Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.

Background: To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC). Materials and methods: We reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity. Results: Among 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05-63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4-5 toxicity. Conclusions: IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

Stereotactic Ablative Body Radiotherapy for Primary Non-Small-Cell Lung Cancer: Achieving Local Control with a Lower Biologically Effective Dose.

We conducted a retrospective study of stereotactic ablative radiotherapy (SABR) for 94 patients with non-small-cell lung cancer at our institution. The patients were treated with either 50 Gy in five treatments or 48 Gy in four treatments, corresponding to biologically effective doses (BED) of 100 Gy or 105.6 Gy, respectively. The results demonstrate that, with relatively low BEDs, we can achieve excellent local control with minimal toxicity.

Radiotherapy in the Management of Orbital Lymphoma: A Single Institution's Experience Over 4 Decades.

PURPOSE: To report our institution's treatment techniques, disease outcomes, and complication rates after radiotherapy for the management of lymphoma involving the orbits. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 44 patients curatively treated with radiotherapy for stage IAE (75%) or stage IIAE (25%) orbital lymphoma between 1969 and 2013. Median follow-up was 4.9 years. Thirty-eight patients (86%) had low-grade lymphoma and 6 (14%) had high-grade lymphoma. Radiation was delivered with either a wedge-pair (61%), single-anterior (34%), or anterior with bilateral wedges (5%) technique. The median radiation dose was 25.5 Gy (range, 15 to 47.5 Gy). Lens shielding was performed when possible. Cause-specific survival and freedom from distant relapse were calculated using the Kaplan-Meier method. RESULTS: The 5-year local control rate was 98%. Control of disease in the orbit was achieved in all but 1 patient who developed an out-of-field recurrence after irradiation of a lacrimal tumor. The 5-year regional control rate was 91% (3 patients failed in the contralateral orbit and 1 patient failed in the ipsilateral parotid). Freedom from disease, cause-specific survival, and overall survival rates at 5 and 10 years were 70% and 55%, 89% and 89%, and 76% and 61%, respectively. Acute toxicity was minimal. Ten patients (23%) reported worsened vision following radiotherapy, and cataracts developed in 17 patients. Cataracts developed in 13 of 28 patients treated without lens shielding (46%) and 4 of 16 patients (25%) treated with lens shielding. CONCLUSION: Radiotherapy is a safe and effective local treatment in the management of orbital lymphoma.

Stereotactic body radiation therapy for oligoprogression of metastatic disease from gastrointestinal cancers: A novel approach to extend chemotherapy efficacy.

Chemotherapy and targeted therapies are effective palliative options for numerous unresectable or metastatic cancers. However, treatment resistance inevitably develops leading to mortality. In a subset of patients, systemic therapy appears to control the majority of tumors leaving 5 or less to progress, a phenomenon described as oligoprogression. Reasoning that the majority of lesions remain responsive to ongoing systemic chemotherapy, we hypothesized that local treatment of the progressing lesions would confer a benefit. The present study describes the cases of 5 patients whose metastatic disease was largely controlled by chemotherapy. The oligoprogressive lesions (≤5) were treated with stereotactic body radiotherapy (SBRT), justifying continued use of an effective systemic regimen. A total of 5 patients with metastatic disease on chemotherapy, with ≤5 progressing lesions amenable to SBRT, were treated with ablative intent. Primary tumor site and histology were as follows: 2 with metastatic colon adenocarcinoma, 2 with metastatic rectal adenocarcinoma and 1 with metastatic pancreatic adenocarcinoma. Imaging was performed prior to SBRT and every 3 months after SBRT. In total, 4 out of the 5 patients achieved disease control for >7 months with SBRT, without changing chemotherapy regimen. The median time to chemotherapy change was 9 months, with a median follow-up time of 9 months. The patient who failed to respond developed progressive disease outside of the SBRT field at 3 months. In conclusion, the addition of SBRT to chemotherapy is an option for the overall systemic control of oligoprogressive disease.

Laparoscopic Ovarian Transposition Before Pelvic Cancer Treatment: Ovarian Function and Fertility Preservation.

Survivors of pelvic cancer treatment live with the ramifications of pelvic radiation for many years after their cure. Several options are available to preserve ovarian function and fertility in reproductive age women undergoing pelvic radiation. Laparoscopic ovarian transposition is an under-utilized, yet fairly simple surgical procedure to relocate the ovaries away from the radiation field. Although randomized-controlled trials on the outcomes of ovarian transposition are scarce, there is a growing body of evidence on the risks and benefits of this procedure, in terms of prevention of premature ovarian failure, and potentially preserving fertility. In this review, we summarize the available data on the indications, patient selection and outcomes of ovarian transposition, as well as illustrate the technique of the procedure.

