Development and validation of prognostic models for anal cancer outcomes using distributed learning: protocol for the international multi-centre atomCAT2 study.

BACKGROUND: Anal cancer is a rare cancer with rising incidence. Despite the relatively good outcomes conferred by state-of-the-art chemoradiotherapy, further improving disease control and reducing toxicity has proven challenging. Developing and validating prognostic models using routinely collected data may provide new insights for treatment development and selection. However, due to the rarity of the cancer, it can be difficult to obtain sufficient data, especially from single centres, to develop and validate robust models. Moreover, multi-centre model development is hampered by ethical barriers and data protection regulations that often limit accessibility to patient data. Distributed (or federated) learning allows models to be developed using data from multiple centres without any individual-level patient data leaving the originating centre, therefore preserving patient data privacy. This work builds on the proof-of-concept three-centre atomCAT1 study and describes the protocol for the multi-centre atomCAT2 study, which aims to develop and validate robust prognostic models for three clinically important outcomes in anal cancer following chemoradiotherapy. METHODS: This is a retrospective multi-centre cohort study, investigating overall survival, locoregional control and freedom from distant metastasis after primary chemoradiotherapy for anal squamous cell carcinoma. Patient data will be extracted and organised at each participating radiotherapy centre (n = 18). Candidate prognostic factors have been identified through literature review and expert opinion. Summary statistics will be calculated and exchanged between centres prior to modelling. The primary analysis will involve developing and validating Cox proportional hazards models across centres for each outcome through distributed learning. Outcomes at specific timepoints of interest and factor effect estimates will be reported, allowing for outcome prediction for future patients. DISCUSSION: The atomCAT2 study will analyse one of the largest available cross-institutional cohorts of patients with anal cancer treated with chemoradiotherapy. The analysis aims to provide information on current international clinical practice outcomes and may aid the personalisation and design of future anal cancer clinical trials through contributing to a better understanding of patient risk stratification.

Establishing a colorectal cancer research database from routinely collected health data: the process and potential from a pilot study.

OBJECTIVE: Colorectal cancer is a common cause of death and morbidity. A significant amount of data are routinely collected during patient treatment, but they are not generally available for research. The National Institute for Health Research Health Informatics Collaborative in the UK is developing infrastructure to enable routinely collected data to be used for collaborative, cross-centre research. This paper presents an overview of the process for collating colorectal cancer data and explores the potential of using this data source. METHODS: Clinical data were collected from three pilot Trusts, standardised and collated. Not all data were collected in a readily extractable format for research. Natural language processing (NLP) was used to extract relevant information from pseudonymised imaging and histopathology reports. Combining data from many sources allowed reconstruction of longitudinal histories for each patient that could be presented graphically. RESULTS: Three pilot Trusts submitted data, covering 12 903 patients with a diagnosis of colorectal cancer since 2012, with NLP implemented for 4150 patients. Timelines showing individual patient longitudinal history can be grouped into common treatment patterns, visually presenting clusters and outliers for analysis. Difficulties and gaps in data sources have been identified and addressed. DISCUSSION: Algorithms for analysing routinely collected data from a wide range of sites and sources have been developed and refined to provide a rich data set that will be used to better understand the natural history, treatment variation and optimal management of colorectal cancer. CONCLUSION: The data set has great potential to facilitate research into colorectal cancer.

An international Delphi consensus for pelvic stereotactic ablative radiotherapy re-irradiation.

