PURPOSE To determine whether addition of external beam radiation therapy (EBRT) to brachytherapy (BT) (COMBO) compared with BT alone would improve 5-year freedom from progression (FFP) in intermediate-risk prostate cancer. METHODS Men with prostate cancer stage cT1c-T2bN0M0, Gleason Score (GS) 2-6 and prostate-specific antigen (PSA) 10-20 or GS 7, and PSA < 10 were eligible. The COMBO arm was EBRT (45 Gy in 25 fractions) to prostate and seminal vesicles followed by BT prostate boost (110 Gy if 125-Iodine, 100 Gy if 103-Pd). BT arm was delivered to prostate only (145 Gy if 125-Iodine, 125 Gy if 103-Pd). The primary end point was FFP: PSA failure (American Society for Therapeutic Radiology and Oncology [ASTRO] or Phoenix definitions), local failure, distant failure, or death. RESULTS Five hundred eighty-eight men were randomly assigned; 579 were eligible: 287 and 292 in COMBO and BT arms, respectively. The median age was 67 years; 89.1% had PSA < 10 ng/mL, 89.1% had GS 7, and 66.7% had T1 disease. There were no differences in FFP. The 5-year FFP-ASTRO was 85.6% (95% CI, 81.4 to 89.7) with COMBO compared with 82.7% (95% CI, 78.3 to 87.1) with BT (odds ratio [OR], 0.80; 95% CI, 0.51 to 1.26; Greenwood T P = .18). The 5-year FFP-Phoenix was 88.0% (95% CI, 84.2 to 91.9) with COMBO compared with 85.5% (95% CI, 81.3 to 89.6) with BT (OR, 0.80; 95% CI, 0.49 to 1.30; Greenwood T P = .19). There were no differences in the rates of genitourinary (GU) or GI acute toxicities. The 5-year cumulative incidence for late GU/GI grade 2+ toxicity is 42.8% (95% CI, 37.0 to 48.6) for COMBO compared with 25.8% (95% CI, 20.9 to 31.0) for BT ( P < .0001). The 5-year cumulative incidence for late GU/GI grade 3+ toxicity is 8.2% (95% CI, 5.4 to 11.8) compared with 3.8% (95% CI, 2.0 to 6.5; P = .006). CONCLUSION Compared with BT, COMBO did not improve FFP for prostate cancer but caused greater toxicity. BT alone can be considered as a standard treatment for men with intermediate-risk prostate cancer.

To the Editor: Radiation therapy (RO) in times of disasters has recently garnered much interest among those in the specialty, and the Red Journal recently devoted an edition to it. 1 Yom S.S. Zietman A.L. Radiation therapy in a time of disaster. Int J Radiat Oncol Biol Phys. 2018; 100: 832-833 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar We felt compelled to observe that hurricanes, with their associated flooding that poses a particular threat to RO departments, are neither rare nor sudden events. From 1851 to 2017, there were 286 direct hurricane hits on the mainland of Florida, Texas, Louisiana, and North Carolina (NC) alone (∼1.7 hurricanes/year). 2 Griggs B. No other state gets hit by hurricanes as often as Florida. CNN. https://www.cnn.com/2017/09/11/us/hurricanes-landfall-by-state-trnd/index.htmlDate accessed: September 18, 2018 Google Scholar NC recently had 2 particularly devastating storms: Matthew (2016) and Florence (2018) both caused catastrophic flooding in eastern NC. For Florence, there was ample warning: On September 7, 2018, Governor Roy Cooper declared a state of emergency; by September 11 over 1 million residents had been ordered to evacuate, and by September 14 the storm made landfall. With a full week's notice, why did we feel so unprepared? Radiation Therapy in a Time of DisasterInternational Journal of Radiation Oncology, Biology, PhysicsVol. 100Issue 4PreviewWhat constitutes a disaster? The United Nations defines it as “a serious disruption of the functioning of a community or a society [exceeding its ability] to cope” and requiring assistance from external sources, perhaps national or international (1). These bleak features—precipitous social disruption and conditions of extreme dependency and need—separate the vastness and isolation of “disaster” from other relief aid terminologies, such as “hazard,” “risk,” “emergency,” or “epidemic,” which are more anticipatory, classificatory, or managerial in nature. Full-Text PDF

Purpose: Prostate cancer survivors who receive androgen deprivation therapy (ADT) are at increased risk of cardiovascular disease. They require coordinated care between cancer specialists and primary care physicians to monitor for cancer control and manage cardiovascular risk factors. Methods and Materials: We prospectively enrolled 103 men receiving ADT with radiation therapy (RT) from 7 institutions to assess cardiovascular risk factors and survivorship care. Medical records, fasting laboratory test values, and patient-reported outcomes using a validated instrument were assessed at baseline (pretreatment) and 1 year post-RT. Results: Cardiovascular disease (39%) and risk factors (diabetes, 22%; hypertension, 63%; hyperlipidemia, 31%) were prevalent at baseline. During the first year after RT completion, 63% received cardiovascular monitoring concordant with American Heart Association guidelines. Fasting laboratory test values at 1 year showed 24% with inadequately controlled blood sugar and 22% elevated cholesterol. Patient perceptions about care coordination were relatively low. At 1 year, 57% reported that their primary care physicians "always knowabout the care I receive at other places," 67% reported that their cancer physician "communicated with other providers I see," and 65% reported that the cancer care physician "knows the results of my visits with other doctors." Conclusions: Patients with prostate cancer who receive ADT and RT are a vulnerable population with prevalent baseline cardiovascular disease and risk factors and suboptimal survivorship care specifically related to coordinated care and cardiovascular monitoring. Clinical trials examining ways to improve the care and outcomes of these survivors are needed. (C) 2018 Elsevier Inc. All rights reserved.

