Internal motion of the vagina after hysterectomy for gynaecological cancer

Background and purpose

The purpose of this study was to investigate position changes of the vagina after hysterectomy for early stage cervical or endometrial cancer and their impact on CTV-PTV margins. We also studied their correlation with surrounding organ filling.

Materials and methods

Fifteen patients underwent T2-weighted MR scans before and weekly during the course of their EBRT. The vaginal CTVs and the surrounding organs were delineated. PTV margins were derived from the boundaries of the CTVs in the main directions and correlated with changes in the volumes of organs at risk. Additionally we investigated the impact of margin sizes on CTV coverage.

Results

The vaginal CTVs change their position in the pelvis during time with a maximum in anterior-posterior direction. The 95% confidence level was 2.3 cm into the anterior or posterior direction, 1.8 cm to left or right and 1.5 cm towards the cranial. With a homogenous 1.5 cm CTV-PTV margin ?5% inadequately covered vaginal CTV was seen in only 3.3% of the measurements. This increased to 20.6% with a margin of 1.0 cm. Concerning the impact of organ filling on vaginal position changes we found the only significant correlation with rectal volume and shift of the vagina towards anterior-posterior.

Conclusion

To accommodate the changes in the position of the vaginal CTV inhomogeneous PTV margins should be generated with the largest size in the anterior-posterior direction. The position shifts were only weakly related to the volume of the rectum and not at all to the volumes of other parts of the bowel and the bladder.     

Increasing treatment accuracy for cervical cancer patients using correlations between bladder-filling change and cervix-uterus displacements: Proof of principle

Purpose

To investigate application of pre-treatment established correlations between bladder-filling changes and cervix-uterus displacements in adaptive therapy.

Materials and methods

Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40 Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1 h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (ToU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40 Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner.

Results

Target displacement in VBF-scans ranged from up to 65 mm in a single direction to almost 0 mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1 mm ± 10.8 with a residual of only 2.2 mm ± 1.7. For the marker-CoM, the 8.4 mm ± 5.3 mean positioning error was predicted with a residual of 0.9 mm ± 0.7. After 40 Gy, the mean ToU displacement was 26.8 mm ± 15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0 mm ± 3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (−18.5 mm ± 11.2 for systematic errors in SI-direction).

Conclusions

Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors.     

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.     

Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: A meta-analysis

Aims

Whether gemcitabine based chemoradiotherapy (GEM-based CRT) is superior to 5-fluorouracil based chemoradiotherapy (5-FU-based CRT) for locally advanced pancreatic cancer (LAPC) remains uncertain. The aim of the present study was to evaluate the effect of GEM-based CRT compared with 5-FU-based CRT.

Methods

Electronic database including Medline, Embase, Cochrane controlled trials register, PubMed (update to December 2010) and manual bibliography searches were carried out. A meta-analysis of all randomized clinical trials (RCTs) or other comparative studies comparing GEM-based CRT and 5-FU-based CRT were performed.

Results

Three RCTs and one retrospective comparative study including 229 patients were assessed. Meta-analysis showed survival advantage of GEM-based CRT compared with 5-FU-based CRT for 12-month (12-mo) survival rates (SRs) (RR = 1.54, 95% CI 1.05-2.26, p = 0.03). Moreover, there were also trends of benefit for SR after 6-months (RR 1.13, 95% CI 0.98-1.30, p = 0.09) and 24-months (24-mo: RR 2.41, 95% CI 0.90-6.48, p = 0.08), though the trends did not reach statistical significance. More frequent severe acute hematologic toxicities were found in the GEM-based CRT group.

Conclusions

The meta-analysis found that GEM-based CRT was better than 5-FU-based CRT in the treatment of LAPC, especially for 12-mo SRs. However, the acute toxicity should be carefully regarded.     

Geometric accuracy of a novel gimbals based radiation therapy tumor tracking system

Purpose

VERO is a novel platform for image guided stereotactic body radiotherapy. Orthogonal gimbals hold the linac-MLC assembly allowing real-time moving tumor tracking. This study determines the geometric accuracy of the tracking.