INTRODUCTION: Stereotactic Ablative Radiotherapy (SABR) is increasingly used to treat metastatic oligorecurrence and locoregional recurrences but limited evidence/guidance exists in the setting of pelvic re-irradiation. An international Delphi study was performed to develop statements to guide practice regarding patient selection, pre-treatment investigations, treatment planning, delivery and cumulative organs at risk (OARs) constraints. MATERIALS AND METHODS: Forty-one radiation oncologists were invited to participate in three online surveys. In Round 1, information and opinion was sought regarding participants' practice. Guidance statements were developed using this information and in Round 2 participants were asked to indicate their level of agreement with each statement. Consensus was defined as ≥75% agreement. In Round 3, any statements without consensus were re-presented unmodified, alongside a summary of comments from Round 2. RESULTS: Twenty-three radiation oncologists participated in Round 1 and, of these, 21 (91%) and 22 (96%) completed Rounds 2 and 3 respectively. Twenty-nine of 44 statements (66%) achieved consensus in Round 2. The remaining 15 statements (34%) did not achieve further consensus in Round 3. Consensus was achieved for 10 of 17 statements (59%) regarding patient selection/pre-treatment investigations; 12 of 13 statements (92%) concerning treatment planning and delivery; and 7 of 14 statements (50%) relating to OARs. Lack of agreement remained regarding the minimum time interval between irradiation courses, the number/size of pelvic lesions that can be treated and the most appropriate cumulative OAR constraints. CONCLUSIONS: This study has established consensus, where possible, in areas of patient selection, pre-treatment investigations, treatment planning and delivery for pelvic SABR re-irradiation for metastatic oligorecurrence and locoregional recurrences. Further research into this technique is required, especially regarding aspects of practice where consensus was not achieved.

A multicentre retrospective review of SABR reirradiation in rectal cancer recurrence.

BACKGROUND AND PURPOSE: Locally recurrent rectal cancer (LRRC) is associated with considerable morbidity, poor quality of life and an overall survival of 9 months. The non-operative treatment of LRRC is an understudied area, there is no consensus on management in this setting. We aim to perform a retrospective, multicentre analysis of patients treated with SABR reirradiation. MATERIALS AND METHODS: All patients were identified who received SABR re-irradiation for LRRC, at 3 UK centres, between August 2015 and September 2020. Eligible patients had pelvic recurrence and were either not suitable/opted not for surgery, or margin positive after exenturative surgery. Patients were treated with 30 Gy in 5 fractions and followed up with clinical review and CT scan at 3, 6, 12, 18 and 24 months. RESULTS: 69 patients with 81 lesions were identified and median follow up was 28 months. Median progression free survival (PFS) and overall survival (OS) were 12.1 months (10.4, 17.7) and 38.7 months (28.9,-) respectively. 2-year OS was 0.77 (0.66, 0.89). 58.3% of deaths were as a result of consequences of local relapse. 42.6% of patients had local relapse at death or last follow up. CONCLUSION: Our outcomes are encouraging for a population who had R1 resections, refused or were refused surgery; as they are similar to those in surgical series. Prospective data including details of survival, local relapse and QOL; with an optimised SABR technique, is required to establish SABR as an alternative to surgery.

Rectal cancer: Watch-and-wait and continuing the rectal-preserving strategy with local excision for incomplete response or limited regrowth.

BACKGROUND: Deferral of conventional surgery for rectal cancer after neo-adjuvant chemo-radiotherapy is gaining increasing interest, particularly for patients who are too frail to undergo major surgery but also those who wish to avoid the adverse effects of major surgery. We elected to undertake a pragmatic approach to include all comers in a cohort with the aim of reflecting the clinical outcomes for patients on a deferral from conventional rectal surgery pathway, treated with neo-adjuvant chemo-radiation (CRT) with or without selective local excision (LE) offered to those who failed to demonstrate a complete clinical response (cCR). METHODS: Rectal cancer patients treated with neo-adjuvant CRT were stratified to a group of complete responders to CRT on a "watch and wait" (WW) pathway and a group who were treated with an additional local excision for persistent tumour. RESULTS: Regrowth was noted in 26% (11/42) in the WW group after 2 years surveillance, disease free survival was 94.5% (80-99%) at 1 year and 74.9% (44-76.4%) at 3 years. Recurrence was noted in 45% (10/22) in the CRT + LE group, disease free survival at 1 and 3 years was 74% (53.4-88.1) and 66.2% (45.6-82.4) respectively. CONCLUSION: A WW strategy for cCR is a viable pathway in the non-operative management of rectal cancer. We found the use of CRT + LE is a useful option for those who hope to avoid surgery but caution should be exercised due to substantially higher risk of recurrence.

