Palliative Lung Radiotherapy: Higher Dose Leads to Improved Survival?

AIMS: Choosing the optimal palliative lung radiotherapy regimen is challenging. Guidance from The Royal College of Radiologists recommends treatment stratification based on performance status, but evidence suggests that higher radiotherapy doses may be associated with survival benefits. The aim of this study was to investigate the effects of fractionation regimen and additional factors on the survival of palliative lung cancer radiotherapy patients. MATERIALS AND METHODS: A retrospective univariable (n = 925) and multivariable (n = 422) survival analysis of the prognostic significance of baseline patient characteristics and treatment prescription was carried out on patients with non-small cell and small cell lung cancer treated with palliative lung radiotherapy. The covariates investigated included: gender, age, performance status, histology, comorbidities, stage, tumour location, tumour side, smoking status, pack year history, primary radiotherapy technique and fractionation scheme. The overall mortality rate at 30 and 90 days of treatment was calculated. RESULTS: Univariable analysis revealed that performance status (P < 0.001), fractionation scheme (P < 0.001), comorbidities (P = 0.02), small cell histology (P = 0.02), 'lifelong never' smoking status (P = 0.01) and gender (P = 0.06) were associated with survival. Upon multivariable analysis, only better performance status (P = 0.01) and increased dose/fractionation regimens of up to 30 Gy/10 fractions (P < 0.001) were associated with increased survival. Eighty-five (9.2%) and 316 patients (34%) died within 30 and 90 days of treatment, respectively. CONCLUSION: In this retrospective single-centre analysis of palliative lung radiotherapy, increased total dose (up to and including 30 Gy/10 fractions) was associated with better survival regardless of performance status.

Protocol for PIT: a phase III trial of prophylactic irradiation of tracts in patients with malignant pleural mesothelioma following invasive chest wall intervention.

INTRODUCTION: Histological diagnosis of malignant mesothelioma requires an invasive procedure such as CT-guided needle biopsy, thoracoscopy, video-assisted thorascopic surgery (VATs) or thoracotomy. These invasive procedures encourage tumour cell seeding at the intervention site and patients can develop tumour nodules within the chest wall. In an effort to prevent nodules developing, it has been widespread practice across Europe to irradiate intervention sites postprocedure--a practice known as prophylactic irradiation of tracts (PIT). To date there has not been a suitably powered randomised trial to determine whether PIT is effective at reducing the risk of chest wall nodule development. METHODS AND ANALYSIS: In this multicentre phase III randomised controlled superiority trial, 374 patients who can receive radiotherapy within 42 days of a chest wall intervention will be randomised to receive PIT or no PIT. Patients will be randomised on a 1:1 basis. Radiotherapy in the PIT arm will be 21 Gy in three fractions. Subsequent chemotherapy is given at the clinicians' discretion. A reduction in the incidence of chest wall nodules from 15% to 5% in favour of radiotherapy 6 months after randomisation would be clinically significant. All patients will be followed up for up to 2 years with monthly telephone contact and at least four outpatient visits in the first year. ETHICS AND DISSEMINATION: PIT was approved by NRES Committee North West-Greater Manchester West (REC reference 12/NW/0249) and recruitment is currently on-going, the last patient is expected to be randomised by the end of 2015. The analysis of the primary end point, incidence of chest wall nodules 6 months after randomisation, is expected to be published in 2016 in a peer reviewed journal and results will also be presented at scientific meetings and summary results published online. A follow-up analysis is expected to be published in 2018. TRIAL REGISTRATION NUMBER: ISRCTN04240319; NCT01604005; Pre-results.

Primary radiotherapy for carcinoma of the retromolar trigone: a useful alternative to surgery.

