggested efficacy of131 I-MIBG in adult NET patients, but the overall tumour response rate from131 I-MIBG was 27–75% for malignant neuroblastoma, paraganglioma or pheochromocytoma. Haematological toxicities were the main severe side-effects after131 I-MIBG and 4% of patients developed secondary malignancies in one study. To date, peptide receptor radionuclide therapy seems to be an acceptable option and is relatively safe in adult advanced NET patients with receptor uptake positive on scintigraphy, but patients’ renal function must be monitored.131 I-MIBG may be effective for malignant neuroblastoma, paraganglioma or pheochromocytoma, but its side-effects need to be considered. No strong evidence exists to support that one therapeutic radiopharmaceutical is more effective than others. Well-designed and good-quality randomised controlled trials are required on this research topic.
Abstract Aims The effect of patient- and treatment-related factors in the development of late normal tissue toxicity after radiotherapy is not yet fully established. The aim of this study was to elucidate the relative importance of such factors in the development of late toxicity after breast-conserving surgery and adjuvant breast radiotherapy. Materials and methods Patient- and treatment-related factors were analysed in 1014 patients who had received adjuvant radiotherapy to the breast in the Cambridge Breast Intensity-modulated Radiotherapy (IMRT) Trial. Late toxicity data were collected using photographic and clinical assessments and patient-reported questionnaires at 2 years after radiotherapy. Results On multivariate analysis, a larger breast volume was statistically significantly associated with the development of breast shrinkage assessed by serial photographs (odds ratio per litre increase in breast volume = 1.98, 95% confidence interval 1.41, 2.78; P < 0.0005), telangiectasia (odds ratio = 3.94, 95% confidence interval 2.49, 6.24; P < 0.0005), breast oedema (odds ratio = 3.65, 95% confidence interval 2.54, 5.24; P < 0.0005) and pigmentation (odds ratio = 1.75, 95% confidence interval 1.21, 2.51; P = 0.003). Current smokers had an increased risk of developing pigmentation (odds ratio = 2.09, 95% confidence interval 1.23, 3.54; P = 0.006). Patients with a moderate or poor post-surgical cosmesis had a greatly increased risk of moderate or poor overall cosmesis (odds ratio = 38.19; 95% confidence interval 21.9, 66.7; P < 0.0005). Postoperative infection requiring antibiotics was associated with increased risk of telangiectasia (odds ratio = 3.39, 95% confidence interval 1.94, 5.91; P < 0.0005) and breast oversensitivity (odds ratio = 1.78, 95% confidence interval 1.27, 2.49; P = 0.001). Conclusions In this study, the greatest risk factors for the development of late toxicity 2 years after breast-conserving surgery and adjuvant radiotherapy were larger breast volume, baseline pre-radiotherapy surgical cosmesis, postoperative infection and possibly smoking. These factors seem to be more important than relatively small differences in dose inhomogeneity and the addition of boost radiotherapy at 2 years after the completion of radiotherapy. The modification of potentially preventable risk factors, such as postoperative infection and smoking, may limit the development of late toxicity after breast radiotherapy.
Abstract Aims Volumetric-modulated arc therapy (VMAT) allows rapid delivery of radiotherapy. The aim of this planning study was to evaluate VMAT and dynamic intensity-modulated radiotherapy (IMRT) using a simultaneous integrated boost technique Patients and methods Planning computed tomography data from 10 patients with locoregionally advanced oropharynx or nasopharynx carcinoma were selected. The prescription dose was 70, 63 and 56 Gy to the high-dose, intermediate-dose and low-dose planning target volume (PTV), respectively, and planning parameters were according to Radiation Therapy Oncology Group IMRT protocols. VMAT and IMRT plans were calculated, and dose–volume histograms were created for plan evaluation and comparison. Results Clinically acceptable plans were achieved for both IMRT and VMAT plans, although IMRT plans typically required three times the number of monitor units. The coverage of 95% of the PTV70 was between 96 and 100% of the prescribed dose for IMRT plans and 100% for all VMAT plans. There was a trend of improved dose conformity for IMRT plans. Both IMRT and VMAT achieved acceptable plans in terms of sparing of the spinal cord and brainstem. Contralateral parotid sparing was improved with VMAT, with a mean dose of 25.08 Gy (range 21.35–30.02 Gy) for oropharynx and 31.37 Gy (range 23.47–35.52 Gy) for nasopharynx cases. Conclusion Simultaneous integrated boost VMAT achieved comparable plans to dynamic IMRT in complex head and neck cases and used two-thirds less monitor units.
