Thomas A. DiPetrillo

Factors influencing cosmetic outcome and complication risk after conservative surgery and radiotherapy for early-stage breast carcinoma.

PURPOSE The study was undertaken to assess the relationship among cosmesis and complications to factors related to disease presentation, surgical and radiotherapeutic technique, and adjuvant systemic therapy in conservative treatment for early-stage breast carcinoma. PATIENTS AND METHODS Between 1982 and 1988, 234 women with stage I/II breast carcinoma were treated with conservation therapy by a highly standardized protocol of limited excision and radiotherapy. Radiation boost and/or reexcision were determined by careful quantitation of the normal tissue margin around the primary tumor. Boosts to 20 Gy were preferentially performed with interstitial iridium-192 (192Ir) implants. Axillary node dissections were performed in all patients aged less than 70 years. Adjuvant therapy consisted of cyclophosphamide, methotrexate, (doxorubicin), and fluorouracil (CM[A]F) six to eight times for node-positive premenopausal women and tamoxifen for node-positive or -negative postmenopausal women. Median follow-up was 50 months (range, 20 to 80 months). Cosmesis was graded by defined criteria, and complications were individually scored. RESULTS Factors found to impact cosmesis adversely were palpable tumors (P = .046), volume of breast tissue resected (P = .027), reexcision of the tumor bed (P = .01), number of radiation fields (P = .03), radiation boost (P = .01), and chest wall separation (P = .01). There was a trend toward worse cosmesis (P = .062) in patients receiving tamoxifen. Cosmesis was not adversely affected by interstitial implant in spite of a higher prescribed dose. Factors influencing complication risk were axillary node dissection (P = .02), number of lymph nodes harvested (P = .05), and chemotherapy (P = .03). CONCLUSIONS Optimal cosmesis and minimal complication risk require careful attention to the technical details of surgery and radiotherapy. The impact of systemic therapies needs to be more thoroughly examined.

Microwave Ablation of Lung Malignancies: Effectiveness, CT Findings, and Safety in 50 Patients

PURPOSE To retrospectively evaluate effectiveness, follow-up imaging features, and safety of microwave ablation in 50 patients with intraparenchymal pulmonary malignancies. MATERIALS AND METHODS This HIPAA-compliant study was approved by the institutional review board; informed consent was waived. From November 10, 2003, to August 28, 2006, 82 masses (mean, 1.42 per patient) in 50 patients (28 men, 22 women; mean age, 70 years) were percutaneously treated in 66 microwave ablation sessions. Each tumor was ablated with computed tomographic (CT) guidance. Follow-up contrast material-enhanced CT and positron emission tomographic (PET) scans were reviewed. Mixed linear modeling and logistic regression were performed. Time-event data were analyzed (Kaplan-Meier survival estimates and log-rank statistic). All event times were the time to a patients first event (alpha level = .05, all analyses). RESULTS At follow-up (mean, 10 months), 26% (13 of 50) of patients had residual disease at the ablation site, predicted by using index size of larger than 3 cm (P = .01). Another 22% (11 of 50) of patients had recurrent disease resulting in a 1-year local control rate of 67%, with mean time to first recurrence of 16.2 months. Kaplan-Meier analysis yielded an actuarial survival of 65% at 1 year, 55% at 2 years, and 45% at 3 years from ablation. Cancer-specific mortality yielded a 1-year survival of 83%, a 2-year survival of 73%, and a 3-year survival of 61%; these values were not significantly affected by index size of larger than 3 cm or 3 cm or smaller or presence of residual disease. Cavitation (43% [35 of 82] of treated tumors) was associated with reduced cancer-specific mortality (P = .02). Immediate complications included pneumothorax (Common Terminology Criteria for Adverse Events [CTCAE] grades 1 [18 of 66 patients] and 2 [eight of 66 patients]), hemoptysis (four of 66 patients), and skin burns (CTCAE grades 2 [one of 66 patients] and 3 [one of 66 patients]). CONCLUSION Microwave ablation is effective and may be safely applied to lung tumors. (c) RSNA, 2008.

