Either External Beam Radiotherapy Research Articles

Long-Term Adherence to Adjuvant Endocrine Therapy Following Various Radiotherapy Modalities in Early Stage Hormone Receptor Positive Breast Cancer

IntroductionWe compared the rates of long-term adjuvant endocrine therapy (AET) adherence after various radiation therapy (RT) modalities among patients with early stage breast cancer. Materials and MethodsMedical records from patients with stage 0, I, or IIA (tumors ≤3 cm), hormone receptor (HR) positive breast cancer that received adjuvant radiation therapy (RT) from 2013 to 2015 at a single institution were retrospectively reviewed. All patients received breast conserving surgery (BCS) followed by adjuvant RT via one of the following modalities: whole breast radiotherapy (WBI), partial breast irradiation (PBI) with either external beam radiation therapy (EBRT) or fractionated intracavitary high-dose rate (HDR) brachytherapy, or single fraction HDR-brachytherapy intraoperative-radiation therapy (IORT). ResultsOne hundred fourteen patients were reviewed. Thirty patients received WBI, 41 PBI, and 43 IORT with a median follow up of 64.2, 72.0, and 58.6 months, respectively. For the entire cohort, AET adherence was approximately 64% at 2 years and 56% at 5 years. Among patients in the IORT clinical trial, adherence to AET was approximately 51% at 2 years and 40% at 5 years. After controlling for additional factors, DCIS histology (vs invasive disease) and IORT (compared to other radiation modalities) were associated with decreased endocrine therapy adherence (P < 0.05). ConclusionDCIS histology and receipt of IORT were associated with lower rates of adherence to AET at 5 years. Our findings suggest that examination of the efficacy of RT interventions such as PBI and IORT in patients who do not receive AET is warranted.

Single Photon Emission Computed Tomography (SPECT) Functional Liver Imaging to Facilitate Reirradiation for Liver Malignancies: A Phase 1 Trial

<h3>Purpose/Objective(s)</h3> Functional imaging, such as Tc-99m- sulfur colloid single photon emission computed tomography (SPECT), may allow preferential sparing of functional liver volume and facilitate safe reirradiation. The primary objective of this study is to evaluate the safety of hypofractionated reirradiation for patients with hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (IHC) or liver metastases (LM) who received prior radiation with either external beam radiotherapy (EBRT) or yttrium-90 radioembolization (Y90 RE) when using SPECT functional liver imaging for planning. <h3>Materials/Methods</h3> This is a Phase I trial with a 3+3 design used to test three levels of dose constraints for safety. Eligible patients had a diagnosis of HCC, IHC or LM and received EBRT >/=12 months prior or Y90 RE >/=6 months prior. After giving informed consent, patients underwent simulation and subsequent SPECT scan in the treatment position. Functional liver was estimated based on 40% maximum intensity as threshold. The prescription dose was 45Gy-67.5Gy in 15 fractions. Composite constraints were bowel/duodenum/stomach Dmax <45Gy, esophagus Dmax <50Gy, common bile duct Dmax <60Gy, and V45Gy <10% for the heart. The mean functional liver dose constraint was <20Gy or 18Gy for patients treated with EBRT and Y90 RE, respectively. The volumetric dose constraint for functional liver volume receiving <22Gy depended on the dose level of trial enrollment: level 0 was ≥400cc, level -1 was 500cc and level +1 was 300cc. Dose limiting toxicities (DLTs), including grade 3 hypoalbuminemia, increase in INR, increase in bilirubin, ascites or hepatic failure as well as any grade 4 toxicity related to reirradiation, were assessed within 2 months after re-radiation. Any liver decompensation qualifying as a DLT was attributed to radiation therapy. The maximal dose constraint (MDC) is defined as the highest constraint level at which no more than one patient has experienced DLT in six patients treated at that dose constraint. <h3>Results</h3> A total of thirteen patients were enrolled between May 2018 and April 2021. The median [IQR] reirradiation GTV volume was 57cc [32-287cc]. The median [IQR] liver-minus-GTV and functional liver volumes were 1402cc [1141-1481cc] and 869 [784-1077], respectively. All plans spared >/=500ccs of functional liver from receiving ≥22Gy (median [IQR] 726 [637-783]). The median [IQR] mean function liver volume dose was 14.9Gy [10.4-18.6Gy]. The first 3 patients in dose level 0 and the next 3 patients treated in dose level +1 experienced no DLTs. Of the next seven patients treated using dose level +1 constraints, one developed a DLT possibly attributable to radiation. <h3>Conclusion</h3> SPECT functional imaging facilitates safe reirradiation for primary and metastatic liver tumors. Due to the ability to spare >/=500ccs of functional liver from >22Gy for all patients with only 1 of 13 patients experiencing DLT, we conclude this to be a reasonable constraint for reirradiation.

