J. Xie

Pelvic Radiotherapy for Cancer of the Cervix: Is What You Plan Actually What You Deliver?

PURPOSE Whole pelvic intensity-modulated radiotherapy (IMRT) is increasingly being used to treat cervix cancer and other gynecologic tumors. However, tumor and normal organ movement during treatment can substantially detract from the benefits of this approach. This study explored the effect of internal anatomic changes on the dose delivered to the tumor and organs at risk using a strategy integrating deformable soft-tissue modeling with simulated dose accumulation. METHODS AND MATERIALS Twenty patients with cervix cancer underwent baseline and weekly pelvic magnetic resonance imaging during treatment. Interfraction organ motion and delivered (accumulated) dose was modeled for three treatment scenarios: four-field box, large-margin whole pelvic IMRT (20-mm planning target volume, but 10 mm inferiorly) and small-margin IMRT (5-mm planning target volume). RESULTS Individually, the planned dose was not the same as the simulated delivered dose; however, when taken as a group, this was not statistically significant for the four-field box and large-margin IMRT plans. The small-margin IMRT plans yielded adequate target coverage in most patients; however, significant target underdosing occurred in 1 patient who displayed excessive, unpredictable internal target movement. The delivered doses to the organs at risk were significantly reduced with the small-margin plan, although substantial variability was present among the patients. CONCLUSION Simulated dose accumulation might provide a more accurate depiction of the target and organ at risk coverage during fractionated whole pelvic IMRT for cervical cancer. The adequacy of primary tumor coverage using 5-mm planning target volume margins is contingent on the use of daily image-guided setup.

Auto‐segmentation of normal and target structures in head and neck CT images: A feature‐driven model‐based approach

PURPOSE Intensity modulated radiation therapy (IMRT) allows greater control over dose distribution, which leads to a decrease in radiation related toxicity. IMRT, however, requires precise and accurate delineation of the organs at risk and target volumes. Manual delineation is tedious and suffers from both interobserver and intraobserver variability. State of the art auto-segmentation methods are either atlas-based, model-based or hybrid however, robust fully automated segmentation is often difficult due to the insufficient discriminative information provided by standard medical imaging modalities for certain tissue types. In this paper, the authors present a fully automated hybrid approach which combines deformable registration with the model-based approach to accurately segment normal and target tissues from head and neck CT images. METHODS The segmentation process starts by using an average atlas to reliably identify salient landmarks in the patient image. The relationship between these landmarks and the reference dataset serves to guide a deformable registration algorithm, which allows for a close initialization of a set of organ-specific deformable models in the patient image, ensuring their robust adaptation to the boundaries of the structures. Finally, the models are automatically fine adjusted by our boundary refinement approach which attempts to model the uncertainty in model adaptation using a probabilistic mask. This uncertainty is subsequently resolved by voxel classification based on local low-level organ-specific features. RESULTS To quantitatively evaluate the method, they auto-segment several organs at risk and target tissues from 10 head and neck CT images. They compare the segmentations to the manual delineations outlined by the expert. The evaluation is carried out by estimating two common quantitative measures on 10 datasets: volume overlap fraction or the Dice similarity coefficient (DSC), and a geometrical metric, the median symmetric Hausdorff distance (HD), which is evaluated slice-wise. They achieve an average overlap of 93% for the mandible, 91% for the brainstem, 83% for the parotids, 83% for the submandibular glands, and 74% for the lymph node levels. CONCLUSIONS Our automated segmentation framework is able to segment anatomy in the head and neck region with high accuracy within a clinically-acceptable segmentation time.

Automated Weekly Replanning for Intensity-Modulated Radiotherapy of Cervix Cancer

PURPOSE The adoption of intensity-modulated radiotherapy (IMRT) to treat cervical malignancies has been limited in part by complex organ and tumor motion during treatment. This study explores the limits of a highly adaptive, small-margin treatment scenario to accommodate this motion. In addition, the dosimetric consequences of organ and tumor motion are modeled using a combination of deformable registration and fractional dose accumulation techniques. METHODS AND MATERIALS Thirty-three cervix cancer patients had target volumes and organs-at-risk contoured on fused, pretreatment magnetic resonance-computed tomography images and weekly magnetic resonance scans taken during treatment. The dosimetric impact of interfraction organ and target motion was compared for two hypothetical treatment scenarios: a 3-mm margin plan with no replanning, and a 3-mm margin plan with an automated replan performed on the updated weekly patient geometry. RESULTS Of the 33 patients, 24 (73%) met clinically acceptable target coverage (98% of the clinical target volume receiving at least 95% of the prescription dose) using the 3-mm margin plan without replanning. The range in dose to 98% of the clinical target volume across all patients was 7.9% of the prescription dose if no replanning was performed. After weekly replanning, this range was tightened to 2.6% of the prescription dose and all patients met clinically acceptable target coverage while maintaining organ-at-risk dose sparing. CONCLUSIONS The dosimetric impact of anatomical motion underscores the challenges of applying IMRT to treat cervix cancer. An appropriate adaptive strategy can ensure target coverage for small-margin IMRT treatments and maintain favorable organ-at-risk dose sparing.

