Clinical Oncology

Positron Emission Tomography Scanning in Oesophageal Cancer — Stuck at the First Hurdle?

Stephen Falk — 2011-08-24

Oesophageal cancer remains a poor prognosis disease and most patients present with either locally advanced or metastatic disease, typically with poor functional status, and are unsuitable for aggressive therapies. The incidence of oesophageal cancer has doubled in the last two decades throughout the world, and the age-standardised 5 year relative survival ratio in the UK remains dismal at 8%, with a 1 year survival rate of 27–30%. There is no effective potentially curative therapy that is not aggressive. Oeosphagectomy, in particular, has considerable morbidity, even as the procedure becomes predominantly laparoscopic so-called ‘minimally invasive’, with grade III toxicity in up to 40% of patients and a fearsome list of potential complications, including anastomotic leak (12%), pneumonia (8%), vocal cord palsy (4%), chylothorax (3%), gastric tip necrosis (3%), myocardial infarction (2%), delayed gastric emptying (2%), acute respiratory disease (2%), pancreatitis (1%), deep vein thrombosis (1%), pulmonary embolus (1%), tracheal tear (1%) and renal failure (1%) . Even with thorough staging, up to 19% of these patients will succumb in the first 3 months from progressive disease . Anything that can better select patients and thus prevent harm is welcome.

Evidence-based Guideline Recommendations on the use of Positron Emission Tomography Imaging in Oesophageal Cancer

R. Wong, C. Walker-Dilks, A. Raifu — 2011-09-30

Abstract: Aims: To provide evidence-based practice guideline recommendations on the use of fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) for diagnosis, staging, assessing treatment response, liver metastasis and restaging or recurrence of oesophageal cancer.Materials and methods: A systematic review by Facey et al. (Health Technology Assessment 2007;11(44):iii–iv, xi–267) was used as the evidence base for recommendation development. As the review was limited to August 2005, the evidence base was updated to May 2010 using the same search strategies for MEDLINE and EMBASE used in the original review. The authors of the current systematic review drafted recommendations, which were reviewed, adapted and accepted by consensus by the Ontario provincial Gastrointestinal Disease Site Group and a special meeting of clinical experts.Results: The results from the Facey et al. review for oesophageal cancer included four other systematic reviews and six primary studies. The 2005 to 2010 updated search included two additional systematic reviews and 29 primary studies. Recommendations were developed based on this evidence and accepted by consensus.Conclusions: PET is recommended to improve the accuracy of M staging for the staging work-up of patients with oesophageal cancer who are potential candidates for curative therapy. Due to insufficient evidence, no recommendation was made for or against the use of PET for the assessment of treatment response and the evaluation of suspected recurrence.

A Prognostic Model to Identify Patients with Advanced Pancreas Adenocarcinoma Who Could Benefit from Second-line Chemotherapy

2011-03-08

Abstract: Aims: The role of salvage chemotherapy after first-line therapy in advanced pancreatic cancer has not yet been established. We intended to identify prognostic factors for long-term survival of advanced pancreatic adenocarcinoma patients with second-line chemotherapy and to devise a prognostic model of clinical parameters.Patients and methods: We analysed 90 patients who had received second-line chemotherapy after the failure of first-line therapy in recurrent or metastatic pancreatic adenocarcinoma between August 2003 and December 2008.Results: The median age at the time of second-line chemotherapy was 61.9 years (range 39.8–74.9) and the median Eastern Cooperative Oncology Group (ECOG) performance status was 1 (0–2). Median progression-free survival and overall survival for second-line chemotherapy were 2.1 and 4.5 months, respectively, with an overall response rate of 10%. In multivariate analysis, an ECOG performance status of 2 or more, non-responder for first-line chemotherapy and albumin level of <3.5mg/dl were independent prognostic factors for decreased overall survival for all 90 patients. Overall survival was estimated based on the number of adverse prognostic factors: zero or one (good prognostic group), two (intermediate group) or three (poor prognostic group). The median overall survival for good (n=50), intermediate (n=24) and poor (n=16) prognostic groups was 5.5, 3.3 and 2.1 months, respectively (P<0.001).Conclusion: Our result suggests that second-line chemotherapy may be beneficial for overall survival in patients with ECOG performance status 0–1, albumin level ≥3.5mg/dl and response to first-line chemotherapy.

