Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study.

BACKGROUND: The role of temozolomide chemotherapy in newly diagnosed 1p/19q non-co-deleted anaplastic gliomas, which are associated with lower sensitivity to chemotherapy and worse prognosis than 1p/19q co-deleted tumours, is unclear. We assessed the use of radiotherapy with concurrent and adjuvant temozolomide in adults with non-co-deleted anaplastic gliomas. METHODS: This was a phase 3, randomised, open-label study with a 2 × 2 factorial design. Eligible patients were aged 18 years or older and had newly diagnosed non-co-deleted anaplastic glioma with WHO performance status scores of 0-2. The randomisation schedule was generated with the electronic EORTC web-based ORTA system. Patients were assigned in equal numbers (1:1:1:1), using the minimisation technique, to receive radiotherapy (59·4 Gy in 33 fractions of 1·8 Gy) alone or with adjuvant temozolomide (12 4-week cycles of 150-200 mg/m2 temozolomide given on days 1-5); or to receive radiotherapy with concurrent temozolomide 75 mg/m2 per day, with or without adjuvant temozolomide. The primary endpoint was overall survival adjusted for performance status score, age, 1p loss of heterozygosity, presence of oligodendroglial elements, and MGMT promoter methylation status, analysed by intention to treat. We did a planned interim analysis after 219 (41%) deaths had occurred to test the null hypothesis of no efficacy (threshold for rejection p<0·0084). This trial is registered with ClinicalTrials.gov, number NCT00626990. FINDINGS: At the time of the interim analysis, 745 (99%) of the planned 748 patients had been enrolled. The hazard ratio for overall survival with use of adjuvant temozolomide was 0·65 (99·145% CI 0·45-0·93). Overall survival at 5 years was 55·9% (95% CI 47·2-63·8) with and 44·1% (36·3-51·6) without adjuvant temozolomide. Grade 3-4 adverse events were seen in 8-12% of 549 patients assigned temozolomide, and were mainly haematological and reversible. INTERPRETATION: Adjuvant temozolomide chemotherapy was associated with a significant survival benefit in patients with newly diagnosed non-co-deleted anaplastic glioma. Further analysis of the role of concurrent temozolomide treatment and molecular factors is needed. FUNDING: Schering Plough and MSD.

Do statins, ACE inhibitors or sartans improve outcome in primary glioblastoma?

Glioblastomas are malignant brain tumors with poor prognosis. Lately, data from clinical studies assessing the role of co-medications in different cancer types suggested reduced mortality and potential anti-tumor activity for statins, angiotensin-I converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (sartans). Here, we analysed the association of co-treatment with statins, ACEI or sartans with outcome in a cohort of 810 patients enrolled in the phase III CENTRIC and phase II CORE trials on the role of the integrin antagonist, cilengitide, in newly diagnosed glioblastoma with or without O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. Progression-free survival (PFS) and overall survival (OS) were analysed for each medication in the pooled patient group. No association was found for co-medication with either drug for PFS or OS. Median OS was 22.1 (statins) versus 22.2 (control) months (HR 1.06, 95% CI 0.81-1.39, p = 0.69), 20.4 (ACEI) versus 22.6 (control) months (HR 1.25, 95% CI 0.96-1.62, p = 0.10), and 21.7 (sartans) versus 22.3 (control) months (HR 0.86, 95% CI 0.61-1.21, p = 0.38). None of the comparisons showed a signal for different PFS or OS when analyses were controlled for MGMT promoter methylation or treatment group (TMZ/RT â†’ TMZ vs. RT + CIL + TMZ â†’ TMZ + CIL). This secondary analysis of two large glioblastoma trials thus was unable to detect evidence for an association of the use of statins, ACEI or sartans with outcome in patients with newly diagnosed glioblastoma. These data challenge the rationale for prospective studies on the possible role of these non-tumor-specific drugs within the concept of drug repurposing.