An Estimate of Local Failure in the TARGIT-A Trial of Pre-pathology Intraoperative Radiation Therapy for Early Breast Cancer

TARGIT-A was a pragmatic randomized noninferiority trial including women with early-stage breast cancer treated postlumpectomy with either external beam radiation therapy (EBRT) or 50 kV x-rays delivered intraoperatively with or without EBRT, as indicated. The long-term update of the pre-pathology cohort did not include a 10-year estimate of the primary endpoint of local failure (although tabular 5-year data was provided). Here, we used the data from the pre-pathology manuscript to estimate the cumulative incidence of local failure. Using digitizer software and the published survival curves, we extracted the Kaplan-Meier rate of local recurrence-free survival and overall survival. The extracted data were calibrated to the published point-estimates to within ±0.5%. The data were then fit to parametric survival models, and overall survival and local recurrence-free survival curves were subtracted to give the estimate of local failure in the presence of the competing risk of death. Bootstrap resampling was used to assess for parameter uncertainty in the modeling process. Our analysis estimated that the risk of local failure at 10 years in the TARGIT-A pre-pathology cohort is approximately 1.7% with EBRT (95% confidence interval [CI], 0%-4.3%) and 5.5% in the pragmatic risk-adapted TARGIT strategy (95% CI, 2.9%-8.0%). A weighted average estimate suggests that the risk of local failure in low-risk women treated with TARGIT alone is approximately 6.6% at 10 years (95% CI, 3.3%-10.0%), with an estimated difference of 4.9% (95% CI, 0.6%-9.2%) compared with EBRT. These data allow for contextualization and informed decisions when considering megavoltage EBRT, kilovoltage intraoperatively, or omission of radiation therapy entirely.

Long-Term Adherence to Adjuvant Endocrine Therapy Following Various Radiotherapy Modalities in Hormone Receptor Positive Breast Cancer

Adjuvant endocrine therapy (AET) is standard of care following breast-conserving surgery (BCS) for hormone receptor (HR) positive breast cancer. We compared the rates of long-term AET adherence after various radiation therapy (RT) modalities among patients with estrogen receptor (ER) and/or progesterone receptor (PR) positive breast cancer treated with BCS.Medical records from patients with stage 0 or stage 1, ER and/or PR positive breast cancer that received adjuvant RT between 2013 and 2015 at a single institution were retrospectively reviewed. We excluded patients with prior breast cancer or ductal carcinoma in situ (DCIS), HR-negative disease, primary tumors > 3cm, involved nodes, and those for whom AET was contraindicated. All patients received BCS followed by adjuvant RT via one of the following modalities: whole breast radiotherapy (WBI), accelerated partial breast irradiation (APBI) with either external beam radiation therapy (EBRT) or fractionated intracavitary high dose rate (HDR) brachytherapy, or single fraction HDR-brachytherapy intraoperative-radiation therapy (IORT) delivered at the time of lumpectomy, on a clinical trial (Precision Breast IORT). Only patients from the completed phase of the protocol were included. All patients were evaluated for up to five years of adherence to AET. Patient and treatment factors were evaluated via a Cox Regression analysis with backward selection of variables based upon P < 0.10 on univariate analysis (UVA) for inclusion in the final model. The Kaplan Meier method was used to model and further evaluate rates of AET adherence based on RT modality and histology as well as among the entire cohort.Ninety-seven patients were eligible for analysis. Thirty patients were treated with WBI, 41 with APBI, and 26 with IORT on clinical trial with a median follow up of 64.2, 72.0, and 58.6 months, respectively. Follow up schedule and evaluation of AET adherence was similar between all groups. For the entire cohort, AET adherence was approximately 67% at 2 years and 58% at 5 years. Among patients in the IORT clinical trial, adherence to AET was 53% at 2 years and 41% at 5 years. In the Cox regression model, histology (DCIS) and RT modality (IORT) were associated with decreased AET adherence at 5 years, with odds ratio (OR) 1.974 (CI: 1.018-3.828, P = 0.044) and OR 2.177 (CI: 1.132-4.186, P = 0.02), respectively.For early stage, HR positive breast cancer, the rate of AET adherence was approximately 58% at 5 years, consistent with prior reports. DCIS histology and receipt of IORT on clinical trial were associated with lower rates of adherence to AET at 5 years. Our findings suggest a potential need for further research aimed at addressing adherence to AET. Additionally, examination of the efficacy of more convenient RT interventions such as APBI and IORT in patients who do not receive AET is warranted.