To assess differences in patient (pt)-reported outcomes (PROs) between combined external beam therapy (EBT) and transperineal interstitial permanent brachytherapy (B) among pts with intermediate risk prostate cancer (PC). The primary endpoint reported that the addition of EBT to B did not result in superior PFS compared to B alone. Men with intermediate risk PC were randomized to either 45 Gy partial pelvis EBT+B or B alone. The Expanded Prostate Index Composite (EPIC) was used to measure change in PROs from baseline to 4 and 24-mos. EPIC assesses 4 PC-specific PRO domains: bowel, urinary (with 2 subscales; incontinence and irritative/obstructive), sexual, and hormonal. Hormonal domain was excluded as concurrent use was exclusionary and prior neoadjuvant use was low (8%). Scoring is on a Likert scale with responses transformed to 0-100, with higher scores indicating better PC-specific PROs. EPIC change (Δ) domain/ subscale scores were calculated as 4 or 24 mo. score - baseline score. To assess treatment differences, effect sizes (ES) ≥ 0.5 standard deviations (SD) were considered clinically significant and t-tests tested for treatment differences > 0. There were 530/579 (92%) eligible pts on study had baseline EPIC: 255 (89%) on EBRT + B arm and 275 (94%) on B arm. There were no significant (sig) differences in baseline characteristics between arms; median age 66, 78% were White and 17% were Black; 89% had GS 7/PSA < 10, 66% were T1 and 96% had Zubrod Performance Status of 0. Grade 3+ toxicities: acute were similar (6%) but late were 13% and 8% for EBT+B and B, respectively. There are no statistically sig differences in any of the baseline mean scores between arms. At 4 mos, mean ± SD of Δ scores for urinary, urinary-irritative, and bowel had sig differences (all p < 0.0001) between arms, all in favor of B alone (ES 0.40, 0.44, 0.31, respectively); none for urinary-incontinence, sexual. At 24 mos, sig differences between arms for urinary, urinary-irritative, bowel, & sexual, all in favor of B alone (see Table). Among men with intermediate risk PC in this study, the addition of EBT to B resulted in poorer urinary, bowel, and sexual PROs, with meaningful effect sizes for urinary and bowel, although not meeting the protocol-defined clinically significant level. This study demonstrates that value-based care strongly supports B over EBT + B in this population since B has similar PFS, lower toxicity, better patient reported outcomes and ostensibly less cost compared to the combination.Abstract 3; TableDomain/ Subscale24 mos Δ mean ± SDp-value (|μB - μEBT+B|> 0)Effect SizeEBT+BBUrinary-11.2 ± 15.7-5.6 ± 13.60.00020.38Urinary-irritative-11.9 ± 17.4-4.8 ± 14.3<0.00010.44Bowel-7.1 ± 12.6-2.4 ± 9.9<0.00010.42Sexual-16.7 ± 23.4-10.6 ± 21.00.00720.27 Open table in a new tab

Purpose: Recent data indicate consolidative radiation therapy improves progression-free survival (PFS) for patients with oligometastatic non-small cell lung cancer (NSCLC). Data on long-term outcomes are limited. Methods and Materials: This prospective, multicenter, single-arm, phase 2 trial was initiated in 2010 and enrolled patients with oligometastatic NSCLC. Oligometastatic disease was defined as a maximum of 5 metastatic lesions for all disease sites, including no more than 3 active extracranial metastatic lesions. Limited mediastinal lymph node involvement was allowed. Patients achieving a partial response or stable disease after 3 to 6 cycles of platinum-based chemotherapy were treated with CRT to the primary and metastatic sites of disease, followed by observation alone. The primary endpoint was PFS, with secondary endpoints of local control, overall survival (OS), and safety. Results: Twenty-nine patients were enrolled between October 2010 and October 2015, and 27 were eligible for consolidative radiation therapy. The study was closed early because of slow accrual but met its primary endpoint for success, which was PFS >6 months (P < .0001). The median PFS (95% confidence interval) was 11.2 months (7.6-15.9 months), and the median OS was 28.4 months (14.5-45.8 months). Survival outcomes were not significantly different for patients with brain metastases (P = .87 for PFS; P = .12 for OS) or lymph node involvement (P = .74 for PFS; P = .86 for OS). Conclusions: For patients with oligometastatic NSCLC, chemotherapy followed by consolidative radiation therapy without maintenance chemotherapy was associated with encouraging long-term outcomes. (C) 2018 Elsevier Inc. All rights reserved.

Clinical data indicates that delivery of larger daily doses of radiation may improve the therapeutic ratio for prostate cancer compared to conventional fractionation. A phase II study of stereotactic body radiotherapy with real-time motion management and daily plan re-optimization for low to intermediate risk prostate cancer was undertaken to evaluate this hypothesis. This report details the toxicity and quality of life following treatment.

10102 Background: Survivorship care planning upon treatment completion is especially important for prostate cancer patients treated with ADT. These patients need coordinated oncologic and primary care, the latter monitoring cardiovascular disease risk factors. In a multicenter prospective cohort, we assessed coordination of care (COC) and satisfaction with care (SC) using validated patient-reported outcome instruments. Methods: 100 men with non-metastatic prostate cancer to be treated with RT and ADT at 8 institutions were enrolled before treatment and followed prospectively for 1 year. Patients completed validated surveys on COC (specifically between radiation oncologist and primary care; 4 questions each scored on 5 point Likert scale) and SC (9 questions each scored on a 6 point Likert scale). Overall score for each instrument was calculated as the mean of all questions. Results: Median age was 67 and 89% had ACE-27 score >0 indicating baseline comorbid illness. At baseline (pre-treatment) 66-70% of patients indicated that their cancer provider communicates with other providers and follows up on problems, but only 17% indicated that their cancer provider was aware of other medical care (Table). At one year COC did not change dramatically. No significant difference in COC was seen among patients with ACE-27 score 0-1 vs. >1. Change in overall COC score from baseline to 1 year was significantly associated with change in patient-reported SC score (p=.03). Conclusions: Patients reported that their cancer specialist was not aware of health care received elsewhere. This is one of the first studies to show that improved coordination is associated with increased patient satisfaction. For prostate cancer survivors receiving ADT, this is especially relevant given the need for coordinated oncologic and primary care. Clinical trial information: NCT02003417.% of patients reporting agree/strongly agree on Coordination of Care questions. My cancer provider Baseline (%) 1 Year (%) - always knows about the care I receive other places 17 24 - communicates with the other providers I see 71 70 - knows the results of my visits with other doctors 66 69 - always follow up on a problem I’ve had 71 83