Toxicity of Three-Dimensional Conformal Radiotherapy for Accelerated Partial Breast Irradiation

PURPOSE To assess the incidence and severity of late normal tissue toxicity using three-dimensional conformal radiotherapy to deliver accelerated partial breast irradiation. METHODS AND MATERIALS A total of 60 patients were treated with three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Treatment planning and delivery were in strict accordance with the technique and specified dose-volume constraints of the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol. Late toxicity was evaluated according to the Radiation Therapy Oncology Group grading schema. The cosmetic outcome was scored using the Harvard criteria. Univariate logistic regression analysis was performed to evaluate the correlation of dosimetric variables with outcome. RESULTS At a median follow-up of 15 months, moderate-to-severe late toxicity developed in 10% of patients. The most pronounced late toxicity was subcutaneous fibrosis: 25% Grade 2-4 and 8.3% Grade 3-4. The modified planning tumor volume/whole breast volume ratio, ratio of the volume of breast tissue receiving 5%, 20%, 50%, and 80% of the prescription dose to the whole breast volume, and maximal dose within the breast correlated with the development of fibrosis (p = .10, p = .03, p = .04, p = .06, p = .09, and p = .046, respectively). The overall cosmetic outcome was good to excellent in 81.7%, fair in 11.7%, and poor in 6.7%. The presence of subcutaneous fibrosis, modified planning tumor volume/whole breast volume ratio, ratio of the volume of breast tissue receiving 5% and 20% of the prescription dose to the whole breast volume, and pathologic specimen volume correlated with the risk of a fair/poor cosmetic outcome (p < .001, p = .02, p = .05, p = .04, p = .01, respectively). CONCLUSION The three-dimensional conformal radiotherapy technique for accelerated partial breast irradiation as specified in the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol resulted in a remarkably high rate of moderate-to-severe late normal tissue effects, despite the relatively brief follow-up period. The toxic events correlated clearly with several dose-volume parameters.

Percutaneous radiofrequency ablation of painful osseous metastases: A multicenter American College of Radiology Imaging Network trial

The study was conducted to determine whether radiofrequency ablation (RFA) can safely reduce pain from osseous metastatic disease.

Clinically evident fat necrosis in women treated with high-dose-rate brachytherapy alone for early-stage breast cancer

PURPOSE To investigate the incidence of and variables associated with clinically evident fat necrosis in women treated on a protocol of high-dose-rate (HDR) brachytherapy alone without external-beam whole-breast irradiation for early-stage breast carcinoma. METHODS AND MATERIALS From 6/1997 until 8/1999, 30 women diagnosed with Stage I or II breast carcinoma underwent surgical excision and postoperative irradiation via HDR brachytherapy implant as part of a multi-institutional clinical Phase I/II protocol. Patients eligible included those with T1, T2, N0, N1 (< or = 3 nodes positive), M0 tumors of nonlobular histology with negative surgical margins, no extracapsular lymph-node extension, and a negative postexcision mammogram. Brachytherapy catheters were placed at the initial excision, re-excision, or at the time of axillary sampling. Direct visualization, surgical clips, ultrasound, or CT scans assisted in delineating the target volume defined as the excision cavity plus 2-cm margin. High activity (192)Ir (3-10 Ci) was used to deliver 340 cGy per fraction, 2 fractions per day, for 5 consecutive days to a total dose of 34 Gy to the target volume. Source position and dwell times were calculated using standard volume optimization techniques. Dosimetric analyses were performed with three-dimensional postimplant dose and volume reconstructions. The median follow-up of all patients was 24 months (range, 12-36 months). RESULTS Eight patients (crude incidence of 27%) developed clinically evident fat necrosis postimplant in the treated breast. Fat necrosis was determined by clinical presentation including pain and swelling in the treated volume, computed tomography, and/or biopsy. All symptomatic patients (7 of 8 cases) were successfully treated with 3 to 12 months of conservative management. Continuous variables that were found to be associated significantly with fat necrosis included the number of source dwell positions (p = 0.04), and the volume of tissue which received fractional doses of 340 cGy, 510 cGy, and 680 cGy (p = 0.03, p = 0.01, and p = 0.01, respectively). Other continuous variables including patient age, total excised tissue volume, tumor size, number of catheters, number of days the catheters were in place, planar separation, dose homogeneity index (DHI), and uniformity index (UI) were not significant. Discrete variables including the presence/absence of DCIS, sentinel versus full axillary nodal assessment, receptor status, presence/absence of diabetes, and the use of chemotherapy or hormone therapy were not found to have a significant association with the risk of fat necrosis. CONCLUSIONS In this study of HDR brachytherapy of the breast tumor excision cavity plus margin, treatment was planned and delivered in accordance with the dosimetric parameters of the protocol resulting in a high degree of target volume dose homogeneity. Nonetheless, at a median follow-up of 24 months, a high rate of clinically definable fat necrosis occurred. The overall implant volume as reflected in the number of source dwell positions and the volume of breast tissue receiving fractional doses of 340, 510, and 680 cGy were significantly associated with fat necrosis. Future dosimetric optimization algorithms for HDR breast brachytherapy will need to include these factors to minimize the risk of fat necrosis.

