Sharon S. Lum

Partial Breast Radiation Therapy With Proton Beam: 5-Year Results With Cosmetic Outcomes

PURPOSE We updated our previous report of a phase 2 trial using proton beam radiation therapy to deliver partial breast irradiation (PBI) in patients with early stage breast cancer. METHODS AND MATERIALS Eligible subjects had invasive nonlobular carcinoma with a maximal dimension of 3 cm. Patients underwent partial mastectomy with negative margins; axillary lymph nodes were negative on sampling. Subjects received postoperative proton beam radiation therapy to the surgical bed. The dose delivered was 40 Gy in 10 fractions, once daily over 2 weeks. Multiple fields were treated daily, and skin-sparing techniques were used. Following treatment, patients were evaluated with clinical assessments and annual mammograms to monitor toxicity, tumor recurrence, and cosmesis. RESULTS One hundred subjects were enrolled and treated. All patients completed the assigned treatment and were available for post-treatment analysis. The median follow-up was 60 months. Patients had a mean age of 63 years; 90% had ductal histology; the average tumor size was 1.3 cm. Actuarial data at 5 years included ipsilateral breast tumor recurrence-free survival of 97% (95% confidence interval: 100%-93%); disease-free survival of 94%; and overall survival of 95%. There were no cases of grade 3 or higher acute skin reactions, and late skin reactions included 7 cases of grade 1 telangiectasia. Patient- and physician-reported cosmesis was good to excellent in 90% of responses, was not changed from baseline measurements, and was well maintained throughout the entire 5-year follow-up period. CONCLUSIONS Proton beam radiation therapy for PBI produced excellent ipsilateral breast recurrence-free survival with minimal toxicity. The treatment proved to be adaptable to all breast sizes and lumpectomy cavity configurations. Cosmetic results appear to be excellent and unchanged from baseline out to 5 years following treatment. Cosmetic results may be improved over those reported with photon-based techniques due to reduced breast tissue exposure with proton beam, skin-sparing techniques, and the dose fractionation schedule used in this trial.

Partial breast irradiation delivered with proton beam: results of a phase II trial.

BACKGROUND AND PURPOSE A phase II trial sought to determine the safety and efficacy of proton beam irradiation to deliver partial breast radiotherapy after lumpectomy for early-stage breast cancer. PATIENTS AND METHODS Eligible patients included women with invasive nonlobular carcinoma ≤ 3 cm. Surgical therapy included lumpectomy with negative margins and negative axillary lymph nodes on sampling. Postoperative proton radiotherapy to the surgical bed with an additional 1-cm margin was delivered by 40 Gy in 10 fractions over a 2-week course. Patients received systemic therapy as recommended after proton treatment. Patients had clinical evaluations every 6 months and annual mammograms. RESULTS Fifty patients were enrolled; median follow-up was 48 months. All patients completed the prescribed treatment. Acute toxicities were limited to mild radiation dermatitis. Late skin toxicities included 3 grade 1 telangiectasias. There were no posttreatment infections or ulcerations and no cases of fat necrosis, rib fractures, radiation pneumonitis, or cardiac events. Actuarial 5-year overall survival and disease-free survival rates were 96% and 92%, respectively. No local failures occurred. Ipsilateral breast cancer developed in 1 patient 5.5 years after treatment. Dose-volume histogram analysis showed near-complete elimination of dose to the contralateral breast, lung, and heart. CONCLUSION Proton partial breast radiotherapy appeared to be a feasible method of treatment and provided excellent disease control within the ipsilateral breast. Treatment-related toxicity was minimal and no technical limitations prevented treatment delivery. The incidence of posttreatment complications may be less than that reported when using more invasive techniques; comparative trials should be considered.

Quantitating the impact of stage migration on staging accuracy in colorectal cancer.

