Kristine E. Kokeny

Effect of Breast Conservation Therapy vs Mastectomy on Disease-Specific Survival for Early-Stage Breast Cancer

IMPORTANCE To our knowledge, there are no recent studies that directly compare survival after breast conservation therapy (BCT) vs mastectomy. OBJECTIVE To compare the breast cancer-specific survival rates of patients undergoing BCT, mastectomy alone, or mastectomy with radiation using a contemporary cohort of patients. DESIGN, SETTING, AND PARTICIPANTS We performed univariate, multivariate logistic regression, and propensity analyses to compare the hazard of death for female patients with early-stage invasive ductal carcinoma treated with BCT, mastectomy alone, or mastectomy with radiation during the period from 1998 to 2008. The data were extracted from the Surveillance, Epidemiology, and End Results database. Early-stage breast cancer was defined as having a tumor size of 4 cm or smaller with 3 or less positive lymph nodes. EXPOSURE Breast conservation therapy, mastectomy alone, or mastectomy with radiation. MAIN OUTCOMES AND MEASURES Hazard of death due to breast cancer for patients undergoing BCT, mastectomy alone, or mastectomy with radiation. RESULTS A total of 132,149 patients were included in this analysis. Breast conservation therapy was used to treat 70% of patients, mastectomy alone was used to treat 27% of patients, and mastectomy with radiation was used to treat 3% of patients. The 5-year breast cancer-specific survival rates of patients who underwent BCT, a mastectomy alone, or a mastectomy with radiation were 97%, 94%, and 90%, respectively (P < .001); the 10-year breast cancer-specific survival rates were 94%, 90%, and 83%, respectively (P < .001). Multivariate analysis showed that women undergoing BCT had a higher survival rate than those undergoing mastectomy alone (hazard ratio, 1.31; P < .001) or mastectomy with radiation (hazard ratio, 1.47; P < .001). When propensity score stratification was used, the effect of treatment method on survival was similar. CONCLUSIONS AND RELEVANCE Patients who underwent BCT have a higher breast cancer-specific survival rate compared with those treated with mastectomy alone or mastectomy with radiation for early-stage invasive ductal carcinoma. Further investigation is warranted to understand what may be contributing to this effect.

Radiation therapy for clinically node-positive prostate adenocarcinoma is correlated with improved overall and prostate cancer-specific survival

PURPOSE To evaluate the effect of radiation therapy on prostate cancer-specific and overall survival with node-positive cancer in a retrospective Surveillance, Epidemiology and End RESULTS (SEER) population based study. METHODS AND MATERIALS The survival of subjects with cT1-T4,cN1,M0 prostate adenocarcinoma diagnosed between 1988 and 2006 were compared with univariate and multivariate Cox regression analysis. RESULTS A total of 1100 subjects, with a median age of 69 years and median follow-up time of 90 months, were identified. The 10-year cancer-specific survival for men who had no definitive therapy was 50.3% and for those who had radiation therapy 62.7%. This was significantly different favoring radiation therapy (hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.54 to 0.82, P ≤ .01). On multivariate analysis evaluating age, histologic grade, T stage, year of diagnosis, marital status, SEER registry and radiation therapy, radiation therapy (HR = 0.67, 95% CI = 0.54 to 0.84, P ≤ .01), year of diagnosis (HR = 0.96, 95% CI = 0.93 to 0.99, P = .01), and low and intermediate grade disease were correlated with improved CSS. The number needed to treat to prevent 1 prostate cancer-specific death at 10 years was 8 persons. A cause of death analysis revealed non-prostate cancer deaths were not statistically different in the comparison groups. CONCLUSIONS Radiation therapy is correlated with a clinically significant reduction in all cause and prostate cancer-specific death.