Cilengitide combined with standard treatment for patients with newly diagnosed glioblastoma with methylated MGMT promoter (CENTRIC EORTC 26071-22072 study): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: Cilengitide is a selective αvß3 and αvß5 integrin inhibitor. Data from phase 2 trials suggest that it has antitumour activity as a single agent in recurrent glioblastoma and in combination with standard temozolomide chemoradiotherapy in newly diagnosed glioblastoma (particularly in tumours with methylated MGMT promoter). We aimed to assess cilengitide combined with temozolomide chemoradiotherapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. METHODS: In this multicentre, open-label, phase 3 study, we investigated the efficacy of cilengitide in patients from 146 study sites in 25 countries. Eligible patients (newly diagnosed, histologically proven supratentorial glioblastoma, methylated MGMT promoter, and age ≥18 years) were stratified for prognostic Radiation Therapy Oncology Group recursive partitioning analysis class and geographic region and centrally randomised in a 1:1 ratio with interactive voice response system to receive temozolomide chemoradiotherapy with cilengitide 2000 mg intravenously twice weekly (cilengitide group) or temozolomide chemoradiotherapy alone (control group). Patients and investigators were unmasked to treatment allocation. Maintenance temozolomide was given for up to six cycles, and cilengitide was given for up to 18 months or until disease progression or unacceptable toxic effects. The primary endpoint was overall survival. We analysed survival outcomes by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00689221. FINDINGS: Overall, 3471 patients were screened. Of these patients, 3060 had tumour MGMT status tested; 926 patients had a methylated MGMT promoter, and 545 were randomly assigned to the cilengitide (n=272) or control groups (n=273) between Oct 31, 2008, and May 12, 2011. Median overall survival was 26·3 months (95% CI 23·8-28·8) in the cilengitide group and 26·3 months (23·9-34·7) in the control group (hazard ratio 1·02, 95% CI 0·81-1·29, p=0·86). None of the predefined clinical subgroups showed a benefit from cilengitide. We noted no overall additional toxic effects with cilengitide treatment. The most commonly reported adverse events of grade 3 or worse in the safety population were lymphopenia (31 [12%] in the cilengitide group vs 26 [10%] in the control group), thrombocytopenia (28 [11%] vs 46 [18%]), neutropenia (19 [7%] vs 24 [9%]), leucopenia (18 [7%] vs 20 [8%]), and convulsion (14 [5%] vs 15 [6%]). INTERPRETATION: The addition of cilengitide to temozolomide chemoradiotherapy did not improve outcomes; cilengitide will not be further developed as an anticancer drug. Nevertheless, integrins remain a potential treatment target for glioblastoma. FUNDING: Merck KGaA, Darmstadt, Germany.

Adjustment and support needs of glioma patients and their relatives: serial interviews.

OBJECTIVE: To understand factors influencing the process of adjustment to a diagnosis of glioma. METHODS: Twenty-six patients and 23 relatives took part in 80 in-depth qualitative interviews conducted at five key stages: before formal diagnosis, at start of treatment, on completion of treatment, 6 months post treatment, and post bereavement. RESULTS: High levels of distress were reported, particularly preceding and following diagnosis. Many participants described lack of specific information in the early part of their illness and a lack of clarity about what was wrong and what was going to happen next. They often desired more procedural information, as well as information about their condition and treatments available, although there was variation in the timing of when people were ready to hear this. Receiving reassurance and support was essential to patients and their relatives to help them come to terms with their illness. This need was particularly acute during the early phase of the illness when distress and uncertainty were at a peak and lessened over time as people adjusted to their illness. CONCLUSIONS: Offering suitable information about what to expect early and frequently in a supportive way is much appreciated by patients. There is an important balance between ensuring that patients and their families are fully informed and fostering adaptive coping that allows for hope.

ESTRO-EANO guideline on target delineation and radiotherapy details for glioblastoma.

BACKGROUND AND PURPOSE: Target delineation in glioblastoma is still a matter of extensive research and debate. This guideline aims to update the existing joint European consensus on delineation of the clinical target volume (CTV) in adult glioblastoma patients. MATERIAL AND METHODS: The ESTRO Guidelines Committee identified 14 European experts in close interaction with the ESTRO clinical committee and EANO who discussed and analysed the body of evidence concerning contemporary glioblastoma target delineation, then took part in a two-step modified Delphi process to address open questions. RESULTS: Several key issues were identified and are discussed including i) pre-treatment steps and immobilisation, ii) target delineation and the use of standard and novel imaging techniques, and iii) technical aspects of treatment including planning techniques and fractionation. Based on the EORTC recommendation focusing on the resection cavity and residual enhancing regions on T1-sequences with the addition of a reduced 15 mm margin, special situations are presented with corresponding potential adaptations depending on the specific clinical situation. CONCLUSIONS: The EORTC consensus recommends a single clinical target volume definition based on postoperative contrast-enhanced T1 abnormalities, using isotropic margins without the need to cone down. A PTV margin based on the individual mask system and IGRT procedures available is advised; this should usually be no greater than 3 mm when using IGRT.

Current concepts and management of glioblastoma.