International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct.

PURPOSE: To compare cisplatin plus fluorouracil (FU) versus carboplatin plus paclitaxel in chemotherapy-naïve advanced anal cancer to establish the optimal regimen. PATIENTS AND METHODS: Patients who had not received systemic therapy for advanced anal cancer were randomly assigned 1:1 to intravenous cisplatin 60 mg/m2 (day 1) plus FU 1,000 mg/m2 (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m2 (days 1, 8, and 15) every 28 days for 24 weeks, until disease progression, intolerable toxicity, or withdrawal of consent. Primary end point was objective response rate (ORR). Primary and secondary end points were assessed in a hierarchic model to compare the regimens and pick the winner. RESULTS: We conducted an international multicenter randomized phase II study in 60 centers between December 2013 and November 2017. Median follow-up was 28.6 months. A total of 91 patients were randomly assigned: 46 to cisplatin plus FU and 45 to carboplatin plus paclitaxel. ORR was 57% (95% CI, 39.4% to 73.7%) for cisplatin plus FU versus 59% (95% CI, 42.1% to 74.4%) for carboplatin plus paclitaxel. More serious adverse events were noted in the cisplatin plus FU arm (62%) compared with the carboplatin plus paclitaxel arm (36%; P = .016). Median progression-free survival was 5.7 months (95% CI, 3.3 to 9.0 months) for cisplatin plus FU compared with 8.1 months (95% CI, 6.6 to 8.8 months) for carboplatin plus paclitaxel. Median overall survival was 12.3 months for cisplatin plus FU (95% CI, 9.2 to 17.7 months) compared with 20 months (95% CI, 12.7 months to not reached) for carboplatin plus paclitaxel (hazard ratio, 2.00; 95% CI, 1.15 to 3.47; P = .014). CONCLUSION: This is the first international randomized trial to our knowledge conducted in chemotherapy-naïve advanced anal cancer. Although there was no difference in ORR, the association with clinically relevant reduced toxicity and a trend toward longer survival suggest that carboplatin plus paclitaxel should be considered as a new standard of care.

Oxygen-enhanced MRI MOLLI T1 mapping during chemoradiotherapy in anal squamous cell carcinoma.

BACKGROUND AND PURPOSE: Oxygen-enhanced magnetic resonance imaging (MRI) and T1-mapping was used to explore its effectiveness as a prognostic imaging biomarker for chemoradiotherapy outcome in anal squamous cell carcinoma. MATERIALS AND METHODS: T2-weighted, T1 mapping, and oxygen-enhanced T1 maps were acquired before and after 8-10 fractions of chemoradiotherapy and examined whether the oxygen-enhanced MRI response relates to clinical outcome. Patient response to treatment was assessed 3 months following completion of chemoradiotherapy. A mean T1 was extracted from manually segmented tumour regions of interest and a paired two-tailed t-test was used to compare changes across the patient population. Regions of subcutaneous fat and muscle tissue were examined as control ROIs. RESULTS: There was a significant increase in T1 of the tumour ROIs across patients following the 8-10 fractions of chemoradiotherapy (paired t-test, p < 0.001, n = 7). At baseline, prior to receiving chemoradiotherapy, there were no significant changes in T1 across patients from breathing oxygen (n = 9). In the post-chemoRT scans (8-10 fractions), there was a significant decrease in T1 of the tumour ROIs across patients when breathing 100% oxygen (paired t-test, p < 0.001, n = 8). Out of the 12 patients from which we successfully acquired a visit 1 T1-map, only 1 patient did not respond to treatment, therefore, we cannot correlate these results with clinical outcome. CONCLUSIONS: These clinical data demonstrate feasibility and potential for T1-mapping and oxygen enhanced T1-mapping to indicate perfusion or treatment response in tumours of this nature. These data show promise for future work with a larger cohort containing more non-responders, which would allow us to relate these measurements to clinical outcome.