Cavernous Sinus Metastasis from Carcinoma of Buccal Mucosa- A Rare Case Report and Review of Literature

Distant metastasis from Head and Neck Squamous Cell Carcinomas (HNSCC) is uncommon, Cavernous Sinus (CS) metastasis being very rare. Infrequent presentation and misdiagnosis makes it a difficult entity to identify and treat. Hereby, Authors present a rare case of 47 year old male of CS metastasis from postoperative carcinoma of buccal mucosa. The patient was a histopathologically proven case of poorly differentiated Squamous Cell Carcinoma (SCC) of left buccal mucosa for which he underwent definitive surgery. During adjuvant Radiotherapy (RT) he developed severe headache, diplopia and ptosis. 18Fluorodeoxy-Glucose-Positron Emission Tomography-Computed Tomography (18FDG PET-CT) revealed an FDG avid lesion in left CS suggestive of CS metastasis. In view of local recurrence and CS metastasis palliative RT was given. Patient responded well to palliative RT but succumbed to the disease within months. CS metastasis has poor prognosis with limited treatment options which include palliative RT, either External Beam Radiotherapy (EBRT) or radiosurgery to CS. Chemotherapy for disseminated disease has limited benefits due to lesser penetration of the blood brain barrier.

Metastatic spine disease in lung cancer patients: national patterns of radiation and surgical care.

Lung cancer is the most common source of spinal metastases. As our treatment of spinal metastases evolves, national trends in radiation therapy (RT), including spinal stereotactic neurosurgery, have yet to been established. We performed a retrospective review of lung cancer patients within the National Cancer Database (NCDB) between 2004 and 2014 who received radiation to the vertebral column. A total of 29,144 lung cancer patients received either external beam RT (EBRT), stereotactic radiosurgery (SRS), or particle-based RT to the spine. EBRT was the most common modality throughout all years, though SRS use increased over time (Spearman's rank correlation, P<0.01). A surgical procedure on a distant metastasis was performed in 1,547 (5.3%) patients. Median survival was 6.24 months for patients receiving EBRT and 9.3 months for those receiving SRS, a significant difference (log rank test, P<0.01), which persisted when adjusting for other predictors (multivariable Cox regression, P<0.01). In conclusion, spinal SRS is steadily growing in the treatment of lung metastases to the spine, and surgery on distant metastases is becoming more frequent. There was a survival advantage for patients receiving SRS over EBRT. As the use of SRS-in addition to separation surgery-grows in radioresistant pathology, further study of improved survival and recurrence rates are needed.

MP22-18 RISK OF SECONDARY BLADDER CANCER AFTER HIGH DOSE RATE BRACHYTHERAPY FOR PROSTATE CANCER

MP22-18 RISK OF SECONDARY BLADDER CANCER AFTER HIGH DOSE RATE BRACHYTHERAPY FOR PROSTATE CANCER

Pre-radiotherapy PSA progression is anegative prognostic factor in prostate cancer patients using 5‑alpha-reductase inhibitors.

To investigate the impact of 5‑alpha-reductase inhibitor (5-ARI) use on radiotherapy outcomes for localized prostate cancer. We included 203patients on a5-ARI from our institutional database comprising over 2500patients who had been treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients received a5-ARI for urinary symptoms or active surveillance. Cancer progressions at the time of definitive treatment were analyzed according to the following criteria:(a) progression of Gleason score or increase in cancer volume on biopsy, (b)first biopsy positive for cancer after being treated for urinary symptoms with a5-ARI, and (c)prostate-specific antigen (PSA) progression with or without aprevious cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. At amedian follow-up of 38.2months (standard deviation 22.2months), 10(4.9%) patients experienced BF. Concerning prostate cancer progression criteria, 52% of men demonstrated none, 37% showed only one criterion, and 11% showed two. Using univariate analysis, PSA progression (p= 0.004) and appearance of apositive biopsy (p< 0.001) were significant predictive factors for BF, while Gleason progression (p= 0.3) was not. In multivariate analysis adjusted for cancer aggressiveness, rising PSA (hazard ratio, HR,5.7; 95% confidence interval, CI,1.1-28.8; p= 0.04) and the number of cancer progression factors (HR2.9, 95%CI1.2-7.0, p= 0.02) remained adverse risk factors. PSA progression experienced during 5‑ARI treatment before radiotherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