Glioblastoma is the most common malignant primary brain tumor in adults. Its often rapid clinical course, with many medical and psychosocial challenges, requires a multidisciplinary management. Modern multimodality treatment and care improve patients' life expectancy and quality of life. This review covers major aspects of care of glioblastoma patients with a focus on the management of common symptoms and complications. We aim to provide a guide for clinicians confronted with glioblastoma patients in their everyday practice.

Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial.

PURPOSE: In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase-wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. PATIENTS AND METHODS: From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. RESULTS: Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19; 95% confidence interval (CI), 0.82-1.71] or progression-free survival (HR, 0.87; 95% CI, 0.61-1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. CONCLUSIONS: In this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.

Prognostic significance of genome-wide DNA methylation profiles within the randomized, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma.

BACKGROUND: Survival in patients with IDH1/2-mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related to outcome in IDH1/2mt anaplastic astrocytoma patients. METHODS: The CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant temozolomide. The presence of necrosis and/or microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were used for genome-wide DNA methylation analysis and the determination of copy number variations (CNV). Two DNA methylation-based tumor classifiers were used for risk stratification. Next-generation sequencing (NGS) was performed using 1 of the 2 glioma-tailored NGS panels. The primary endpoint was overall survival measured from the date of randomization. RESULTS: Full analysis (genome-wide DNA methylation and NGS) was successfully performed on 654 tumors. Of these, 432 tumors were IDH1/2mt anaplastic astrocytomas. Both epigenetic classifiers identified poor prognosis patients that partially overlapped. A predictive prognostic Cox proportional hazard model identified that independent prognostic factors for IDH1/2mt anaplastic astrocytoma patients included; age, mini-mental state examination score, treatment with concurrent and/or adjuvant temozolomide, the epigenetic classifiers, PDGFRA amplification, CDKN2A/B homozygous deletion, PI3K mutations, and total CNV load. Independent recursive partitioning analysis highlights the importance of these factors for patient prognostication. CONCLUSION: Both clinical and molecular factors identify IDH1/2mt anaplastic astrocytoma patients with worse outcome. These results will further refine the current WHO criteria for glioma classification.

Brain tumor research in the United Kingdom: current perspective and future challenges. A strategy document from the NCRI Brain Tumor CSG.

The National Cancer Research Institute (NCRI) is a partnership of charity and government research funders whose purpose is to improve health and quality of life by accelerating progress in cancer-related research through collaboration. Under this umbrella, the NCRI Brain Tumor Clinical Studies Group is focused on improving clinical outcomes for adult patients with brain and central nervous system tumors, including those with brain metastasis from other primary sites. This document discusses the current state of clinical brain tumor research in the United Kingdom and the challenges to increasing study and trial opportunities for patients. The clinical research priorities are defined along with a strategy to strengthen the existing brain tumor research network, improve access to tissue and imaging and to develop the future leadership for brain tumor research in the United Kingdom. This strategy document may serve as a framework for other organizations and countries.

International comparisons of survival from lung cancer: pitfalls and warnings.

Population-based survival data can provide valuable comparative data on outcome but should be interpreted with caution. Differences in data collection and analysis, patient and tumor characteristics and treatment options can have an impact on reported results. Ideally, data from the whole population, including clinical-only diagnoses, should be reported and the methods of case identification described. The relative survival rates should preferably be given. Data on patient characteristics such as age, sex, ethnicity and socioeconomic deprivation should be described, together with tumor details such as pathology and clinical stage. Whenever possible, details on the use of treatments should be reported.

What will be the radiotherapy machine capacity required for optimal delivery of radiotherapy in Scotland in 2015?

AIMS: Lack of radiotherapy capacity has been cited as a reason for poor cancer outcomes reported in the United Kingdom. This modelling study was conducted to ensure sufficient capacity in the future and to aid health service planning. METHODS: The predicted changes in the incidence of each cancer type to 2015 were calculated using the age-period-cohort technique. To develop the model the indications for radiotherapy now and in 2015 were established, as were the fractionation schedules for each clinical scenario. The optimal radiotherapy utilisation rates and required radiotherapy capacity were estimated for 2005 and for 2015. RESULTS: Cancer incidence is expected to rise by 18.9% by 2015. In Scotland, the estimated optimal radiotherapy utilisation rate during initial management is 44.2-47.9%. The model suggested that currently for optimal delivery, the capacity for 195,300-256,300 fractions is required. Due to predicted changes in the patient population, it is anticipated that requirements will increase to between 276,400 and 354,200 fractions per annum by 2015. Based on the current working practices, this is a 20-54% increase in current capacity, or from 5 to 6-7.6 machines per million head of population. CONCLUSIONS: In order to meet the current and projected demand, a marked increase in the provision of radiotherapy machine capacity will be required in Scotland by 2015.

