Patient-reported acute GI symptoms in locally advanced cervical cancer patients correlate with rectal dose

Background and purpose: To investigate relationships between patient-reported acute gastro-intestinal symptoms in a locally advanced cervical cancer (LACC) prospective cohort and clinical and dosimetric parameters, while also taking spatial dose into account. Material and methods: A total of 103 patients was included, receiving radiotherapy based on a plan-library-based plan-of-the-day protocol, combined either with concurrent chemotherapy or with neo-adjuvant chemotherapy and concomitant hyperthermia. Toxicity endpoints were extracted from questionnaires sent out weekly during treatment and regularly in the acute phase after treatment. Endpoints were defined for symptoms concerning obstipation, diarrhea, fecal leakage, bowel cramps and rectal bleeding. Dose surface maps were constructed for the rectum. Clinical parameters and dosimetric parameters of the bowel ba

PORTEC-4a: International randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer

Background Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with highintermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients’ risk of recurrence based on molecular tumor characteristics. Primary objectives To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecularintegrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy Study hypothesis Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant t

Optimal Patient Positioning (Prone Versus Supine) for VMAT in Gynecologic Cancer: A Dosimetric Study on the Effect of Different Margins

It is unknown whether the historically found dosimetric advantages of treating gynecologic cancer with the patient in a prone position with use of a small-bowel displacement device (belly-board) remain when volumetric arc therapy (VMAT) is used and whether these advantages depend on the necessary margin between clinical target volume (CTV) and planning target volume (PTV). The aim of this study is to determine the best patient position (prone or supine) in terms of sparing organs at risk (OAR) for various CTV-to-PTV margins and VMAT dose delivery. In an institutional review board-approved study, 26 patients with gynecologic cancer scheduled for primary (9) or postoperative (17) radiation therapy were scanned in a prone position on a belly-board and in a supine position on the same day. The primary tumor CTV, nodal CTV, bladder, bowel, and rectum were delineated on both scans. The PTVs were created each with a different margin for the primary tumor and nodal CTV. The VMAT plans were generated with our in-house system for automated treatment planning. For all margin combinations, the supine and prone plans were compared with consideration of all OAR dose-volume parameters but with highest priority given to bowel cavity V45Gy (cm(3)). For both groups, the prone position reduced the bowel cavity V45Gy, in particular for nodal margins ≥10 mm (ΔV45Gy = 23.9 ± 10.6 cm(3)). However, for smaller margins, the advantage was much less pronounced (ΔV45Gy = 6.5 ± 3.0 cm(3)) and did not reach statistical significance. The rectum mean dose (Dmean) was significantly lower (ΔDmean = 2.5 ± 0.3 Gy) in the prone position for both patient groups and for all margins, and the bladder Dmean was significantly lower in the supine position (ΔDmean = 2.6 ± 0.4 Gy) only for the postoperative group. The advantage of the prone position was not present if it needed a larger margin than the supine position. For patients with gynecologic cancer, the historically found dosimetric advantages for the prone position remain for modern dose delivery techniques if large margins are needed. However, the advantage is lost for small margins and if the prone position needs a larger margin than the supine positio

Validation of Fully Automated VMAT Plan Generation for Library-Based Plan-of-the-Day Cervical Cancer Radiotherapy

<div><p>Purpose</p><p>To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer.</p><p>Material and Methods</p><p>Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-arc VMAT treatment plan libraries for cervical cancer patients. For each of 34 patients, automatically generated VMAT plans (autoVMAT) were compared to manually generated, clinically delivered 9-beam IMRT plans (CLINICAL), and to dual-arc VMAT plans generated manually by an expert planner (manVMAT). Furthermore, all plans were benchmarked against 20-beam equi-angular IMRT plans (autoIMRT). For all plans, a PTV coverage of 99.5% by at least 95% of the prescribed dose (46 Gy) had the highest planning priority, followed by minimization of V_45Gy for small bowel (SB). Other OARs considered were bladder, rectum, and sigmoid.</p><p>Results</p><p>All plans had a highly similar PTV coverage, within the clinical constraints (above). After plan normalizations for exactly equal median PTV doses in corresponding plans, all evaluated OAR parameters in autoVMAT plans were on average lower than in the CLINICAL plans with an average reduction in SB V_45Gy of 34.6% (<i>p</i><0.001). For 41/44 autoVMAT plans, SB V_45Gy was lower than for manVMAT (<i>p</i><0.001, average reduction 30.3%), while SB V_15Gy increased by 2.3% (<i>p</i> = 0.011). AutoIMRT reduced SB V_45Gy by another 2.7% compared to autoVMAT, while also resulting in a 9.0% reduction in SB V_15Gy (<i>p</i><0.001), but with a prolonged delivery time. Differences between manVMAT and autoVMAT in bladder, rectal and sigmoid doses were ≤ 1%. Improvements in SB dose delivery with autoVMAT instead of manVMAT were higher for empty bladder PTVs compared to full bladder PTVs, due to differences in concavity of the PTVs.</p><p>Conclusions</p><p>Quality of automatically generated VMAT plans was superior to manually generated plans. Automatic VMAT plan generation for cervical cancer has been implemented in our clinical routine. Due to the achieved workload reduction, extension of plan libraries has become feasible.</p></div

Measured treatment delivery times for autoVMAT and autoIMRT using the MLCi2 and Agility MLCs.