External beam radiation therapy with or without low-dose-rate brachytherapy: Analysis of favorable and unfavorable intermediate-risk prostate cancer patients

PurposeTo compare the tumor control and toxicity in men with intermediate-risk prostate cancer treated with either external beam radiation therapy (EBRT) or EBRT plus low-dose-rate brachytherapy (combo-RT). Methods and MaterialsBetween 1995 and 2012, 579 men with intermediate-risk prostate cancer were treated with either EBRT (n = 388) or combo-RT (n = 191). Outcomes assessed included biochemical recurrence–free survival (bRFS), distant metastasis–free survival (DMFS), and cumulative incidence of genitourinary (GU) and gastrointestinal toxicity. Favorable and unfavorable intermediate-risk subgroups were analyzed. ResultsMedian followup was 7.5 years. Combo-RT group had improved 10-year bRFS compared with EBRT (91.7% vs. 75.4%, p = 0.014). On multivariable analysis, combo-RT (hazard ratio, 0.48; 95% confidence interval: 0.25, 0.92; p = 0.03) was associated with improved bRFS. Combo-RT had significantly improved bRFS compared with EBRT in the unfavorable subgroup (p = 0.02) but not in the favorable subgroup (p = 0.37). DMFS was similar within the entire cohort and by risk group. Combo-RT was associated with an increased rate in the 6-year cumulative incidence of Grade 3 GU toxicity (hazard ratio, 3.48; 95% confidence interval: 1.1, 11.1; p = 0.026); however, 57% of Grade 3 GU toxicity was resolved, 29% had partial improvement, and only 1 patient had persistent Grade 3 GU toxicity. ConclusionsIn intermediate-risk prostate cancer, combo-RT improved bRFS but not DMFS and increased Grade 3 GU toxicity. The bRFS benefit was limited to unfavorable intermediate-risk patients.

Prostate brachytherapy, either alone or in combination with external beam radiation, is associated with longer overall survival in men with favorable pathologic Group 4 (Gleason score 8) prostate cancer

PurposeConventional prostate cancer risk stratification results in considerable heterogeneity within each prognostic group. Men with pathologic grade Group 4 (Gleason score 8) but otherwise low-risk features have been identified as a favorable subset of high-risk prostate cancer. Given recent randomized data supporting improved cancer outcome with brachytherapy in intermediate- and high-risk prostate cancer, we sought to evaluate brachytherapy utilization and overall survival (OS) for these patients. Methods and MaterialsWe queried the National Cancer Database for clinical T1c–T2a N0 M0 prostate cancer with prostate-specific antigen <10 ng/mL and Gleason score 8 adenocarcinoma on biopsy. All patients received androgen deprivation therapy and either external beam radiation therapy (EBRT) alone, brachytherapy alone, or a combination of EBRT with brachytherapy boost (brachytherapy + EBRT). Kaplan–Meier OS estimates as well as univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score–matched analyses were performed to further control for baseline confounders. ResultsFour thousand four hundred ninety-six patients were identified with a median followup of 62.5 months (range, 2.3–119.8). Median age was 72 years (range, 41–90+). Utilization of brachytherapy decreased from 2004 to 2009. The odds ratio for brachytherapy by year (continuous variable) was 0.86 (p < 0.001). Five-year OS was 84%, 88%, and 89% for the EBRT alone, brachytherapy alone, and brachytherapy + EBRT groups, respectively. On multivariate analysis, higher median income, low comorbidity score, and treatment with brachytherapy alone (hazard ratio, 0.66; p = 0.005) or brachytherapy + EBRT (hazard ratio, 0.70; p = 0.001) remained associated with longer OS. Propensity score matching confirmed longer OS associated with either brachytherapy regimen. ConclusionsOf those men with World Health Organization pathologic grade Group 4 (Gleason score 8) prostate cancer and otherwise favorable prognostic features treated with androgen deprivation therapy and radiation therapy, longer OS was achieved when prostate brachytherapy was included, whether used alone or in combination with supplemental EBRT. In spite of these excellent outcomes, prostate brachytherapy utilization is declining in the United States.

Pre-treatment PSA- progression as a negative prognostic factor in patients using 5-alpha-reductase inhibitors prior to radiotherapy for prostate cancer.

