[en] Purpose: To measure patient-based minimal clinically important effect sizes (minimal incremental benefit that an individual would require to accept one treatment option over another) for pain relief between two contrasting palliative radiotherapy regimens for painful pelvic recurrences from rectal cancer. Methods and Materials: Forty-three patients with a history of cancer pain without prior pelvic radiotherapy participated in decision aid-facilitated trade-off exercises. The clinical scenario and treatment options of a 5-day vs. a 20-day course of radiotherapy were described. The duration of pain relief for the 20-day regimen was increased until the respondents' preferences switched to the 20-day regimen. The exercises were repeated for different probabilities of benefit and pain intensity at the time of decision making. Results: When the probability of pain relief was unchanged, the median switch point for the duration of pain relief was 6.7 and 7.2 months for severe and mild pain, respectively. The cumulative percentage frequency curve for the switch points approximated a sigmoid distribution. Conclusion: Determining the minimal clinically important effect sizes for symptom relief for palliative therapies is feasible. This type of information can be used to incorporate patient values into clinical trial designs. Modification of this method can be used to improve our understanding of shared (physician and patient) decision making

[en] To assess the baseline albumin-bilirubin (ALBI) score as a predictor of toxicity and survival in a prospective cohort of Western patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) in 2 prospective trials.

[en] Purpose: To describe the degree of interobserver and intraobserver variability in target and field definition when using three-dimensional (3D) volume- vs. two-dimensional (2D) field-based planning. Methods and Materials: Standardized case scenario and diagnostic imaging for 9 palliative cases (3 bone metastases, 3 palliative lung cancer, and 3 abdominal pelvis soft-tissue disease) were presented to 5 study radiation oncologists. After a decision on what the intended anatomic target should be, observers created two sets of treatment fields, first using a 2D field-based and then a 3D volume-based planning approach. Percent overlap, under-coverage, and over-coverage were used to describe interobserver and intraobserver variations in target definition. Results: The degree of interobserver variation for 2D and 3D planning was similar with a degree of overlap of 76% (range, 56%-85%) and 74% (range, 55%-88%), respectively. When comparing the treatment fields defined by the same observer using the two different planning methods, the mean degree of overlap was 78%; over-coverage, 22%; and under-coverage, 41%. There was statistically significantly more under-coverage when field-based planning was used for bone metastases (33%) vs. other anatomic sites (16%) (p = 0.02). In other words, 2D planning is more likely to result in geographic misses in bone metastases compared with other areas. Conclusions: In palliative radiotherapy clinically significant interobserver and intraobserver variation existed when using both field- and volume-based planning approaches. Strategies that would reduce this variability deserve further investigation.

[en] Purpose: Reduction of respiratory motion is desirable to reduce the volume of normal tissues irradiated, to improve concordance of planned and delivered doses, and to improve image guided radiation therapy (IGRT). We hypothesized that pretreatment lorazepam would lead to a measurable reduction of liver motion. Methods and Materials: Thirty-three patients receiving upper abdominal IGRT were recruited to a double-blinded randomized controlled crossover trial. Patients were randomized to 1 of 2 study arms: arm 1 received lorazepam 2 mg by mouth on day 1, followed by placebo 4 to 8 days later; arm 2 received placebo on day 1, followed by lorazepam 4 to 8 days later. After tablet ingestion and daily radiation therapy, amplitude of liver motion was measured on both study days. The primary outcomes were reduction in craniocaudal (CC) liver motion using 4-dimensional kV cone beam computed tomography (CBCT) and the proportion of patients with liver motion ≤5 mm. Secondary endpoints included motion measured with cine magnetic resonance imaging and kV fluoroscopy. Results: Mean relative and absolute reduction in CC amplitude with lorazepam was 21% and 2.5 mm respectively (95% confidence interval [CI] 1.1-3.9, P=.001), as assessed with CBCT. Reduction in CC amplitude to ≤5 mm residual liver motion was seen in 13% (95% CI 1%-25%) of patients receiving lorazepam (vs 10% receiving placebo, P=NS); 65% (95% CI 48%-81%) had reduction in residual CC liver motion to ≤10 mm (vs 52% with placebo, P=NS). Patients with large respiratory movement and patients who took lorazepam ≥60 minutes before imaging had greater reductions in liver CC motion. Mean reductions in liver CC amplitude on magnetic resonance imaging and fluoroscopy were nonsignificant. Conclusions: Lorazepam reduces liver motion in the CC direction; however, average magnitude of reduction is small, and most patients have residual motion >5 mm