The Effect of Radiation on Complication Rates and Patient Satisfaction in Breast Reconstruction using Temporary Tissue Expanders and Permanent Implants

The optimal method of reconstruction following mastectomy for breast cancer patients receiving radiation therapy (RT) is controversial. This study evaluated patient satisfaction and complication rates among patients who received implant‐based breast reconstruction. The specific treatment algorithm analyzed included patients receiving mastectomy and immediate temporary tissue expander (TE), followed by placement of a permanent breast implant (PI). If indicated, RT was delivered to the fully expanded TE. Records of 218 consecutive patients with 222 invasive (85%) or in situ (15%) breast lesions from the Salt Lake City region treated between 1998 and 2009 were retrospectively reviewed, 28% of whom received RT. Median RT dose was 50.4 Gy, and 41% received a scar boost at a median dose of 10 Gy. Kaplan–Meier analyses were performed to evaluate the cumulative incidence of surgical complications, including permanent PI removal. Risk factors associated with surgical events were analyzed. To evaluate cosmetic results and patient satisfaction, an anonymous survey was administered. Mean follow‐up was 44 months (range 6–144). Actuarial 5‐year PI removal rates for non‐RT and RT patients were 4% and 22%, respectively. On multivariate analysis (MVA), the only factor associated with PI removal was RT (p = 0.009). Surveys were returned describing the outcomes of 149 breasts. For the non‐RT and RT groups, those who rated their breast appearance as good or better were 63% versus 62%, respectively. Under 1/3 of each group was dissatisfied with their reconstruction. RT did not significantly affect patient satisfaction scores, but on MVA RT was the only factor associated with increased PI removal. This reconstruction technique may be considered an acceptable option even if RT is needed, but the increased complication risk with RT must be recognized.

Hypofractionated Postmastectomy Radiation Therapy Is Safe and Effective: First Results From a Prospective Phase II Trial.

Purpose Conventionally fractionated postmastectomy radiation therapy (PMRT) takes approximately 5 to 6 weeks. Data supporting hypofractionated PMRT is limited. We prospectively evaluated a short course of hypofractionated PMRT, in which therapy was completed in 15 treatment days. Patients and Methods We delivered PMRT at a dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days to the chest wall and the draining regional lymph nodes, followed by an optional mastectomy scar boost of four fractions of 3.33 Gy. Our primary end point was freedom from any grade 3 or higher toxicities. We incorporated early stopping criteria on the basis of predefined toxicity thresholds. Results We enrolled 69 women with stage II to IIIa breast cancer, of whom 67 were eligible for analysis. After a median follow-up of 32 months, there were no grade 3 toxicities. There were 29 reported grade 2 toxicities, with grade 2 skin toxicities being the most frequent (16 of 67; 24%). There were two patients with isolated ipsilateral chest wall tumor recurrences (2 of 67; crude rate, 3%). Three-year estimated local recurrence-free survival was 89.2% (95% CI, 0.748 to 0.956). The 3-year estimated distant recurrence-free survival was 90.3% (95% CI, 0.797 to 0.956). Forty-one patients had chest wall reconstructions; three had expanders removed for infection before radiation therapy. The total rate of implant loss or failure was 24% (9 of 38), and the unplanned surgical correction rate was 8% (3 of 38), for a total complication rate of 32%. Conclusion To our knowledge, our phase II prospective study offers one of the shortest courses of PMRT reported, delivered in 11 fractions to the chest wall and nodes and 15 fractions inclusive of a boost. We demonstrated low toxicity and high local control with this schedule. On the basis of our data, we have designed a cooperative group phase III prospective, randomized trial of conventional versus hypofractionated PMRT that will activate soon.

In the Modern Treatment Era, Is Breast Conservation Equivalent to Mastectomy in Women Younger Than 40 Years of Age? A Multi-Institution Study

