Overall Treatment Time and Charlson Score Impact on Toxicity of Intensity Modulated Arc Therapy With Simultaneous Integrated Boost to Prostate for Intermediate- or High-Risk Prostate Cancer

Volume 93  Number 3S  Supplement 2015

Poster Viewing Session E211

Poster Viewing Abstracts 2530; Table Percent of Each Stage Per Year Overall (Prostate Percentages in Parentheses) Stage 0 I II III IV

2005 2.13 13.14 27.71 20.87 36.15

(0.9) (78.92) (9.42) (10.76)

2006 2.61 13.48 31.9 18.6 33.42

(0.82) (86.01) (8.23) (4.94)

2007 1.02 12.43 35.81 17.9 32.84

(1.32) (88.08) (5.3) (5.3)

2008 1.32 14.81 37.3 15.7 30.86

(2.49) (87.26) (5.82) (4.43)

2009 1.61 15.96 34.92 16.12 31.39

(0.56) (89.94) (3.63) (5.87)

Purpose/Objective(s): Prostate cancer patients undergoing radiation therapy (RT) require adequate bladder filling to ensure the small bowel is displaced out of field and to minimize the volume of bladder treated. Patients with poor bladder filling (because of incontinence or overactive bladder) are at risk for toxicity because of excess normal tissue radiation. A penile compression device presents a unique solution for this patient group. Materials/Methods: Eight Patients (3 radical and 5 post-op) with incontinence were treated using the clamp. Patients underwent computed tomography (CT) simulation without and with the clamp to document improved bladder filling. Volumetric modulated arc therapy intensity modulated RT (XRT) plans were applied to pre- and postclamp scans. Patients were treated with 66 Gy in 33 fractions (post-op group) and 76 Gy in 38 fractions (radical group). Pre- and postclamp plans were scored for ability to meet Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) bladder dose constraints. Acute and late Radiation Therapy Oncology Group toxicity was scored. Daily cone beam images were analyzed for bladder volumes and compared to baseline CT simulation bladder volumes. Results: All patients tolerated the clamp and safely completed XRT. One patient required nonnarcotic analgesics for pain. Acute toxicity was limited to grade 1 proctitis and grade 1cystitis. There have been no cases of stricture or late grade >1 cystitis. Bladder volumes (mL) mean (range) were 99 (62-136) without clamp and 327 (156-514) with clamp. QUANTEC bladder dose constraints were met in none of the preclamp studies and in all 8 postclamp studies. Bladder DV65 mean (range) was 91% (75%-100%) preclamp and 32% (13%-45%) postclamp. During treatment adequate bladder volumes were maintained and small bowel remained outside of the high dose volume in all cases. Conclusion: The clamp improves bladder filling, was well tolerated, and reduces the volume of bladder treated. Patients treated with the clamp met QUANTEC bladder dose constraints. Penile clamps represent a unique solution for patients unable to maintain bladder filling for radiation. Author Disclosure: S. Malone: None. G. Wright: None. M. Lacelle: None. L. Buckley: None. R. Studinski: None. A. Haridass: None. C. Malone: None. B. Musclow: None. S.C. Morgan: None.

2530 The Impact of Prostate Cancer on Overall Cancer Stage Migration From 2005 to 2014 in an Academic Radiation Oncology Practice J.P. Ciezki, C.A. Reddy, and E.A. Klein; Cleveland Clinic, Cleveland, OH Purpose/Objective(s): To define cancer stage migration according to year of diagnosis and type of cancer at the time of cancer diagnosis. Materials/Methods: The stage, diagnosis, and year of diagnosis information was retrieved from a prospectively maintained database in a single academic radiation oncology practice from 2005 to 2014. Trends in changes in stage over time were assessed using the Jonckheere-Terpstra test. Results: From 2005 to 2014, 12,807 newly diagnosed patients were seen in our practice. The distribution of patients by stage was 2% stage 0, 17% stage I, 33% stage II, 16% stage III, and 32% stage IV patients. The pattern of stage distribution significantly changed over time as seen in the table (PZ.0016). For 4 of the 5 most commonly seen disease sites (female breast, lung, esophagus, head and neck, and prostate; 73% of all patients), there was evidence of fewer late-stage cancers being diagnosed or evidence of no change in stage over time. The notable exception was for prostate