To determine if combined external beam therapy (EBT) and transperineal interstitial permanent brachytherapy (B) results in better progression-free survival (PFS) at 5 years compared to B alone, among selected intermediate-risk prostatic carcinoma patients (pts). This is the initial primary endpoint report. Men with prostate cancer, clinical stage T1c-T2b and either Gleason Score (GS) 2-6/PSA 10-20 or GS 7/PSA <10 were eligible and randomized to receive either 45 Gy partial pelvis EBT and brachy (EBT + B) or B alone. External beam therapy could be delivered by 3D or IMRT. Transperineal interstitial permanent brachytherapy allowed the use of I-125 or Pd-103, prescribed to 110 Gy or 100 Gy boost dose respectively, in the EBT + B arm and 145 Gy or 125 Gy, respectively, in the B arm. The study was designed to test for a 10% increase in 5-year PFS for the EBT + B arm, with a 1-sided α of 0.025, 90% statistical power, and 5 interim analyses requiring 586 pts. Progression-free survival (failure: ASTRO PSA, clinical, or death from any cause) was estimated by the Kaplan-Meier method, and arms were compared using a 2-sample binomial test. Protocol-specified interim efficacy and futility analyses were conducted and presented to an external Data Monitoring Committee (DMC). Efficacy testing used Haybittle-Peto at an α of 0.001 and futility was tested by reversing the null and alternative hypotheses at an α of 0.0001. Between June 2003 and February 2012, 588 men were randomized; 287 EBT + B and 292 B eligible, with median follow-up of 6.7 years. There were no significant differences in baseline characteristics between arms; median age 67, 89% had GS 7/PSA < 10, and 67% were T1. At the fifth interim analysis, of the required 443 pts with 5 years of follow-up, 5-year PFS (95% CI) was 85% (80, 89) for the EBT + B arm and 86% (81, 90) for the B arm (HR = 1.02, futility P = 0.0006). Based on these futility results, the DMC recommended early release for the initial reporting of the primary endpoint. Acute overall ≥ grade 3 toxicity was similar, with 8% for EBT + B and 8% for B. Overall ≥ grade 3 late toxicity was 12% for EBT + B compared to 7% for B. Grade 3 or higher GU toxicity was 7% and 3%, while GI was 3% and 2% in the EBT + B and B arms, respectively. Analyses of secondary efficacy and other objectives are forthcoming. Among men with intermediate-risk prostate cancer in this study, the addition of external beam therapy to brachytherapy did not result in superior PFS compared to brachytherapy alone in this initial report. Toxicity in both groups was limited, but there were fewer late effects, mostly GU, noted in the brachytherapy alone arm. Supported by NCI grants U10CA21661, U24CA81647, U10CA37422, U10CA180868, U10CA180822, U10CA10953, and U24CA180803

Sexual dysfunction is common in prostate cancer survivors after radiation therapy. Preclinical and small studies suggested benefit of L-arginine based nutritional supplementation (LAS) to improve erectile dysfunction(ED). We completed a placebo-controlled trial evaluating a commercially available LAS. Eight-week, randomized, placebo-controlled double-blinded trial. Eligibility: prostate cancer survivors ≥ 6 months after active treatment, no active cancer, successful sexual activity prior to radiation therapy, self-identified concern with sexual quality of life, and agree to one intercourse attempt weekly during study. Serum testosterone normal range if prior androgen suppression. Patients randomized to two dose levels of LAS or placebo (Arm 1: 6 capsules placebo bid; Arm 2: 3 capsules LAS and 3 capsules placebo BID; Arm 3: 6 capsules LAS bid). Each capsule contains L-arginine (500 mg), gingko biloba (8.3 mg), ginseng (33.3 mg), and multivitamins. Stratification by age (>/< 65 years) and current usage PDE-5I. Third party analysis verified LAS contents. Primary outcome: erectile function score from International Index Erectile Function (IIEF) at 8 weeks. Secondary outcomes: other subscale scores from IIEF, Expanded Prostate Cancer Index Composite (EPIC-26), a Sexual Encounter Profile, general efficacy questions (GEQ) for successful intercourse and improved erections (yes/no), FACT-Prostate, and retention, adherence, and toxicity measures. Assessments made at baseline, 4 and 8 weeks. One hundred forty patients between October 2010 and November 2013; Arm 1 - 48 patients, Arm 2 - 45 patients, and Arm 3 - 47 patients. Ages ranged from 48 to 80 with a median of 68 years. Sixty-four percent of the patients were white, 34% black, 1% Hispanic, and 1% Asian. Eighty-five percent were married. Forty-nine (35%) used concurrent PDE-5I. Median BMI was 29.6 overweight). Overall retention was 79% at 8 weeks and not different between arms (p = 0.85). Self-reported compliance through returned diaries was 96%. No SAE possibly or definitely related to LAS occurred. The most common toxicity: grade 1 to 2 dyspepsia in 8 cases total. Mean IIEF baseline score of avg 13.2 across 3 arms suggesting moderate ED. No difference in IIEF erectile function domain (primary end-point) was seen in LAS treatment arms at 8 wks (p = 0.12). No benefit was seen at high or low dose levels compared to placebo for EPIC-26, IIEF all domains, and all FACT scales (all p > 0.1). For the GEQ, no difference with placebo; approximately 20-30% of patients on all 3 arms felt improvement with the LAS or placebo suggesting placebo effect. In a post-radiation therapy prostate cancer population with moderate erectile dysfunction, L-arginine based supplementation did not show benefit versus placebo. Toxicity was minimal. Based on these results, further study of this supplement is not warranted in this population.

