Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer.

INTRODUCTION: This study aims to report the outcome and toxicity of combined hyperthermia (HT) and radiation therapy (RT) in treatment of locally advanced or loco-regionally recurrent breast cancer. PATIENTS AND METHODS: Patients treated with HT and RT from January 1991 to December 2007 were reviewed. RT doses for previously irradiated patients were > 40 Gy and for RT naïve patients > 60 Gy, at 1.8-2 Gy/day. HT was planned for 2 sessions/week, immediately after RT, for a minimum of 20 min and for > 4 sessions. Superficial or interstitial applicators were used with temperature measured by superficial or interstitial thermistors based on target thickness. HT treatment was assessed by thermal equivalent dose (TED), > 42.5 °C and > 43 °C. Endpoints included treatment response, lack of local progression (local control), and survival. RESULTS: 127 patients received HT and RT to 167 sites. These included the intact breast (24.4%), chest wall/skin (67.7%), and breast/chest wall and nodes (7.9%). At a median follow-up of 13 months (mean 30 ± 38), improved overall survival was significantly associated with increasing RT dose (p < 0.0001), median TED 42.5 °C ≥ 200 min (p = 0.003), and local control (p = 0.0002). Local control at last follow-up was seen in 55.1% of patients. Complete response was significantly associated with median TED 42.5 °C ≥ 200 min (p = 0.002) and median TED 43 °C ≥ 100 min (p = 0.03). CONCLUSION: HT and RT are effective for locally advanced or recurrent breast cancer in patients that have been historically difficult to treat by RT alone. Over 50% of patients achieved control of locoregional disease. Overall survival was improved with local control.

Optimization for high-dose-rate brachytherapy of cervical cancer with adaptive simulated annealing and gradient descent.

PURPOSE: To validate an in-house optimization program that uses adaptive simulated annealing (ASA) and gradient descent (GD) algorithms and investigate features of physical dose and generalized equivalent uniform dose (gEUD)-based objective functions in high-dose-rate (HDR) brachytherapy for cervical cancer. METHODS: Eight Syed/Neblett template-based cervical cancer HDR interstitial brachytherapy cases were used for this study. Brachytherapy treatment plans were first generated using inverse planning simulated annealing (IPSA). Using the same dwell positions designated in IPSA, plans were then optimized with both physical dose and gEUD-based objective functions, using both ASA and GD algorithms. Comparisons were made between plans both qualitatively and based on dose-volume parameters, evaluating each optimization method and objective function. A hybrid objective function was also designed and implemented in the in-house program. RESULTS: The ASA plans are higher on bladder V75% and D2cc (p=0.034) and lower on rectum V75% and D2cc (p=0.034) than the IPSA plans. The ASA and GD plans are not significantly different. The gEUD-based plans have higher homogeneity index (p=0.034), lower overdose index (p=0.005), and lower rectum gEUD and normal tissue complication probability (p=0.005) than the physical dose-based plans. The hybrid function can produce a plan with dosimetric parameters between the physical dose-based and gEUD-based plans. The optimized plans with the same objective value and dose-volume histogram could have different dose distributions. CONCLUSIONS: Our optimization program based on ASA and GD algorithms is flexible on objective functions, optimization parameters, and can generate optimized plans comparable with IPSA.

Multi-institutional review of repeat irradiation of chest wall and breast for recurrent breast cancer.

PURPOSE: To review the toxicity and clinical outcomes for patients who underwent repeat chest wall or breast irradiation (RT) after local recurrence. METHODS AND MATERIALS: Between 1993 and 2005, 81 patients underwent repeat RT of the breast or chest wall for locally recurrent breast cancer at eight institutions. The median dose of the first course of RT was 60 Gy and was 48 Gy for the second course. The median total radiation dose was 106 Gy (range, 74.4-137.5 Gy). At the second RT course, 20% received twice-daily RT, 54% were treated with concurrent hyperthermia, and 54% received concurrent chemotherapy. RESULTS: The median follow-up from the second RT course was 12 months (range, 1-144 months). Four patients developed late Grade 3 or 4 toxicity. However, 25 patients had follow-up >20 months, and no late Grade 3 or 4 toxicities were noted. No treatment-related deaths occurred. The development of Grade 3 or 4 late toxicity was not associated with any repeat RT variables. The overall complete response rate was 57%. No repeat RT parameters were associated with an improved complete response rate, although a trend was noted for an improved complete response with the addition of hyperthermia that was close to reaching statistical significance (67% vs. 39%, p = 0.08). The 1-year local disease-free survival rate for patients with gross disease was 53% compared with 100% for those without gross disease (p < 0.0001). CONCLUSIONS: The results of our study have shown that repeat RT of the chest wall for patients with locally recurrent breast cancer is feasible, because it is associated with acceptable acute and late morbidity and encouraging local response rates.