A Randomised Double-blind Placebo-controlled Trial to Determine the Effect of Cranberry Juice on Decreasing the Incidence of Urinary Symptoms and Urinary Tract Infections in Patients Undergoing Radiotherapy for Cancer of the Bladder or Cervix

2011-06-23

Abstract: Aims: Radical pelvic radiotherapy is one of the main treatment modalities for cancers of the bladder and cervix. The side-effects of pelvic radiotherapy include urinary symptoms, such as urinary frequency and cystitis. The therapeutic effects of cranberry juice in the prevention and treatment of urinary tract infections in general are well documented. The purpose of this study was to evaluate the effectiveness of cranberry juice on the incidence of urinary tract infections and urinary symptoms in patients undergoing pelvic radiotherapy for cancer of the bladder or cervix.Materials and methods: The study was a placebo-controlled, double-blind design. Participants were randomised to receive cranberry juice, twice a day (morning and night) for the duration of their radiotherapy treatment and for 2 weeks after treatment (6 weeks in total) or a placebo beverage, for the same duration.Results: The incidence of increased urinary symptoms or urinary tract infections was 82.5% on cranberry and 89.3% on placebo (P=0.240, adjusted odds ratio [cranberry/placebo] 0.48, 95% confidence interval 0.14–1.63).Conclusions: The power of the study to detect differences was limited by the below target sample size and poor compliance. Further research is recommended, taking cognisance of the factors contributing to the limitations of this study.

Evaluation of Set-up Uncertainties with Daily Kilovoltage Image Guidance in External Beam Radiation Therapy for Gynaecological Cancers

H. Kim, S. Beriwal, M.S. Huq, N. Kannan, G. Shukla, C. Houser — 2011-09-26

Abstract: Aims: To assess the set-up uncertainty for gynaecological cancer patients treated with external beam radiation therapy using daily kilovoltage image guidance and to estimate set-up margins for treatment and factors that would predict higher set-up uncertainty.Materials and methods: Alignment data from daily two-dimensional kilovoltage planar images and three-dimensional kilovoltage cone beam images for 52 patients treated on a Varian 2300iX linear accelerator with On Board Imaging (OBI; version 1.4) capability were analysed. The mean displacements of translational shifts, population systematic errors and random errors were calculated. Using van Herk’s formula, the clinical target volume (CTV) to planning target volume (PTV) margins for set-up uncertainties were calculated. The differences in set-up error were calculated with respect to the type of cancer, imaging type and body mass index (BMI).Results: Population systematic and random errors were 1.1mm, 2.3mm, 2.3mm and 3.9mm, 5.0mm, 3.5mm in the anterior–posterior (AP), medial–lateral (ML) and superior–inferior (SI) directions, respectively, for the entire patient population. Using van Herk’s formula, the CTV to PTV margins for set-up uncertainties were found to be 5.5, 9.1 and 8.3mm in the AP, ML and SI directions respectively. The mean displacements in the AP, ML and SI directions for BMI≥30 (28 patients) versus <30 (24 patients) were −0.1mm, 0.9mm and 1.0mm versus −0.1mm, 0.1mm and 0.4mm, respectively, (P=0.02).Conclusions: Daily imaging helps to assess set-up uncertainty. The set-up margin for CTV to PTV was larger for patients with BMI≥30 without image guidance and these patients would benefit more from daily image guidance.

Mapping Use of Radiotherapy for Patients with Non-small Cell Lung Cancer in the Netherlands between 1997 and 2008

