[en] Purpose: To investigate the importance to outcome of treatment, for squamous cell carcinomas of the tonsillar fossa, of dose per fraction, overall treatment duration, and total dose. Methods and Materials: A collaborative retrospective study was undertaken in nine centers that used widely different dose-fractionation patterns for external beam radiation therapy. Results: There were 676 eligible cases treated only with photon beams during the years 1976-1985. The probability of local control (of the tonsillar fossa primary) was influenced by both T-stage and N-stage. Significant treatment parameters were total dose and overall treatment duration, but not dose per fraction. Over the range of about 40 to 90% and for a constant overall treatment duration, local tumor control probability increased by nearly 2% for each 1 Gy increase in total dose. For a constant total dose there was a decrease in the probability of local control associated with prolongation of overall treatment duration, presumed to result from accelerated regrowth of surviving tumor clonogens during the course of treatment. If it is assumed that accelerated regrowth occurred at a constant rate and began within 9 days of the start of treatment, an average of 0.53 Gy extra dose per day's extension of treatment would be required to maintain a constant probability of local control. Correspondingly, the probability of local control from a constant dose would be lowered by an average of at least 1% for each day's extension of treatment duration. However, the data are slightly more consistent with an average delay of as long as 30 days before onset of accelerated repopulation, with a consequent increase to an average of 0.73 Gy per day for the value of the compensatory dose. The α/β ratio for this tumor is high enough that the effect of fraction size on the probability of local control can be ignored; a precise estimate is not possible because the best value for β was close to zero. After accounting for the significant variables studied (treatment time, T-stage, N-stage), the dose-response curves for tumor control were still shallow, suggesting that there are additional causes for heterogeneity of responses among these tumors. Conclusions: Total dose is important to treatment outcome: After accounting for other treatment variables, there is about a 2% per Gy increase in probability of tumor control over the ranges of control commonly achieved. Overall treatment duration is important: There is at least a 1% per day decrease in tumor control probability if delivery of a constant total dose is prolonged, requiring a compensatory increase in dose by 0.5-0.7 Gy per day to achieve a constant rate of tumor control. Fraction size is not, of itself, an important factor in the response of primary carcinoma of the tonsil. If a tumor has demonstrated a capacity for metastatic spread to lymph nodes, a higher total dose should be considered to achieve control rates at the primary site equivalent to those in node negative patients. Even after accounting for variables such as tumor stage, total dose, and overall treatment duration, there is sufficient heterogeneity in other undocumented determinants of tumor control to cause the tumor control probability curve to be a shallow function of dose

[en] Purpose: To evaluate the influence of dose fractionation and other factors on the development of late complications in mandibular bone, muscle, and mucosa of the oral cavity after external beam radiation therapy for carcinoma of the tonsil. Methods and Materials: A retrospective analysis was made of the results in 676 patients treated with a spectrum of fractionation regimens in nine centers during the years 1976-1985. Only severe (Grades 3-4) late complications were analyzed. Results: With more than 5 years follow-up, it was found that total dose was a factor for all three types of complications, but that in other respects, the radiobiology of late-(> 3 months) developing mucosal ulcerations was different from that for mandibular necrosis and muscle injury. Dose per fraction was a significant factor for bone and muscle (estimated α/β values of 0.85 Gy and 3.1 Gy, respectively). By contrast, mucosa showed no influence on response from change in fraction size over the range of approximately 1.0-3.5 Gy. Complications in bone and muscle were not related to overall treatment duration, whereas there was a significant inverse relationship for mucosa breakdown. The rate of development of complications was fastest in mucosa and slowest in bone. The appearance of complications by 4 years after treatment was about 80% of those developing by 8 years in the mucosa, 66% in muscle, and about 50% in bone. The high α/β ratio, inverse relationship with overall treatment duration, and faster development of mucosal complications suggests that they may develop as a consequence of earlier mucosal injury. As anticipated, adequate retrospective analysis of acute complications could not be made even when objective criteria such as weight loss, unplanned delays in completing treatment, or hospitalization during treatment were the measures. Field size was a significant factor for mandible complications, but not for muscle or mucosa. Conclusion: The radiobiological characteristics of bone and muscle were those characteristic of other late-responding tissues, whereas late sequelae in mucosa had radiobiological parameters similar to those for acute responses. Field size was a significant factor for bone complications but not for others