Hybrid adaptive radiotherapy with on-line MRI in cervix cancer IMRT

PURPOSE Substantial organ motion and tumor shrinkage occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes, therefore the adaptation of treatment plans may be warranted. Image guidance with off-line replanning, i.e. hybrid-adaptation, is recognized as one of the most practical adaptation strategies. In this study, we investigated the effects of soft tissue image guidance using on-line MR while varying the frequency of off-line replanning on the adaptation of cervix IMRT. MATERIALS AND METHOD 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. 5 patients of 33 were identified in a previous retrospective adaptive planning study, in which the coverage of gross tumor volume/clinical target volume (GTV/CTV) was not acceptable given single off-line IMRT replan using a 3mm PTV margin with bone matching. These 5 patients and a randomly selected 10 patients from the remaining 28 patients, a total of 15 patients of 33, were considered in this study. Two matching methods for image guidance (bone to bone and soft tissue to dose matrix) and three frequencies of off-line replanning (none, single, and weekly) were simulated and compared with respect to target coverage (cervix, GTV, lower uterus, parametrium, upper vagina, tumor related CTV and elective lymph node CTV) and OAR sparing (bladder, bowel, rectum, and sigmoid). Cost (total process time) and benefit (target coverage) were analyzed for comparison. RESULTS Hybrid adaptation (image guidance with off-line replanning) significantly enhanced target coverage for both 5 difficult and 10 standard cases. Concerning image guidance, bone matching was short of delivering enough doses for 5 difficult cases even with a weekly off-line replan. Soft tissue image guidance proved successful for all cases except one when single or more frequent replans were utilized in the difficult cases. Cost and benefit analysis preferred (soft tissue) image guidance over (frequent) off-line replanning. CONCLUSIONS On-line MRI based image guidance (with combination of dose distribution) is a crucial element for a successful hybrid adaptive radiotherapy. Frequent off-line replanning adjuvantly enhances adaptation quality.

Tumor and normal tissue dosimetry changes during MR-guided pulsed-dose-rate (PDR) brachytherapy for cervical cancer

BACKGROUND AND PURPOSE To analyze systematic changes in tumor and normal tissue anatomy and dosimetry using serial MR imaging during pulsed dose rate brachytherapy (PDR BT) for cervical cancer. MATERIAL AND METHODS Forty-three patients with cervical cancer underwent MR-guided PDR BT using an intrauterine applicator alone after external beam radiotherapy. MR imaging was repeated on days 2 and 3 of treatment and the day 1 plan was applied to the re-contoured volumes. RESULTS The mean uterine volume and mean HR CTV increased during treatment. This resulted in a decrease in the mean HR CTV D90 relative to the day 1 planned dose. There was no change in the mean bladder volume during treatment but the mean rectal volume increased. This correlated with an increase in the mean rectal dose. There were four local recurrences. There was no apparent relationship between either the planned or the delivered HR CTV D90 and local recurrence. There was only one case of late bladder toxicity but nine patients developed late rectal toxicity. The cumulative rectal dose during treatment was a better predictor of late rectal toxicity than the planned dose. CONCLUSIONS Significant changes in tumor and normal tissue anatomy and dosimetry can occur during PDR BT and should be tracked and corrected using serial imaging and plan adaptation, especially when the day 1 tumor or normal tissue doses are close to the planning constraints.

Association of Apparent Diffusion Coefficient with Disease Recurrence in Patients with Locally Advanced Cervical Cancer Treated with Radical Chemotherapy and Radiation Therapy