2010 1.91 20.25 34.58 14.89 28.37

(14.8) (75.18) (4.77) (5.25)

2011 1.38 21.07 34.99 15.29 27.27

(14.25) (77.01) (4.14) (4.6)

2012 1.19 22.05 30.7 14.58 31.47

(17.91) (72.46) (4.55) (5.08)

2013 1.64 19.49 28.93 14.57 35.36

(18.54) (71.53) (3.04) (6.99)

2014 1.09 17.53 28.86 13.89 38.63

(19.21) (67.8) (4.52) (8.47)

cancer, the largest of the 5 most common disease sites (26.5% of total). The changes in prostate cancer staging drove the entire population’s stage migration. In 2005, 10.76% of new prostate cancer cases presented with stage IV disease, dipped to 4.6% in 2011, and subsequently rose to 8.47% in 2014 (P<.0001). The changes in stage I definition accounted for the increase seen in stage I disease but could not account for the dip and subsequent increase in stage IV disease. Conclusion: The presentation of cancer by stage has changed over time. The change was predominately driven by prostate cancer. The changes seen in stage IV prostate cancer incidence in which it fell and then rose over the study period suggests that global practice changes may be present. Changes such as increased preference for active surveillance, recommendations for avoiding prostate-specific antigen screening, and increasing insurance deductibles may have favored a delay in treating and diagnosing prostate cancer patients in the recent past. Author Disclosure: J.P. Ciezki: Honoraria; ASTRO/Red Journal. C.A. Reddy: Honoraria; ASTRO/Red Journal. E.A. Klein: department chairman; Cleveland Clinic.

2531 Overall Treatment Time and Charlson Score Impact on Toxicity of Intensity Modulated Arc Therapy With Simultaneous Integrated Boost to Prostate for Intermediate- or High-Risk Prostate Cancer F. Ferrer,1 G. Mendez,1,2 C. Chiruzzi,1,3 H.A. Letelier,1 A. Boladeras,1 R. De Blas,1 R. Pin˜eiro,1 M. Galdeano,1 D. Najjari,1 E. Zardoya,1 R. Chavez,1 M. Ventura,1 E. Martinez,1 C. Gutierrez,1 C. Picon,1 J. Pera,1 and F. Guedea1,4; 1Catalan Institute of Oncology, L’Hospitalet-Barcelona, Spain, 2Instituto Nacional de Cancerologı´a, Mexico, 3Istituto Nazionale dei Tumori, Milan, Italy, 4University of Barcelona, L’HospitaletBarcelona, Spain Purpose/Objective(s): To explore if overall treatment time and Charlson score were prognostic factors for toxicity in patients with intermediate- or high-risk prostate cancer treated by intensity modulated arc therapy (IMAT) with simultaneous integrated boost (SIB). Materials/Methods: One hundred forty consecutive patients, diagnosed with intermediate- or high-risk prostate cancer, were treated definitively between September 2011 and May 2014. Androgen suppression was administered considering disease risk factors. Data on comorbidity was recorded in order to calculate Charlson score. The IMAT plans were designed to deliver 60 Gy (in 2 Gy per fraction) in 30 fractions to the prostate, seminal vesicles plus margin while delivering simultaneously to the prostate plus margin 70.8 Gy in 30 fractions (2.36 Gy per fraction). Univariate and multivariate analysis with logistic regression were performed looking for relations among patient characteristics and toxicity. Common Terminology Criteria for Adverse Events version 3.0 morbidity scores were used to assess acute and late toxicities. Toxicity and biochemical response were assessed prospectively. Results: Median age of patients was 72 years (range 58 to 81 years). Pathologically centralized Gleason score was 7 for 81.7 % of patients. Mean prostate-specific antigen (PSA) value was 9.6 ng/mL (from 2 to 36 ng/mL). Forty-one percent of patients were classified as T1-T2a, 37.5% as T2b-c, and 21.5% as T3. Median International Prostate Symptom Score and Charlson score were 5 (0 to15) and 4 (1 to 11), respectively. The median follow-up period was 14.8 months. All patients received the prescribed dose in 30 fractions delivered between 36 to 57days. Median radiation overall treatment time (OTT) was 47 days. Seventy-five percent of