Materials and methods

To determine the tracking error, an 1D moving phantom produced sinusoidal motion with frequencies up to 30 breaths per minute (bpm). Tumor trajectories of patients were reproduced using a 2D robot and pursued with the gimbals tracking system prototype. Using the moving beam light field and a digital-camera-based detection unit tracking errors, system lag and equivalence of pan/tilt performance were measured.

Results

The system lag was 47.7 ms for panning and 47.6 ms for tilting. Applying system lag compensation, sinusoidal motion tracking was accurate, with a tracking error 90% percentile E_90% < 0.82 mm and similar performance for pan/tilt. Systematic tracking errors were below 0.14 mm. The 2D tumor trajectories were tracked with an average E_90% of 0.54 mm, and tracking error standard deviations of 0.20 mm for pan and 0.22 mm for tilt.

Conclusions

In terms of dynamic behavior, the gimbaled linac of the VERO system showed to be an excellent approach for providing accurate real-time tumor tracking in radiation therapy.     

Target volume delineation variation in radiotherapy for early stage rectal cancer in the Netherlands

Purpose

The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer.

Methods and materials

The CTV’s for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed.

Results

The average delineated CTV volume decreased from 620 to 460 cc (p < 0.001) in phase 2. Variation in the caudal CTV border was reduced significantly from 1.8 to 1.2 cm SD (p = 0.01), while it remained 0.7 cm SD for the cranial border. The local surface distance variation (cm SD) reduced from 1.02 to 0.74 for anterior, 0.63 to 0.54 for lateral, 0.33 to 0.25 for posterior and 1.22 to 0.46 for the sphincter region, respectively.

Conclusions

The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement.     

Multicenter phase II study of an opioid-based pain control program for head and neck cancer patients receiving chemoradiotherapy

Background

The aim of this multi-center phase II study was to clarify the clinical benefit of an opioid-based pain control program for head and neck cancer patients during chemoradiotherapy.

Patients and methods

Head and neck cancer patients who were to receive definitive or postoperative chemoradiotherapy were enrolled. The opioid-based pain control program consisted of a three-step ladder, with basic regimens of:

Step 1: acetaminophen at 500-1000 mg three times a day.

Step 2: fast-acting morphine at 5 mg three times a day before meals for a single day.

Step 3: long-acting morphine administered around-the-clock, with a starting dosage of 20 mg/day and no upper limit set in principle.

The primary endpoint of this study was compliance with radiotherapy.

Results

A total of 101 patients from 10 institutions were registered between February 2008 and May 2009 and included in the analysis. The major combination chemotherapy regimen was cisplatin alone (76%). The rate of completion of radiotherapy was 99% and the rate of unplanned breaks in radiotherapy was 13% (13/101, 90% confidence interval: 9.9-16.5%). Median maximum quantity of morphine used per day was 35 mg (range 0-150 mg).

Conclusions

Use of a systematic pain control program may improve compliance with CRT.     

Volumetric modulated arc therapy versus conventional intensity modulated radiation therapy for stereotactic spine radiotherapy: A planning study and early clinical data

Background and purpose

Outcomes for selected patients with spinal metastases may be improved by dose escalation using stereotactic body radiation therapy (SBRT). As target geometry is complex, we compared SBRT plans using volumetric modulated arc radiotherapy (RapidArc®, RA) and conventional intensity-modulated radiotherapy (IMRT).

Materials and methods

RA and IMRT plans to deliver a fraction of 16 Gy to at least 90% of planning target volume (PTV) were compared for PTV coverage, normal organ sparing and estimated delivery times. Group 1 consisted of PTVs to only vertebral body (n = 3), while group 2 had PTVs encompassing the entire vertebra (n = 4). Finally, RA delivery parameters in four patients were assessed.

Results

Both techniques delivered 16 Gy to a mean of 95% and 85% of the PTV in groups 1 and 2, respectively. Spinal cord sparing was comparable; mean V_{10-partial cord} for RA and IMRT in group 1 was 3.6%, and was 9.4% versus 11.5%, respectively, in group 2. Estimated mean treatment times for RA with 2-3 arcs and IMRT were comparable. Clinical RA beam-on times ranged from 11 to 15.4 min.