Is more better? The impact of extended adjuvant temozolomide in newly diagnosed glioblastoma: a secondary analysis of EORTC and NRG Oncology/RTOG.

BACKGROUND: Radiation with concurrent and adjuvant (6 cycles) temozolomide (TMZ) is the established standard of postsurgical care for newly diagnosed glioblastoma (GBM). This regimen has been adopted with variations, including extending TMZ beyond 6 cycles. The optimal duration of maintenance therapy remains controversial. METHODS: We performed pooled analysis of individual patient data from 4 randomized trials for newly diagnosed GBM. All patients who were progression free 28 days after cycle 6 were included. The decision to continue TMZ was per local practice and standards, and at the discretion of the treating physician. Patients were grouped into those treated with 6 cycles and those who continued beyond 6 cycles. Progression-free and overall survival were compared, adjusted by age, performance status, resection extent, and MGMT methylation. RESULTS: A total of 2214 GBM patients were included in the 4 trials. Of these, 624 qualified for analysis 291 continued maintenance TMZ until progression or up to 12 cycles, while 333 discontinued TMZ after 6 cycles. Adjusted for prognostic factors, treatment with more than 6 cycles of TMZ was associated with a somewhat improved progression-free survival (hazard ratio [HR] 0.80 [0.65-0.98], P = .03), in particular for patients with methylated MGMT (n = 342, HR 0.65 [0.50-0.85], P < .01). However, overall survival was not affected by the number of TMZ cycles (HR = 0.92 [0.71-1.19], P = .52), including the MGMT methylated subgroup (HR = 0.89 [0.63-1.26], P = .51). CONCLUSIONS: Continuing TMZ beyond 6 cycles was not shown to increase overall survival for newly diagnosed GBM.

Prospective audit showing improved patient-assessed skin toxicity with use of betamethasone cream for those at high risk of radiation dermatitis.

This audit was conducted before and after introduction of a risk-based skincare policy with prophylactic steroids recommended for those at high risk. Comparison of the two cohorts confirmed results seen in trials with significant reduction in redness, itch, discomfort, sleep disturbance, and use of analgesia with the addition of steroids.

ESTRO-ACROP guideline "target delineation of glioblastomas".

BACKGROUND AND PURPOSE: Target delineation in glioblastoma (GBM) varies substantially between different institutions and several consensus statements are available. This guideline aims to develop a joint European consensus on the delineation of the clinical target volume in patients with a glioblastoma (GBM). MATERIAL AND METHODS: A literature search was conducted in PubMed that evaluated adults with GBM. Both MeSH terms and text words were used and the following search strategy was applied: ("Glioblastoma/radiotherapy" [MeSH] OR "glioblastoma" OR "malignant glioma" OR high-grade glioma) AND ((delineation) OR (target volume) OR (CTV) OR (PTV) OR (margin) OR (recurrence pattern) OR (contouring) OR (organs at risk)). In parallel, abstracts from ESTRO and ASTRO 2010-2015 were analysed and separately reviewed. The ACROP committee identified 14 European experts in close interaction with the ESTRO clinical committee who discussed and analysed the body of evidence concerning GBM target delineation. RESULTS: Several key issues were identified and are discussed including (i) pre-treatment steps and immobilization, (ii) target delineation and the use of standard and novel imaging techniques, and (iii) technical aspects of treatment including planning techniques, and fractionation. Based on the EORTC recommendation focusing on the resection cavity and residual enhancing regions on T1-sequences with the addition of a 20mm margin, special situations are presented with corresponding potential adaptations depending on the specific clinical situation. CONCLUSIONS: Currently, based on the EORTC consensus, a single clinical target volume definition based on postoperative T1/T2 FLAIR abnormalities is recommended, using isotropic margins without the need to cone down. A PTV margin based on the individual mask system and IGRT procedures available is advised, usually of the order of 3-5mm.

Identifying radiotherapy target volumes in brain cancer by image analysis.