[en] Purpose: We evaluated the effect of consecutive protocols on overall survival (OS) for cervical esophageal carcinoma (CEC). Methods and Materials: All CEC cases that received definitive radiation therapy (RT) with or without chemotherapy from 1997 to 2013 in 3 consecutive protocols were reviewed. Protocol 1 (P1) consisted of 2-dimensional RT of 54 Gy in 20 fractions with 5-fluorouracil plus either mitomycin C or cisplatin. Protocol 2 (P2) consisted of 3-dimensional conformal RT (3DRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Protocol 3 (P3) consisted of intensity modulated RT (IMRT) of ≥60 Gy in 30 fractions plus elective nodal irradiation plus cisplatin. Multivariable analyses were used to assess the effect of the treatment protocol, RT technique, and RT dose on OS, separately. Results: Of 81 cases (P1, 21; P2, 23; and P3, 37), 34 local (P1, 11 [52%]; P2, 12 [52%]; and P3, 11 [30%]), 16 regional (P1, 6 [29%]); P2, 3 [13%]; and P3, 7 [19%]), and 34 distant (P1, 10 [48%]; P2, 9 [39%]; and P3, 15 [41%]) failures were identified. After adjusting for age (P=.49) and chemotherapy (any vs none; hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.3-0.9; P=.023), multivariable analysis showed P3 had improved OS compared with P1 (HR 0.4, 95% CI 0.2-0.8; P=.005), with a trend shown for benefit compared with P2 (HR 0.6, 95% CI 0.3-1.0; P=.061). OS between P1 and P2 did not differ (P=.29). Analyzed as a continuous variable, higher RT doses were associated with a borderline improved OS (HR 0.97, 95% CI 0.95-1.0; P=.075). IMRT showed improved OS compared with non-IMRT (HR 0.57, 95% CI 0.3-0.8; P=.008). Conclusions: The present retrospective consecutive cohort study showed improved OS with our current protocol (P3; high-dose IMRT with concurrent high-dose cisplatin) compared with historical protocols. The outcomes for patients with CEC remain poor, and novel approaches to improve the therapeutic ratio are warranted.

[en] Purpose: External beam radiotherapy (RT) is commonly indicated for the palliation of symptomatic bone metastases, but there is evidence of underutilization of this treatment modality in palliative care for cancer populations. This study was conducted to investigate factors that influenced the use of palliative RT services at a regional comprehensive cancer center. Methods and Materials: A cohort of patients with radiographically confirmed bone metastases and first-time users of palliative RT between 2003 and 2005 was retrospectively reviewed from the time of initial diagnosis of bone metastases to death or last follow-up. Type of radiation treatment service provider used (rapid access or routine access) and patient-, tumor-, and treatment-related factors were analyzed for their influences on the number of treatment courses given over the duration of disease. Results: A total of 887 patients received 1,354 courses of palliative RT for bone metastases at a median interval of 4.0 months between courses. Thirty-three percent of patients required more than one RT course. Increased age and travel distance reduced the likelihood and number of treatment courses, while service through a rapid access clinic was independently associated with an increase in subsequent use of palliative RT. Conclusions: A rapid access service model for palliative RT facilitated access to RT. Travel distance and other factors remained substantial barriers to use of palliative RT services. The pattern of practice suggests an unmet need for symptom control in patients with bone metastases.