Purpose The combination of cisplatin and radiotherapy is a standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Cetuximab-radiotherapy is superior to radiotherapy alone in this population, validating epidermal growth factor receptor (EGFR) as a target. Erlotinib is a small-molecule inhibitor of EGFR. Adding EGFR inhibition to standard cisplatin-radiotherapy may improve efficacy. Patients and Methods Patients with locally advanced SCCHN were randomly assigned to receive cisplatin 100 mg/m2 on days 1, 22, and 43 combined with 70 Gy of radiotherapy (arm A) or the same chemoradiotherapy with erlotinib 150 mg per day, starting 1 week before radiotherapy and continued to its completion (arm B). The primary end point was complete response rate (CRR), evaluated by central review. The secondary end point was progression-free survival (PFS). Available tumors were tested for p16 and EGFR by fluorescent in situ hybridization. Results Between December 2006 and October 2011, 204 patients were randomly assigned. Arms were well balanced for all patient characteristics including p16, with the exception of more women on arm A. Patients on arm B had more rash, but treatment arms did not differ regarding rates of other grade 3 or 4 toxicities. Arm A had a CRR of 40% and arm B had a CRR of 52% (P = .08) when evaluated by central review. With a median follow-up time of 26 months and 54 progression events, there was no difference in PFS (hazard ratio, 0.9; P = .71). Conclusion Erlotinib did not increase the toxicity of cisplatin and radiotherapy in patients with locally advanced HNSCC but failed to significantly increase CRR or PFS.

5503 Background: The combination of cisplatin and radiotherapy is a standard treatment for patients with locally advanced SCCHN. Cetuximab-radiotherapy is superior to radiotherapy alone in this population, validating EGFR as a target. Erlotinib, a small molecule inhibitor of EGFR, has activity in recurrent/metastatic disease. Adding EGFR inhibition to standard cisplatin-radiotherapy may improve efficacy. Methods: Patients with locally advanced SCCHN were randomized to receive cisplatin 100mg/m2 on days 1,22 and 43 combined with 70Gy of radiotherapy (arm A) or the same chemoradiotherapy combined with erlotinib 150mg/day, starting one week prior to radiotherapy and continued to its completion (arm B). Randomizing 204 patients had 80% power to compare a 60% complete response rate (CRR) to a 40% null rate. Available tumors were tested for p16, ERCC1 and EGFR FISH. Results: Between June 2006 and October 2011, 204 patients were randomized. Results presented are based on intention to treat. There were more females on arm A however no other differences in patient characteristics, including p16 positivity. Patients on arm B had more rash and gastrointestinal adverse events, but treatment arms did not differ for rates of other grade III/IV toxicities or serious adverse events (SAEs). Arm A had a CRR of 61% and arm B had a CRR of 68% (p=0.3). With a median follow-up of 23 months, there were only 29 events in the overall survival analysis and 46 in the progression-free survival (PFS) analysis. The 2 and 3 year PFS were 71% and 63% for arm A and 78% and 73% for arm B (p=0.61). Conclusions: The addition of erlotinib did not increase the rate of SAEs but failed to significantly increase CRR. As seen in other recent trials, our results in both arms are superior to historical comparisons. Updated PFS data will be presented. Supported by a grant from the investigator-initiated trial program of Genentech/OSI.

5515 Background: This study evaluated the expression of p16 and ERCC1 and EGFR amplification as predictive and prognostic factors in a recently completed phase II randomized trial comparing cisplatin (100 mg/m2 on d 1, 22, 43) with radiotherapy (70Gy) +/- erlotinib (150 mg/d during radiotherapy) in locally advanced SCCHN. p16 (HPV surrogate) is a known prognostic factor in oropharyngeal SCCHN, and high ERCC1 expression has been correlated with resistance to cisplatin. EGFR gene copy number may be prognostic in SCCHN and alter response to erlotinib. Methods: Pretreatment formalin-fixed, paraffin-embedded tumor tissue was available for 84/204 patients. EGFR copy number was assessed using Vysis LSI DNA probes, and immunohistochemistry was performed on Leica Bond III machines using Lab Vision ERCC-1 (8F1) and CINtec p16 antibodies. All assays were performed in accordance with manufacturer instructions; all studies were reviewed by a single Pathologist (MA) who was blinded to patient outcome. Logistic regression and Cox regression models fit a treatment arm by marker interaction and tested selected linear contrasts. Results: Efficacy analysis showed no difference in complete response rate (CRR) and progression-free survival (PFS) between treatment arms. However, PFS in both arms was better than historical comparisons, with only 46 events over a median follow-up of 23 months. Positivity in p16 was associated with greater CRR (OR 3.5, p=0.03) and longer PFS (HR=0.38; p= 0.07). The CRR effect was greater for the erlotinib arm (OR 8.1, p=0.01) than for Arm A (OR 1.5, p=0.56). The ERCC1 (+) rate was 46% (39/84).ERCC1 expression above the median was not associated with worse CRR (OR 0.69; p=0.46) or PFS (HR 0.99; p=0.98). Only 4 tumors showed EGFR amplification precluding further analysis. Conclusions: p16(+) tumors had a better outcome, similar to other recent trials, and erlotinib seemed to increase the CRR among p16(+) tumors. ERCC1 expression did not predict chemoradioresistance in this study. EGFR amplification was too rare in the tested population to assess predictive or prognostic value.