Discordant HER2 expression and response to neoadjuvant chemoradiotherapy in esophagogastric adenocarcinoma.

BACKGROUND: Targeting human epidermal growth factor receptor 2 (HER2) with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival. The impact of HER2 inhibition in combination with chemoradiotherapy (CRT) in early stage EGA is under investigation. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients who underwent neoadjuvant CRT followed by surgery. METHODS: All patients with EGA who underwent standard neoadjuvant CRT followed by esophagectomy at the University of Florida were included. Demographics, risk factors, tumor features, and outcome data were analyzed. Descriptive statistics, Chi-square exact test, uni- and multivariate analyses, and Kaplan Meier method were used. HER2 expression determined by immunohistochemical (IHC) was scored as negative (0, 1+), indeterminate (2+) or positive (3+). RESULTS: Among 49 sequential patients (41 M/8 F) with matched-pair tumor samples, 9/49 patients (18%) had pathologic complete response (pCR), 10/49 had near pCR or not enough tumor (NET) to examine in the post- treatment samples. Patients with initial HER2 negativity demonstrated conversion to HER2 positivity after neoadjuvant CRT (7/30 cases; 23%). Baseline HER2 overexpression was more common in lower stage/node negative patients (67% in stages I, IIA vs. 33% in stages IIB, III) and did not correlate with treatment response or survival. CONCLUSIONS: Although limited by a relatively small sample size, our study failed to demonstrate that baseline HER2 protein over-expression in EGA predicts response to standard CRT. However, our data suggested that HER2 was up regulated by CRT resulting in unreliable concordance between pre-treatment (pre-tx) and post-treatment (post-tx) samples. Pre-therapy HER2 expression may not reliably reflect the HER2 status of persistent or recurrent disease.

Monitoring ABC-assisted deep inspiration breath hold for left-sided breast radiotherapy with an optical tracking system.

PURPOSE: Recent knowledge on the effects of cardiac toxicity warrants greater precision for left-sided breast radiotherapy. Different breath-hold (BH) maneuvers (abdominal vs thoracic breathing) can lead to chest wall positional variations, even though the patient's tidal volume remains consistent. This study aims to investigate the feasibility of using optical tracking for real-time quality control of active breathing coordinator (ABC)-assisted deep inspiration BH (DIBH). METHODS: An in-house optical tracking system (OTS) was used to monitor ABC-assisted DIBH. The stability and localization accuracy of the OTS were assessed with a ball-bearing phantom. Seven patients with left-sided breast cancer were included. A free-breathing (FB) computed tomography (CT) scan and an ABC-assisted BH CT scan were acquired for each patient. The OTS tracked an infrared (IR) marker affixed over the patient's xiphoid process to measure the positional variation of each individual BH. Using the BH within which the CT scan was performed as the reference, the authors quantified intra- and interfraction BH variations for each patient. To estimate the dosimetric impact of BH variations, the authors studied the positional correlation between the marker and the left breast using the FB CT and BH CT scans. The positional variations of 860 BHs as measured by the OTS were retrospectively incorporated into the original treatment plans to evaluate their dosimetric impact on breast and cardiac organs [heart and left anterior descending (LAD) artery]. RESULTS: The stability and localization accuracy of the OTS was within 0.2 mm along each direction. The mean intrafraction variation among treatment BHs was less than 2.8 mm in all directions. Up to 12.6 mm anteroposterior undershoot, where the patient's chest wall displacement of a BH is less than that of a reference BH, was observed with averages of 4.4, 3.6, and 0.1 mm in the anteroposterior, craniocaudal, and mediolateral directions, respectively. A high positional correlation between the marker and the breast was found in the anteroposterior and craniocaudal directions with respective Pearson correlation values of 0.95 and 0.93, but no mediolateral correlation was found. Dosimetric impact of BH variations on breast coverage was negligible. However, the mean heart dose, mean LAD dose, and max LAD dose were estimated to increase from 1.4/7.4/18.6 Gy (planned) to 2.1/15.7/31.0 Gy (delivered), respectively. CONCLUSIONS: In ABC-assisted DIBH, large positional variation can occur in some patients, due to their different BH maneuvers. The authors' study has shown that OTS can be a valuable tool for real-time quality control of ABC-assisted DIBH.

Low-kilovoltage, single-dose intraoperative radiation therapy for breast cancer: results and impact on a multidisciplinary breast cancer program.

