Harvey Quon

A treatment planning study comparing helical tomotherapy with intensity-modulated radiotherapy for the treatment of anal cancer

PURPOSE A planning study to compare helical tomotherapy (HT) and intensity-modulated radiotherapy (IMRT) for the treatment of anal canal cancer. MATERIALS AND METHODS Sixteen (8 males and 8 females) patients with anal cancer previously treated radically were identified. HT and IMRT plans were generated and dosimetric comparisons of the plans were performed. The planning goals were to deliver 54Gy to the tumor (PTV(54Gy)) and 48Gy to the nodes at risk (PTV(Node)) in 30 fractions. RESULTS PTVs: HT plans were more homogeneous for both men and women. Male patients: HT vs. IMRT: D(max): 55.87+/-0.58 vs. 59.17+/-3.24 (p=0.036); D(min): 52.91+/-0.36 vs. 44.09+/-6.84 (p=0.012); female patients: HT vs. IMRT: D(max): 56.14+/-0.71 vs. 59.47+/-0.81 (p=0.012); D(min): 52.36+/-0.87 vs. 50.97+/-1.42 (p=0.028). OARs: In general, HT plans delivered a lower dose to the peritoneal cavity, external genitalia and the bladder and IMRT plans resulted in greater sparing of the pelvic bones (iliac crest/femur) for both men and women. Iliac crest/femur: the difference was significant only for the mean V10Gy of iliac crest in women (p< or =0.012). External genitalia: HT plans achieved better sparing in women compared to men (p< or =0.046). For men, the mean doses were 18.96+/-3.17 and 15.72+/-3.21 for the HT and IMRT plan, respectively (p< or =0.017). Skin: both techniques achieved comparable sparing of the non-target skin (p=NS). CONCLUSIONS HT and IMRT techniques achieved comparable target dose coverage and organ sparing, whereas HT plans were more homogeneous for both men and women.

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials

PURPOSE To compare biochemical outcome and toxicities of two prospective 5-fraction stereotactic ablative radiotherapy (SABR) studies in prostate cancer. MATERIALS AND METHODS 84 patients in pHART3 received 35 Gy, 30 patients in pHART6 received 40 Gy in 5-fractions to the prostate alone, once weekly. 4mm and 5mm PTV margins were used, respectively. Biochemical outcome, acute, late and cumulative genitourinary (GU)/gastrointestinal (GI) toxicities were compared. RESULTS Median follow-up was 74 and 36 months, respectively. Median prostate specific antigen nadir was 0.4 ng/ml and 0.3 ng/ml. 2-, 4- and 6-year biochemical relapse-free survival (bRFS-2+nadir) was 100%, 98.7% and 95.9% in pHART3; 100%, 100% and not reached in pHART6 (p=0.91). There was one acute grade 3 GU (retention) and late grade 4 GI (fistula) toxicity in pHART3, none in pHART6. One patient in each study had persisting grade 2+ toxicity at the last follow-up. pHART6 patients had a greater grade 2+ cumulative GU (5% versus 24.2%) and GI (7.6% versus 26.2%) toxicities. CONCLUSIONS Patients receiving dose-escalated SABR had slightly lower PSA nadir and similar bRFS, longer follow-up is needed to better estimate biochemical outcomes. There was a greater risk of grade 2 toxicity in pHART6 but not grade 3+ toxicities. Persisting toxicity at the last follow-up is similar.

Dose-Escalated Stereotactic Body Radiation Therapy for Prostate Cancer: Quality-of-Life Comparison of Two Prospective Trials

Introduction The optimal prostate stereotactic body radiation therapy (SBRT) dose-fractionation scheme is controversial. This study compares long-term quality of life (QOL) from two prospective trials of prostate SBRT to investigate the effect of increasing dose (NCT01578902 and NCT01146340). Material and methods Patients with localized prostate cancer received SBRT 35 or 40 Gy delivered in five fractions, once per week. QOL was measured using the Expanded Prostate Cancer Index Composite at baseline and every 6 months. Fisher’s exact test and generalized estimating equations were used to analyze proportions of patients with clinically significant change and longitudinal changes in QOL. Results One hundred fourteen patients were included, 84 treated with 35 Gy and 30 treated with 40 Gy. Median QOL follow-up was 56 months [interquartile range (IQR) 46–60] and 38 months (IQR 32–42), respectively. The proportion of patients reporting clinically significant declines in average urinary, bowel, and sexual scores were not significantly different between dose levels, and were 20.5 vs. 24.1% (p = 0.60), 26.8 vs. 41.4% (p = 0.16), and 42.9 vs. 38.5% (p = 0.82), respectively. Similarly, longitudinal analysis did not identify significant differences in QOL between treatment groups. Conclusion Dose-escalated prostate SBRT from 35 to 40 Gy in five fractions was not associated with significant decline in long-term QOL.

Stereotactic ablative radiotherapy in the treatment of low and intermediate risk prostate cancer: Is there an optimal dose?