2011-07-22

Abstract: Aim: After the publication of several reports that the utilisation rate of radiotherapy for patients with non-small cell lung cancer (NSCLC) varies for both medical and non-medical reasons, the utilisation of radiotherapy was studied in four regions in the Netherlands.Materials and methods: Data from 1997–2008 were collected from the population-based cancer registries of four comprehensive cancer centres (‘regions’), which represent about half of the Dutch population, resulting in 24 185 non-metastatic patients with NSCLC. Treatment had to be started or planned within 6 months of diagnosis. We evaluated the utilisation of radiotherapy according to age, gender and period for each region.Results: The utilisation of radiotherapy alone decreased over time (from 35 to 19%), whereas the utilisation of radiotherapy in combination with chemotherapy increased (from 5 to 19%). The total utilisation rate remained rather stable at about 40%. The differences between the four regions remained in general no more than 15%. Elderly patients with stage I and II disease had increased odds of receiving radiotherapy (≥75 versus <50 years: odds ratio 2.6, 95% confidence interval 2.0–3.3, whereas this was the opposite for patients with stage III disease: odds ratio 0.5, 95% confidence interval 0.4–0.6). For 17–24% of all patients, especially the elderly, best supportive care was applied.Conclusions: In the Netherlands, with good accessibility to medical care and well-implemented national guidelines, variation between the four regions is limited for the treatment of non-metastatic NSCLC with radiotherapy.

Update on the Systematic Review of Palliative Radiotherapy Trials for Bone Metastases

E. Chow, L. Zeng, N. Salvo, K. Dennis, M. Tsao, S. Lutz — 2011-11-30

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.

Assessment of Health-related Quality of Life with the European Organization for Research and Treatment of Cancer QLQ-C15-PAL after Palliative Radiotherapy of Bone Metastases

2011-09-14

Abstract: Aims: To assess health-related quality of life (HRQOL) after palliative radiotherapy for painful bone metastases using a palliative questionnaire (European Organization for Research and Treatment of Cancer QLQ-C15-PAL).Materials and methods: Patients scheduled to receive palliative radiotherapy for painful bone metastases (n=178) completed the QLQ-C15-PAL questionnaire before treatment and at week 1, week 2, month 1 and month 2 after the first day of radiotherapy. A partial response (PR) or a complete response (CR) to radiotherapy was defined according to the International Consensus criteria. General linear regression was used to analyse changes in QOL in the entire cohort and within responders and non-responders to radiotherapy at all follow-up periods.Results: The overall radiotherapy response was 45% at week 1 (n=21) (41% PR, 4% CR), 62% at week 2 (n=28) (58% PR, 4% CR), 62% at month 1 (n=58) (60% PR, 2% CR) and 65% at month 2 (n=38) (60% PR, 5% CR). In general, a significant decrease in pain (P<0.0001), insomnia (P<0.0001) and constipation (P=0.004) was seen by month 1 after radiotherapy. In patients who responded to radiotherapy, overall QOL significantly improved by month 2 after radiotherapy (P=0.002). Radiotherapy responders also reported an improvement in emotional functioning together with a decrease in symptoms such as insomnia and constipation at month 1. No improvements were seen in any of the QLQ-C15-PAL scores for patients whose pain did not respond to radiotherapy.Conclusion: Radiotherapy responders showed not only an improvement in pain, but also in HRQOL as assessed by QLQ-C15-PAL. As early as 1 week after radiotherapy for bone metastases, a pain relief response was reported by patients.

A Survey of Expectations and Understanding of Palliative Radiotherapy from Patients with Advanced Cancer

2011-10-03

Abstract: Aims: : To assess patients’ understanding of their illness and expectations of palliative radiotherapy for symptomatic metastases before and after consultation and to explore the relationship between response and demographics/Edmonton Symptom Assessment Scale (ESAS) scores.Materials and methods: In total, 100 participants completed a survey before and after consultation from March to October 2009. Descriptive statistics and statistical analyses were conducted to compare responses and to determine any relationship between responses and demographics or ESAS variables.Results: Up to 25% believed their cancer was curable; there was no change in belief that radiotherapy would cure their cancer (17% before and 15% after) or prolong their life (40% before and 45% after). There were significant differences in radiotherapy expectation for symptom relief (P=0.0094) and for patients who did not know the role of radiotherapy (P=0.0025). Patient anxiety was reduced after consultation on questions about radiotherapy (P<0.001), concerns on effectiveness (P<0.0001) and side-effects of treatment (P<0.0001); 96, 24 and 46% said after consultation that they were satisfied with information from the team, better understood their diagnosis of cancer and the role of radiotherapy, respectively.Conclusion: A significant proportion of patients with advanced disease believe their cancer is curable, expect that radiotherapy will cure their cancer and prolong their life despite understanding the intent of radiotherapy is for symptom relief. After consultation, patients say they have a better understanding of their cancer and feel more confident about treatment. More work is needed to improve patients’ understanding of their illness and expectations of the role of palliative radiotherapy.