<p>Measured treatment delivery times for autoVMAT and autoIMRT using the MLCi2 and Agility MLCs.</p

Percentage differences in mean OAR plan parameter values for all evaluated planning strategies, compared to autoVMAT.

<p><b>(a) for all 44 plans, (b) and (c) for the 10 patients with large bladder filling induced PTV displacements.</b> Positive values point at an advantage for autoVMAT. ^*: difference with autoVMAT is statistically significant. Average absolute values for autoVMAT: SB V_45Gy = 15.4%, SB V_15Gy = 68.7%, SB D_mean = 25.5 Gy, Bladder D_mean = 43.5 Gy, Rectum D_mean = 42.9 Gy, Sigmoid D_mean = 42.3 Gy and CI_95% = 1.174.</p

Pair-wise comparisons of planning strategies.

<p>Pair-wise comparisons of planning strategies.</p

FIFTEEN-YEAR RADIOTHERAPY OUTCOMES OF THE RANDOMIZED PORTEC-1 TRIAL FOR ENDOMETRIAL CARCINOMA

PurposeTo evaluate the very long-term results of the randomized Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-1 trial for patients with Stage I endometrial carcinoma (EC), focusing on the role of prognostic factors for treatment selection and the long-term risk of second cancers.Patients and MethodsThe PORTEC trial (1990–1997) included 714 patients with Stage IC Grade 1–2 or Stage IB Grade 2–3 EC. After surgery, patients were randomly allocated to external-beam pelvic radiotherapy (EBRT) or no additional treatment (NAT). Analysis was by intention to treat.Results426 patients were alive at the date of analysis. The median follow-up time was 13.3 years. The 15-year actuarial locoregional recurrence (LRR) rates were 6% for EBRT vs. 15.5% for NAT (p < 0.0001). The 15-year overall survival was 52% vs. 60% (p = 0.14), and the failure-free survival was 50% vs. 54% (p = 0.94). For patients with high-intermediate risk criteria, the 15-year overall survival was 41% vs. 48% (p = 0.51), and the 15-year EC-related death was 14% vs. 13%. Most LRR in the NAT group were vaginal recurrences (11.0% of 15.5%). The 15-year rates of distant metastases were 9% vs. 7% (p = 0.25). Second primary cancers had been diagnosed over 15 years in 19% of all patients, 22% vs. 16% for EBRT vs. NAT (p = 0.10), with observed vs. expected ratios of 1.6 (EBRT) and 1.2 (NAT) compared with a matched population (p = NS). Multivariate analysis confirmed the prognostic significance of Grade 3 for LRR (hazard ratio [HR] 3.4, p = 0.0003) and for EC death (HR 7.3, p < 0.0001), of age >60 (HR 3.9, p = 0.002 for LRR and 2.7, p = 0.01 for EC death) and myometrial invasion >50% (HR 1.9, p = 0.03 and HR 1.9, p = 0.02).ConclusionsThe 15-year outcomes of PORTEC-1 confirm the relevance of HIR criteria for treatment selection, and a trend for long-term risk of second cancers. EBRT should be avoided in patients with low- and intermediate-risk EC

Long-Term Outcome and Quality of Life of Patients With Endometrial Carcinoma Treated With or Without Pelvic Radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) Trial

Purpose To determine the long-term outcome and health-related quality of life (HRQL) of patients with endometrial carcinoma (EC) treated with or without pelvic radiotherapy in the Post Operative Radiation Therapy in Endometrial Carcinoma 1 (PORTEC-1) trial. Patients and Methods Between 1990 and 1997, 714 patients with stage IC grade 1 to 2 or IB grade 2 to 3 EC were randomly allocated to pelvic external-beam radiotherapy (EBRT) or no additional treatment (NAT). HRQL was evaluated with the Short Form 36-Item (SF-36) questionnaire; subscales from the European Organisation for Research and Treatment of Cancer (EORTC) PR25 module for bowel and bladder symptoms and the OV28 and CX24 modules for sexual symptoms; and demographic questions. Analysis was by intention-to-treat. Results Median follow-up was 13.3 years. The 15-year actuarial locoregional recurrence rates were 5.8% for EBRT versus 15.5% for NAT (P <.001), and 15-year overall survival was 52% versus 60% (P = .14). Of the 351 patients confirmed to be alive with correct address, 246 (70%) returned the questionnaire. Patients treated with EBRT reported significant (P <.01) and clinically relevant higher rates of urinary incontinence, diarrhea, and fecal leakage leading to more limitations in daily activities. Increased symptoms were reflected by the frequent use of incontinence materials after EBRT (day and night use, 42.9% v 15.2% for NAT; P <.001). Patients treated with EBRT reported lower scores on the SF-36 scales "physical functioning" (P = .004) and "role-physical" (P = .003). Conclusion EBRT for endometrial cancer is associated with long-term urinary and bowel symptoms and lower physical and role-physical functioning, even 15 years after treatment. Despite its efficacy in reducing locoregional recurrence, EBRT should be avoided in patients with low-and intermediate-risk EC. J Clin Oncol 29:1692-1700. (C) 2011 by American Society of Clinical Oncolog

For a study patient, sagittal views of the empty bladder CT scan with the empty-to-half-full-bladder PTV (blue) projected on it (left), and of the full bladder CT scan with the half-full-to-full-bladder PTV (red) on the (right).

<p>The higher degree of concavity of the empty-to-half-full-bladder PTV increases the complexity of small bowel sparing in manual planning.</p