PURPOSE To investigate if stereotactic ablative radiotherapy (SABR) dose is associated with PSA at 3years (PSA3y) in the treatment of localized prostate cancer and to explore predictors of late genitourinary (GU) toxicity. MATERIALS AND METHODS Three prospective trials of SABR were undertaken at our institution: 1) 35Gy/5 fractions/29days; 2) 40Gy/5 fractions/29days; 3) 40Gy/5 fractions/11 or 29days. PSA3y was analyzed as a continuous variable. Toxicity was defined as the worst new toxicity and assessed using the radiation therapy oncology group (RTOG) late morbidity scheme. Univariate and multivariable regression analyses were conducted to assess the association between dose and PSA3y, and to explore predictors of late grade 2+ GU toxicity. RESULTS Median PSA3y was 0.64 (intraquartile range (IQR): 0.41-1.12) and 0.27 (IQR: 0.12-0.55) ng/mL for patients treated with 35 and 40Gy respectively. A dose of 40Gy was an independent predictor of lower PSA3y on multivariable analysis (p<0.001). Dose of 40Gy (odds ratio (OR): 16.69, 95%CI: 5.78, 48.20, p<0.001) and higher International Prostate Symptom Score (OR: 1.01, 95%CI: 1.04, 1.16, p=0.001) predicted for late grade 2+ GU toxicity on multivariable logistic regression. CONCLUSIONS This analysis suggests that higher SABR dose is associated with lower PSA3y. Strategies to allow safe SABR dose escalation should be further investigated.

Dose escalation for prostate stereotactic ablative radiotherapy (SABR): Late outcomes from two prospective clinical trials

PURPOSE Optimal prostate SABR dose-fractionation is unknown. This study compares long-term outcomes from two prospective trials. METHODS Study1 patients had low-risk PCa and received 35 Gy/5. Study2 patients had low/intermediate-risk PCa and received 40 Gy/5. Biochemical failure (BF) was defined as nadir + 2. RESULTS 114 patients were included (study1, n = 84; study2, n = 30). Median follow-up was 9.6 years and 6.9 years. Median nPSA was 0.4 and 0.1 ng/ml. Nine patients had BF (8 in study1, 1 in study2); two were managed with ADT and four had local salvage. The BF rate was 2.5% and 12.8% at 5 and 10 years for study1 and 3.3% at 5 years for study 2. BF probability was 0% if PSA <0.4 at 4 years, and 20.5% at 10 years if PSA ≥0.4 (p = 0.02). Nine patients died, none of PCa. No patient has metastases or castrate-resistance. At 10 years, OS and CSS were 90.4% (p = 0.25) and 100%. CONCLUSIONS Dose-escalated prostate SABR was associated with lower nPSAs but no difference in BF, OS, CSS or MFS. PSA <0.4 at 4 years was a predictor of biochemical control. Half of patients with BF were successfully salvaged. Given that this is a favorable-risk cohort, longer follow-up will be needed to see if the lower nPSA translates into lower BF rates.

Once-weekly versus every-other-day stereotactic body radiotherapy in patients with prostate cancer (PATRIOT): A phase 2 randomized trial

BACKGROUND AND PURPOSE Prostate stereotactic body radiotherapy (SBRT) regimens differ in time, dose, and fractionation. We completed a multicentre, randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL). MATERIAL AND METHODS Men with low and intermediate-risk prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered once per week (QW) vs. every other day (EOD). QOL was assessed using the Expanded Prostate Cancer Index Composite. The primary endpoint was the proportion with a minimum clinically important change (MCIC) in bowel QOL during the acute (≤12 week) period, and analysis was by intention-to-treat. ClinicalTrials.gov NCT01423474. RESULTS 152 men from 3 centres were randomized with median follow-up of 47 months. Patients treated QW had superior acute bowel QOL with 47/69 (68%) reporting a MCIC compared to 63/70 (90%) treated EOD (p = 0.002). Fewer patients treated QW reported moderate-severe problems with bowel QOL during the acute period compared with EOD (14/70 [20%] vs. 40/70 [57%], p < 0.001). Acute urinary QOL was also better in the QW arm, with 52/67 (78%) vs 65/69 (94%) experiencing a MCIC (p = 0.006). There were no significant differences in late urinary or bowel QOL at 2 years or last follow-up. CONCLUSION Prostate SBRT delivered QW improved acute bowel and urinary QOL compared to EOD. Patients should be counselled regarding the potential for reduced short-term toxicity and improved QOL with QW prostate SBRT.

Framework for the quantitative assessment of adaptive radiation therapy protocols