Frequency of Reporting and Predictive Factors for Anxiety and Depression in Patients with Advanced Cancer

2011-06-08

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.

Treatment of Glioblastoma Multiforme — The Oxford Cancer Centre Experience

A. Medisetti, R. Jampana, N. Warner, C. Blesing — 2011-11-10

Sir — Glioblastoma multiforme (GBM) is an aggressive primary brain tumour. In 2005, a landmark European Organization for Research and Treatment of Cancer/National Cancer Institute Canada (EORTC/NCIC) trial showed that the addition of concomitant and adjuvant temozolomide to radical radiotherapy gives patients improved survival . The presence of MGMT promoter hypermethylation silences the MGMT gene, thereby reducing resistance to alkylating agents. This is associated with longer survival in patients who receive alkylating agents and is also an independent prognostic factor .

Radiotherapy and Cervix Cancer — University Hospitals Birmingham Experience with Patients Not Suitable for Concurrent Chemoradiotherapy with Cisplatin

E. Beaumont, I.N. Fernando — 2011-11-11

Sir — The most effective treatment for patients with cervical cancer is concurrent chemoradiotherapy using cisplatin . However, this is not suitable for all patients. Over 5 years, 74 patients in our practice did not have cisplatin. We therefore reviewed the reasons for this and the results.

The Role of mp-MRI in the Detection of Prostate Cancer

M. Abd Alazeez, H. Ahmed, C. Moore, A. Kirkham, A. Freeman, M. Emberton — 2012-03-01

Introduction: Multi-parametric MRI (mp-MRI) has the potential to serve as a non-invasive triage test for men at risk of prostate cancer. We present a preliminary analysis of a paired dataset in which mp-MRI was applied prior to a 5mm 3D template prostate mapping (TPM) in men at risk.

Single Fraction HDR Boost and Dose Escalation for Intermediate and High Risk Prostate Cancer. A Report of Toxicity from a Single Centre Experience

C. Arthur, P. Mandall, R. Swindell, J.P. Logue, J.P. Wylie — 2012-03-01

Introduction: High dose rate (HDR) brachytherapy, delivered with hypofractionated external beam radiotherapy (EBRT), enables dose escalation with improvements in tumour control and rates of biochemical failure. Balancing these benefits against the risk of bladder and bowel toxicity remains a therapeutic challenge. We report our experience of medium-term toxicities following HDR brachytherapy as a single fraction boost of 12.5Gy or 15Gy prior to EBRT.

Pelvic External Beam Radiotherapy and High Dose Rate Image Guided Interstitial Brachytherapy Boost for High Risk Prostate Cancer

P. De Ieso, U. Schick, D. Ward, R. Hughes, P. Ostler, P. Hoskin — 2012-03-01

Introduction: Evaluation of pelvic nodal external beam radiotherapy (EBRT) with interstitial high dose rate brachytherapy (HDRB) boost to prostate and seminal vesicles for high risk prostate adenocarcinoma.

Acute Toxicity Rates in Patients Receiving Salvage Radical Prostate Irradiation Following Primary High Intensity Focused Ultrasound (HIFU) for Localised Prostate Cancer

A. Aggarwal, R. Davda, M. Emberton, H. Payne — 2012-03-01

Introduction: HIFU is used in the treatment of primary prostate cancer. It aims to achieve cancer control while offering a potentially more favourable toxicity profile [1]. Long term randomised data are currently unavailable to support this [2]. Approximately 15% of patients receiving primary HIFU will require additional treatment [3], depending on the stage and grade at relapse. There are no published UK data on efficacy or safety of radical radiotherapy after primary HIFU. We present a case series reporting acute radiotherapy toxicity in patients treated with primary HIFU.

