Derek R. McHaffie

OUTCOMES AFTER ACCELERATED PARTIAL BREAST IRRADIATION IN PATIENTS WITH ASTRO CONSENSUS STATEMENT CAUTIONARY FEATURES

PURPOSE To evaluate outcomes among women with American Society for Radiation Oncology (ASTRO) consensus statement cautionary features treated with brachytherapy-based accelerated partial breast irradiation (APBI). METHODS AND MATERIALS Between March 2001 and June 2006, 322 consecutive patients were treated with high-dose-rate (HDR) APBI at the University of Wisconsin. A total of 136 patients were identified who met the ASTRO cautionary criteria. Thirty-eight (27.9%) patients possessed multiple cautionary factors. All patients received 32 to 34 Gy in 8 to 10 twice-daily fractions using multicatheter (93.4%) or Mammosite balloon (6.6%) brachytherapy. RESULTS With a median follow-up of 60 months, there were 5 ipsilateral breast tumor recurrences (IBTR), three local, and two loco-regional. The 5-year actuarial rate of IBTR was 4.8%±4.1%. The 5-year disease-free survival was 89.6%, with a cause-specific survival and overall survival of 97.6% and 95.3%, respectively. There were no IBTRs among 32 patients with ductal carcinoma in situ (DCIS) vs. 6.1% for patients with invasive carcinoma (p=0.24). Among 104 patients with Stage I or II invasive carcinoma, the IBTR rate for patients considered cautionary because of age alone was 0% vs. 12.7% in those deemed cautionary due to histopathologic factors (p=0.018). CONCLUSIONS Overall, we observed few local recurrences among patients with cautionary features. Women with DCIS and patients 50 to 59 years of age with Stage I/II disease who otherwise meet the criteria for suitability appear to be at a low risk of IBTR. Patients with tumor-related cautionary features will benefit from careful patient selection.

Phase I Trial of Pelvic Nodal Dose Escalation with Hypofractionated IMRT for High Risk Prostate Cancer

PURPOSE Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5½ weeks. METHODS AND MATERIALS Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. RESULTS The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving ≥30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 ± 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. CONCLUSIONS Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose escalation may be an option in any future exploration of potential benefits of pelvic radiation therapy in high-risk prostate cancer patients.

Chemoradiation for organ preservation in the treatment of muscle-invasive bladder cancer

INTRODUCTION Standard therapy for muscle invasive bladder cancer includes neoadjuvant chemotherapy followed by radical cystectomy with urinary diversion. Three decades of interest in primary radiation and chemotherapy for bladder preservation have yielded mature that deserve closer examination. METHODS We reviewed the literature with an emphasis on outcomes from major clinical trials and prospective studies, while highlighting important aspects of effective treatment delivery and unanswered questions surrounding this approach. RESULTS There are no randomized trials comparing radical cystectomy to primary chemotherapy and radiation for bladder preservation, and future phase III comparisons are unlikely to be planned. Mature results from single institution protocols and phase II cooperative group trials demonstrate favorable disease-specific survival and bladder preservation rates. Here we review the results of relevant clinical trials, including cancer-related and patient functional outcomes. We outline multi-modal treatment specifics with respect to radiation delivery, incorporation of transurethral resection and chemotherapy selection, and future directions for optimizing results of non-operative strategies. CONCLUSIONS Combination chemotherapy and radiation can be used as an alternative to conserve the native bladder in appropriately selected patients, mirroring successful non-operative treatment paradigms used for organ-preservation for other cancer sites.

Outcomes Following Accelerated Partial Breast Irradiation in ASTRO Consensus Statement Unsuitable Patients.

Purpose/Objective: There are limited data to guide patient selection for accelerated partial breast irradiation (APBI). In the recent ASTRO consensus statement, an unsuitable group was defined for whom APBI should only be offered in the context of a clinical trial. In this analysis, we reviewed the outcomes in this cohort of potentially higher risk patients.Materials/Methods: Between 2/2001 and 6/2006, a total of 322 consecutive patients were treated with HDR APBI at the University of Wisconsin. A total of 107 “unsuitable” patients were identified: 80 pts (74.7%) age 3 cm, and 2 pts (1.9%) with multifocal disease. 17 pts (15.9%) had multiple unsuitable features. In addition, 53 pts (49.5%) possessed “cautionary” features, including 19 pts (17.8%) ER negative and 10 pts (9.3%) with pure DCIS. The median age at diagnosis was 47 (range 25 – 84). All patients received 32 – 34 Gy in 8 - 10 bid fractions using multicatheter (93.5%) or Mammosite balloon (6.5%) HDR brachytherapy.Results: With a median follow-up of 60 months (range 1.1 - 97.8 months), there were 8 loco-regional recurrences (3 local only, 2 regional and 3 loco-regional and distant). Four of 5 patients without distant disease were successfully salvaged and had no evidence of disease at last follow-up. The 6 yr actuarial loco-regional control rate is 91.3% +/- 5.9%, with a latency to recurrence ranging from 10 – 41 months. The 6 yr disease free survival for the entire cohort is 89%, with a cause-specific survival and overall survival of 92.5% and 89%, respectively. There were no loco-regional recurrences observed among those with age 3 cm, multifocality) or cautionary (ER -, EIC, tumor 2 – 3 cm, lobular histology, DCIS, 3 cm.Conclusions: Currently, uncertainty exists regarding patient selection for APBI. Based upon the observed local recurrence rates in the current analysis and the well-established benefits of whole breast radiotherapy, we continue to encourage clinical trial participation among this cohort of patients, specifically RTOG 0412/NSABP B-39. Although not statistically significant, the absence of local failures among women Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 955.