96 Background: To investigate the impact of 5-alpha-reductase inhibitors (5-ARIs) usage on radiotherapy outcomes for localized prostate cancer. Methods: From our institutional database of over 2500 patients, we identified 203 patients on a 5-ARI. They were all treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients receiving a 5-ARI were analyzed according to the following prostate cancer progression criteria: a) progression of Gleason score or increase in cancer volume on the biopsy, b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. Results: At a median follow-up of 36 months (interquartile range [IQR] 22-52 months), 10 (4.9%) patients experienced BF. 52% of men demonstrated none of the progression criteria, 37% showed only one prostate cancer progression criteria and 11% showed two. Using a univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p &lt; 0.001) but not Gleason progression (p = 0.3) were a significant predictive factor of BF. With separate multivariate analysis adjusted for the CAPRA score (HR 1.7, 95% CI 1.2-2.3, p = 0.003), a rising PSA (HR 5.7, 95% CI 1.1-28.8, p = 0.04) and the number of cancer progression factors (HR 2.9, 95%CI 1.2-7.0, p = 0.02) remained adverse risk factors. Both Gleason score progression (p = 0.4) and first biopsy positive for cancer (p = 0.13) failed to remain significant. Age and obesity were not significant factors in univariate or multivariate analysis. Conclusions: A PSA progression experienced while under 5-ARI treatment before EBRT or brachytherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

Combination therapy improves prostate cancer survival for patients with potentially lethal prostate cancer: The impact of Gleason pattern 5.

To investigate the impact of Gleason pattern 5 (GP5) prostate cancer after either external beam radiotherapy (EBRT) or the combination of EBRT with low-dose rate brachytherapy boost (combo). Between 1998 and 2008, 467 patients with National Comprehensive Cancer Network high-risk prostate cancer were treated with EBRT (n = 326) or combo (low-dose rate to 90-108 Gy using I-125 followed by EBRT) (n = 141). Freedom from biochemical failure, freedom from metastasis (FFM), cancer-specific survival (CSS), and overall survival were evaluated. Combo patients were younger (66 vs. 72 years, p < 0.001) and had fewer comorbidities (Charlson comorbidity index 3.7 vs. 4.4, p < 0.001). EBRT patients had higher tumor stages (T3-4: 30% vs. 21%, p = 0.03) and lower Gleason scores (8-10: 61% vs. 75%, p = 0.01). Androgen deprivation therapy use was similar between cohorts (85% vs. 87%, p = 0.5), but EBRT patients had longer androgen deprivation therapy use (median 14 vs. 12 months, p = 0.05). GP5 predicted worse FFM (p < 0.001, hazard ratio [HR] 3.3, 95% confidence interval [CI]1.8-6.2]) and CSS (p < 0.001, HR 5.9, 95% CI 2.7-12.9) for the EBRT group, but not for the combo group (p = 0.86, HR 0.48, 95% CI 0.1-2.4 for metastasis and p = 0.5, HR 1.6, 95% CI 0.33-8.0 for CSS). In those with GP5 (n = 143), combo was associated with improved outcomes in all endpoints. On univariate analysis, 5-year outcomes for combo vs. EBRT were as follows: freedom from biochemical failure 89% vs. 65%, FFM 89% vs. 67%, CSS 93% vs. 78%, and overall survival 88% vs. 67% (p < 0.05 for all). Combo was associated with improved outcomes for men with GP5 prostate cancer. This highlights the importance of local therapy, especially in patients with the highest pathologic grade disease.

The Quadrella: A Novel Approach in Analyzing Optimal Outcomes after Permanent Seed Prostate Brachytherapy

In past years, urologists have assessed the combination of cancer control with adequate functional outcomes after prostatectomy, known as Trifecta. No such attempt for a composite endpoint has been made for either external beam radiotherapy (EBRT) or brachytherapy (PB) of prostate cancer. In the present study, we define a Quadrella outcome in regard to disease control and preservation of urinary, gastrointestinal (GI) and sexual functions in a cohort of patients submitted to permanent seed prostate brachytherapy.