Preoperative chemoradiation for rectal cancer: results of multimodality management and analysis of prognostic factors.

BACKGROUND: Our goals were to examine the impact of neoadjuvant chemoradiation for rectal cancer on surgical outcomes and to determine prognostic factors predicting improved survival. METHODS: Retrospective cohort of 56 male and 44 female patients. RESULTS: After preoperative chemoradiation, 73% of patients had sphincter-preserving surgery. The 5-year disease-free (DFS) and overall survival rates were 77% and 81%, respectively. Twenty-five percent of patients showed a complete pathologic response. T-level downstaging and pathologic T stage did not correlate with recurrence or survival rates. Pathologic nodal stage was associated with a significant difference in recurrence rates (N(0) 19%, N1 20%, and N2 75%, P = .038) and DFS (N0/N1 vs. N2, 79% vs. 25%, P = .002). CONCLUSION: Neoadjuvant chemoradiation resulted in a high rate of sphincter preservation. Complete pathologic responses after surgery were frequent and although pathologic T stage after surgery did not affect recurrence rates, pathologic nodal response was associated with improved recurrence and survival rates.

Supraclavicular nodal failure in patients with one to three positive axillary lymph nodes treated with breast conserving surgery and breast irradiation, without supraclavicular node radiation.

The purpose of this study was to evaluate the risk factors associated with supraclavicular nodal failure (SCF) in patients with one to three positive axillary nodes treated with breast conserving surgery and axillary dissection without supraclavicular node radiation (S/C RT) to aid in the selection of patients for S/C RT. Two hundred two breast conservation patients with one to three positive axillary nodes on axillary dissection treated with breast irradiation without S/C RT and 20 patients with S/C RT between August 1985 and May 2002 were identified and retrospectively evaluated. The Kaplan-Meier method was used to determine SCF-free and overall survival curves. Risk factors for SCF were examined. The median follow-up from surgery was 72 months (range: 4-195). Nine of 202 patients (4%) failed in the ipsilateral breast, 4 (2%) in the ipsilateral supraclavicular lymph nodes, 4 (2%) in the ipsilateral axillary and/or internal mammary nodes and 30 (15%) distantly. The 5- and 10-year SCF-free survival was 97.92%. The overall survival at 5, 10, and 15 years was 91.35%, 75.58%, and 67.18%, respectively. SCFs were associated with high grade or ER negative cancers, but not with number of positive nodes. Two of the four SCFs were associated with distant metastases, and two with local failures. One patient with a SCF was salvaged and is disease-free at 134 months. The overall low incidence of SCF in patients with one to three positive nodes treated with breast radiation alone after breast conserving surgery and adequate axillary dissection suggests that additional S/C RT is unnecessary in this cohort. When it occurs, supraclavicular nodal failure is often associated with distant metastases.

Management of T1a breast cancer.

Identification of early-stage breast cancers has increased over the past 2 decades primarily because of mammographic screening. The general guidelines to management of breast cancer may not apply to the smallest of these tumors, as their metastatic potential may be smaller than larger tumors. Tumors < 5 mm (T1a) carry an excellent prognosis, despite a variety of treatment approaches. However, some patients' cancer returns. There appear to be some histologic features that can predict a higher risk of axillary metastases, and therefore, a higher risk of distant metastases. Controversy exists over the extent of treatment, as to whether less than conventional treatment, such as mastectomy, axillary evaluation, and breast-conserving surgery and radiation, can be done. T1a lesions associated with extensive ductal carcinoma in situ and T1a lesions in young patients should be treated with caution if less than conventional breast treatment is to be considered. In older patients with good histologic features, axillary assessment may not be necessary. Very wide excision alone may be appropriate for some patients, but partial breast irradiation is under study and may provide a reasonable compromise. Systemic therapy for node-negative patients is not recommended. Recurrences within the breast occur later in early-stage breast cancers than with extensive-stage breast cancers, requiring annual imaging and evaluation for many years.