Response of FDG avid pelvic bone marrow to concurrent chemoradiation for anal cancer.

BACKGROUND AND PURPOSE: To determine if suppression of active bone marrow, as defined on FDG PETCT, is seen in on-treatment imaging of anal cancer patients receiving concurrent chemoradiation. METHODS AND MATERIALS: Scans from 26 patients participating in the ART trial (full title: Anal squamous cell carcinoma: Investigation of functional imaging during chemoRadioTherapy), a single center observational study with FDG PETCT prior to radiotherapy and at fraction 8-10 of concurrent chemoradiation were analysed. Active bone marrow was contoured in both the pelvis and un-irradiated thoracic spine. SUV and volume of active bone marrow after 8-10 fractions of treatment were compared to baseline. Dose metrics to pelvic active bone marrow were extracted and compared to reduction in SUV/active bone marrow volume and to blood count nadir using linear regression. RESULTS: Suppression of active bone marrow is seen in the pelvis by a reduction in mean SUV and volume of active bone marrow after 8-10 fractions of treatment. Suppression is not seen in un-irradiated thoracic spine. Dose metrics were associated with reduced SUV and reduced volume of active bone marrow. Volume of active bone marrow receiving <20 Gy was associated with WCC/ANC nadir. 20 Gy was identified as the most likely clinically meaningful dose threshold for toxicity. Volume of active bone marrow receiving <20 Gy correlated to WCC and ANC with an increase of 100 cc being associated with an increase of 0.4 and 0.3 respectively. CONCLUSION: The effect of concurrent chemoradiation in suppression of active bone marrow is seen in on-treatment FDG PETCT scans. Chemotherapy appears well tolerated after 2 weeks of treatment.

Patterns and Predictors of Relapse Following Radical Chemoradiation Therapy Delivered Using Intensity Modulated Radiation Therapy With a Simultaneous Integrated Boost in Anal Squamous Cell Carcinoma.

PURPOSE: Our purpose was to describe the patterns and predictors of treatment failure in patients receiving definitive chemoradiation therapy (CRT) for anal squamous cell carcinoma (ASCC), delivered using intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: Our study was a retrospective cohort analysis of consecutive patients treated with curative intent for ASCC using CRT delivered with a standardized IMRT technique in 5 UK cancer centers. Patients were included from the start of UK IMRT guidance from February 2013 to October 31, 2017. Collected data included baseline demographics, treatment details, tumor control, sites of relapse, and overall survival. Statistical analysis to calculate outcomes and predictive factors for outcome measures were performed using SPSS and R. RESULTS: The medical records of 385 consecutive patients were analyzed. Median follow-up was 24.0 months. Within 6 months of completing CRT, 86.7% of patients achieved a complete response. Three-year disease-free survival and overall survival were 75.6% and 85.6%, respectively. Of all relapses, 83.4% occurred at the site of primary disease. There were 2 isolated relapses in regional nodes not involved at outset. Predictive factors for cancer recurrence included male sex, high N-stage, and failure to complete radiation therapy as planned. CONCLUSIONS: The treatment results compare favorably to published outcomes from similar cohorts using 3-dimensional conformal CRT. The observed patterns of failure support the current UK IMRT voluming guidelines and dose levels, highlighting our prophylactic nodal dose as sufficient to prevent isolated regional relapse in uninvolved nodes. Further investigation of strategies to optimize CR should remain a priority in ASCC because the site of primary disease remains the overwhelming site of relapse.

Toxicity, Tolerability, and Compliance of Concurrent Capecitabine or 5-Fluorouracil in Radical Management of Anal Cancer With Single-dose Mitomycin-C and Intensity Modulated Radiation Therapy: Evaluation of a National Cohort.