Conclusions

Both RA and conventional IMRT plans deliver high quality vertebral SBRT, but plan quality was poorer when the PTV consisted of the entire vertebra.     

A coverage probability based method to estimate patient-specific small bowel planning volumes for use in radiotherapy

Background and purpose

The aim of this work was to develop a statistical method for generation of patient-specific planning organ-at-risk volumes (PRVs) for the small bowel (SB), by efficient use of a few repeat CT scans.

Materials and methods

The PRVs are generated from a coverage probability (CP) matrix of the small bowel wall (SBW) by thresholding. To estimate the CPs, we extend a previously published ‘relative frequency of coverage’ approach by adding a ‘soft margin’ around each SBW instance. This prevents the CP matrix from containing any holes, thus making it more robust. As the number of CTs approach infinity, the ‘soft margin’ approaches zero and the CP matrix converges to the ‘relative frequency of coverage’. The PRVs were evaluated by using the bootstrap method in three patients with different degrees of SB motion: The PRVs from randomly sampled subsets of CTs were compared to the PRVs generated from all 10-11 CT scans, by analysis of sensitivity and specificity. Furthermore, the PRVs generated for CP = 0.005 (i.e. generous patient-specific PRVs) and for CP = 0.03 (i.e. tight patient-specific PRVs) were compared to an intestinal cavity (IC) approach and a population based PRV approach of 10 and 30 mm isotropic planning margins around SB.

Results

The sensitivity and specificity of the PRVs depend on the number of CT scans and the CP threshold. With three CT scans and a threshold of 0.03, an average sensitivity of 94-96% and specificity of 86-97% was obtained. All investigated SB planning volumes had an average overlap >89% of both SB and SBW. The tight patient-specific PRVs and the 10 mm margins had the lowest relative volumes, followed by the generous patient-specific PRVs, the 30 mm margins and the ICs.

Conclusions

Based on a few CTs, our method generates patient-specific SB PRVs which are both sensitive and specific. Compared to conventional approaches, the patient-specific PRVs are either similar or better in predicting for SB voxels, and at the same time they occupy a smaller or similar volume in the patient.     

Three-dimensional conformal radiation therapy for squamous cell carcinoma of the esophagus: A prospective phase I/II study

Purpose

A prospective phase I-II study was conducted to determine the tolerance and local control rate of three-dimensional conformal radiotherapy (3-DCRT) for esophageal squamous cell carcinoma (SCC).

Methods and materials

Thirty patients underwent 3-DCRT for thoracic esophageal SCC. PTV1 composed of a 1.2-1.5 cm margin lateral around GTV and 3.0 cm margin superior/inferior of GTV. PTV2 encompassed GTV with a margin of 0.5-0.7 cm. The dose for PTV1 was 50 Gy in 2 Gy daily fractions; PTV2 received a boost of 16 Gy in 2 Gy daily fractions to a total dose of 66 Gy.

Results

Median follow-up time was 18 months. The most common acute toxicity was esophagitis in 63% of patients with RTOG grades 1-2, and in 3% with grade 3. RTOG grades 1-2 radiation pneumonitis developed in 27% of patients. One patient developed pulmonary fibrosis RTOG grade 2 and another patient experienced grade 3 pulmonary fibrosis. Two patients developed mild esophageal stricture requiring dilatation. Two-year overall survival, local disease progression-free rate, and distant metastasis-free rate were 69%, 36% and 56%, respectively.

Conclusions

Although 3-DCRT to 66 Gy for esophageal SCC was well tolerated, the local control was disappointing. The result supports the use of chemoradiation as the standard care for esophageal SCC.     

Post-operative radiotherapy in N2 non-small cell lung cancer: A retrospective analysis of 175 patients

Background and purpose

Post-operative radiotherapy (PORT) in radically resected non-small cell lung cancer (NSCLC) has the aim to reduce loco regional recurrence and to improve overall survival. PORT has been evaluated in several trials but indication to post-operative treatment in N2 patients is still debated.

