Patricia Diez

A New Method for Synthesizing Radiation Dose–Response Data From Multiple Trials Applied to Prostate Cancer

PURPOSE A new method is presented for synthesizing dose-response data for biochemical control of prostate cancer according to study design (randomized vs. nonrandomized) and risk group (low vs. intermediate-high). METHODS AND MATERIALS Nine published prostate cancer dose escalation studies including 6,539 patients were identified in the MEDLINE and CINAHL databases and reviewed to assess the relationship between dose and biochemical control. A novel method of analysis is presented in which the normalized dose-response gradient, gamma(50), is estimated for each study and subsequently synthesized across studies. Our method does not assume that biochemical control rates are directly comparable between studies. RESULTS Nonrandomized studies produced a statistically significantly higher gamma(50) than randomized studies for intermediate- to high-risk patients (gamma(50) = 1.63 vs. gamma(50) = 0.93, p = 0.03) and a borderline significantly higher (gamma(50) = 1.78 vs. gamma(50) = 0.56, p = 0.08) for low-risk patients. No statistically significant difference in gamma(50) was found between low- and intermediate- to high-risk patients (p = 0.31). From the pooled data of low and intermediate- to high-risk patients in randomized trials, we obtain the overall best estimate of gamma(50) = 0.84 with 95% confidence interval 0.54-1.15. CONCLUSIONS Nonrandomized studies overestimate the steepness of the dose-response curve as compared with randomized trials. This is probably the result of stage migration, improved treatment techniques, and a shorter follow-up in higher dose patients that were typically entered more recently. This overestimation leads to inflated expectations regarding the benefit from dose-escalation and could lead to underpowered clinical trials. There is no evidence of a steeper dose response for intermediate- to high-risk compared with low-risk patients.

Dosimetric analysis of urethral strictures following HDR 192Ir brachytherapy as monotherapy for intermediate- and high-risk prostate cancer

BACKGROUND AND PURPOSE To evaluate dosimetric parameters related to urethral strictures following high dose-rate brachytherapy (HDRBT) alone for prostate cancer. MATERIAL AND METHODS Ten strictures were identified in 213 patients treated with HDRBT alone receiving 34Gy in four fractions, 36Gy in four fractions, 31.5Gy in 3 fractions or 26Gy in 2 fractions. A matched-pair analysis used 2 controls for each case matched for dose fractionation schedule, pre-treatment IPSS score, number of needles used and clinical target volume. The urethra was divided into membranous urethra and inferior, mid and superior thirds of the prostatic urethra. RESULTS Stricture rates were 3% in the 34Gy group, 4% in the 36Gy group, 6% in the 31.5Gy group and 4% in the 26Gy group. The median time to stricture formation was 26months (range 8-40). The dosimetric parameters investigated were not statistically different between cases and controls. No correlation was seen between stricture rate and fractionation schedule. CONCLUSIONS Urethral stricture is an infrequent complication of prostate HDRBT when used to deliver high doses as sole treatment, with an overall incidence in this cohort of 10/213 (4.7%). In a matched pair analysis no association with dose schedule or urethral dosimetry was identified, but the small number of events limits definitive conclusions.

Improving target volume delineation in intact cervical carcinoma: Literature review and step-by-step pictorial atlas to aid contouring

PURPOSE Accurate delineation of target volume and normal tissue is critical for intensity modulated radiation therapy (IMRT) use in cervical cancer. Phase III Multicentre Trial of Weekly Induction Chemotherapy Followed by Standard Chemoradiation versus Standard Chemoradiation Alone in Patients With Locally Advanced Cervical Cancer (INTERLACE) radiation therapy quality assurance (RTQA) has highlighted significant interobserver delineation variation. Prescriptive guidelines reduce interobserver variation in other cancers. METHODS AND MATERIALS A literature search using PubMed/Medline database of guidelines for target anatomy delineation in cervical cancer was undertaken. Differences in practice in these publications and INTERLACE trial RTQA were identified. Consensus best practice delineation was derived and a pictorial atlas produced. The proportion of outlines complying with protocol in test and real-time cases was compared before and after atlas implementation within the INTERLACE RTQA pack. RESULTS Seven key papers were reviewed. Eleven areas of variation were identified. These included the definition and editing of bowel, definition of the femur, vagina, parametria, inferior and superior nodal borders, nodal clinical target volume (CTV) editing, para-aortic nodal CTV definition, and the margin to be used around enlarged nodes. The average proportion of outlines (of 4; primary CTV, nodal CTV, bladder, rectum) complying with protocol in test and real-time cases improved from 1.8 to 2.7 (difference, 0.9; 95% confidence interval, 0.3-1.5; P = .003) with atlas use. CONCLUSION Differences exist in the published literature and clinical practice. This pictorial atlas reflects consensus recommendations and is now available to INTERLACE participating centers. Atlas use has reduced interobserver delineation variation in this trial setting.