PURPOSE: Chemoradiation therapy (CRT) with mitomycin C (MMC) and 5-fluorouracil (5-FU) is established as the standard of care for the radical treatment of patients with anal squamous cell carcinoma (ASCC). The use of the oral fluoropyrimidine-derivative capecitabine is emerging as an alternative to 5-FU despite limited evidence of its tolerability and toxicity. METHODS AND MATERIALS: A national cohort evaluation of ASCC management within the United Kingdom National Health Service was undertaken from February to July 2015. The toxicity rates were prospectively recorded. For the present analysis, we report data from ASCC patients who underwent intensity modulated RT and a single dose of MMC with either 5-FU (5-FU/MMC) or capecitabine (capecitabine/MMC). All were treated with radical intent and intensity modulated radiation therapy (IMRT) was delivered in accordance with UK guidance. RESULTS: Of the 242 patients received from 40 centers across the United Kingdom, 147 met the inclusion criteria; 52 of whom were treated with capecitabine/MMC and 95 with 5-FU/MMC. No treatment-related deaths and no overall difference were found in the proportion of patients experiencing any grade ≥3 toxicity between the capecitabine and 5-FU groups (45% vs 55%; P = .35). However, significantly fewer patients in the capecitabine/MMC group experienced grade 3 hematologic toxicity (4% vs 27%; P = .001). A lower proportion of patients completed their planned chemotherapy course in the capecitabine cohort, although this did not reach statistical significance (81% vs 90%; P = .21). The median RT duration was 38 days (interquartile range 38-39) for both groups. No difference was found in the 1-year oncologic outcomes. CONCLUSIONS: Capecitabine/MMC resulted in similar levels of grade 3/4 toxicity overall compared with 5-FU/MMC as CRT for ASCC, although differences were found in the patterns of observed toxicities, with less hematologic toxicity with capecitabine. Further studies of capecitabine/MMC are required to understand the acute toxicity profile and long-term oncologic outcomes of this combination with intensity modulated RT for ASCC.

What To Do With Lateral Nodal Disease in Low Locally Advanced Rectal Cancer? A Call for Further Reflection and Research.

BACKGROUND: There remains a lack of international consensus on the appropriate management of lateral nodal disease. Although the East manages this more aggressively with lateral lymph node dissections, the West aims to eradicate small-volume disease with neoadjuvant chemoradiotherapy and lateral nodal disease is not considered for routine surgical treatment. However, recent studies have shown that, despite neoadjuvant treatment, a significant number of patients with lateral nodal disease develop local recurrence in the lateral compartment after total mesorectal excision. OBJECTIVE: The aim of this study is to assess the role of the pretreatment features of lateral nodes on MRI in regard to local recurrence. DESIGN: All patients operated on for low locally advanced rectal cancer over a 5-year period were evaluated retrospectively. SETTINGS: This study was conducted at a single expert center. PATIENTS: The MRIs of a total of 313 patients were reviewed, and only those with rectal cancers up to 8 cm from the anorectal junction, measured on MRI, were selected. This left 185 patients; of these, 58 patients had clinical T1 or T2 tumors as assessed on MRI, identifying 127 patients who had cT3/T4 tumors that were included in this study. MAIN OUTCOME MEASURES: The primary outcomes measured were lateral local recurrence and multivariate analyses. RESULTS: The lateral local recurrence rate was significantly higher (33.3% 4-year rate) in patients with nodes larger than 10 mm than in patients with smaller nodes (10.1%, p = 0.03), despite patients being irradiated in the lateral compartment. LIMITATIONS: Because this is a relatively uncommon disease, patient numbers are low, and a multicenter study is needed to further address lateral nodal disease in low rectal cancer. CONCLUSIONS: Chemoradiotherapy with total mesorectal excision might not be sufficient in a selected group of patients. Further research is needed about which pretreatment features of the lateral nodes predict local recurrence and what is needed to prevent these from developing. See Video Abstract at http://links.lww.com/DCR/A338.