Material and methods

We retrospectively analyzed 175 patients treated at University of Florence between 1988 and 2004 with completely resected NSCLC stages IIIA-IIIB, N2 disease. Surgery consisted in a lobectomy in 58.9% and in a bi-lobectomy or in a pneumonectomy in 41.1% of patients. One hundred and nineteen patients underwent PORT and 56 patients did not receive PORT (no-PORT).

Results

At a median follow-up of 27.6 months (range 4-233 months), we found a significant reduction in local recurrence (LR) in PORT group (log-rank test p = 0.015; HR: 0.45; 95%CI: 0.24-0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p = 0.92). Concerning other prognostic factors, male sex emerged as statistically significant (HR:4.33;1.04-18.02) on local progression free survival (LPFS) at univariate analysis. Acute and long-term toxicity was mild.

Conclusion

Our retrospective analysis showed that PORT may improve local disease control in N2 NSCLC patients with an acceptable treatment-related toxicity.     

Potential of image-guidance, gating and real-time tracking to improve accuracy in pulmonary stereotactic body radiotherapy

Purpose

To evaluate the potential of image-guidance, gating and real-time tumor tracking to improve accuracy in pulmonary stereotactic body radiotherapy (SBRT).

Materials and methods

Safety margins for compensation of inter- and intra-fractional uncertainties of the target position were calculated based on SBRT treatments of 43 patients with pre- and post-treatment cone-beam CT imaging. Safety margins for compensation of breathing motion were evaluated for 17 pulmonary tumors using respiratory correlated CT, model-based segmentation of 4D-CT images and voxel-based dose accumulation; the target in the mid-ventilation position was the reference.

Results

Because of large inter-fractional base-line shifts of the tumor, stereotactic patient positioning and image-guidance based on the bony anatomy required safety margins of 12 mm and 9 mm, respectively. Four-dimensional image-guidance targeting the tumor itself and intra-fractional tumor tracking reduced margins to <5 mm and <3 mm, respectively. Additional safety margins are required to compensate for breathing motion. A quadratic relationship between tumor motion and margins for motion compensation was observed: safety margins of 2.4 mm and 6 mm were calculated for compensation of 10 mm and 20 mm motion amplitudes in cranio-caudal direction, respectively.

Conclusion

Four-dimensional image-guidance with pre-treatment verification of the target position and online correction of errors reduced safety margins most effectively in pulmonary SBRT.     

Analysis of dose-volume histogram parameters for radiation pneumonitis after definitive concurrent chemoradiotherapy for esophageal cancer

Purpose

To evaluate dose-volume histogram (DVH) parameters as predictors of radiation pneumonitis (RP) in esophageal cancer patients treated with definitive concurrent chemoradiotherapy.

Patients and methods

Thirty-seven esophageal cancer patients treated with radiotherapy with concomitant chemotherapy consisting of 5-fluorouracil and cisplatin were reviewed. Radiotherapy was delivered at 2 Gy per fraction to a total of 60 Gy. For most of the patients, two weeks of interruption was scheduled after 30 Gy. The percentage of lung volume receiving more than 5-50 Gy in increments of 5 Gy (V5-V50, respectively), and the mean lung dose (MLD) were analyzed.

Results

Ten (27%) patients developed RP of grade 2; 2 (5%), grade 3; 0 (0%), grade 4; and 1 (3%), grade 5. By univariate analysis, all DVH parameters (i.e., V5-V50 and MLD) were significantly associated with grade ?2 RP (p < 0.01). The incidences of grade ?2 RP were 13%, 33%, and 78% in patients with V20s of ?24%, 25-36%, and ?37%, respectively. The optimal V20 threshold to predict symptomatic RP was 30.5% according to the receiver operating characteristics curve analysis.

Conclusion

DVH parameters were predictors of symptomatic RP and should be considered in the evaluation of treatment planning for esophageal cancer.     

Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

Background and purpose

RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5 mm margin).

Materials/methods

Patients with ?10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p < 0.05 for statistical significance.

Results

1133 metastases were identified in 371 patients. Metastases within 5 mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7-11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm³ increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p = 0.003) for the presence of perihippocampal metastasis.