PURPOSE Mastectomy is often recommended for women ≤40 years of age with breast cancer, as young women were under-represented in the landmark trials comparing breast conservation therapy (BCT) to mastectomy. We hypothesized that, in the modern treatment era, BCT and mastectomy result in equivalent local control rates in young women. METHODS AND MATERIALS Breast cancer cases arising between 1975 and 2013 in women ≤40 years old were collected from the tumor registries of 2 large healthcare systems in Utah. Kaplan-Meier estimates and Cox proportional hazards models were used to analyze freedom from locoregional recurrence (FFLR), overall survival (OS), and relapse-free survival (RFS). RESULTS This analysis identified 853 BCT candidates. A comparison of BCT to mastectomy after 2000 showed FFLR, RFS, and OS were all similar. Rate for FFLR at 10 years was 94.9% versus 92.1% for BCT and mastectomy, respectively (P=.57). For women whose cancer was diagnosed after 2000, who received BCT, FFLR and RFS rates were improved compared to those whose cancer was diagnosed prior to 2000 (P<.05), whereas OS (P=.46) rates were similar. Among those who underwent mastectomy, FFLR, OS, and RFS were significantly improved (P<.05) with diagnosis after 2000. CONCLUSIONS FFLR rates for young women, ≤40 years of age, have significantly improved for BCT and mastectomy over time. If patients were treated after 2000, BCT appears to be safe and equivalent to mastectomy at 10 years in terms of FFLR, OS, and RFS.

Primary Pulmonary Carcinoid Tumor: A Long-term Single Institution Experience.

Objectives: Primary carcinoid tumors of the lung are rare tumors which comprise approximately 0.5% to 5% of all lung malignancies in adults and roughly 20% to 30% of all carcinoid tumors. The purpose of this retrospective, descriptive study was to describe the incidence, characteristics, and outcomes of patients treated for primary pulmonary carcinoid tumor at a single institution. Materials and Methods: All patients with a diagnosis of primary pulmonary carcinoid tumor treated from 1989 to 2009 were reviewed. Data collected included demographics, pathology, tobacco use, clinical presentation, tumor location, tumor spread, treatment, and survival. Results: There were 59 cases of pulmonary carcinoid tumors: 47 typical (80%) and 12 atypical (20%). All but 4 patients underwent surgery, including 54 (92%) lung-sparing resections and 1 pneumonectomy. Five of 55 patients received concurrent adjuvant chemoradiation therapy; 4 patients with atypical and 1 with typical histology. Three additional patients with atypical carcinoid were treated only with adjuvant radiotherapy, palliative radiotherapy, or palliative chemotherapy, respectively. The Kaplan-Meier 5- and 10-year overall survivals were both 80% within the entire population. In the 88% of patients who achieved complete remission, disease-free survival was 98%. A review of a large series from the literature is also presented. Conclusions: Surgical resection was primary and adequate therapy for most typical carcinoid tumors with high overall survival and disease-free survival. Adjuvant chemotherapy or radiotherapy might be considered for patients with atypical carcinoid tumors who present with adverse pathologic findings.

Postoperative Radiotherapy in Locally Invasive Malignancies of the Thymus: Patterns of Care and Survival.

Introduction: Our purpose was to determine the overall survival (OS) benefit of postoperative radiotherapy (PORT) in patients with advanced thymic malignancies and the associated predictors of PORT receipt. Methods: We queried the National Cancer Data Base for all stage II to III thymic malignancies. Trends in PORT use over time were analyzed using least squares linear regression. Factors predictive of PORT and OS were identified by using multivariate logistic and Cox regression analysis, respectively. Results: We identified 1156 patients between 2004 and 2012 who met the inclusion criteria. The utilization of PORT was found to increase over the study period by 41% (37% to 52% [p = 0.01]). On multivariate analysis, the factors found to be the most predictive of receipt of PORT were positive surgical margins (adjusted OR = 1.98 [p < 0.01]) and treatment at a nonacademic facility (adjusted OR = 1.44 [p = 0.01]). The 5‐year OS was superior for patients receiving PORT compared with for those who did not (83% versus 79%, p = 0.03). Receipt of PORT was associated with a trend toward decreased risk for death on multivariate analysis (hazard ratio = 0.75 [p = 0.09]). In addition, a positive macroscopic margin was the most important predictor of survival (hazard ratio = 3.48 [p < 0.01]). On subgroup analysis, patients with thymic carcinoma and WHO histologic types A and AB were associated with an OS benefit with PORT, whereas types B1, B2, and B3 were not. Patients with positive margins were not associated with an OS benefit with PORT. Conclusions: The use of PORT in patients with advanced thymic malignancies is increasing over time and is determined by both clinical and demographic factors. Receipt of PORT was associated with improved OS. The OS benefit with PORT was dependent on the WHO histologic type.

