H. Ye

Comparison of dose-escalated, image-guided radiotherapy vs. dose-escalated, high-dose-rate brachytherapy boost in a modern cohort of intermediate-risk prostate cancer patients

PURPOSEnWe compared outcomes in intermediate-risk prostate cancer patients treated with dose-escalated adaptive image-guided radiation therapy (IGRT) or dose-escalated high-dose-rate brachytherapy boost (HDR-B).nnnMETHODS AND MATERIALSnPatients with intermediate-risk prostate cancer by National Comprehensive Cancer Network criteria were treated with either CT-based off-line adaptive IGRT (n = 734) or HDR-B (n = 282). IGRT was delivered with 3D-conformal or intensity-modulated radiation therapy with a median dose of 77.4 Gy. For HDR-B, the whole pelvis received a median 46 Gy, and the prostate 2 implants of 9.5 Gy (n = 71), 10.5 Gy (n = 155), or 11.5 Gy (n = 56).nnnRESULTSnMedian followup was 3.7 years for IGRT and 8.0 years for HDR-B (p < 0.001). Eight-year biochemical control was 86% for IGRT and 91% for HDR-B (p = 0.22), disease-free survival 67% for IGRT and 79% for HDR-B (p = 0.006), and overall survival 75% for IGRT and 86% for HDR-B (p = 0.009). Cause-specific survival (8-year, 100% vs. 99%), freedom from distant metastases (98% vs. 97%), and freedom from local recurrence (98% vs. 98%) did not differ (p > 0.50 each). A worse prognosis group was defined by percent positive prostate biopsy cores >50%, perineural invasion, or stage T2b-c, encompassing 260 (35%) IGRT and 171 (61%) HDR-B patients. These patients evidenced a 5-year biochemical control of 96% for HDR-B and 87% for IGRT (p = 0.002).nnnCONCLUSIONSnDose-escalated IGRT and HDR-B both yield excellent clinical outcomes for patients with intermediate-risk prostate cancer. Improved biochemical control with HDR-B for patients with worse pretreatment characteristics suggests that a subgroup of intermediate-risk prostate cancer patients may benefit from dual-modality treatment.

An age-corrected matched-pair study of erectile function in patients treated with dose-escalated adaptive image-guided intensity-modulated radiation therapy vs. high-dose-rate brachytherapy for prostate cancer

PURPOSEnTo compare erectile dysfunction (ED) after adaptive dose-escalated image-guided intensity-modulated radiotherapy (IG-IMRT) and high-dose-rate interstitial brachytherapy (HDR) monotherapy.nnnMETHODS AND MATERIALSnLow- and intermediate-risk prostate cancer patients treated with IG-IMRT or HDR were matched on pretreatment ED, age, Gleason score, T-stage, and prostate specific antigen. Patients who received androgen deprivation therapy were excluded. ED was graded by Common Terminology Criteria for Adverse Events v4. Actuarial rates of ED were computed by the Kaplan-Meier method.nnnRESULTSnThere were 384 patients with median followup of 2.0 years (0.5-6.1) for IG-IMRT and 2.0 years (0.5-8.7) for HDR. The median IG-IMRT dose was 75.6xa0Gy and HDR dose 38xa0Gy in four fractions. For patients with no pretreatment ED, actuarial rates of requiring intervention (Grade ≥2 ED) at 3 years were 31% for IG-IMRT and 19% for HDR (p=0.23), and impotence despite medical intervention (Grade 3) were 0% for IG-IMRT and 6% for HDR (p=0.06). For patients with Grade 1 pretreatment ED, Grade ≥2 ED at 3 years were 47% for IG-IMRT and 34% for HDR (p=0.79), and Grade 3 ED were 15% in both groups (p=0.59). For patients with Grade 2 pretreatment ED, Grade 3 ED at 3 years were 22% for IG-IMRT and 37% for HDR (p=0.70). No variables were predictive of Grade ≥2 ED following treatment.nnnCONCLUSIONSnRates of ED requiring medical intervention for both IG-IMRT and HDR are low and equivalent. Even patients with ED before treatment are likely to maintain potency with medication use at 3 years following treatment.