AIMS: Squamous cell carcinoma of the retromolar trigone is uncommon. The standard initial treatment is primary surgery, which usually involves microvascular reconstruction with a composite flap. Some patients are considered unsuitable for this procedure. This retrospective study examined the outcome and toxicity for patients with squamous cell carcinoma of the retromolar trigone treated with definitive radiotherapy in a single centre. MATERIALS AND METHODS: Between 1991 and 2000, 43 patients were treated with definitive radiotherapy with a median dose of 50Gy in 16 fractions over 21 days. Hospital case notes and radiotherapy records were analysed. RESULTS: The median age was 66 years (range 39-84 years). Nodal disease was evident in 13 (30.2%) patients. Twenty-one patients (51.2%) had stage I/II disease and 20 patients (48.8%) had stage III/IV disease. After a median follow-up of 59 months, 13 (30.2%) patients were alive and well, nine (20.9%) patients had died of an intercurrent illness and 21 (48.8%) had died of their disease. Five-year locoregional control was 46.5% (95% confidence interval 29.7-61.7), cause-specific survival was 45.7% (95% confidence interval 29.1-60.8) and overall survival was 30.9% (95% confidence interval 17.5-46.3). Osteoradionecrosis was documented in two patients. DISCUSSION: This hypofractionated regimen is convenient for this patient population and produced comparable outcomes to longer fractionation schedules without an increase in late toxicity.

The impact of lymphovascular invasion on survival in oral carcinoma.

Data was retrospectively analysed on 72 consecutive patients treated primarily with resection and concomitant neck dissection for intraoral carcinomas. Twenty prognostic variables were assessed by univariate analysis to assess their influence on survival. Seven variables were significant at the 5% level. Survival was negatively influenced by six tumour related factors, increasing T stage (P=0.039), increasing N stage (P=0.004), greater than two nodes histologically positive nodal disease (P=0.017), tumour size > 4 cm (P=0.022), residual disease at the primary site (P=0.012), extracapsular nodal spread (P=0.01) and the one treatment related factor analysed, adjuvant radiotherapy (P=0.039). Subsequent multivariate analysis was performed via the cox stepwise regression method to assess the influence on survival of all factors which achieved significance at the 20% level. There were only two variables which made a significant difference (P<0.05) to the multivariate model. The presence of lymphovascular invasion (P=0.015) and histological evidence of mandibular invasion (P=0.047). Lymphovascular invasion appeared in the final model despite not achieving statistical significance at the 5% level on univariate analysis. A final cox survival model was constructed. The relative risk of death for those with cervical metastases (N2 and above) at diagnosis was 3.74 (P=0.005). The addition of lymphovascular invasion to the cox model revealed an increase in the relative risk of death in the presence of lymphovascular invasion of 2.99 (P=0.015). Patients with nodal negative disease and one single node positive provided the baseline risk as there was no significant difference between these two groups. The presence of histological evidence of lymphovascular invasion in oral carcinoma surgical specimens has a significant impact on survival outcome in oral carcinoma patients.

Radiotherapy for small-cell lung cancer-Where are we heading?

Radiotherapy has an established role in the management of limited-disease small-cell lung cancer. However, essential questions related to the optimisation of thoracic radiotherapy remain unanswered including (i) optimal total dose, (ii) fractionation, (iii) timing and sequencing of radiation, (iv) volume of irradiation, and (v) concurrent chemotherapy combinations. The role of thoracic radiotherapy for extensive-disease small-cell lung cancer is more poorly understood but evidence suggests radiotherapy may have an important role in this setting. This review highlights the need for well-designed multi-national trials aimed at the optimisation and standardisation of radiotherapy for SCLC.

When should the seminal vesicles be included in the target volume in prostate radiotherapy?

External beam radiotherapy to the prostate and seminal vesicles as a radical treatment for prostate cancer can result in a significant dose being delivered to the rectum. This can be reduced if the target volume includes the prostate only. Using a Medline search, published studies are reviewed to show that the risk of seminal vesicle involvement can be accurately predicted using readily available pre-treatment parameters. We recommend when to exclude the seminal vesicles from a target volume, and the proportion of seminal vesicles that should be included in a target volume in higher risk patients.