Conclusion

With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.     

The effect of delineation method and observer variability on bladder dose-volume histograms for prostate intensity modulated radiotherapy

Purpose

To quantify the effect of delineation method on bladder DVH, observer variability (OV) and contouring time for prostate IMRT plans.

Materials and methods

Planning CT scans and IMRT plans of 30 prostate cancer patients were anonymized. For 20 patients, 1 observer delineated the bladder using 9 methods. The effect of delineation method on the DVH curve, discrete dose levels and delineation time was quantified. For the 10 remaining CTs, 6 observers delineated bladder wall using 4 methods. Observer-based volume variation and intraclass correlation coefficient (ICC) were used to describe the dosimetric effects of OV.

Results

Manual delineation of the bladder wall (BW_m) was significantly slower than any other method (mean: 20 min vs. ?13 min) and the dosimetric effect of OV was significantly larger (V70 Gy ICC: 0.78 vs. 0.98). Only volumes created using a 2.5 mm contraction from the outer surface, and a method providing a consistent wall volume, showed no notable dosimetric differences from BW_m in both absolute and relative volume.

Conclusions

Automatic contractions from the outer surface provide quicker, more reproducible and reasonably accurate substitutes for BW_m. The widespread use of automatic contractions to create a bladder wall volume would assist in the consistent application of IMRT dose constraints and the interpretation of reported dose.     

Association of urethral toxicity with dose exposure in combined high-dose-rate brachytherapy and intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

Introduction

To report acute and late toxicities in patients with intermediate- and high-risk prostate cancer treated with combined high-dose-rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT).

Materials and methods

From March 2003 to September 2005, 64 men were treated with a single implant HDR-B with 21 Gy given in three fractions, followed by 50 Gy IMRT along with organ tracking. Median age was 66.1 years, and risk of recurrence was intermediate in 47% of the patients or high in 53% of the patients. Androgen deprivation therapy was received by 69% of the patients. Toxicity was scored according to the CTCAE version 3.0. Median follow-up was 3.1 years.

Results

Acute grade 3 genitourinary (GU) toxicity was observed in 7.8% of the patients, and late grades 3 and 4 GU toxicity was observed in 10.9% and 1.6% of the patients. Acute grade 3 gastrointestinal (GI) toxicity was experienced by 1.6% of the patients, and late grade 3 GI toxicity was absent. The urethral V₁₂₀ (urethral volume receiving ?120% of the prescribed HDR-B dose) was associated with acute (P = .047) and late ? grade 2 GU toxicities (P = .049).

Conclusions

Late grades 3 and 4 GU toxicity occurred in 10.9% and 1.6% of the patients after HDR-B followed by IMRT in association with the irradiated urethral volume. The impact of V₁₂₀ on GU toxicity should be validated in further studies.     

Toxicity after reirradiation of pulmonary tumours with stereotactic body radiotherapy

Purpose

To assess toxicity and feasibility of reirradiation with stereotactic body radiotherapy (SBRT) after prior lung SBRT for primary lung cancer or lung metastases.

Patients and materials

Twenty-nine patients reirradiated with SBRT on 32 lung lesions (11 central, 21 peripheral) were retrospectively reviewed. Median follow-up time was 12 months (range 1-97). The primary endpoint was toxicity, secondary endpoints were local control and overall survival time. Toxicity was scored according to the NCI-CTCAE version 3.

Results

Grade 3-4 toxicity was scored 14 times in eight patients. Three patients died because of massive bleeding (grade 5). Larger clinical target volumes (CTV) and central tumour localization were associated with more severe toxicity. There was no correlation between mean lung dose (MLD) and lung toxicity. Local control at 5 months after reirradiation was 52%, as assessed by CT-scan (n = 12) or X-thorax (n = 3). A larger CTV was associated with poorer local control. Kaplan-Meier estimated 1- and 2-year survival rates were 59% and 43%, respectively.

Conclusions

Reirradiation with SBRT is feasible although increased risk of toxicity was reported in centrally located tumours. Further research is warranted for more accurate selection of patients suitable for reirradiation with SBRT.     