[en] Background and purpose: Intensity modulated radiotherapy (IMRT) allows the delivery of higher and more homogeneous radiation dose to head and neck tumours. This study aims to determine the safety of dose-escalated chemo-IMRT for larynx preservation in locally advanced head and neck cancer. Methods: Patients with T2-4, N1-3, M0 squamous cell carcinoma of the larynx or hypopharynx were treated with a simultaneous-boost IMRT. Two radiation dose levels (DL) were tested: In DL 1, 63 Gy/28F was delivered to primary tumour and involved nodes and 51.8 Gy/28F to elective nodes. In DL 2, the doses were 67.2 Gy/28F and 56 Gy/28F, respectively, representing a 9% dose escalation for the primary. All patients received 2 cycles of neoadjuvant cisplatin and 5-fluorouracil, and concomitant cisplatin. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) were collected. Results: Thirty patients were entered, 15 in each dose level. All patients completed the treatment schedule. In DL 1, the incidences of acute G3 toxicities were 27% (pain), 20% (radiation dermatitis), 0% (xerostomia) and 67% required gastrostomy tubes. For DL 2 the corresponding incidences were 40%, 20%, 7%, and 87%. G3 dysphagia and pain persisted longer in DL 2. With regard to mucositis, a prolonged healing time for DL 2 was found, with prevalence of G2 of 58% in week 10. No acute grade 4 toxicity was observed. At 6 months, 1 patient in DL 2 had G3 late toxicity (dysphagia). No dose limiting toxicity was found. Complete response rates were 80% in DL 1, and 87% in DL 2. Conclusion: Moderately accelerated chemo-IMRT is safe and feasible with good compliance and acceptable acute toxicity. Dose escalation was possible without a significant difference in acute toxicity. Longer follow-up is required to determine the incidence of late radiation toxicities, and tumour control rates

[en] Purpose: To undertake the first multicentre fully ‘end to end’ dosimetry audit for HDR cervix brachytherapy, comparing planned and delivered dose distributions around clinical treatment applicators, with review of local procedures. Materials and methods: A film-dosimetry audit was performed at 46 centres, including imaging, applicator reconstruction, treatment planning and delivery. Film dose maps were calculated using triple-channel dosimetry and compared to RTDose data from treatment planning systems. Deviations between plan and measurement were quantified at prescription Point A and using gamma analysis. Local procedures were also discussed. Results: The mean difference between planned and measured dose at Point A was −0.6% for plastic applicators and −3.0% for metal applicators, at standard uncertainty 3.0% (k = 1). Isodose distributions agreed within 1 mm over a dose range 2–16 Gy. Mean gamma passing rates exceeded 97% for plastic and metal applicators at 3% (local) 2 mm criteria. Two errors were found: one dose normalisation error and one applicator library misaligned with the imaged applicator. Suggestions for quality improvement were also made. Conclusions: The concept of ‘end to end’ dosimetry audit for HDR brachytherapy has been successfully implemented in a multicentre environment, providing evidence that a high level of accuracy in brachytherapy dosimetry can be achieved