Multi-institutional Outcome Following LDR Brachytherapy in Patients with Higher Risk Prostate Cancer

R. Conroy, P. Hoskin, D. Bottomley, P. Mandall, R. Swindell, J. Wylie — 2012-03-01

Introduction: We report the outcomes for a cohort of men with higher risk prostate adenocarcinoma treated with LDR brachytherapy in a multi-institutional UK practice. Materials and methods: 217 men treated between 2003 and 2007 with iodine-125 brachytherapy at Christie, Leeds and Mount Vernon were identified from a multi-institutional database. Higher risk was defined as patients with≥2 D'Amico intermediate risk factors (PSA 10–20, GS 7 or clinical T2c) or ≥1 high risk factor (PSA>20, GS≥8). Kaplan–Meier methods were used to estimate biochemical relapse free survival (BRFS) defined using both Phoenix and ASTRO definitions. A univariate analysis was performed to assess the significance of Gleason score, PSA, T-stage, pre- or post-implant dosimetry, and additional hormones on BRFS.

Sunitinib Malate in the Treatment of Metastatic Renal Cell Carcinoma: the North of England Cancer Network (NECN) Experience

2012-03-01

Introduction: Metastatic renal cell carcinoma (mRCC) has a poor prognosis. Treatment aims to improve progression free survival (PFS) and overall survival (OS). Sunitinib gained NICE approval in March 2009 as first line treatment and experience with it is growing. The NECN was the first in the UK to approve the use of Sunitinib in July 2007. This retrospective re-audit compares the NECN patient outcomes with published literature, updating previous NECN work from 2008.

Intensity Modulated Radiotherapy (IMRT) in the Treatment of Pelvic Lymph Nodes in Locally Advanced Prostate Cancer (LAPCa): a Single UK Institution Experience

M. Hadaki, H.V. Janes, R. Venkitaraman, C.D. Scrase — 2012-03-01

Introduction: Evidence is in favour of localised radiotherapy in the treatment of LAPCa. Whether there is added disease control by including the pelvic lymph nodes in the irradiation volume is less clear. This paper describes our experience in using IMRT to treat the pelvic nodes in this patient population.

Analysis of Malignant Spinal Cord Compression Patients treated in a Regional Neuro-oncology Centre

S. Kennedy, J. Law, G. Skailes, A. Birtle — 2012-03-01

Introduction: Since December 2009 there has been a spinal cord compression coordinator in the Lancashire and Cumbria cancer network to enable patients to receive care as per NICE 2008 guidelines [1]. We conducted a retrospective analysis of patient management between December 2009 and January 2011 and reviewed survival outcomes.

Radical Radiotherapy for Localised Hormone Refractory Prostate Cancer

A. Pascoe, S. Sundar — 2012-03-01

Introduction: Since PR07 and the Scandinavian Prostate Cancer Group showed survival benefit from adding radical radiotherapy (RT) to androgen deprivation therapy, prostate RT is routinely offered to fit patients with locally advanced prostate cancer [1,2]. Previously these patients were treated with hormones alone and followed up. Adding prostate RT when they become hormone refractory (and still have radiologically localised cancer) is controversial, but there is some evidence that patients with locally advanced hormone refractory prostate cancer (HRPC) may benefit [3]. The natural history of non-metastatic HRPC is unknown and treatment options are limited. Metastatic HRPC is associated with poor prognosis; widely quoted survival being 12–18 months, which with PSA lead time may be an underestimate [4]. The only treatment in metastatic HRPC with proven survival benefit is Docetaxel chemotherapy, which improves survival by 4 months with a 45% response in PSA [5].

Clinical Outcomes of a Phase II Open-labelled, Randomised Study Investigating the Tolerability and Efficacy of Anti-androgen Manipulation versus Taxotere and Anti-androgen Manipulation in Patients with Hormone Naive High Risk/Metastatic Prostate Cancer

2012-03-01

Introduction: Androgen ablation (AA) is considered the standard initial therapy for men with high risk/metastatic prostate cancer. The role of chemotherapy and androgen ablation (TAA) is still undefined in this patient population. Here we present the clinical data from a phase II trial investigating clinical outcome and gene profiling of prostate cancer patients before and after AA or TAA.

Meetings Notice

2012-03-01