Recommendations for Radiotherapy Technique and Dose in Extra-nodal Lymphoma

Extra-nodal sites may be involved in around 40% of patients with non-Hodgkin lymphoma. The general principles for target volume delineation in this setting are presented, together with specific examples. In general, the entire organ affected should be encompassed in the clinical target volume with an expansion of at least 10 mm, increased in some instances to account for patterns of potential lymphatic flow. Adjacent lymph nodes may be treated using standard techniques for nodal irradiation. Doses for extra-nodal lymphoma follow the same principles as nodal lymphoma, delivering 30 Gy in 15 fractions for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy in 12 fractions for indolent lymphomas, with the exception of certain palliative situations, mycosis fungoides, central nervous system lymphoma and natural killer/T-cell lymphoma.

OC-0271: A multicentre audit of HDR and PDR brachytherapy absolute dosimetry in association with the INTERLACE trial

Conclusions: The SourceCheck 4Pi ionization chamber shows an additional dependence with the air density which is clearly linear. The air density dependence of the three analyzed chambers can be represented by the same function, showing that there is not a significative variability between them regarding this dependence. Acknowledgement: We are grateful for financial and material support from PTW. References [1] Tornero-López AM, et al. Med Phys 2013;40:122103. [2] Griffin SL, et al. Med Phys 2005;32:700-9.

PD-0266: A survey of UK practice in cervical cancer radiotherapy aimed at developing trial specific quality assurance

Purpose/Objective: To determine the current variation in radiotherapy practice for the treatment of cervical cancer across the United Kingdom (UK) with the aim of developing a comprehensive radiotherapy quality assurance (QA) programme for both external beam radiotherapy (EBRT) and brachytherapy within the context of the INTERLACE trial: a phase III trial of weekly induction chemotherapy and chemoradiation versus standard chemoradiation. The data will also be used to help determine the need for a national brachytherapy dosimetry audit. Materials and Methods: A pre-trial questionnaire was circulated to 31 radiotherapy centres that had expressed interest in participating in INTERLACE. In addition to external beam radiotherapy (EBRT) details, in depth information on brachytherapy technique and QA was collected. Results: To date, 22 questionnaires have been completed and evaluated. Local practice was seen to vary significantly between centres with particular variation in brachytherapy techniques. For EBRT, all but 2 centres localise using CT and MRI modalities, only 6 of these also utilise PET imaging. Seven out of 22 centres use 3D virtual simulation (Vsim) techniques for EBRT planning. With respect to total EQD2 dose, 9 out of 22 centres did not achieve the proposed minimum dose requirement for the trial of 78 Gy, with values ranging from 68.3 to 83.9 Gy. The intended trial requirement for the overall treatment time of ≤ 50 days was also not met by 7 of the 22 centres. Out of 21 brachytherapy centres, 18 use 3D imaging for the planning of all fractions. Twelve of these optimise their plans for each individual patient; 6 to the target volume and 6 to OAR volumes or ICRU points, while the remaining 9 use standard plans. Six out of 21 centres have not participated in any brachytherapy dosimetry audit to date. Conclusions: The INTERLACE pre-trial questionnaire has revealed a wide variation in dose fractionation and treatment techniques being used in centres across the UK. Following our results new minimum standards for centres wishing to participate in the INTERLACE trial have been set. Now Vsim techniques for EBRT planning will not be permitted from UK centres. This will therefore require an advance in technique to 3D conformal planning for some centres. Several centres will be required to increase their total EQD2 dose for trial patients. The overall treatment time has now been amended to up to 56 days. Finally our results have highlighted the need for a national brachytherapy dosimetry audit which is now currently under development.