Purpose: To investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head-and-neck squamous cell carcinoma (HNSCC).Methods and Materials: Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25-Gy fractions b.i.d. to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07, and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m(2)/week was started Week 1. Patients completed the Quality of Life Radiation Therapy Instrument pretreatment (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12 months. Overall survival (OS), progression-free (PFS), LRC, and toxicities were assessed.Results: Of 39 patients, 30(77%) were alive without disease at median follow-up of 37.5 months. Actuarial 3-year OS, PFS, and LRC were 80%, 82%, and 87%, respectively. No failures occurred in the electively irradiated neck and there were no isolated neck failures. Head and neck QOL was significantly worse in 18 of 35 patients (51 %): mean 7.8 PRE vs. 3.9 EOT. By month 1, H&N QOL returned near baseline (mean 6.2, SD = 1.7). The most common acute Grade 3+ toxicities were mucositis (38%), fatigue (28%), dysphagia (28%), and leukopenia (26%).Conclusions: Hyperfractionated IMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity and QOL. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol. (C) 2011 Elsevier Inc.

Abstracts of Oral and Poster Presentations 20th Annual Meeting of the American College of Radiation Oncology February 25–27, 2010 Orlando, Florida Chair of the Scientific Program: Gregg Franklin, MD, PhD, FACROs of Oral and Poster Presentations 20th Annual Meeting of the American College of Radiation Oncology February 25–27, 2010 Orlando, Florida Chair of the Scientific Program: Gregg Franklin, MD, PhD, FACRO Oral Presentations (Saturday, February 27, 2010: 11:30 am–12:30 pm) 1: Phase II Trial of Hyperfractionated IMRT and Concurrent Weekly Cisplatin for Stage III and IVa Head and Neck Cancer Patrick Maguire, Michael Papagikos, Sue Hamann, Charles Neal, Martin Meyerson, Neil Hayes, Peter Ungaro, Kenneth Kotz, Marion Couch, Hoke Pollock, Joel Tepper New Hanover Regional Medical Center, Wilmington, NC, United States, University of North Carolina, Chapel Hill, NC, United States Purpose: To investigate a novel chemoradiation regimen designed to maximize locoregional control (LRC) and minimize toxicity for patients with advanced head and neck squamous cell carcinoma (HNSCC). Patients and Methods: Patients received hyperfractionated intensity modulated radiation therapy (HIMRT) in 1.25 Gy fractions bid to 70 Gy to high-risk planning target volume (PTV). Intermediate and low-risk PTVs received 60 Gy and 50 Gy, at 1.07 and 0.89 Gy per fraction, respectively. Concurrent cisplatin 33 mg/m/week was started week 1. Patients completed the Quality of Life Radiation Therapy Instrument prior to (PRE), at end of treatment (EOT), and at 1, 3, 6, 9, and 12 months. LRC, progression-free (PFS), overall survival (OS), and toxicities were assessed. Results: Thirty-nine patients were enrolled, of whom 35 were evaluable for QOL. Head and neck QOL was significantly worse in 18 of 35 patients (51%): Mean 7.8 PRE versus 3.9 EOT. Swallowing QOL was also worse: Mean 7.6 PRE versus 3.4 EOT. By month 1, H&N and swallowing QOL returned near baseline: Mean 6.2 (SD 1.7) and 6.1 (SD 2.6). Estimated 2-year LRC, PFS, and OS were 89%, 78%, and 85%, respectively. No failures occurred in the electively irradiated neck. Most common acute grade 3 toxicities were mucositis (38%), fatigue (28%), dysphagia (28%) and leukopenia (26%). Conclusions: HIMRT with low-dose weekly cisplatin resulted in good LRC with acceptable toxicity. Lack of elective nodal failures despite very low dose per fraction has led to an attempt to further minimize toxicity by reducing elective nodal doses in our subsequent protocol. 2: The Impact of Tumor Volume and Radiotherapy Dose on Outcome in Previously-Irradiated Recurrent Squamous-Cell Carcinoma of the Head and Neck Treated With Stereotactic Body Radiation Therapy Jean-Claude Rwigema, Dwight Heron, Robert Ferris, Regiane Andrade, Michael Gibson, Yong Yang, Cihat Ozhasoglu, Athanassios Argiris, Jennifer Grandis, Steven Burton University of Pittsburgh Cancer Institute, Pittsburgh, PA, United States Purpose: Recurrent squamous cell carcinoma of the head and neck (rSCCHN) remains a clinical challenge with few salvage options. Improvements in local control can potentially lead to enhancement in patient survival, as more than 50% of patients who die of the disease have locoregional disease as the only site of failure. We sought to assess the impact of gross tumor volume (GTV) and radiation dose on outcome of stereotactic body radiotherapy (SBRT) in patients with previously-irradiated rSCCHN. Methods: 96 patients (70 M, 26 F) with previously-irradiated rSCCHN were treated with SBRT using Cyberknife and Trilogy-IMRS. Kaplan-Meyer survival analyses were used to estimate local control (LC) rates in different dose groups. Pearson correlation coefficients were used to estimate the relationship between tumor volume and time to treatment failure (TTF). Response was evaluated using and PET/CT or CT and detailed physical examination, and classified according to RECIST criteria. All toxicities were graded according to the CTCAE v.3.0. Results: The median follow-up for all patients was 13 months (2–39 months). The median dose of prior radiation was 68.4 Gy (32–170 Gy). Patients were divided into 4 SBRT dose groups: I (15–28 Gy, n 29), II (30–36 Gy, n 22), III (40 Gy, n 18), IV (44–50 Gy, n 27). The median GTV was 24.3 ml (2.5–162 ml). Thirty-nine (40.6%) patients received concurrent cetuximab with SBRT, and there was no significant difference in cetuximab use among the different SBRT dose groups (P 0.05). For GTV 25 ml (n 50), complete response (CR) rates were 27.8%, 30%, 45.5%, and 45.5%, and for GTV 25 ml (n 46), CR rates were 20%, 25%, 42.8%, and 50% for SBRT groups I–IV respectively. Overall treatment responses were 46.7% CR, 37.8% PR, 8.9% SD, and 6.7% PD for 40–50 Gy, whereas for 15–36 Gy, they were 25.5% CR, 35.3% PR, 25.5% SD, and 13.7% PD. The 1-/2-/3-year LC rates for doses 40–50 Gy were 69.4%, 57.8%, and 41.1% respectively, whereas for 15–36 Gy, they were 51.9%, 31.7%, and 15.9%, respectively (P 0.02). Among those patients with initial response followed by disease progression at last follow-up (n 47), the median TTF was 6.97 months. There was a significant inverse correlation between TTF and tumor volume (P 0.001, R 0.56). The incidence of acute toxicities was 37.5%, 17.7%, and 5.2% for grade-1/2/-3, respectively. For late toxicities, there were 16.7% and 9.3% for grade 1 and 2, respectively. Conclusion: Higher SBRT doses were associated with significantly higher LC rates. Larger GTV required higher SBRT doses ( 44 Gy) to achieve maximum CR rates compared to smaller GTV ( 40 Gy). Tumor volume had significant inverse relationship with TTF. Most toxicities were mild and not statistically different among different dose groups. 3: Brain Metastases Secondary to NSCLC: Does the Number of Brain Tumors Treated Matter in the Management of Brain Metastases? Beatriz Amendola, Aizik L Wolf, Sammie R Coy, Marco Amendola Miami Neuroscience Center, Miami, FL, United States Introduction: It is estimated that more than 170,000 new cases of brain metastases occur in the United States each year. Lung cancer, the leading American Journal of Clinical Oncology • Volume 33, Number 2, April 2010 198 | www.amjclinicaloncology.com cause of cancer death in the United States, is responsible for almost half of all cases of brain metastasis. Symptomatic brain metastases develop in about 30% of patients with lung cancer (NSCLC) and if left untreated will lead to the patient’s demise in one month. Objective: To evaluate the role of radiosurgery (RS) in the management of brain metastases from lung cancer and to determine if number of lesions treated matter in the outcome. To compare our patient population with the published data for WBRT in the management of brain metastases from NSCLC. Methods: This is a retrospective review of 370 patients with brain metastases from NSCLC who were treated with Gamma Knife radiosurgery (GKRS) independent of primary status from October 20th, 1993 through October 2009. The rationale of treatment was to improve s brain control and survival. Results: One third of the patients presented with a single metastasis and the remaining of the patients presented with multiple brain metastases. All patients were treated in a single treatment session. There were 2 patients groups; one was treated with RS alone and the other with WBRT and RS. An average of 1.8 procedures was done over the life of the patients. The mean minimum dose was 15.7 Gy. The follow up ranged from 1 to 174 months. Prognostic factors were: age and KPS. There was no significant difference in survival with sex or with the use WBRT in our series. The median actuarial survival after GKRS was 7.2 months. Local control was 93%. Three percent of lesions were fully or partially retreated. Majority of the patients died from systemic disease and only 9.5% succumbed from progression of brain metastases. Conclusions: Patients with brain metastases from lung cancer treated with radiosurgery achieved high local control of brain disease using a single fraction of RS. They also had improved survival independent of the primary status and the use of WBRT. RS is an effective treatment option and is optimal for addressing quality of life issues and cost effectiveness. 4: Gamma Knife Radiosurgery (GKRS) in the Management of Parkinson’s Disease and Essential Tremor: Long-Term FollowUp Report of 186 Cases Rufus Mark, Harold Smith, Deane Jacques, Ronald Young, Brian Copcutt, Ching Chen, Paul Anderson, Robin Akins, Murali Nair Joe Arrington Cancer Center, Lubbock, TX, United States, Good Samaritan Hospital, Los Angeles, CA, United States Purpose: Management options for tremors secondary to Parkinson’s Disease (PD) and Essential Tremor (ET), include medications, Deep Brain Stimulation (DBS), Radiofrequency (RF), and Gamma Knife Radiosurgery (GKRS). Results with GKRS have compared favorably to DBS and RF with respect to tremor relief and complications. We report our updated long-term results with GKRS in the treatment of tremors. Materials and Methods: Between 1991 and 2008, 186 patients underwent MRI Scan targeted GKRS thalamotomy for medically refractory tremors secondary to PD (n 118) and ET (n 68). The target was the Ventralis Inter-Medius (VIM) nucleus. The target received between 140 Gy in a single shot prescribed to Dm using the 4 mm collimator. Treatment planning was accomplished thru the Leksell Treatment Planning System. Pre-operative and post-operative blinded assessments were performed by a team of independent examiners. The Unified Parkinson’s Disease Rating Scale and Clinical Rating Scale for Tremors was used to score tremors. Results: With a median follow-up of 7 years (range 2–17 years), 83.9% (156/186) of patients had significant, or complete resolution of tremors. In patients with PD, 83.0% (98/118) had near or complete tremor resolution, vs. 85.2% (58/68) with ET (P 0.84). Three patients experienced MRI proven edema and transient hemiparesis and speech difficulty. In two patients, t