[en] Background and purpose: Intensity modulated radiotherapy (IMRT) at Royal Marsden Hospital London was introduced in July 2001. Treatment delivery was dynamic using a single-phase technique. Concerns were raised regarding increased clinical workload due to introduction of new technology. The potential increased use of resources was assessed. Patients and methods: IMRT patient selection was within guidelines of clinical trials and included patients undergoing prostate plus pelvic lymph node (PPN) irradiation and head and neck cancer (HNC) treatment. Patient planning, quality assurance and treatment times were collected for an initial IMRT patient group. A comparative group of patients with advanced HNC undergoing two- or three-phase conventional radiotherapy, requiring matched photon and electron fields, were also timed. Results: The median overall total planning time for IMRT was greater for HNC patients compared to the PPN cohort. For HNC the overall IMRT planning time was significantly longer than for conventional. The median treatment time for conventional two- or three-phase HNC treatments, encompassing similar volumes to those treated with IMRT, was greater than that for the IMRT HNC patient cohort. A reduction in radiographer man hours per patient of 4.8 h was recorded whereas physics time was increased by 4.9 h per patient. Conclusions: IMRT currently increases overall planning time. Additional clinician input is required for target volume localisation. Physics time is increased, a significant component of this being patient specific QA. Radiographer time is decreased. For HNC a single phase IMRT treatment has proven to be more efficient than a multiple phase conventional treatment. IMRT has been integrated smoothly and efficiently into the existing treatment working day. This preliminary study suggests that IMRT could be a routine treatment with efficient use of current radiotherapy resources

[en] Background and purpose: To assess the geometric accuracy of the delivery of fractionated stereotactic radiotherapy (FSRT) for brain tumours using the Gill-Thomas-Cosman (GTC) relocatable frame. Accuracy of treatment delivery was measured via portal images acquired with an amorphous silicon based electronic portal imager (EPI). Results were used to assess the existing verification process and to review the current margins used for the expansion of clinical target volume (CTV) to planning target volume (PTV). Patients and methods: Patients were immobilized in a GTC frame. Target volume definition was performed on localization CT and MRI scans and a CTV to PTV margin of 5 mm (based on initial experience) was introduced in 3D. A Brown-Roberts-Wells (BRW) fiducial system was used for stereotactic coordinate definition. The existing verification process consisted of an intercomparison of the coordinates of the isocentres and anatomy between the localization and verification CT scans. Treatment was delivered with 6 MV photons using four fixed non-coplanar conformal fields using a multi-leaf collimator. Portal imaging verification consisted of the acquisition of orthogonal images centred through the treatment isocentre. Digitally reconstructed radiographs (DRRs) created from the CT localization scans were used as reference images. Semi-automated matching software was used to quantify set up deviations (displacements and rotations) between reference and portal images. Results: One hundred and twenty six anterior and 123 lateral portal images were available for analysis for set up deviations. For displacements, the total errors in the cranial/caudal direction were shown to have the largest SD's of 1.2 mm, while systematic and random errors reached SD's of 1.0 and 0.7 mm, respectively, in the cranial/caudal direction. The corresponding data for rotational errors (the largest deviation was found in the sagittal plane) was 0.7 deg. SD (total error), 0.5 deg. (systematic) and 0.5 deg. (random). The total 3D displacement was 1.8 mm (mean), 0.8 mm (SD) with a range of 0.3-3.9 mm. Conclusions: Portal imaging has shown that the existing verification and treatment delivery techniques currently in use result in highly reproducible setups. Random and systematic errors in the treatment planning and delivery chain will always occur, but monitoring and minimising them is an essential component of quality control. Portal imaging provides fast and accurate facility for monitoring patients on treatment and the results of this study have shown that a reduction in CTV to PTV margin from 5 to 4 mm (resulting in a considerable increase in the volume of normal tissue sparing) could be made

[en] Purpose: To evaluate set-up reproducibility of a cabulite shell and determine CTV-PTV margins for head and neck intensity-modulated-radiotherapy. Materials and methods: Twenty patients were entered into the study. A total of 354 anterior and lateral isocentric electronic portal images (EPIs) were compared to simulator reference images. Results: About 94% of all translational displacements were ≤3 mm, and 99% ≤5 mm. The overall systematic error was 0.9 mm (±1.0SD) in the Right-Left, 0.7 mm (±0.9SD) in the Superior-Inferior and -0.02 mm (±1.1SD) in the Anterior-Posterior directions. The corresponding SDs of the random errors were ±0.4, ±0.6 and ±0.7 mm. The estimated margins required from CTV-PTV were calculated according to the Van Herk formula was 2.9, 2.6 and 3.3 mm, respectively. Conclusions: This head and neck immobilisation system is of sufficient accuracy for its use with IMRT treatments and a 3 mm CTV-PTV margin has been adopted