Relationship between sun exposure and melanoma risk for tumours in different body sites in a large case-control study in a temperate climate

Aim

A melanoma case-control study was conducted to elucidate the complex relationship between sun exposure and risk.

Methods

Nine hundred and sixty population-ascertained cases, 513 population and 174 sibling controls recruited in England provided detailed sun exposure and phenotype data; a subset provided serum 25-hydroxyvitamin D₂ + D₃ levels.

Results

Phenotypes associated with a tendency to sunburn and reported sunburn at ?20 years of age were associated with increased melanoma risk (odds ratio (OR) 1.56, 95% confidence intervals (CI) 1.23-1.99). Holiday sun exposure was not associated with an increased melanoma risk although this may be in part because reported sun exposure overall was much lower in those with a sun-sensitive phenotype, particularly among controls. Head and neck melanoma was associated with less sun exposure on holidays at low latitudes (OR 0.39, 95% CI (0.23-0.68) for >13 h/year compared to <3.1). Overall the clearest relationship between reported sun exposure and risk was for average weekend sun exposure in warmer months, which was protective (OR 0.67, 95% CI 0.50-0.89 for highest versus lowest tertile of exposure). Serum vitamin D levels were strongly associated with increased weekend and holiday sun exposure.

Conclusions

Sun-sensitive phenotypes and reported sunburn were associated with an increased risk of melanoma. Although no evidence was seen of a causal relationship between holiday sun exposure and increased risk, this is consistent with the view that intense sun exposure is causal for melanoma in those prone to sunburn. A protective effect of regular weekend sun exposure was seen, particularly for limb tumours, which could be mediated by photoadaptation or higher vitamin D levels.     

Phase I dose escalation trial of hypofractionated limited-field external beam thoracic radiotherapy for limited-stage small cell carcinoma of the lung

Purpose

To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurrent chemotherapy for limited-stage small cell lung cancer.

Materials and methods

Limited-stage small cell lung cancer patients were prescribed 54, 58, 62 or 65 Gy, all given in 25 daily fractions and commenced on or before the second chemotherapy cycle. Dose level accrual was performed sequentially. Conformal radiotherapy techniques were used and targeted gross disease plus margin. Four cycles of platinum-based chemotherapy were prescribed. Primary endpoint was the rate of acute RT toxicities according to NCI Common Toxicity Criteria scales. The dose which caused unacceptable acute radiotherapy toxicity rates according to pre-defined stopping rules defined the maximal tolerated radiotherapy dose.

Results

Six patients were accrued to each of the 54, 58 and 62 Gy dose levels. There were no radiotherapy-related deaths. No grade 3 toxicities occurred in the 54 and 58 Gy groups. There were 2 grade 3 RT toxicities in the 62 Gy group. There were 14 complete responses. Trial accrual has stopped at the 62 Gy group according to trial stopping rules.

Conclusions

The maximal tolerated hypofractionated thoracic radiotherapy dose in this trial was 58 Gy in 25 daily fractions.     

Parotid gland as a risk organ in whole brain radiotherapy

Background and purpose

Since the introduction of CT-based simulation for use in whole brain radiotherapy (WBRT), we have observed that a large volume of the parotid glands is included in the radiation fields. The purpose of this study is to analyze the dose-volume statistics of the parotid glands in patients undergoing WBRT.

Materials and methods

Thirty-two patients received WBRT using CT-based simulation with bilateral two-field arrangement. Daily fraction was 3 Gy with total dose of 30 Gy in 2 weeks. We analyzed the radiation dose from WBRT to the parotid glands.

Results

Average of the mean parotid dose was 17.5 Gy (range, 10.5-26.2) for both glands. Mean parotid doses ?20 and ?25 Gy were observed in 22 (34.4%) and 4 (6.3%) of 64 individual glands. The numbers of patients with a mean parotid dose of both glands ?20 Gy and ?25 Gy were 12 (37.5%) and 1 (3.1%), respectively.

Conclusions

Mean parotid dose was variable in patients with WBRT. According to the parotid dose and combined potential risk factors, parotid glands can be regarded as a risk organ in WBRT for improvement of patient quality of life.