Objective: The objective of this study was to describe a simple model that predicts freedom from biochemical recurrence (FFBR) in men with Prostate cancer after treatment with low-dose rate prostate brachytherapy (LDRPB) alone.Materials and Methods: One hundred thirty-two men were treated with LDRPB alone between September 1997 and April 2001. Sixty-four percent of men had low-risk disease (prostate-specific antigen [PSA] <10, Gleason <7, and T stage = 10, Gleason >= 7, or T stage T2b). The dosimetric quantifier D-90 was calculated from a computed tomography scan performed 1 month after LDRPB. The percent positive biopsies (PPB) were determined for all patients. FFBR was estimated using the product limit method. All P values are 2-sided.Results: The median follow-up is 65 months. The median D-90 is 138 Gy (range, 47-221 Gy). Fourteen men have developed evidence of biochemical relapse at a median of 27 months (range, 6-42 months). The 5-year FFBR rate for the entire cohort is 88%. On univariate analysis, variables found to be associated with FFBR included: PSA, Gleason score, T stage, risk group, PPB, and D-90. Multivariate analysis indicated that D-90, PPB, and risk group were independently associated with FFBR. Patients were categorized based on the following 3 adverse prognostic factors: D-90 <140 Gy, PPB >= 50%, and intermediate-risk group. Group 1 (0 factors, n = 30), group 2 (1 factor, n = 72), and group 3 (>= 2 factors, n = 30) patients had 5-year FFBR rates of 100% (+/- 0%), 92% (+/- 6%), and 67% (+/- 18%) (P < 0.0001).Conclusions: We have developed a simple, robust model based on implant quality and disease factors that predicts FFBR in men with prostate cancer treated with LDRPB alone.