BACKGROUND The number of nodes retrieved is a powerful predictor of survival in node-negative colorectal cancer (CRC). Whether this is because of improved staging or improved surgery, or both, is unclear. We sought to quantitate the impact of stage migration in node-negative colorectal cancer. STUDY DESIGN Between January 1994 and December 2003, 7,192 patients in Region 5 of the California Cancer Registry, diagnosed with node-negative or node-positive colorectal cancer, were reviewed. The number of nodes examined, node-positive rate, and disease-specific survival (DSS) were analyzed. RESULTS The mean number of nodes examined was 9.3 (range 0 to 89 nodes). The 5-year DSS was 84.5% for N0, 65.2% for N1, and 46.8% for N2 disease. The 5-year DSS difference for those who had more than 12 nodes retrieved was 87.3% (95% CI, 85.2% to 89.3%) and for those with 0 to 3 nodes retrieved, 83.7% (95% CI, 80.6% to 86.82%; p = 0.0009). As the number of retrieved nodes increased, the risk of understaging patients decreased. For 0 to 3 nodes, 78.3% of patients were N0; for 4 to 7 nodes, 67.6%; 8 to 9 nodes, 62.1%; 10 to 12 nodes, 59.5%; and only 57.2% for more than 12 nodes examined. Using more than 12 nodes as the definition of an adequate lymphadenectomy and staging, for apparently N0 patients with 0 to 3 nodes retrieved, DSS survival would be affected by approximately 5%. CONCLUSIONS Differences in outcomes between CRC patients with limited numbers of nodes harvested and those with more than 12 nodes harvested are substantial. Stage migration alone can explain the entire DSS difference between patients with more than 12 nodes retrieved and those with smaller numbers of nodes retrieved.

Disparities in BRCA testing: when insurance coverage is not a barrier

BACKGROUND Strategies to reduce the risk of developing breast and ovarian cancer in carriers of deleterious BRCA 1 and 2 mutations are readily available. However, many people who are at high risk of having these genetic mutations are reluctant to obtain the test. We sought to identify factors associated with choice of testing. METHODS We performed a retrospective cohort review of high-risk patients referred to a multidisciplinary breast health center for BRCA testing between January 2001 and March 2008. Demographic variables were compared by using logistic regression between those who completed genetic testing and those who did not. RESULTS A total of 213 patients were referred for BRCA testing. The mean age was 49.2 years (range, 16-84 y). Five patients were male. The majority of individuals (63.4%) were white, 15% were Hispanic, 6.6% were black, and 4.7% were Asian. Insurance coverage for testing was available in 91.1% of patients, of whom 49.2% had private insurance, 26.7% had managed care insurance, and 24.1% had government-sponsored insurance. A total of 111 patients (52.1%) underwent testing. On multivariate analysis, patients were significantly more likely to complete testing if they had a personal history of breast cancer (73.0% of tested patients) (P = .005) and had at least some college education (61.3%) (P = .03). There were no statistically significant differences in tested versus untested groups by age, race, language, family history, parity, marital status, religion, socioeconomic status, or insurance status. Of patients whose insurance plans offered coverage for genetic testing, 51.4% underwent testing and 48.6% did not (P = not significant [NS]). Of those who had no insurance coverage for testing, 41.2% underwent testing and 58.9% did not (P = NS). CONCLUSIONS Our data show that half of those patients at risk for carrying a BRCA mutation do not undergo testing. Insurance coverage for genetic testing does not influence the decision to test. Developing counseling instruments that explain the benefits of testing to unaffected high-risk individuals or targeted to those with a high school level education may be a strategy to improve testing rates.

The Role of the Cancer Center When Using Lymph Node Count as a Quality Measure for Gastric Cancer Surgery

