A. Margaret Bidmead

DOSE-VOLUME CONSTRAINTS TO REDUCE RECTAL SIDE EFFECTS FROM PROSTATE RADIOTHERAPY: EVIDENCE FROM MRC RT01 TRIAL ISRCTN 47772397

PURPOSE Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>/=50 Gy). Evidence is emerging that lower doses could also be important. METHODS AND MATERIALS Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. RESULTS A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<or=80%, V40<or=65%, V50<or=55%, V60<or=40%, V65<or=30%, V70<or=15%, and V75<or=3%. CONCLUSION Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

Dosimetry audit for a multi-centre IMRT head and neck trial

BACKGROUND AND PURPOSE PARSPORT was a multi-centre randomised trial in the UK which compared Intensity-Modulated Radiotherapy (IMRT) and conventional radiotherapy (CRT) for patients with head and neck cancer. The dosimetry audit goals were to verify the plan delivery in participating centres, ascertain what tolerances were suitable for head and neck IMRT trials and develop an IMRT credentialing program. MATERIALS AND METHODS Centres enrolling patients underwent rigorous quality assurance before joining the trial. Following this each centre was visited for a dosimetry audit, which consisted of treatment planning system tests, fluence verification films, combined field films and dose point measurements. RESULTS Mean dose point measurements were made at six centres. For the primary planning target volume (PTV) the differences with the planned values for the IMRT and CRT arms were -0.6% (1.8% to -2.4%) and 0.7% (2.0% to -0.9%), respectively. Ninety-four percent of the IMRT fluence films for individual fields passed gamma criterion of 3%/3mm and 75% of the films for combined fields passed gamma criterion 4%/3mm (no significant difference between dynamic delivery and step and shoot delivery). CONCLUSIONS This audit suggests that a 3% tolerance could be applied for PTV point doses. For dose distributions tolerances of 3%/3mm on individual fields and 4%/3mm for combined fields are proposed for multi-centre head and neck IMRT trials.

Dose-Escalated Intensity-Modulated Radiotherapy Is Feasible and May Improve Locoregional Control and Laryngeal Preservation in Laryngo-Hypopharyngeal Cancers

PURPOSE To determine the safety and outcomes of induction chemotherapy followed by dose-escalated intensity-modulated radiotherapy (IMRT) with concomitant chemotherapy in locally advanced squamous cell cancer of the larynx and hypopharynx (LA-SCCL/H). METHODS AND MATERIALS A sequential cohort Phase I/II trial design was used to evaluate moderate acceleration and dose escalation. Patients with LA-SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions (Fx) to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin. Acute and late toxicities and tumor control rates were recorded. RESULTS Between September 2002 and January 2008, 60 patients (29 DL1, 31 DL2) with Stage III (41% DL1, 52% DL2) and Stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 51.2 (12.1-77.3) months and for DL2 was 36.2 (4.2-63.3) months. Acute Grade 3 (G3) dysphagia was higher in DL2 (87% DL2 vs. 59% DL1), but other toxicities were equivalent. One patient in DL1 required dilatation of a pharyngeal stricture (G3 dysphagia). In DL2, 2 patients developed benign pharyngeal strictures at 1 year. One underwent a laryngo-pharyngectomy and the other a dilatation. No other G3/G4 toxicities were reported. Overall complete response was 79% (DL1) and 84% (DL2). Two-year locoregional progression-free survival rates were 64.2% (95% confidence interval, 43.5-78.9%) in DL1 and 78.4% (58.1-89.7%) in DL2. Two-year laryngeal preservation rates were 88.7% (68.5-96.3%) in DL1 and 96.4% (77.7-99.5%) in DL2. CONCLUSIONS At a mean follow-up of 36 months, dose-escalated chemotherapy-IMRT at DL2 has so far been safe to deliver. In this study, DL2 delivered high rates of locoregional control, progression-free survival, and organ preservation and has been selected as the experimental arm in a Cancer Research UK Phase III study.

Comparison of a multi-leaf collimator with conformal blocks for the delivery of stereotactically guided conformal radiotherapy.

Stereotactically-guided conformal radiotherapy is a practical technique for irradiating irregular lesions in the brain. The shaping of the conformal fields may be achieved using lead alloy blocks, a conventional multi-leaf collimator (MLC) or a mini/micro-MLC. Although the former gives more precise shaping, it is labour intensive. The latter methods are more practical as both mould room and treatment room times are reduced, but the shaping is limited by the finite leaf-width. This study compares treatment plans, in terms of normal tissue doses and tumour coverage, for fields shaped using conformal blocks and a conventional MLC in two series of geometrical shapes and nine patient tumours. For the range of tumour sizes considered (volumes 14-264 cm3, minimum dimension 30 mm, maximum 102 mm), the MLC treats, on average, 14% (range 3-34%) and 17% (range 0-36%) more normal brain tissue than conformal blocks to >50% and >80% of the prescription dose, respectively. The large variability is due to strong dependence on tumour shape and the presence of partial leaf-widths in the MLC fit. It is therefore important to consider both of these effects when deciding whether the MLC is appropriate for a particular target volume.

A quality assurance procedure for the Varian multi-leaf collimator

A quick, simple set of tests has been devised to assess and record the quality assurance aspects of the Varian multi-leaf collimator (MLC) when used for clinical treatments on a regular basis. Pre-treatment, daily and weekly checks are performed by the radiographers while more detailed quality assurance is carried out at monthly and quarterly intervals by physicists.

A comparison of multileaf collimator with conformal blocks for the boost phase of dose-escalated conformal prostate radiotherapy

A multileaf collimator (MLC) is compared with conformal blocks for delivering the boost phase of dose-escalated conformal prostate radiotherapy. When using conformal blocks, the volume of rectum irradiated to 90% (V90) is lower (1.4+/-1.3%, 1 SD) for a three-field plan with gantry angles 0 degree, 90 degrees, 270 degrees than for a six-field plan with gantry angles 50 degrees, 90 degrees, 130 degrees, 230 degrees, 270 degrees, 310 degrees (2.1 +/- 1.3%, P = 0.002). However, when using an MLC in which the leaves and wedge are oriented at right angles, V90 is higher (4.7 +/- 3.0%) for a three-field plan than for a six-field plan (2.7 +/- 1.6%, P=0.05). The larger increase in V90 for the three-field plan when changing from conformal blocks to MLC is mainly due to the limitation imposed upon the MLC orientation by the use of wedges.