[en] Purpose: The NCIC CTG Symptom Control.20 randomized trial (SC.20) confirmed the effectiveness of re-irradiation to painful bone metastases. This companion study correlates urinary markers of osteoclast activity with response to re-irradiation, survival and skeletal related events (SREs). Methods: Pain response was assessed using the International Consensus Endpoints. Urinary markers of bone turnover-pyridinoline (PYD), deoxypyridinoline (DPD), N-telopeptide (NTX), Alpha and Beta cross-laps of C-telopeptide (CTX)-before and 1 month after re-irradiation were correlated to response to re-irradiation and then to both, either or none of the initial and re-irradiation: frequent responders (response to both); eventual responders (response to re-irradiation only); eventual non-responders (response to initial radiation only), and absolute non-responders (no response to both). Results: Significant differences between 40 responders and 69 non-responders to re-irradiation existed for PYD (p = 0.03) and DPD (p = 0.04) at baseline. When patients were categorized as frequent responders (N = 34), eventual responders (6), eventual non-responders (59) and absolute non-responders (10), the mean values of all markers in the absolute non-responders at baseline and the follow-up were about double those for the other three groups with statistically significant difference for DPD (p = 0.03) at baseline. Absolute non-responders had the worst survival. The few occurrences of the SREs did not allow meaningful comparisons among the groups. Conclusion: There were significant differences between responders and non-responders to re-irradiation for PYD and DPD at baseline. The urinary markers in the absolute non-responders were markedly elevated at both baseline and follow-up with a statistically significant difference for DPD at baseline

[en] Purpose: To develop a cone-beam computed tomography (CT)–enabled one-step simulation-to-treatment process for the treatment of bone metastases. Methods and Materials: A three-phase prospective study was conducted. Patients requiring palliative radiotherapy to the spine, mediastinum, or abdomen/pelvis suitable for treatment with simple beam geometry (≤2 beams) were accrued. Phase A established the accuracy of cone-beam CT images for the purpose of gross tumor target volume (GTV) definition. Phase B evaluated the feasibility of implementing the cone-beam CT–enabled planning process at the treatment unit. Phase C evaluated the online cone-beam CT–enabled process for the planning and treatment of patients requiring radiotherapy for bone metastases. Results: Eighty-four patients participated in this study. Phase A (n = 9) established the adequacy of cone-beam CT images for target definition. Phase B (n = 45) established the quality of treatment plans to be adequate for clinical implementation for bone metastases. When the process was applied clinically in bone metastases (Phase C), the degree of overlap between planning computed tomography (PCT) and cone-beam CT for GTV and between PCT and cone-beam CT for treatment field was 82% ± 11% and 97% ± 4%, respectively. The oncologist’s decision to accept the plan under a time-pressured environment remained of high quality, with the cone-beam CT–generated treatment plan delivering at least 90% of the prescribed dose to 100% ± 0% of the cone-beam CT planning target volume (PTV). With the assumption that the PCT PTV is the gold-standard target, the cone-beam CT–generated treatment plan delivered at least 90% and at least 95% of dose to 98% ± 2% and 97% ± 5% of the PCT PTV, respectively. The mean time for the online planning and treatment process was 32.7 ± 4.0 minutes. Patient satisfaction was high, with a trend for superior satisfaction with the cone-beam CT–enabled process. Conclusions: The cone-beam CT–enabled palliative treatment process is feasible and is ready for clinical implementation for the treatment of bone metastases using simple beam geometry, providing a streamlined one-step process toward palliative radiotherapy.

[en] Purpose: The purpose of this study was to assess the accuracy of a virtual consultation (VC) process in determining treatment strategy for patients with malignant epidural spinal cord compression (MESCC). Methods and Materials: A prospective clinical database was maintained for patients with MESCC. A virtual consultation process (involving exchange of key predetermined clinical information and diagnostic imaging) facilitated rapid decision-making between oncologists and spinal surgeons. Diagnostic imaging was reviewed retrospectively (by R.R.) for surgical opinions in all patients. The primary outcome was the accuracy of virtual consultation opinion in predicting the final treatment recommendation. Results: After excluding 20 patients who were referred directly to the spinal surgeon, 125 patients were eligible for virtual consultation. Of the 46 patients who had a VC, surgery was recommended in 28 patients and actually given to 23. A retrospective review revealed that 5/79 patients who did not have a VC would have been considered surgical candidates. The overall accuracy of the virtual consultation process was estimated at 92%. Conclusion: The VC process for MESCC patients provides a reliable means of arriving at a multidisciplinary opinion while minimizing patient transfer. This can potentially shorten treatment decision time and enhance clinical outcomes.

[en] Background and purpose: To determine maximum tolerated dose (MTD) and toxicities of sorafenib combined with stereotactic radiotherapy (SBRT) or whole liver radiotherapy (WLRT) in patients with liver metastases.