Purpose/Objective(s)For the purposes of prognosis and treatment selection, men diagnosed with prostate cancer (PC) are routinely assigned to one of three mutually exclusive "risk-groups" based on initial PSA (iPSA), Gleason score (GS), and T stage. These risk-groups are known to correlate with prostate cancer specific mortality. The purpose of this report is to identify the role that race and insurance status has on the risk-group distribution of patients at the time of presentation for radiation oncology consultation.Materials/MethodsA total of 673 men seen from 1998-2007 (25% African-American [AA], 75% Caucasian [CA]) had data available to determine risk-group, race, and insurance status. All had previously untreated, non-metastatic adenocarcinoma of the prostate and were assigned a risk-group using the D'Amico classification: Low (PSA<10 and GS ≤6 and T stage ≤T2a), Intermediate (PSA ≥10 and <20 or GS 7 or T2b), or High (PSA ≥20 or GS ≥8 or T2c-T4). Insurance status was defined as private (P) vs. other (O), including Medicaid, Medicare without a supplement, or self pay. A 2x2 contingency tables using Fischer's exact test were used to analyze the impact of race and insurance status on risk-group, iPSA, GS, and T stage. The Student's t test was used to compare means of iPSA and age.ResultsFifty-eight percent were low-risk, 25% were intermediate-risk, and 17% were high-risk. There were no statistically significant differences between AA and CA with regard to clinical T stage or GS. The median age for AA was 4 years younger than CA (64 vs. 68 years, p < 0.0001). The AAs were more likely to have iPSA values >10 ng/mL (38% vs. 26%, p = 0.002) and >20 ng/mL (21% vs. 8%, p < 0.0001). The relative risk (RR) of having a PSA ≥20 was 2.74 (p < 0.0001) for AA. African-American men presented with high-risk (HR) prostate cancer at nearly twice the rate as CA (RR 1.94, 95% CI, 1.4-2.6, p = 0.0002). Other (O) insurance status had a similar effect on HR group presentation (RR 1.82, 95% CI, 1.3-2.7, p = 0.0044). AA were significantly more likely to have O insurance (RR 3.04, p < 0.0001). On multivariate analysis, both race (chi-square 10.5, p = 0.001) and insurance status (chi-square 4.2, p = 0.04) were independently correlated with HR presentation. O insured AA were nearly three times more likely to present with HR disease than P insured CA (RR 2.7, p = 0.0002).ConclusionsAmong men with prostate cancer in Southeastern NC and referred for radiation oncology consultation, AA present with HR prostate cancer at approximately twice the rate as CA, predominantly due to higher iPSA. This discrepancy persists after accounting for insurance status. Efforts should be made not only to improve PSA screening in the uninsured, but also to increase screening among insured AA. Earlier PSA screening in AA may also be warranted. Purpose/Objective(s)For the purposes of prognosis and treatment selection, men diagnosed with prostate cancer (PC) are routinely assigned to one of three mutually exclusive "risk-groups" based on initial PSA (iPSA), Gleason score (GS), and T stage. These risk-groups are known to correlate with prostate cancer specific mortality. The purpose of this report is to identify the role that race and insurance status has on the risk-group distribution of patients at the time of presentation for radiation oncology consultation. For the purposes of prognosis and treatment selection, men diagnosed with prostate cancer (PC) are routinely assigned to one of three mutually exclusive "risk-groups" based on initial PSA (iPSA), Gleason score (GS), and T stage. These risk-groups are known to correlate with prostate cancer specific mortality. The purpose of this report is to identify the role that race and insurance status has on the risk-group distribution of patients at the time of presentation for radiation oncology consultation. Materials/MethodsA total of 673 men seen from 1998-2007 (25% African-American [AA], 75% Caucasian [CA]) had data available to determine risk-group, race, and insurance status. All had previously untreated, non-metastatic adenocarcinoma of the prostate and were assigned a risk-group using the D'Amico classification: Low (PSA<10 and GS ≤6 and T stage ≤T2a), Intermediate (PSA ≥10 and <20 or GS 7 or T2b), or High (PSA ≥20 or GS ≥8 or T2c-T4). Insurance status was defined as private (P) vs. other (O), including Medicaid, Medicare without a supplement, or self pay. A 2x2 contingency tables using Fischer's exact test were used to analyze the impact of race and insurance status on risk-group, iPSA, GS, and T stage. The Student's t test was used to compare means of iPSA and age. A total of 673 men seen from 1998-2007 (25% African-American [AA], 75% Caucasian [CA]) had data available to determine risk-group, race, and insurance status. All had previously untreated, non-metastatic adenocarcinoma of the prostate and were assigned a risk-group using the D'Amico classification: Low (PSA<10 and GS ≤6 and T stage ≤T2a), Intermediate (PSA ≥10 and <20 or GS 7 or T2b), or High (PSA ≥20 or GS ≥8 or T2c-T4). Insurance status was defined as private (P) vs. other (O), including Medicaid, Medicare without a supplement, or self pay. A 2x2 contingency tables using Fischer's exact test were used to analyze the impact of race and insurance status on risk-group, iPSA, GS, and T stage. The Student's t test was used to compare means of iPSA and age. ResultsFifty-eight percent were low-risk, 25% were intermediate-risk, and 17% were high-risk. There were no statistically significant differences between AA and CA with regard to clinical T stage or GS. The median age for AA was 4 years younger than CA (64 vs. 68 years, p < 0.0001). The AAs were more likely to have iPSA values >10 ng/mL (38% vs. 26%, p = 0.002) and >20 ng/mL (21% vs. 8%, p < 0.0001). The relative risk (RR) of having a PSA ≥20 was 2.74 (p < 0.0001) for AA. African-American men presented with high-risk (HR) prostate cancer at nearly twice the rate as CA (RR 1.94, 95% CI, 1.4-2.6, p = 0.0002). Other (O) insurance status had a similar effect on HR group presentation (RR 1.82, 95% CI, 1.3-2.7, p = 0.0044). AA were significantly more likely to have O insurance (RR 3.04, p < 0.0001). On multivariate analysis, both race (chi-square 10.5, p = 0.001) and insurance status (chi-square 4.2, p = 0.04) were independently correlated with HR presentation. O insured AA were nearly three times more likely to present with HR disease than P insured CA (RR 2.7, p = 0.0002). Fifty-eight percent were low-risk, 25% were intermediate-risk, and 17% were high-risk. There were no statistically significant differences between AA and CA with regard to clinical T stage or GS. The median age for AA was 4 years younger than CA (64 vs. 68 years, p < 0.0001). The AAs were more likely to have iPSA values >10 ng/mL (38% vs. 26%, p = 0.002) and >20 ng/mL (21% vs. 8%, p < 0.0001). The relative risk (RR) of having a PSA ≥20 was 2.74 (p < 0.0001) for AA. African-American men presented with high-risk (HR) prostate cancer at nearly twice the rate as CA (RR 1.94, 95% CI, 1.4-2.6, p = 0.0002). Other (O) insurance status had a similar effect on HR group presentation (RR 1.82, 95% CI, 1.3-2.7, p = 0.0044). AA were significantly more likely to have O insurance (RR 3.04, p < 0.0001). On multivariate analysis, both race (chi-square 10.5, p = 0.001) and insurance status (chi-square 4.2, p = 0.04) were independently correlated with HR presentation. O insured AA were nearly three times more likely to present with HR disease than P insured CA (RR 2.7, p = 0.0002). ConclusionsAmong men with prostate cancer in Southeastern NC and referred for radiation oncology consultation, AA present with HR prostate cancer at approximately twice the rate as CA, predominantly due to higher iPSA. This discrepancy persists after accounting for insurance status. Efforts should be made not only to improve PSA screening in the uninsured, but also to increase screening among insured AA. Earlier PSA screening in AA may also be warranted. Among men with prostate cancer in Southeastern NC and referred for radiation oncology consultation, AA present with HR prostate cancer at approximately twice the rate as CA, predominantly due to higher iPSA. This discrepancy persists after accounting for insurance status. Efforts should be made not only to improve PSA screening in the uninsured, but also to increase screening among insured AA. Earlier PSA screening in AA may also be warranted.