Percutaneous Image-guided Thermal Ablation and Radiation Therapy: Outcomes of Combined Treatment for 41 Patients with Inoperable Stage I/II Non–Small-Cell Lung Cancer

PURPOSE To evaluate the clinical outcomes in patients with early-stage non-small-cell lung cancer (NSCLC) after combined treatment with thermal ablation and radiation therapy (RT). MATERIALS AND METHODS Forty-one patients with inoperable stage I/II NSCLC tumors underwent thermal ablation and RT at our institution between 1998 and 2005. Thirty-seven radiofrequency (RF) ablation procedures and four microwave ablation procedures were performed. Ablations were followed by standard-fraction external-beam RT within 90 days (n = 27) or postprocedural brachytherapy (n = 14). Survival and local recurrence were the primary endpoints evaluated by Kaplan-Meier analysis. RESULTS The median follow-up was 19.5 months. The overall survival rates were 97.6% at 6 months, 86.8% at 1 year, 70.4% at 2 years, and 57.1% at 3 years. Patients with tumors smaller than 3 cm (n = 17) had an average survival time of 44.4 +/- 5.4 months (SE). Patients with tumors 3 cm or larger (n = 24) had an average survival time of 34.6 +/- 7.0 months (P = .08). Local recurrence occurred in 11.8% of tumors smaller than 3 cm after an average of 45.6 +/- 4.1 months and in 33.3% of the larger tumors after an average of 34.0 +/- 7.8 months (P = .03). Outcomes in the brachytherapy and RT groups did not differ significantly. Nine of 15 pneumothoraces required chest tube drainage (22.0%). CONCLUSIONS Thermal ablation followed by RT for inoperable stage I/II NSCLC has a relatively low rate of complications that are easily managed. Combined therapy may result in an improved survival compared with either modality alone.

Limited Resection for Non-Small Cell Lung Cancer: Observed Local Control With Implantation of I-125 Brachytherapy Seeds

BACKGROUND Limited resection for lung cancer has been associated with a relatively high incidence of local recurrence. This retrospective study evaluates the impact of implanting radioactive iodine-125 (125I) seeds along the resection margin in these patients. METHODS Thirty-three patients with lung cancer who were not candidates for lobectomy or pneumonectomy underwent a limited resection of 35 primary non-small cell lung cancers. 125I brachytherapy seeds were implanted along the resection margin to reduce the risk of local recurrence. Survival using the Kaplan-Meier method and sites of recurrence were documented. Follow-up ranged from 20 to 98 months (median, 51 months). RESULTS The 5-year survival was 47% for all patients. For patients with T1N0 tumors, it was 67%, and for patients with T2N0 tumors, it was 39%. However, the cancer-specific survivals were 77% and 53% for patients with T1N0 and T2N0 tumors, respectfully. Ten patients experienced recurrence, with two local (at the resection margin) and six regional recurrences (five mediastinum, one chest wall). Both local recurrences and one regional recurrence occurred in the 19 patients with T1N0 tumors. CONCLUSIONS 125I seed implantation along the resected margin for compromised patients undergoing limited resection of lung cancer results in a relatively low incidence of local recurrence and may prolong survival.