Quantifying target-specific motion in anal cancer patients treated with intensity modulated radiotherapy (IMRT).

BACKGROUND AND PURPOSE: Intensity modulated radiotherapy requires all target areas to be treated by a single radiotherapy plan. In anal cancer, the pelvic nodes, inguinal nodes and primary tumour represent three different targets. We aim to calculate target-specific motion in anal cancer radiotherapy, when delivered using a single pelvic online auto-match. MATERIALS AND METHODS: Twenty consecutive patients treated using IMRT at a single institution were studied. CBCTs were retrospectively re-matched around the inguinal nodes and primary tumour. Match values were recorded relative to origin, defined as pelvic CBCT auto-match. Systematic and random errors were quantified to determine target-specific motion and suggested margins calculated using van Herk formulae. RESULTS: The suggested margins to cover the independent motion of the inguinal and anal targets for LR, CC and AP set up around the inguinal nodes were 1.5mm, 2.7mm and 2.8mm; and the primary tumour were, 4.6mm, 8.9mm and 5.2mm respectively. CONCLUSIONS: Target-specific set up will likely result in reduced treatment volumes and as such reduced toxicity. This is the first time a relationship has been described between pelvic bones, inguinal nodes and primary tumour. The PLATO study will prospectively assess the toxicity and outcomes of this target-specific margins strategy.

Modeling early haematologic adverse events in conformal and intensity-modulated pelvic radiotherapy in anal cancer.

BACKGROUND AND PURPOSE: To determine if there are differences between dose to pelvic bone marrow (PBM) using intensity modulated radiotherapy (IMRT) under UK guidance versus conformal radiotherapy (CRT) per ACT II protocol and if differences translate to rates of early haematological adverse events grade 3 or greater (HT3+). METHODS AND MATERIALS: Two groups of 20+ patients, treated under IMRT and CRT regimes respectively, were identified. All patients underwent weekly blood cell count: haemoglobin (HgB), white cell count (WCC), absolute neutrophil count (ANC) and platelets (plats). Percent volume of PBM and sub structures receiving 5-25 Gy were tested for statistical significance. Regression models were used to test for correlation to blood counts. NTCP modeling was also performed. RESULTS: PMB dose metrics showed a significant increase in the IMRT group. Regression analysis showed iliac and lumbosacral PBM dose metrics to associate with reduced nadir ANC and WCC. NTCP at HT3+ was 0.13 using IMRT relative to 0.07 using CRT (p<0.05). CONCLUSION: Whilst this is a relatively small retrospective study and lacks information on the distribution of active PBM, IMRT treatment has been shown to significantly increase PMB irradiation. PBM dose metrics have been shown to be predictive of WCC and ANC suppression. NTCP modeling predicts much high risk of HT3+. Paradoxically, actual rates of HT3+ were comparable suggesting that differences in the distributions of dose metrics maybe a significant factor and/or that there are insufficiency in the NTCP modeling.

A tumor control probability model for anal squamous cell carcinoma.

BACKGROUND AND PURPOSE: A recent update of the RTOG 9811, reported differing relapse rates for early and late anal squamous cell carcinoma following chemoradiotherapy (CRT). There may be a role for dose-individualization, however the dose-response relationship for anal cancer is not currently known. Intensity-modulated radiotherapy (IMRT) has been widely adopted with multiple series published. The aim is to fit a tumor control probability (TCP) model to the published IMRT data. MATERIALS AND METHODS: We performed a systematic review of PubMed and Embase databases to identify thirteen appropriate papers, including 625 patients. Predefined data fields were collected. A standard linear quadratic TCP model, which included repopulation, was fit by least squares minimization. RESULTS: The fitted TCP curve demonstrated a dose-response relationship with α=0.196 Gy(-1). The curve suggests: in early stage tumours, a dose reduction from 50 Gy to 45 Gy reduces 2 year local control from 98% to 95%; in late stage tumours, a dose escalation from 50 Gy to 55 Gy improves the 2 year local control rate from approximately 50% to 80%. CONCLUSIONS: The published data are broadly consistent with a linear quadratic dose-response model. Dose-individualization in anal cancer should be further investigated in the context of clinical trials.