Initial experience and clinical comparison of two image guidance methods for SBRT treatment: 4DCT versus respiratory-triggered imaging

For Stereotactic Body Radiation Therapy (SBRT) treatment of lung and liver, we quantified the differences between two image guidance methods: 4DCT and ExacTrac respiratory‐triggered imaging. Five different patients with five liver lesions and one lung lesion for a total of 19 SBRT delivered fractions were studied. For the 4DCT method, a manual registration process was used between the 4DCT image sets from initial simulation and treatment day to determine the required daily image‐guided corrections. We also used the ExacTrac respiratory‐triggered imaging capability to verify the target positioning, and calculated the differences in image guidance shifts between these two methods. The mean (standard deviation) of the observed differences in image‐guided shifts between 4DCT and ExacTrac respiratory‐triggered image guidance was left/right (L/R)=0.4(2.0)mm, anterior/posterior (A/P)=1.4(1.7) mm, superior/inferior (S/I)=2.2(2.0) mm, with no difference larger than 5.0 mm in any given direction for any individual case. The largest error occurred in the S/I direction, with a mean of 2.2 mm for the six lesions. This seems reasonable, because respiratory motion and the resulting imaging uncertainties are most pronounced in this S/I direction. Image guidance shifts derived from ExacTrac triggered imaging at two extreme breathing phases (i.e., full exhale vs. full inhale), agreed well (less than 2.0 mm) with each other. In summary, two very promising image guidance methods of 4DCT and ExacTrac respiratory‐triggered imaging were presented and the image guidance shifts were comparable for the patients evaluated in this study. PACS number: 87.55.ne

SU-E-T-527: Comparison of CT-On-Rails and a 3D Surface Imaging System for Image Guided Partial Breast Radiation Therapy

Purpose: We evaluate the feasibility of using a 3D surfaceimaging system (AlignRT) for image guidance for partial breast radiation treatments through comparison with the CT‐on‐rails image guidance currently clinically employed at our institution. Methods/Materials: Four patients receiving external beam partial breast radiation therapy with multiple image guidance datasets were analyzed retrospectively. A total of 51 fractions were studied, each with a CT‐on‐rails dataset and an AlignRT body surface contour snapshot. For each fraction, the patient was aligned to treatment isocenter with room lasers and scanned with both CT‐on‐rails and AlignRT. Image guidance shifts were calculated for both modalities by comparison to the simulation CT and the differences between the two sets of shifts were analyzed. Results: Two patients showed significant change in surgical cavity volume and shape between simulation and fraction 1. For these patients it was found that the discrepancy between CT‐on‐rails based shifts and AlignRT shifts was significant (up to 11.1 mm) indicating that use of AlignRT for image guidance of these cases would be inadvisable. The remaining two patients did not show noticeable change in surgical cavity and the discrepancy between the two sets of shifts for these patients was minimal, thus indicating that AlignRT is potentially valuable for these cases. Conclusion: AlignRT appears to be a reasonable and potentially valuable image guidance approach for partial breast radiation therapy for patients with small changes in surgical cavity between CT simulation and treatment. However, there may be potential for alignment inaccuracies when using AlignRT for patients with dramatic changes in surgical cavity.

Adjuvant therapy for resected pN2 non-small cell lung cancer: sequence is not all that matters

We appreciate the comments from Zhao and Ng (1) regarding our recent National Cancer Database (NCDB) study comparing survival outcomes after postoperative adjuvant concurrent chemoradiotherapy (CRT) versus sequential chemotherapy followed by postoperative radiotherapy (C→PORT) for locally advanced or incompletely resected non-small cell lung cancer (NSCLC).