Implementation and utility of a daily ultrasound-based localization system with intensity-modulated radiotherapy for prostate cancer

PURPOSE To evaluate the clinical feasibility of daily computer-assisted transabdominal ultrasonography for target position verification in the setting of intensity-modulated radiotherapy (IMRT) for prostate cancer. METHODS AND MATERIALS Twenty-three patients with clinically localized prostate cancer were treated using a sequential tomotherapy IMRT technique (Peacock) and daily computer-assisted transabdominal ultrasonography (BAT) for target localization. Patients were instructed to maintain a full bladder and were placed in the supine position using triangulation tattoos and a leg immobilizer to minimize pelvic rotation. The BAT ultrasound system is docked to the treatment collimator and electronically imports the CT simulation target contours and isocenter. The system is able to use the machine isocenter as a reference point to overlay the corresponding CT contours onto the ultrasound images captured in the transverse and sagittal planes. A touch screen menu is used to maneuver the CT contours in three dimensions such that they match the ultrasound images. The system then displays the three-dimensional couch shifts required to produce field alignment. Data were prospectively collected to measure the frequency by which useful ultrasound images were obtained, the amount of time required for localization/setup, and the direction/magnitude of the positional adjustments. RESULTS Of the 23 patients, the BAT ultrasound system produced images of sufficient quality to perform the overlay of the CT contours in 19 patients such that positional verification could be reliably performed. Poor image quality was associated with patient inability to maintain a full bladder, large body habitus, or other anatomic constraints. Of the 19 assessable patients, a total of 185 treatment alignments were performed (mean 8.8/patient). For all cases, the average time required for the daily ultrasound imaging and positional adjustments was 11.9 min. After the initial 5 cases, the user experience skills improved such that the time required for image verification/positional adjustments decreased to a mean of 5.6 min. The average right-left, AP, and cranial-caudal adjustment was 2.6 +/- 2.1 mm, 4.7 +/- 2.7 mm, and 4.2 +/- 2.8 mm, respectively. Positional adjustments >10 mm were infrequent and related primarily to misidentification of the target structures on the ultrasound image, patient movement, or improper registration of the triangulation tattoos. CONCLUSION Daily computer-assisted BAT ultrasound positional verification of the prostate can be successfully performed through the acquisition of high-quality images in most patients with only a modest increase in treatment setup time. Positional data obtained with this system resulted in clinically meaningful adjustments in daily setup for sequential IMRT that would not be otherwise apparent from other verification modalities.

Long‐term follow‐up of a prospective policy of margin‐directed radiation dose escalation in breast‐conserving therapy

A prospectively applied treatment policy for breast‐conserving therapy used margin assessment as the exclusive guide to the intensity of radiation therapy directed at the tumor bed.

Chemoradiotherapy and Gefitinib in Stage III Non-small Cell Lung Cancer with Epidermal Growth Factor Receptor and KRAS Mutation Analysis: Cancer and Leukemia Group B (CALEB) 30106, a CALGB-Stratified Phase II Trial

Introduction: This study evaluated the addition of gefitinib to sequential or concurrent chemoradiotherapy (CRT) in unresectable stage III non-small cell lung cancer. Methods: Between May 2002 and April 2005, 63 patients were entered before the study closing early. All received two cycles paclitaxel 200 mg/m2 and carboplatin area under the curve 6 intravenous plus gefitinib 250 mg daily. Poor risk stratum 1 (≥5% weight loss and/or performance status 2) received radiotherapy 200 cGy for 33 fractions (6600 cGy) and gefitinib 250 mg daily. Good-risk stratum 2 (performance status: 0–1weight loss and <5%) received the same RT with gefitinib 250 mg daily and weekly paclitaxel 50 mg/m2 plus carboplatin AUC 2. Consolidation gefitinib until progression was started after all toxicities were grade ≤2. Results: Acute high-grade infield toxicities were not clearly increased compared with historical CRT data. Poor-risk (N = 21) median progression-free survival was 13.4 months (95% confidence interval [CI]: 6.4–25.2) and median overall survival 19.0 months (95% CI: 9.9–28.4). Good-risk (N = 39) median progression-free survival was 9.2 months (95% CI: 6.7–12.2), and median overall survival was 13 months (95% CI: 8.5–17.2). Thirteen of 45 tumors analyzed had activating epidermal growth factor receptor (EGFR) mutations, and 2 of 13 also had T790M mutations. Seven tumors of 45 had KRAS mutations. There was no apparent survival difference with EGFR-activating mutations versus wild type or KRAS mutation versus wild type. Conclusions: Survival of poor-risk patients with wild type or mutated EGFR receiving sequential CRT with gefitinib was promising. Survival for good-risk patients receiving concurrent CRT plus gefitinib was disappointing even for tumors with activating EGFR mutations.