Abstract Aims The prevalence of anxiety and depression in patients with advanced cancer has been reported to be on average 25% and to significantly affect patients’ quality of life. Despite high prevalence rates, these disorders remain underdiagnosed and undertreated. The purpose of our study was to examine the self-report rates of anxiety and depression with the Edmonton Symptom Assessment System (ESAS) and to assess the predictive factors for these reports in cancer patients with metastatic disease. Materials and methods Consecutive patients who attended the Rapid Response Radiotherapy Program (RRRP) completed the ESAS as well as baseline demographic information. Ordinal logistic regression analysis was used to determine factors that significantly predicted anxiety and/or depression. Pearson χ2 was used to test goodness-of-fit for categorical variables and established whether or not an observed frequency distribution differed from a predicted frequency distribution. A univariate analysis was conducted first and those variables with a P value < 0.100 were included in a multivariate analysis. A score test was used to test the proportional odds assumption. Results In total, 1439 patients seen in the RRRP between January 1999 and October 2009 completed ESAS questionnaires. Fifty-five per cent of patients reported at least mild symptoms of depression and 65% reported at least mild anxiety. In the univariate analysis, patients who were female, who had a lower performance status score, or primary lung cancer were more likely to report depressed and anxious feelings. Primary prostate cancer patients were significantly less likely to report depression and anxiety. Patients referred for spinal cord compression were significantly less depressed. The multivariate models showed that younger patients were significantly more anxious than older patients and females reported more anxiety than males. Patients who reported higher feelings of nausea, tiredness, drowsiness, dyspnoea, and worse appetite and overall well-being on the ESAS tool were more likely to report feelings of depression. Patients who reported higher nausea, drowsiness, dyspnoea and worse overall well-being more often reported higher feelings of anxiety. Conclusion The self-report rates of anxiety and depression were consistent with published prevalence rates. However, the explained variance based on factors included in the model remains low. Additional predictive factors should be examined in future studies in this population. The ESAS tool seems to be an efficient screening tool for anxiety and depression; however, future studies should examine its correlative properties with other known screening tools in the advanced cancer population. A prospective study should be conducted to assess the severity cut-off point in which the ESAS scores most frequently lead to a further diagnosis of an anxiety or depressive disorder in the advance cancer population.
Abstract Aims To assess whether routine mid-treatment replanning in head and neck squamous cell carcinoma patients results in meaningful improvements in target or normal tissue dosimetry and to assess which patients derive the greatest benefit. Materials and methods Twenty patients treated with either postoperative chemoradiotherapy or definitive chemoradiotherapy with primary or nodal disease ≥3 cm in size were included in this prospective pilot study. Seven patients received adjuvant chemoradiotherapy and 13 received definitive chemoradiotherapy. Patients were planned and treated on a helical tomotherapy system. All patients had a second computed tomography scan after 15 fractions and a new plan based on this was initiated from fraction 20. Results Relative volume changes between computed tomography scans were: GTV 29%; CTV60 (adjuvant patients) 4%; parotid volume 17.5%; median reduction in neck separation 6–7 mm; weight loss 3%. For the group overall and for the definitively treated patient cohort, respectively, adapted plans resulted in reductions in PTV66 D1 (0.3 Gy, P = 0.01 and 0.5 Gy, P = 0.01); PTV54 D1 (0.6 Gy, P < 0.0001 and 0.9 Gy, P = 0.0002); spinal cord maximum (0.5 Gy, P = 0.004 and 0.6 Gy, P = 0.04) and volume of skin receiving ≥50 Gy (16 cm2 , P = 0.01 and 19 cm2 , P = 0.001). Definitively treated patients also had a reduction in mean parotid dose (0.6 Gy, P = 0.046) and volume of normal tissue receiving ≥50 Gy (67 cm3 , P = 0.02). Patients with nasopharyngeal carcinoma received the greatest benefits with treatment adaptation with reduction in spinal cord maximum 1.2 Gy, mean parotid dose 1.2 Gy and parotid V26 6.3%. There was no significant benefit for adjuvant patients. Other factors associated with greater benefits were greater weight loss and greater reduction in neck separation and higher T stage. Conclusions There is minimal benefit to routine adaptive replanning in unselected patients, and no benefit in adjuvantly treated patients. Patients with nasopharyngeal carcinoma or with greater weight loss or reduction in neck separation did have clinically significant benefits. These patients should be targeted for adaptive strategies.
Abstract Cancer-induced bone pain (CIBP) is common and challenging to treat. Common therapies, such as opioids, radiotherapy and bisphosphonates, are often only partially effective. CIBP is a different entity to inflammatory or neuropathic pain and needs to be considered as such. This overview examines the mechanisms of CIBP; the imbalance of bone turnover, peripheral and central nervous involvement and key neurochemical mediators. The current understanding of the underlying pathophysiology of CIBP is discussed.
Abstract Aims To evaluate the feasibility and outcome of image-guided brachytherapy (IGBT) for treating cervical cancer using magnetic resonance imaging (MRI)-based planning for the first fraction followed by computed tomography (CT)-based planning for subsequent fractions. Materials and methods Forty-four patients with cervical cancer were treated with three-dimensional high dose rate IGBT. The brachytherapy dose was 5.0–6.0 Gy × five fractions. All but five patients received concurrent weekly cisplatinum at 40 mg/m2 . All patients received external beam radiotherapy (EBRT) with a median dose of 45 Gy over 25 fractions. Total doses for the high-risk clinical target volume (HRCTV) and organs at risk, including the rectum, bladder and sigmoid, from EBRT and brachytherapy were summated and normalised to a biologically equivalent dose of 2 Gy per fraction (EQD2 ). At 3 months after therapy, any early response was assessed with positron emission tomography (PET)/CT imaging. Results The mean D90 for the HRCTV was 83.3 (3.0) Gy. The mean 2 cm3 dose to the bladder, rectum and sigmoid colon organs was 79.7 (5.1), 57.5 (4.4) and 66.8 (5.7) Gy, respectively. All but one (2.3%) patient had a complete response. Follow-up PET/CT was carried out in 41 (93.0%) patients, of whom 38 (92.5%) had a complete response. Of the 38 patients with a complete response on PET/CT, two had local recurrences at 6 and 8 months, respectively. Actuarial 2 year local control, disease-specific and overall survival rates were 88, 85 and 86%, respectively. Conclusion This is the first report of three-dimensional high dose rate IGBT for the treatment of cervical cancer using a hybrid MRI/CT approach. Early results have shown the feasibility of this approach with excellent local control. Additional studies are needed to assess long-term outcomes of local control and associated morbidities.