Comparison of chronic toxicities between brachytherapy-based accelerated partial breast irradiation and whole breast irradiation using intensity modulated radiotherapy

PURPOSEnBrachytherapy-based APBI (bAPBI) shortens treatment duration and limits dose to normal tissue. While studies have demonstrated similar local control when comparing bAPBI and whole breast irradiation using intensity modulated radiotherapy (WBI-IMRT), comparison of late side effects is limited. Here, we report chronic toxicity profiles associated with these two treatment modalities.nnnMETHODSn1034 patients with early stage breast cancer were treated at a single institution; 489 received standard-fractionation WBI-IMRT between 2000 and 2013 and 545 received bAPBI (interstitial 40%, applicator-based 60%) between 1993 and 2013. Chronic toxicity was evaluated ≥6 months utilizing CTCAE version 3.0; cosmesis was evaluated using the Harvard scale.nnnRESULTSnMedian follow-up was 4.6 years (range 0.1-13.4) for WBI-IMRT versus 6.7 years (range 0.1-20.1) for bAPBI (p < 0.001). Compared to WBI-IMRT, bAPBI was associated with higher rates of ≥grade 2 seroma formation (14.4% vs 2.9%, p < 0.001), telangiectasia (12.3% vs 2.1%, p = 0.002) and symptomatic fat necrosis (10.2% vs 3.6%, p < 0.001). Lower rates of hyperpigmentation were observed (5.8% vs 14.5%; p = 0.001). Infection rates were similar (3.3% vs 1.3%, p = 0.07). There was no difference between rates of fair (6.1% vs. 4.1%, p = 0.30) or poor (0.2% vs. 0.5%, p = NS) cosmesis. Mastectomy rates for local recurrence (3.1% for WBI-IMRT and 1.2% for bAPBI, p = 0.06), or for other reasons (0.8% and 0.6%, p = 0.60) were similar between groups.nnnCONCLUSIONnWith 5-year follow-up, WBI-IMRT and bAPBI are associated with similar, acceptable rates of toxicity. These data further support the utilization of bAPBI as a modality to deliver adjuvant radiation in a safe and efficacious manner.

Increasing Fractional Doses Increases the Probability of Benign PSA Bounce in Patients Undergoing Definitive HDR Brachytherapy for Prostate Cancer

PURPOSEnProstate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size.nnnMETHODS AND MATERIALSnBetween 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950xa0cGy × 4 fractions, 1200xa0cGy × 2 fractions, 1350xa0cGy × 2 fractions, 1900xa0cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0xa0ng/mL above the prior nadir with a subsequent return to the nadir.nnnRESULTSnThe median follow-up period was 3.7xa0years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0xa0ng/mL, respectively. The 3-year rate of PSA bounce >0.2xa0ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2xa0ng/mL for patients receiving a single fraction of 1900xa0cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2xa0ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025).nnnCONCLUSIONSnThe incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures.

Matched-Pair Analysis of High Dose Versus Standard Dose Definitive Chemoradiation for Locally Advanced Non–Small-Cell Lung Cancer

Background Recent data have called into question the use of dose‐escalated radiotherapy for locally advanced non–small‐cell lung cancer and the effect of cardiac radiotherapy doses. We compared the outcomes after chemoradiation using standard‐dose (SD; ≤ 64 Gy) or high‐dose (HD; > 64 Gy) radiotherapy. Patients and Methods A matched‐pair analysis was performed of 178 patients with stage IIB‐IIIB non–small‐cell lung cancer for SD versus HD groups using age ± 5 years, gender, stage, tumor size ± 2 cm, yielding 86 patients. The clinical endpoints were estimated using the Kaplan‐Meier method. Univariate and multivariate analyses were performed using the Cox regression method. Results The median follow‐up was 16.8 months for the entire cohort (HD, 21.6 months; SD, 12.1 months; P = .06). No significant differences were found in disease stage, histologic type, age, performance status, gender, or tumor size between the 2 groups. The median overall survival was 23.1 months for the HD group (95% confidence interval, 20.6‐25.5) versus 13.6 months for the SD group (95% confidence interval, 9.6‐17.5; P = .03). The 2‐year freedom from locoregional recurrence was 48.7% for the SD and 65.3% for the HD groups (P = .07). The 2‐year freedom from distant metastasis was 46.7% for the SD and 70.3% for the HD groups (P = .05). A higher cardiac V30 dose (P = .03) was the strongest predictor of survival besides clinical stage (P = .02). Conclusion Dose‐escalated radiotherapy resulted in improved survival and recurrence rates. A higher cardiac dose was a significant predictor of decreased survival. Micro‐Abstract Recent data have shown a survival detriment with dose‐escalated radiation for locally advanced non–small‐cell lung cancer with concurrent chemotherapy. Using data from a single institution, a matched‐pair analysis comparing patients treated with standard versus dose escalation was performed, yielding 86 patients. Higher dose radiotherapy was associated with improved outcomes, but a lower cardiac dose was a significant predictor of survival.