Potential benefits and pitfalls of respiratory-gated radiotherapy in the treatment of thoracic malignancy.

AIM: Despite advances in radiotherapy delivery, the prognosis of lung cancer remains poor. Higher doses of radiation have been associated with improved outcomes but may result in higher toxicities. Respiratory gated radiotherapy (RGRT) has the potential to reduce pulmonary toxicity but there are significant limitations and pitfalls to its use. The aim of this article is to (i) describe the RGRT technique currently employed at Nepean and Westmead Hospitals; (ii) discuss the practical issues of implementing such a program; (iii) present the results of our RGRT program and (iv) review the potential uncertainties in using this technique and the methods we have used to overcome these. METHODS: A retrospective review of all patients who had a 4D-computed tomography (4D-CT) scan was undertaken. Records from treatment planning systems were used to assess the prospective gating program. RESULTS: Between September 2007 and June 2011, 53 patients at Nepean and 26 patients at Westmead Hospital underwent a 4D-CT. Between April and August 2011, 26 patients at Westmead Hospital underwent a prospective 4D-CT scan as treatment verification. Two of the 26 patients (7.7%) were found to have incomplete coverage of the planning target volume. Both patients underwent respiratory re-coaching, alleviating the need for replanning. CONCLUSION: RGRT may reduce doses to organs at risk with the potential for dose escalation. However its implementation requires significant staff training, treatment time and resources. Treatment verification with image guided radiation therapy are essential for safe delivery.

Minimal benefit of respiratory-gated radiation therapy in the management of thoracic malignancy.

BACKGROUND: Respiratory-gated radiotherapy (RGRT) is used in several centres around the world. However, there is continuing controversy regarding the benefit of this technique. The aims of this study are to quantify the dosimetric benefits and the potential predictive factors. METHODS: Thirty-four consecutive patients were planned using the RGRT and the Free Breathing (FB) approach and compared with regard to target volume coverage and normal tissue parameters. Potential predictive factors were also evaluated. RESULTS: Tumour coverage was similar 94.4% versus 95.5%. Use of RGRT was not associated with a significant reduction in spinal cord, oesophagus or cardiac dosimetric parameters. However, it did reduce the lung mean dose by 1.33 Gy (P < 0.001) and V20 by 2.2% (P < 0.001). Only superior/inferior displacement of >1 cm was predictive of a >5% reduction in lung V20 parameter, and these patients all had a gross tumour volume (GTV) of <100 cm(3). CONCLUSIONS: The dosimetric benefit of applying RGRT is small when applied in an unselected population of patients. Superior/inferior displacement of >1 cm for tumours with GTV less than 100 cm(3) may be used to select patients who may derive a >5% reduction in lung V20 parameters.

Use of megavoltage cine-images for studying intra-thoracic motion during radiotherapy for locally advanced lung cancer.