BACKGROUND: The Intrabeam (Carl Zeiss) brachytherapy device (IB) is an electronic brachytherapy device that can be used to deliver low energy x-rays (50 kV) to a lumpectomy cavity at the time of lumpectomy for breast cancer. Reported experience with IB for breast cancer in the United States has been extremely limited. Here we describe our experience and analyze the impact of IB on our multidisciplinary breast cancer program. STUDY DESIGN: This is a retrospective review of a prospectively collected breast cancer database. Patient characteristics, treatment characteristics, recurrence, and cosmesis were analyzed. Cost data were also analyzed to determine the impact of IB on the breast cancer program. RESULTS: Seventy-eight patients underwent 80 IB treatments in this series between November 2010 and October 2012. Most patients had invasive ductal carcinoma. Mean total operative time for patients receiving lumpectomy, sentinel node biopsy, and IB was 132 minutes (range 79 to 243 minutes). Intrabeam brachytherapy was the only adjuvant radiation required in 81% of patients, and only 15% of patients required additional operation after the index lumpectomy procedure. At 12 months of follow-up, cosmesis was good to excellent in 92% of patients. There have been no local recurrences in patients treated in this series. Intrabeam brachytherapy is associated with considerably lower costs ($1,857) than conventional whole breast radiation therapy ($9,653). CONCLUSIONS: Implementation of IB impacts treatment planning and operating room use in a multidisciplinary breast cancer program. The safety profile, ease of administration, and reduced costs of IB favor its more widespread use in selected patients with early-stage breast cancer.

Outcomes of patients with non-Hodgkin's lymphoma treated with Bexxar with or without external-beam radiotherapy.

PURPOSE: To compare the efficacy and toxicity of external-beam radiotherapy (EBRT) to sites of bulky lymphadenopathy in patients with chemotherapy-refractory low-grade non-Hodgkin's lymphoma (NHL) immediately before receiving Bexxar (tositumomab and (131)I) vs. in patients receiving Bexxar alone for nonbulky disease. METHODS AND MATERIALS: Nineteen patients with chemotherapy-refractory NHL were treated with Bexxar at our institution (University of Florida, Gainesville, FL) from 2005 to 2008. Seventeen patients had Grade 1-2 follicular lymphoma. Ten patients received a median of 20 Gy in 10 fractions to the areas of clinical involvement, immediately followed by Bexxar (EBRT + Bexxar); 9 patients received Bexxar alone. The median tumor sizes before EBRT + Bexxar and Bexxar alone were 4.8 cm and 3.3 cm, respectively. All 5 patients with a tumor diameter >5 cm were treated with EBRT + Bexxar. A univariate analysis of prognostic factors for progression-free survival (PFS) was performed. RESULTS: The median follow-up was 2.3 years for all patients and 3.1 years for 12 patients alive at last follow-up. Of all patients, 79% had a partial or complete response; 4 of the 8 responders in the EBRT + Bexxar group achieved a durable response of over 2 years, including 3 of the 5 with tumors >5 cm. Three of 9 patients treated with Bexxar alone achieved a durable response over 2 years. Actuarial estimates of 3-year overall survival and PFS for EBRT + Bexxar and Bexxar alone were 69% and 38% and 62% and 33%, respectively. The median time to recurrence after EBRT + Bexxar and Bexxar alone was 9 months. Having fewer than 4 involved lymph-node regions was associated with superior PFS at 3 years (63% vs. 18%). There was no Grade 4 or 5 complications. CONCLUSIONS: Adding EBRT immediately before Bexxar produced PFS equivalent to that with Bexxar alone, despite bulkier disease. Hematologic toxicity was not worsened. EBRT combined with Bexxar adds a safe and effective therapeutic treatment for managing recurrent low-grade follicular NHL.

Accuracy of breast cancer axillary lymph node treatment plans based on 2-dimensional imaging: what we should know before interpreting 2-dimensional treatment-planning era studies.

OBJECTIVE: To investigate axillary 2-dimensional treatment planning accuracy. METHODS: Computed tomography (CT) simulation data for 16 breast cancer cases taken after level I-II axillary dissection were analyzed. An additional 6 patients underwent CT simulation using the historical 90-degree position (HP), and the standard-bore CT position (CT-P). Two physicians identified the lateral and medial borders of the coracoid process (CCP) on digitally reconstructed radiography (DRR). The DRR-identified x coordinates were compared with the CT-measured x coordinates. x coordinates differences between the most medial surgical clip and the borders of the CCP as identified on CT were analyzed. Fields were designed to cover various amounts of the axilla, and treatment plans were generated to compare doses to the most medial surgical clip. RESULTS: In 11 and 6 cases for each physician, respectively (lateral border), and in all cases for both physicians (medial border), the DRR identification of the CCP was medial to that on CT. In 9 and 8 cases, the most medial surgical clip was lateral to the medial and lateral borders of the CCP, respectively. In all data sets, the average difference was larger in the HP compared with CT position. The number of patients who received more than 90% of the prescribed dose when using the plans with the mid humeral head border, lateral border of the CCP, and medial border of the CCP were as follows: 6, 1, and 0, respectively. CONCLUSIONS: When using 2-dimensional treatment planning, the dose to the undissected axilla can vary depending on the anatomic landmark used to define the lateral border of the axillary field. This may account for outcome differences found in older radiotherapy studies.