Risk for Developing Myelodysplastic Syndromes in Prostate Cancer Patients Definitively Treated With Radiation

Exposure to ionizing radiation has been linked to myelodysplastic syndromes (MDS); it is not clear whether therapeutic radiation doses used for prostate cancer pose an increased MDS risk. We performed a retrospective cohort study of prostate cancer patients diagnosed between 1986 and 2011 at Cleveland Clinic, comparing those who underwent definitive treatment with radical prostatectomy (RP) to radiotherapy either external beam radiotherapy (EBRT) or prostate interstitial brachytherapy (PI) and to population-based registries. Competing risk regression analyses were used to determine the cumulative risk of developing MDS. All statistical tests were two-sided. Of 10924 patients, 5119 (47%) received radiation (n = 2183 [43%] in EBRT group and n = 2936 [57%] in PI group) and 5805 (53%) were treated with RP. Overall, 31 cases of MDS were observed, with age-adjusted incidence rates no higher than in population-based registries. In univariate analyses, advancing age (hazard ratio [HR] = 1.14; 95% confidence interval [CI] = 1.09 to 1.20; P < .001) and radiotherapy exposure (HR = 3.44; 95% CI = 1.41 to 8.37; P = .007) were statistically significantly associated with development of MDS. In multivariable analyses, although advanced age (HR = 1.13; 95% CI = 1.06 to 1.19; P < .001) remained statistically associated with MDS, radiation did not, although a small non-statistically significant trend existed for PI-treated patients. MDS rates were no higher than in population-based registries. With relatively short follow-up, prostate cancer patients definitively treated with radiation did not appear to have a statistically increased risk of subsequent MDS.

Direct 2-Arm Comparison Shows Benefit of High-Dose-Rate Brachytherapy Boost vs External Beam Radiation Therapy Alone for Prostate Cancer

To evaluate the outcomes of patients treated for intermediate- and high-risk prostate cancer with a single schedule of either external beam radiation therapy (EBRT) and high-dose-rate brachytherapy (HDRB) boost or EBRT alone. From 2001-2006, 344 patients received EBRT with HDRB boost for definitive treatment of intermediate- or high-risk prostate cancer. The prescribed EBRT dose was 46 Gy in 23 fractions, with a HDR boost of 19.5 Gy in 3 fractions. This cohort was compared to a contemporaneously treated cohort who received EBRT to 74 Gy in 37 fractions, using a matched pair analysis. Three-dimensional conformal EBRT was used. Matching was performed using a propensity score matching technique. High-risk patients constituted 41% of the matched cohorts. Five-year clinical and biochemical outcomes were analyzed. Initial significant differences in prognostic indicators between the unmatched treatment cohorts were rendered negligible after matching, providing a total of 688 patients. Median biochemical follow-up was 60.5 months. The 5-year freedom from biochemical failure was 79.8% (95% confidence interval [CI], 74.3%-85.0%) and 70.9% (95% CI, 65.4%-76.0%) for the HDRB and EBRT groups, respectively, equating to a hazard ratio of 0.59 (95% CI, 0.43-0.81, P=.0011). Interaction analyses showed no alteration in HDR efficacy when planned androgen deprivation therapy was administered (P=.95), but a strong trend toward reduced efficacy was shown compared to EBRT in high-risk cases (P=.06). Rates of grade 3 urethral stricture were 0.3% (95% CI, 0%-0.9%) and 11.8% (95% CI, 8.1%-16.5%) for EBRT and HDRB, respectively (P<.0001). No differences in clinical outcomes were observed. This comparison of 2 individual contemporaneously treated HDRB and EBRT approaches showed improved freedom from biochemical progression with the HDR approach. The benefit was more pronounced in intermediate- risk patients but needs to be weighed against an increased risk of urethral toxicity.

Does Hormone Therapy Exacerbate the Adverse Effects of Radiotherapy in the Treatment of Men with Prostate Cancer? A Quality of Life Study