BACKGROUND AND PURPOSE: Use of planning 4-dimensional CT (4DCT) scans often permits use of smaller target volumes for thoracic tumors but this assumes a reproducible pattern of motion during radiotherapy. We compared cranio-caudal (CC) motion on MV cine-images acquired during treatment with that seen on planning 4DCT. METHODS AND MATERIALS: A pre-programmable respiratory motion phantom and a software tool for motion assessment were used to validate the use of MV cine-images for motion detection. MV cine-images acquired in 20 patients with node-positive lung cancer were analyzed using the same software. Intra-fraction CC motion on 6 MV cine-images from each patient was compared with CC motion on their planning 4DCT. RESULTS: Software-based motion measurement on MV cine-images from the phantom corresponded to actual motion. Mean CC motion of primary tumor, carina and hilus on 4DCT was 7.3mm (range 2-13.8mm), 6.8mm (1.8-21.2) and 11.0mm (4.2-15.1), respectively. Corresponding intra-fraction motion on MV cine was 4.1mm (0.6-13.6mm); 2.7mm (0-10mm) and 6.0mm (1.8-14.4mm), respectively. The tumor, hilus and carina could be tracked in 95%, 88% and 38% of the MV cine-images, respectively. CONCLUSIONS: Intra-fraction motion can be reliably measured using MV-cine images from a phantom. Motion discrepancies identified on MV cine-images can identify patients in whom planning 4DCT scans are not representative.

Improving target delineation on 4-dimensional CT scans in stage I NSCLC using a deformable registration tool.

INTRODUCTION: Correct target definition is crucial in stereotactic radiotherapy for lung tumors. We evaluated use of deformable registration (DR) for target contouring on 4-dimensional (4D) CT scans. MATERIALS AND METHODS: Three clinicians contoured gross tumor volume (GTV) in an end-inspiration phase of 4DCT of 6 patients on two occasions. Two clinicians contoured GTVs in all phases of 4DCT and on maximum intensity projections (MIP). The initial GTV was auto-propagated to 9 other phases using a B-spline algorithm (VelocityAI). Internal target volumes (ITVs) generated were (i) ITV(10manual) encompassing all physician-contoured GTVs, (ii) ITV-MIP(optimized) from MIP after review of individual 4DCT phases, (iii) ITV(10deformed) encompassing auto-propagated GTVs using DR, and (iv) ITV(10deformed-optimized), from an ITV(10deformed) target that was modified to form a 'clinically optimal' ITV. Volume-overlaps were scored using Dice's Similarity Coefficients (DSCs). RESULTS: Intra-clinician GTV reproducibility was greater than inter-clinician reproducibility (mean DSC 0.93 vs. 0.88, p<0.0004). In five of 6 patients, ITV-MIP(optimized) differed from the ITV(10deformed-optimized). In all patients, the DSC between ITV(10deformed-optimized) and ITV(10deformed) was higher than that between ITV(10deformed-optimized) and ITV-MIP(optimized) (p<0.02 T-test). CONCLUSION: ITVs created in stage I tumors using DR were closer to 'clinically optimal' ITVs than was the case with a MIP-modified approach.

The potential clinical benefit of respiratory gated radiotherapy (RGRT) in non-small cell lung cancer (NSCLC).

BACKGROUND: There is a great deal of excitement regarding respiratory gated radiotherapy (RGRT), however there remain potential errors and controversies surrounding its use. We aim to predict an improvement in the clinical outcome of RGRT in comparison with that of continuous (non-gated) irradiation by analysing toxicity parameters. MATERIALS AND METHODS: The 4DCT scans of 15 patients, with node-positive lung cancer and > 5 mm of tumour movement, were used for this retrospective analysis. End-inspiration and end-expiration plans were created and the toxicity parameters were compared to continuous (non-gated) 4DCT plans. RESULTS: Median reduction in V20 with inspiratory gating and expiratory gating, using a 10mm set-up margin, was 2.0% (range 0.7% to 3.9%) and 0.6% (range -1.1% to 4.7%), respectively. The reduction in MLD was 2.1 Gy (range 0.6 to 3.9 Gy) and 1.6 Gy (range -1.0 to 3.9 Gy), respectively. CONCLUSIONS: Although there is a widespread excitement regarding this technique, this study demonstrates that there is limited reduction in toxicity parameters with the use of RGRT in comparison with continuous (non-gated) 4DCT irradiation. Due to the additional potential errors involved in RGRT, we feel that currently, it should only be performed if comparative planning of RGRT plans and continuous (non-gated) 4DCT plans has been undertaken and a likely clinical benefit has been confirmed.