To evaluate acute quality of life (QOL) for patients with locally advanced squamous cell cancer of the head and neck (SCCHN) treated with a novel chemoirradiation regimen. Eligible patients with Stage III or IV SCCHN of oropharynx, hypopharynx or larynx (excluding N2c, N3, and M1 disease) received hyperfractionated intensity modulated radiation therapy (IMRT) with attempted sparing of contralateral parotid gland. High-risk planning target volume (PTV) was prescribed to receive 1.25 Gy bid-70 Gy. Intermediate and low-risk PTVs received 60 Gy and 50 Gy, respectively, at lower doses per fraction bid utilizing a single IMRT plan. Concurrent chemotherapy consisted of cisplatin 33 mg/meter2/week. Validated QOL tool consisted of 39 questions: 24 general, 1 overall, and 14 head and neck specific, 2 of which addressed swallowing function. Patients completed QOL questionnaires prior to treatment (PRE), at end of treatment (EOT), at month 1 (MO1) and month 3 (MO3) following completion. Worsening QOL was defined as >50% reduction in mean QOL score compared to PRE. Among 39 patients enrolled, 35 were evaluable, having completed chemoirradiation course and first three QOL questionnaires. Twenty-seven (77%) patients were white, 7 (20%) were African American, and 1 (3%) was Native American. Mean age was 55 years and 29 patients (83%) were male. Twenty-two (63%) patients had Stage IV disease. General mean QOL score was 7.7 PRE, decreasing to 6.2 EOT, then returning to 7.0 MO1 and 7.5 MO3. Head and neck specific mean QOL was 7.8 PRE, decreasing to 3.9 EOT, then rising to 6.1 MO1 and 6.8 MO3. Swallowing QOL was most affected by this regimen: 7.6 PRE, decreasing to 3.4 EOT, then returning to 6.1 MO1 and 7.3 MO3. Among 35 patients completing MO1 questionnaire, three (9%) had persistent worsening head and neck QOL and 7 (20%) had worsening swallowing QOL. Among 31 patients completing MO3 questionnaire by time of this abstract, 2 (6%) had persistent worsening head and neck QOL and 4 (13%) had worsening swallowing QOL. Hyperfractionated IMRT with concurrent weekly cisplatin for locally advanced SCCHN resulted in acute decrement in both general and head and neck specific QOL. Swallowing QOL was most profoundly affected. However, mean QOL scores improved in all categories by 1 month and returned at or near baseline by 3 months post-treatment for most patients. Long-term QOL as well as survival analysis for this phase II trial will be reported upon further patient follow-up.

Radiation therapy (RT) is one of the two main local treatments for clinically localized prostate cancer; radical prostatectomy (RP) is the other. The treatment options that are available for a particular patient are extensive and can include expectant management, RP, external beam radiation therapy (EBRT), interstitial brachytherapy (IB), androgen deprivation therapy (ADT), or any combination of these.