This study examines whether Androgen Deprivation Therapy (ADT) as an adjunct to radiotherapy impacts health-related quality of life (HRQOL) outcomes in patients with localized prostate cancer treated definitively with either external beam radiation therapy (EBRT) or brachytherapy (BT). From 1999 to 2003, patients anticipating treatment for localized prostate cancer were enrolled in a prospective study at UCLA. At defined pre- and post-treatment intervals out to 48 months, participants completed validated tools including the Medical Outcomes Study Short Form-36 (SF-36), the University of California, Los Angeles Prostate Cancer Index (PCI), and the American Urological Association Symptoms Index (AUASI). 81 men were treated with EBRT alone and 67 were treated with EBRT+ADT. 67 patients had EBRT only, 63 had BT monotherapy, and 18 had EBRT+BT. Median ADT duration was 4 months. We compared the time to return to baseline for men who did or did not receive ADT in 6 HRQOL domains: physical and mental composite scores, AUASI, urinary control, sexual function, and bowel function. Univariate and multivariate analysis were performed. Covariates included age, clinical stage, and co-morbidities. Multivariate analysis identified factors associated with longer time to return to baseline mental health, including non-white race (2 months, p = 0.008), history of stroke (6 months, p < 0.001) and history of alcohol use (3 months, p = 0.037). Men treated with BT monotherapy experienced longer time to return to baseline for urinary control (PCI, 2.8 months, p = 0.006) and urinary symptoms (AUASI, 7.4 months, p < 0.001). The time to return to baseline levels in any of the 6 HRQOL domains was not significantly affected by the addition of ADT. Use of erectile dysfunction medications or alpha blockers did not differ between patients receiving ADT or not. Men receiving ADT as an adjunct to radiotherapy had significantly higher-risk prostate cancer. Our study shows that the addition of ADT to definitive radiotherapy does not significantly impact the time to return to baseline scores in 6 patient-reported HRQOL domains. These data may be valuable for patients and physicians when weighing the toxicity and benefits of ADT when added to definitive radiation.

The Use of The UCSF Cancer of the Prostate Risk Assessment for Prediction of Recurrence in Patients Treated with Either Permanent Seed Brachytherapy or External Beam Radiotherapy

Purpose: The University of California, San Francisco (UCSF) Cancer of the Prostate Risk Assessment (CAPRA) is a validated preoperative index which predicts recurrence free survival and the risk of adverse pathological features after prostatectomy. We analyzed the distribution of the CAPRA score in patients with low risk or prostate cancer treated with either external beam radiotherapy (EBRT) or permanent seed prostate brachytherapy (PB).

Assessment of phosphatidylinositol-3 kinase (PI3K) as a prognostic marker in head and neck squamous cell carcinoma (HNSCC)

e17028 Background: Deregulated signaling through phosphatidylinositol 3’-kinase (PI3K) pathway is common in several cancers, including HNSCC. In the present study we investigated the relationship between PI3K protein expression and outcome in patients with HNSCC. Methods: A tissue microarray composed of 122 specimens from primary HNSCC cases treated with either external beam radiotherapy (EBRT) or gross total surgical resection and EBRT was constructed. Protein expression levels for PI3K were analyzed using an immunofluorescence-based assay that provides an automated, quantitative analysis of expression within subcellular compartments (AQUA). Primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance. Results: Mean follow-up time for the cohort was 40 months. Ninety-seven of 122 cases had sufficient tissue for analysis and continuous AQUA scores were divided into quartiles. Survival analysis showed that patients in the top and bottom quartile had a significantly shorter OS (p = 0.015). In multivariable analysis, adjusting for well-characterized prognostic variables, PI3K expression retained its prognostic significance. Conclusions: Our study suggests that in situ quantitative measurement of PI3K stratifies HNSCC into four expression levels where both low and high levels are associated with a worse outcome. We speculate that transmission of growth factor receptor signals that promote tumor aggression in these low expressers may occur via PI3K/Akt independent mechanisms. It is possible that activation of such alternate pathways in some tumors results in the down-regulation of PI3K expression via a feedback mechanism, producing aggressive tumors bearing a PI3K-low phenotype. No significant financial relationships to disclose.

Outcome and molecular features of head and neck squamous cell carcinomas (HNSCC) bearing a p16 high phenotype