Abstract Background Adaptive radiation therapy (ART) “flags,” such as change in external body contour or relative weight loss, are widely used to identify which head and neck cancer (HNC) patients may benefit from replanned treatment. Despite the popularity of ART, few published quantitative approaches verify the accuracy of replan candidate identification, especially with regards to the simple flagging approaches that are considered current standard of practice. We propose a quantitative evaluation framework, demonstrated through the assessment of a single institutions clinical ART flag: change in body contour exceeding 1.5 cm. Methods Ground truth replan criteria were established by surveying HNC radiation oncologists. Patient‐specific dose deviations were approximated by using weekly acquired CBCT images to deform copies of the CT simulation, yielding during treatment “synthetic CTs.” The original plan reapplied to the synthetic CTs estimated interfractional dose deposition and truth table analysis compared ground truth flagging with the clinical ART metric. This process was demonstrated by assessing flagged fractions for 15 HNC patients whose body contour changed by >1.5 cm at some point in their treatment. Results Survey results indicated that geometric shifts of high‐dose volumes relative to image‐guided radiation therapy alignment of bony anatomy were of most interest to HNC physicians. This evaluation framework successfully identified a fundamental discrepancy between the “truth” criteria and the body contour flagging protocol selected to identify changes in central axis dose. The body contour flag had poor sensitivity to survey‐derived major violation criteria (0%–28%). The sensitivity of a random sample for comparable violation/flagging frequencies was 27%. Conclusions These results indicate that centers should establish ground truth replan criteria to assess current standard of practice ART protocols. In addition, more effective replan flags may be tested and identified according to the proposed framework. Such improvements in ART flagging may contribute to better clinical resource allocation and patient outcome.

Dynamics of three-dimensional telomere profiles of circulating tumor cells in patients with high-risk prostate cancer who are undergoing androgen deprivation and radiation therapies ☆

INTRODUCTION Accurate assessment and monitoring of the therapeutic efficacy of locally advanced prostate cancer remains a major clinical challenge. Contrary to prostate biopsies, circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling and could serve as a surrogate marker for treatment efficacy. In this study, we used size-based filtration to isolate and enumerate CTCs from the blood of 20 patients with high-risk (any one of cT3, Gleason 8-10, or prostate-specific antigen>20ng/ml), nonmetastatic, and treatment-naive prostate cancer before and after androgen deprivation therapy (ADT) and radiation therapy (RT). MATERIALS AND METHODS We performed 3D telomere-specific quantitative fluorescence in situ hybridization on isolated CTCs to determine 3D telomere profiles for each patient before and throughout the course of both ADT and RT. RESULTS Based on the distinct 3D telomere signatures of CTC before treatment, patients were divided into 3 groups. ADT and RT resulted in distinct changes in 3D telomere signatures of CTCs, which were unique for each of the 3 patient groups. CONCLUSION The ability of 3D telomere analysis of CTCs to identify disease heterogeneity among a clinically homogeneous group of patients, which reveals differences in therapeutic responses, provides a new opportunity for better treatment monitoring and management of patients with high-risk prostate cancer.

Targeting the Tumor: Assessing the Impact of Bladder Volume and Position on Accuracy of Radiation Delivery for Patients with Bladder Cancer

Context Daily variations in bladder size and position can negatively impact the ability to accurately deliver radiation. Aims We attempted to quantify how bladder volumes and positions change over the course of radiotherapy for muscle invasive bladder cancer and the planning target volume (PTV) margins required to account for such changes. Methods and material Cone-beam computed tomography (CT) images of 28 patients during their first, second, and third fractions and weekly thereafter were acquired. Bladders were contoured and the volume, centre of mass, and the maximal positions were recorded and compared to the planning CT scan. Statistical analysis Bladder parameters were analysed using regression analysis examining for time trends and correlation to the patient, tumour, or treatment-related factors. Results There was great variability in the mean bladder volumes during the radiotherapy courses (154.17 +/- 129.38 cm3). There were no statistically significant trends for volume changes. Deviations in bladder positions were seen but were small in magnitude. No patient factors were identified which could help predict bladder changes clinically. Bladder variability resulted in a high percentage of fractions (39.6%) in which part of the bladder was outside the PTV. Calculated PTV margins (for 90% of the population to receive 95% of the prescription dose) were 1.48 cm right, 1.15 cm left, 2.13 cm posterior, 1.52 cm anterior, 2.23 cm superior, and 0.52 cm inferior. Conclusions Because of random bladder changes, a significant number of fractions were treated in which the clinical target volume (CTV) fell outside of the PTV. Methods to minimize the amount of CTV that is missed on a fraction to fraction basis should be explored.

Dose escalation of five-fraction SABR for prostate cancer: Biochemical outcome and toxicity comparison of two prospective trials.

224 Background: To compare the biochemical outcomes and toxicities of two different 5 fraction stereotactic ablative body radiotherapy (SABR) schedules for the treatment of localized prostate cancer. Methods: Two sequential phase I/II studies of 5-fraction SABR for the treatment of low and intermediate risk (LR and IR) prostate cancer have been conducted. In the first trial, 84 LR patients(pts) received 35 Gy in 5 fractions, once per week over 29 days (Group 1). In the second trial, 30 pts (18 LR, 11 IR) received 40 Gy in 5 fractions, once per week over 29 days (Group 2). Treatment was delivered to the prostate with intensity modulated radiotherapy using daily image guidance and a 4mm (Group 1) or 5 mm (Group 2) CTV-PTV margin. PSA nadir and bRFS(nadir+2 definition) were compared between the two groups. Acute (CTCv3.0), late (RTOG) and cumulative toxicity for late grade ≥ 2 GU/GI toxicities were also compared. Results: Median follow up was 74 (IQR 67-81) and 36 (IQR 32-39) months. Median PSA nadir was 0.4...