To establish the optimal radiotherapy fields for treating brain cancer patients, the tumour volume is often outlined on magnetic resonance (MR) images, where the tumour is clearly visible, and mapped onto computerised tomography images used for radiotherapy planning. This process requires considerable clinical experience and is time consuming, which will continue to increase as more complex image sequences are used in this process. Here, the potential of image analysis techniques for automatically identifying the radiation target volume on MR images, and thereby assisting clinicians with this difficult task, was investigated. A gradient-based level set approach was applied on the MR images of five patients with grades II, III and IV malignant cerebral glioma. The relationship between the target volumes produced by image analysis and those produced by a radiation oncologist was also investigated. The contours produced by image analysis were compared with the contours produced by an oncologist and used for treatment. In 93% of cases, the Dice similarity coefficient was found to be between 60 and 80%. This feasibility study demonstrates that image analysis has the potential for automatic outlining in the management of brain cancer patients, however, more testing and validation on a much larger patient cohort is required.

Thoracic radiotherapy for limited-stage small cell lung cancer: issues of timing, volumes, dose, and fractionation.

Although meta-analysis of randomized trials comparing chemotherapy alone versus chemotherapy plus thoracic irradiation demonstrated that thoracic radiotherapy reduced mortality by 14%, this analysis probably underestimates the effect of optimally delivered thoracic irradiation integrated with appropriate chemotherapy. However, there remains much debate as to the optimal timing of the radiotherapy and the radiotherapy volume, dose, and fractionation. Theoretically, early use of radiotherapy should reduce the probability of chemotherapy and radiation resistance, accelerated repopulation, and metastatic events. Deferred or sequential radiotherapy potentially allows smaller radiotherapy fields. Of the seven randomized controlled trials examining timing, only those with early chemoradiation have 5-year survival rates in excess of 20%. The "chemoradiation package" can be defined as the time from the start of chemotherapy until the completion of radiotherapy. The best median survival and long-term survival rates have been observed in trials with a chemoradiation package time of less than 6 weeks. Protocols combining chemotherapy and radiotherapy must respect radiobiologic principles concerning the time factor derived from radiotherapy fractionation studies.

The effect of overall treatment time on the survival and toxicity of radical radiotherapy for cervical carcinoma.

BACKGROUND AND PURPOSE: Overall treatment time is an important factor in the outcome of radical radiotherapy in head and neck, bladder and lung cancer and in cervix cancer treated over more than 7 weeks. This study analysed the effect of prolongation of overall treatment time on survival and late morbidity for patients receiving radical radiotherapy for cervical cancer treated with a 4-week regimen. MATERIALS AND METHODS: Using the departmental SAS data-base we identified all patients with cervix cancer treated between 1974 and 1988 and investigated the 647 patients who received 20 fractions of external beam radiotherapy plus intracavitary therapy with a total dose to point A of at least 60Gy. A retrospective case-note review identified tumour and treatment-related variables. RESULTS: Four hundred and twenty-five (66%) patients had at least one gap in treatment. Seventy-nine gaps (11%) were due to unavoidable patient or treatment-related causes. We could not find an effect of a treatment gap (P=0.43) or an increased overall treatment time (P=0.79) on the cause specific survival of patients. There was significantly more grade 4 morbidity in those patients treated over a short period (29-32 days) compared to the rest (P=0.005), possibly related to the loss of radiotherapy-free days to weekend intracavitary insertions. CONCLUSIONS: We could not demonstrate a significant effect of overall treatment time in this series of patients, almost all of whom were treated in less than 7 weeks. Those patients treated over the shortest period had an increased incidence of late morbidity.

Portal imaging to assess set-up errors, tumor motion and tumor shrinkage during conformal radiotherapy of non-small cell lung cancer.

PURPOSE: To investigate patient set-up, tumor movement and shrinkage during 3D conformal radiotherapy for non-small cell lung cancer. MATERIALS AND METHODS: In 97 patients, electronic portal images (EPIs) were acquired and corrected for set-up using an off-line correction protocol based on a shrinking action level. For 25 selected patients, the orthogonal EPIs (taken at random points in the breathing cycle) throughout the 6-7 week course of treatment were assessed to establish the tumor position in each image using both an overlay and a delineation technique. The range of movement in each direction was calculated. The position of the tumor in the digitally reconstructed radiograph (DRR) was compared to the average position of the lesion in the EPIs. In addition, tumor shrinkage was assessed. RESULTS: The mean overall set-up errors after correction were 0, 0.6 and 0.2 mm in the x (left-right), y (cranial-caudal) and z (anterior-posterior) directions, respectively. After correction, the standard deviations (SDs) of systematic errors were 1.4, 1.5 and 1.3 mm and the SDs of random errors were 2.9, 3.1 and 2.0 mm in the x-, y- and z-directions, respectively. Without correction, 41% of patients had a set-up error of more than 5 mm vector length, but with the set-up correction protocol this percentage was reduced to 1%. The mean amplitude of tumor motion was 7.3 (SD 2.7), 12.5 (SD 7.3) and 9.4 mm (SD 5.2) in the x-, y- and z-directions, respectively. Tumor motion was greatest in the y-direction and in particular for lower lobe tumors. In 40% of the patients, the projected area of the tumor regressed by more than 20% during treatment in at least one projection. In 16 patients it was possible to define the position of the center of the tumor in the DRR. There was a mean difference of 6 mm vector length between the tumor position in the DRR and the average position in the portal images. CONCLUSIONS: The application of the correction protocol resulted in a significant improvement in the set-up accuracy. There was wide variation in the observed tumor motion with more movement of lower lobe lesions. Tumor shrinkage was observed. The position of the tumor on the planning CT scan did not always coincide with the average position as measured during treatment.