6031 Background: We have previously demonstrated that p16 expression defines a biologically distinct subgroup of oropharyngeal squamous cell cancers (OSCC). Thus, OSCC can be Class I: human papillomavirus (HPV)-, Class II: HPV16+/p16-, or Class III: HPV16+/p16+. Tumors bearing a high p16 phenotype were associated with superior outcome. Using in situ automated quantitative protein expression analysis (AQUA) to explore the biomarker signatures of these 3 classes we found that beta-catenin, epidermal growth factor receptor (EGFR) and Met were upregulated in class III tumors. Our aim was to validate these findings using an independent cohort. Methods: A tissue microarray composed of 122 specimens from primary HNSCC cases treated with either external beam radiotherapy (EBRT) or gross total surgical resection and EBRT was constructed. Protein expression levels for a panel of 13 markers (EGFR, MET, STAT 3, ERK 1/2, pAkt, PI3Kp85, PI3Kp110, PTEN, p53, Bcl-2, E-cadherin, β-catenin, NFκB) were analyzed using AQUA. P16 protein levels were correlated with progression-free (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance.Comparison of expression between the p16 positive and p16 negative groups was done using unpaired t-tests. Results: Mean follow-up time for the cohort was 40 months. AQUA scores were divided into quartiles. Survival analysis showed that patients in the top quartile had a significantly better DFS (p = 0.01) and OS (p = 0.002). In multivariable analysis, adjusting for well-characterized prognostic variables, p16 expression retained its prognostic significance. Expression of E-cadherin and β-catenin was significantly higher in the p16 positive versus the p16 negative group (p = 0.014 and p = 0.006, respectively). p16 positive tumors also expressed higher levels of PTEN (p = 0.0009), PI3Kp110 (p = 0.03), NFκB (p = 0.007), and Bcl-2 (p = 0.005). Conclusions: These results validate p16 as a favorable prognostic marker in HNSCC. They also validate beta-catenin as a distinct biomarker in HNSCC bearing high p16 phenotype. Given that HPV+ tumors are p16+, beta-catenin is a candidate biomarker that distinguishes HPV+ versus HPV- HNSCC. No significant financial relationships to disclose.

Adjuvant high-dose-rate brachytherapy after external beam radiotherapy in nasopharyngeal carcinoma

Purpose : To compare the local control and survival rates obtained with either external beam radiation therapy (ERT) and adjuvant high-dose-rate (HDR) brachytherapy (BRT) or ERT alone in patients with nasopharyngeal cancer. Methods and Materials : Between December 1993 and December 1999, 144 patients (106 male, 38 female) with the diagnosis of nasopharyngeal cancer were treated with either ERT and adjuvant HDR BRT (Group A) or ERT alone (Group B) at our department. BRT was not applied in 38 patients for the following reasons: ( 1) Unit was unavailable ( n = 13), ( 2) Patient was younger than 18 years ( n = 17), ( 3) Patient received accelerated hyperfractionated ERT ( n = 6), and ( 4) Patient refused BRT ( n = 2). The median age for whole group was 43 (range: 9–82 years). According to the AJCC-1997 staging system, there were 11 (7.6%), 35 (24.3%), 38 (26.4%), and 60 (41.7%) patients in Stage I, II, III, and IV, respectively. There were 57 (39.6%) patients with T1, 41 (28.5%) with T2, 20 (13.9%) with T3, and 26 (18.1%) with T4 tumors. Histopathologic diagnosis was WHO 2–3 in 137 (95.2%) patients. ERT doses ranged between 58.8 and 74 Gy (median: 66 Gy). There were significantly more patients with young age, N2 status, and Stage III disease in Group B and with Stage II disease in Group A. Significantly more patients received chemotherapy in Group B. BRT with an HDR 192Ir microSelectron afterloading unit was delivered in 106 patients at the conclusion of ERT using a single-channel nasal applicator. Dose was prescribed at 1 cm from the source, and total dose of 12 Gy in 3 fractions on 3 consecutive days was given immediately after ERT. Besides radiotherapy, 82 (56.9%) patients received cisplatin-based chemotherapy, as well. Follow-up time ranged between 12 and 80 months (median: 32 months). Results : The two groups were comparable in terms of local recurrence, locoregional failure, regional failure, and rate of distant metastasis. Local failure was observed in 11 (10.3%) out of 106 patients in Group A and in 2 (5.2%) out of 38 patients in Group B ( p > 0.05). Three-year disease-free survival rate was 67% and 80% ( p = 0.07), respectively, and 3-year local recurrence-free survival rate was 86% and 94% ( p = 0.23) for Group A and B, respectively. Multivariate analysis showed that advanced nodal status and male gender were significantly unfavorable factors for disease-free survival, and Stage II disease was unfavorable for local recurrence-free survival. The administration of adjuvant HDR BRT was not an independent prognostic factor in multivariate analysis. Out of 106 patients, 42 (39.7%) experienced nasal congestion, transient nasal obstruction, and/or fibrinous exudate in response to antihistaminic treatment. Only three (2.8%) patients experienced nasal synechy related, most probably, to the BRT. Five patients developed severe neural complications; only one out of five was observed in Group A. No severe complication attributed directly to BRT was detected. Conclusion : The acute and late morbidity of adjuvant HDR BRT is acceptable with our treatment scheme, but we did not find any local control difference between our patients treated with adjuvant BRT after ERT and ERT alone. We believe that the exact role of adjuvant HDR BRT can be elucidated only by prospective randomized studies.