Differences between current and historical breast cancer axillary lymph node irradiation based on arm position: implications for radiation oncologists.

PURPOSE: To identify differences in regional node irradiation using historical treatment planning techniques between 2 arm positions. MATERIALS AND METHODS: Sixteen breast cancer patients were scanned using a wide-bore computed tomography (CT) scanner. The patients were scanned in 2 arm positions: historical position (HP), in which the ipsilateral arm is at 90 degrees to the body axis; and standard-bore position (CT-P), in which the arms are above the head. The locations of the axillary lymph nodes were compared between the 2 positions. The dose distribution to the axillary lymph nodes was compared between the HP and the CT-P using fields designed based on bony landmarks. RESULTS: When the arm position changed from the HP to the CT-P, level I lymph nodes moved anteriorly and medially. Level II and III axillary nodes moved posteriorly and medially. If historical treatment planning techniques are used to treat the axillary lymph nodes with the patient in the CT-P, level I nodes could receive a higher dose of radiation and levels II and III could be significantly underdosed as compared with treatment in the HP. The dose distribution for the CT-P was more homogeneous compared with that of the HP. CONCLUSION: Coverage of the axillary lymph nodes varies significantly with arm position when using historical treatment planning techniques. Physicians should accurately contour the lymph node levels on the treatment planning CT and not rely on bony landmarks to design the axillary fields. CT-based treatment planning should be used to ensure adequate coverage of these nodes.

The dynamic tumor bed: volumetric changes in the lumpectomy cavity during breast-conserving therapy.

PURPOSE: To characterize the magnitude of volume change in the postoperative tumor bed before and during radiotherapy, and to identify any factors associated with large volumetric change. METHODS AND MATERIALS: Thirty-six consecutive patients with early-stage or preinvasive breast cancer underwent breast-conserving therapy at our institution between June 2006 and October 2007. Computed tomography (CT) scans of the breast were obtained shortly after surgery, before the start of radiotherapy (RT) for treatment planning, and, if applicable, before the tumor bed boost. Postoperative changes, seroma, and surgical clips were used to define the tumor bed through consensus agreement of 3 observers (B.P., D.I., and J.L.). Multiple variables were examined for correlation with volumetric change. RESULTS: Between the first and last scan obtained (median time, 7.2 weeks), the tumor bed volume decreased at least 20% in 86% of patients (n = 31) and at least 50% in 64% of patients (n = 23). From the postoperative scan to the planning scan (median time, 3 weeks), the tumor bed volume decreased by an average of 49.9%, or approximately 2.1% per postoperative day. From planning scan to boost scan (median interval, 7 weeks), the median tumor bed volume decreased by 44.6%, at an average rate of 0.95% per postoperative day. No single factor was significantly associated with a change in tumor bed volume greater than 20%. CONCLUSIONS: The average postlumpectomy cavity undergoes dramatic volumetric change after surgery and continues this change during RT. The rate of change is inversely proportional to the duration from surgery. In this study no factors studied predicted large volumetric change.

Long-term outcomes in breast cancer patients with ten or more positive axillary nodes treated with combined-modality therapy: the importance of radiation field selection.

PURPOSE: To determine the long-term outcome of a consistent treatment approach with electron beam postmastectomy radiation therapy (PMRT) in breast cancer patients with > or =10 positive nodes treated with combined-modality therapy. METHODS AND MATERIALS: TSixty-three breast cancer patients with > or =10 positive lymph nodes were treated with combined-modality therapy using an electron beam en face technique for PMRT at the University of Florida. Patterns of recurrence were studied for correlation with radiation fields. Potential clinical and treatment variables were tested for possible association with local-regional control (LRC), disease-free survival (DFS), and overall survival (OS). RESULTS: TAt 5, 10, and 15 years, OS rates were 57%, 36%, and 27%, respectively; DFS rates were 46%, 37%, and 34%; and LRC rates were 87%, 87%, and 87%. No clinical or treatment variables were associated with OS or DFS. The use of supplemental axillary radiation (SART) (p = 0.012) and pathologic N stage (p = 0.053) were associated with improved LRC. Patients who received SART had a higher rate of LRC than those who did not. Moderate to severe arm edema developed in 17% of patients receiving SART compared with 7% in patients not treated with SART (p = 0.28). CONCLUSIONS: TA substantial percentage of patients with > or =10 positive lymph nodes survive breast cancer. The 10-year overall survival in these patients was 36%. The addition of SART was associated with better LRC.