Population-based outcomes for small cell lung cancer: impact of standard management policies in British Columbia.

Survival data for small cell lung cancer (SCLC) is typically reported from clinical trials or institutional series that include patients fit enough to meet treatment criteria. The denominator of all SCLC patients from which the treated population is derived is rarely reported and the impact of new treatment strategies on population-based outcomes is difficult to measure. The British Columbia Cancer Agency (BCCA) is a single centralized agency that coordinates cancer treatment services in the province and develops and circulates province-wide treatment guidelines. All SCLC cases diagnosed in BC in 1990 and 1995 (n=331 and 297, respectively) were identified. These 2 years were chosen specifically to examine the impact of a change in practice guidelines from consolidative to early concurrent thoracic radiation (RT) for patients with limited stage disease. Demographic, staging, treatment, and outcome details were obtained for 100% of cases. A total of 628 patients were reviewed, 207 with limited stage disease (LSCLC) and 407 with extensive stage disease (ESCLC); 14 cases diagnosed at post-mortem were excluded. Of the 207 patients with LSCLC disease, 170 (82%) received chemotherapy, and 138 (81%) of those that received chemotherapy also received thoracic radiation. A similar proportion (73 and 70%) of LSCLC patients received thoracic RT in both years but more patients in 1995 received early concurrent versus consolidative thoracic RT compared to those treated in 1990 (64% versus 17%, respectively, P=0.001). Of the 407 patients with ESCLC, 71% received chemotherapy. The median overall survival for all patients was 7 months. Patients with LSCLC who received any chemotherapy had a median survival of 14.3 months (26.9 and 9.9% for 2- and 5-year survival, respectively). Patients with LSCLC who received chemotherapy plus thoracic RT had a median survival of 15.1 months (32 and 12% for 2- and 5-year survival, respectively). Early concurrent thoracic RT in LSCLC was associated with an improved 5-year survival from 9.6 to 16.3% (P=0.91). Patients with ESCLC who received any chemotherapy had a median survival of 8.4 months (7.3 and 2.3% for 2- and 5-year survival, respectively). Standard treatment guidelines generated population-based survival outcomes that are similar to published clinical trials.

Factors influencing the use of thoracic radiotherapy in lung cancer--an analysis of the 1995 Scottish lung cancer audit.

AIMS: To determine the frequency of delivery of thoracic radiotherapy (TRT) to patients with lung cancer in Scotland in 1995, and identify patient, disease and process variables affecting the probability of receiving TRT. METHODS: Retrospective case note audit of all patients with lung cancer diagnosed in Scotland in 1995. RESULTS: 1118 (30.8%) of 3,855 patients diagnosed with lung cancer in Scotland in 1995 for whom the medical records could be traced received TRT. In those who did not have small cell lung cancer, multivariate analysis indicated that diagnosis by a lung cancer specialist, clinical extent of disease and microscopic verification of cancer (all P<0.0001) and age (P=0.0005) were associated with an increased chance of receiving TRT. There was also a wide variation between different Health Boards (HB) of residence in the proportion of patients receiving TRT (P<0.0001). There was no association between the presence of local symptoms (cough, chest pain or haemoptysis) and the delivery of TRT. Of 351 patients with limited stage small cell lung cancer, 51 (14.5%) received chemotherapy and TRT, and 19 (5.4%) chemotherapy and cranial irradiation. CONCLUSIONS: TRT was delivered to fewer than one-third of patients with lung cancer in Scotland in 1995. This is lower than reported in other international audits. The chance of receiving TRT seemed to be associated with service issues rather than clinical need.