E212 patients received a course of hormone deprivation for 6 months at least. One biochemical relapse was observed in this cohort of patients. Five patients died during the follow-up period without cancer relapse or toxicity. Acute genitourinary toxicity was observed in 81% of patients with maximal score of 2 in 40.9% of patients. Charlson score greater than 4 did not predict an increase in toxicity. Rectal acute toxicity grade 2 with mucosal discharge was present in 17.6% of patients. Presence of any acute rectal toxicity risk was increased by 2.3 fold in the shorter OTT (cut-point 47 days). Late rectal toxicity Grade 3 was seen in 1 patient, and 5 more patients showed a grade 2 score. Chronic urinary toxicity grades 1-2 were observed in 27.5% of patients, but only 2 patients had grade 2 urinary toxicity. Conclusion: IMAT with SIB to the prostate was well tolerated, with acceptable rates of acute and early late toxicity. Shorter OTT seems to increase the risk of acute rectal toxicity. Charlson score should not be considered as a predictor factor for toxicity. Additional follow-up is necessary to fully define the long-term toxicity. Author Disclosure: F. Ferrer: None. G. Mendez: None. C. Chiruzzi: None. H. Letelier: None. A. Boladeras: None. R. De Blas: None. R. Pin˜eiro: None. M. Galdeano: None. D. Najjari: None. E. Zardoya: None. R. Chavez: None. M. Ventura: None. E. Martinez: None. C. Gutierrez: None. C. Picon: None. J. Pera: None. F. Guedea: None.

2532 Risk Group and Death From Prostate Cancer Among Men Undergoing Brachytherapy A. Raldow,1 D. Zhang,2 M.H. Chen,2 M.H. Braccioforte,3 B.J. Moran,3 and A.V. D’Amico4; 1Harvard Radiation Oncology Program, Boston, MA, 2 University of Connecticut, Storrs, CT, 3Prostate Cancer Foundation of Chicago, Westmont, IL, 4Brigham and Women’s HospitaleDana-Farber Cancer Institute, Boston, MA Purpose/Objective(s): We estimated prostate cancer-specific mortality (PCSM) risk following brachytherapy with or without neoadjuvant external beam radiation therapy (EBRT) and/or short-course androgen deprivation therapy (ADT) among men with high-, unfavorable intermediate-, favorable intermediate-, and low-risk prostate cancer (PC). Materials/Methods: The prospective study cohort comprised 6595 consecutively treated men with T1-4, N0M0 PC whose treatment included low-dose-rate brachytherapy between October 16, 1997 and May 28, 2013. Men with low- and favorable intermediate-risk PC were treated with brachytherapy, whereas men with unfavorable intermediate-risk PC were treated with brachytherapy and neoadjuvant ADT (median 4 months) with or without neoadjuvant EBRT, and men with high-risk PC received all 3 treatments. Fine and Gray competing risks regression were used to assess whether PCSM risk was increased in men with high-, unfavorable intermediate- and favorable intermediate- risk as compared with low-risk PC, adjusting for age at and year of brachytherapy, as well as known PC prognostic factors. Results: After median follow-up of 7.76 years, 820 men died (12.43%): 72 of PC (8.78%). While men with favorable intermediate-risk PC did not have significantly increased PCSM risk as compared to men with low-risk PC (adjusted hazard ratio [AHR] 1.29, 0.57-2.89 95% confidence interval [CI], P value .54), men with high- (AHR 3.60, 1.07-12.12 95% CI, P value .04), and unfavorable intermediate-risk PC (AHR 2.99, 1.39-6.45 95% CI, P value .005) did. Ten-year unadjusted point estimates of PCSM were 8.09% (5.19%-11.81% 95% CI), 2.85% (1.62%- 4.63% 95% CI), 1.26% (0.72%-2.07% 95% CI), and 0.83% (0.55%-1.22% 95% CI) for men with high-, unfavorable intermediate-, favorable intermediate-, and low-risk PC, respectively. Please see Table for additional results. Conclusion: In the setting of high-dose radiation consisting of EBRT and brachytherapy, men with high-risk PC have low absolute estimates of PCSM (<10%) during the first decade following treatment despite receiving only short course ADT. Whether long-term ADT can lower PCSM risk for these men requires additional study. Table. Multivariable Competing Risks Regression Analysis