PURPOSE To investigate whether volumetrically derived apparent diffusion coefficient (ADC) from pretreatment diffusion-weighted (DW) magnetic resonance (MR) imaging is associated with disease recurrence in women with locally advanced cervical cancer treated with chemotherapy and radiation therapy. MATERIALS AND METHODS An ethics board-approved, retrospective study was conducted in 85 women with stage IB-IVA cervical cancer treated with chemo- and radiation therapy in 2009-2013. All patients underwent MR imaging for staging, including T2-weighted and DW MR imaging series, by using a 1.5- or 3.0-T imager. The mean, median, 75th, 90th, and 95th percentile ADCs (ADCmean, ADC50, ADC75, ADC90, and ADC95, respectively) of all voxels that comprised each tumor were extracted and normalized to the mean urine ADC (nADCmean, nADC50, nADC75, nADC90, and nADC95, respectively) to reduce variability. The primary outcome was disease-free survival (DFS). Uni- and multivariable Cox regression analyses were used to evaluate the association of ADC parameters and relevant clinical variables with DFS. RESULTS Of the 85 women included, 62 were free of disease at last follow-up. Median follow-up was 37 months (range, 5-68 months). Significant variables at univariable analysis included T2-weighted derived tumor diameter, para-aortic nodal involvement, advanced stage, ADC90 and ADC95, nADC75, nADC90, and nADC95. Normalized parameters were more highly associated (hazard ratio per 0.01 increase in normalized ADC, 0.91-0.94; P < .04). Because nADC75, nADC90, and nADC95 were highly correlated, only nADC95 (which had the lowest P value) was included in multivariable analysis. At multivariable analysis, absolute and normalized ADC95 remained associated with DFS (hazard ratio, 0.90-0.98; P < .05). CONCLUSION The volumetric ADC95 may be a useful imaging metric to predict treatment failure in patients with locally advanced cervical cancer treated with chemo- and radiation therapy.

Dosimetrically triggered adaptive intensity modulated radiation therapy for cervical cancer.

PURPOSE The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. METHODS AND MATERIALS Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes and organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). RESULTS Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. CONCLUSIONS A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.

Comparison of dosimetric parameters derived from whole organ and wall contours for bladder and rectum in cervical cancer patients treated with intracavitary and interstitial brachytherapy

For volumes up to 2 cm3 of the bladder and possibly up to 5 cm3 of the rectum, doses computed from the whole organ were good estimates of the doses in the wall in cervix brachytherapy, and there were no significant differences between patients treated with or without interstitial needles.

OC-0049: Phase I/II study of palliative radiation and sorafenib for metastatic enal cell carcinoma and bone metastases

OC-0048 Long term results of the Dutch trial for localized prostate cancer: Impact on biochemical, clinical and local control J. Lebesque, W. Heemsbergen, A. Slot, M. Dielwart, W. van Putten, A. Al-Mamgani The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Radiation Oncology, Amsterdam, The Netherlands Radiotherapeutic Institute Friesland, Radiation Oncology, Leeuwarden, The Netherlands Zeeuws Radiotherapeutic Institute, Radiation Oncology, Vlissingen, The Netherlands Erasmus Medical Centre-Daniel den Hoed Cancer Center, Statistical Department, Rotterdam, The Netherlands Erasmus Medical Centre-Daniel den Hoed Cancer Center, Radiation Oncology, Rotterdam, The Netherlands

TH‐E‐BRA‐08: MR Guided Radiotherapy for Cervix Cancer Treatment; Retrospective Feasibility Study

Purpose: To evaluate the efficacy of on‐line MR guided radiotherapy for cervix cancer patients. MR guidance was simulated in order to optimize the fractional dose to the on‐line targets. Methods: 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. In the previous retrospective adaptive planning study using 3 mm PTV margin, 5 over 33 patient cases were identified and enrolled in this study in which the coverage of GTV/CTVs was not acceptable with single IMRT adaptation with bone matching. MR guidance was simulated in order to maximize online high risk CTV (HRCTV) volume to be within 95% of the prescription dose (95p). Fractional dose after the image guidance was calculated, and was deformed back to the reference (planning) image for dose accumulation. Accumulated dose of the proposed technique was compared with that of current standard image guidance technique, bone matching in terms of the target coverage (cervix, GTV, HRCTV, lower uterus, parametria, and upper vagina) and OAR sparing (bladder, bowl, rectum, and sigmoid). Target coverage was considered acceptable if 95p dose or more was delivered to 98% of the target volume. OAR sparing was evaluated with accumulated V45 and D2cc. Results: On line MR based soft tissue guidance proposed in this study achieved the acceptance of target coverage to 97% from 53% (bone matching). Dose delivery to HRCTV and lower uterus was significantly improved (p<0.001, paired t‐test). The mean D2cc and V45 were reduced in bladder, rectum and sigmoid compared to bone matching. Conclusions: The retrospective study revealed that the on‐line MR based soft‐tissue image guidance is very effective for cervix cancer treatment. The technique significantly and successfully improved target coverage for the most difficult patient group identified from the previous study. Statistically significant improvement in OAR sparing was also noted. Anna Lundin and Henrik Rehbinder are both employees and shareholders of RaySearch Laboratories AB. All other authors have no conflicts to report.