International Journal of Radiation Oncology  Biology  Physics Poster Viewing Abstracts 2532; Table 1 Clinical characteristic

Number of men

Number of PC deaths

AHR (95% CI) P value

Age (years) Year of brachytherapy PSA (ng/ml)

6595 6595

72 72

1.04 (1.01, 1.08) .01 0.85 (0.78, 0.92) <.0001

6595

72

Gleason 8-10 7 6 or less T-category T3-4 T2 T1

280 1395 4920 125 1599 4871

18 20 34 9 35 28

1.004 (1.00, .07 1.008) 2.05 (0.65, 6.47) .22 0.85 (0.44, 1.64) .63 1.0 (Reference) 3.09 (1.16, 8.20) .02 1.83 (1.04, 3.21) .04 1.0 (Reference) -

Author Disclosure: A. Raldow: None. D. Zhang: None. M. Chen: None. M.H. Braccioforte: None. B.J. Moran: None. A.V. D’Amico: None.

2533 The Effect of Milk of Magnesia on the Consistency of Interfraction Rectal Filling During Prostate Cancer Volumetric Modulated Arc Therapy A. Hosni, T. Rosewall, T. Craig, V.C. Kong, A. Bayley, C.N. Catton, and P. Chung; Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada Purpose/Objective(s): To investigate the effect of milk of magnesia (MoM) on interfraction variation in rectal filling and acute rectal toxicity. Materials/Methods: Two groups were retrospectively identified; each consisting of 20 patients with localized prostate cancer treated with volumetric modulated arc therapy (VMAT) to the prostate  seminal vesicles, to a prescribed dose of 78 Gy in 39 fractions over 8 weeks. The first group was instructed to follow a bowel regimen with antiflatulent diet and MoM started 3 days prior to planning computed tomography (P-CT) scan and continued during radiation therapy, while the second group followed simple dietary advice to achieve an empty rectum. The rectum between the superior and inferior extent of the clinical target volume (CTV) was delineated by a single observer on the P-CT and on 8, weekly cone beam CT images (CBCT). Rectal filling was assessed by measurement of anterio-posterior diameter of the rectum at the superior (AP-S), mid (AP-M), and inferior (AP-I) level of the CTV and by calculation of rectal volume (RV) and average cross-sectional rectal area (CSA; defined as the rectal volume divided by length). The differences in these measurements were compared between the 2 groups and data relating to acute Radiation Therapy Oncology Group (RTOG) rectal toxicity was extracted from patients’ medical charts. Results: A total of 360 images, including 40 P-CT and 320 CBCT images from 40 patients were analyzed. In comparison of the 2 groups (MoM vs non-MoM patients), there was no statistically significant difference either in RV (median: 28 cm3 vs 34 cm3, PZ.99); change in RV between P-CT and CBCTs (mean: 3 cm3 vs 1 cm3, PZ.99); average CSA (median: 6 cm2 vs 6 cm2, PZ.98), change in average CSA between P-CT and CBCTs (mean: 0.1 cm2 vs 0.4 cm2, PZ.99); changes in AP-S (mean: 0 cm vs 0.1 cm, PZ.99); AP-M (mean: 0.2 cm vs 0.2 cm, PZ.99); or AP-I (mean: -0.5 cm vs -0.1 cm, PZ.93). In the MoM group, the mean volume of MoM taken by patients was 29 cm3 (range, 15e45 cm3) in the first week and 12 cm3 (range, 0e30 cm3) in the last week. The proportion of patients who took MoM decreased from 100% in the first week to 60% in the last week. Acute RTOG rectal toxicity in MoM/non-MoM groups consisted of G2 diarrhea (nZ 2/1), G1 diarrhea (nZ 13/4), and G1 proctitis (nZ 3/3). Conclusion: MoM did not appear to reduce the interfraction variation in rectal filling compared to simple dietary advice, although the analysis was limited by small patient numbers. MoM may cause diarrhea and a substantial proportion of patients discontinued its use by the end of radiation treatment.