IMPORTANCE Cancer center recognition, offered as accreditation by the American College of Surgeons Commission on Cancer or the National Cancer Institute, and quality measure reporting purport to improve the quality of cancer care. For surgically resectable gastric cancer, removal of 15 or more lymph nodes has been associated with improved outcomes and has been endorsed as a gastric cancer quality measure. OBJECTIVES To determine whether cancer center classification is associated with compliance with the lymph node-count quality measure and the effect of compliance with the measure on overall survival. DESIGN, SETTING, AND PARTICIPANTS A retrospective review of prospectively collected population-based data from the Surveillance, Epidemiology, and End Results Cancer Registry of Greater California and California Cancer Registry was conducted. Participants included patients who underwent surgery for stage I to III gastric adenocarcinoma between January 1, 2004, and December 31, 2010. MAIN OUTCOMES AND MEASURES Compliance with removal of 15 or more lymph nodes and overall survival. RESULTS Of 3321 gastric cancer cases, 42.3% had a minimum of 15 lymph nodes removed. Hospitals with cancer program recognition treated 69.9% of the cases. In hospitals without cancer program approval, 34.8% of the patients had 15 or more lymph nodes removed compared with 45.5% in the facilities with cancer program approval. Logistic regression analysis demonstrated that patients undergoing gastrectomy had significantly higher odds of having 15 or more lymph nodes removed if they were younger (trend P < .001), Asian/other race/ethnicity (adjusted odds ratio [AOR], 1.24; 95% CI, 1.03-1.50), or non-Hispanic black (AOR, 1.37; 95% CI, 1.03-1.82) compared with non-Hispanic white, received diagnosis at a progressively higher stage (trend P < .001), or received diagnosis in a more recent year (trend P < .001). Removal of 15 or more lymph nodes was associated with cancer program recognition (vs no recognition) (odds ratio, 1.48; 95% CI, 1.25-1.74). Cox proportional hazards regression showed that improved survival was predicted by removal of 15 or more lymph nodes (hazard ratio [HR], 0.70; 95% CI, 0.63-0.78) but not by cancer program recognition (HR, 1.03; 95% CI, 0.92-1.15). CONCLUSIONS AND RELEVANCE Although adequate lymph node retrieval is more likely in hospitals with a recognized cancer program, survival outcome is associated with the lymph node count rather than with cancer program classification. Less than half of the cases reviewed in this study met the minimum lymph node-count guideline, indicating the need for process improvement for all hospitals.

Effects of Prior Abdominal Surgery, Obesity, and Lumbar Spine Level on Anterior Retroperitoneal Exposure of the Lumbar Spine

OBJECTIVE To evaluate the effects of prior abdominal surgery and obesity and the level of spine exposure on the technical aspects and complications of anterior retroperitoneal exposure of the lumbar spine (ARES). DESIGN Retrospective review of prospective database. SETTING Academic vascular surgery practice. PATIENTS Patients undergoing ARES from 2001 to 2011. MAIN OUTCOME MEASURES Influence of prior abdominal surgery, obesity, and level of exposure on time to spine exposure and incidence of vascular and perioperative complications. RESULTS Four hundred seventy-six patients underwent ARES. Mean (SD) age was 47.7 (12.6) years; 46.6% had undergone prior abdominal surgery. Mean (SD) body mass index (BMI) was 28.3 (5.5); 61.6% of procedures included the L4-5 disk. Mean (SD) time to exposure was 70.0 (25.5) minutes. Vascular injury occurred in 23.3% (3.8% major). Perioperative complications occurred in 16.4% of cases. Prior abdominal surgery had no effect on time to exposure, vascular injury, and perioperative complications. A BMI of 30 or more had no effect on time to exposure compared with a lower BMI. A BMI of 30 or more led to higher rates of vascular injury (30.8% vs 19.7%; P = .007) and overall complications (21.4% vs 14.0%; P = .04). Exposures involving L4-5 led to increased time to exposure (77.0 vs 56.2 minutes; P < .001) and higher rates of vascular injury (29.7% vs 13.1%; P < .001) but had no effect on overall complications compared with exposures for other levels. CONCLUSION Prior abdominal surgery should not be considered a contraindication to ARES. Caution is warranted in obese patients and exposures involving L4-5.

Predictors of Delayed-Stage Colorectal Cancer: Are We Neglecting Critical Demographic Information?

PURPOSE We sought to distinguish roles of demographic variables and bowel segments as predictors of delayed versus early stage colorectal cancer in California. METHODS Demographic and anatomic variables for 66,806 colorectal cancers were extracted from the California Cancer Registry for 2004-2008 and analyzed using logistic regression as delayed versus early stage. RESULTS Odds ratios (OR) for binary stage categories comparing age <40 (OR=2.58; 95% CI=2.26-2.94), 40-49 (1.71; 95%=1.60-1.83) and 75+ (1.05; 1.02-1.09) relative to 50-74 years were computed. Compared with non-Hispanic whites, ORs for stage categories were: 1.05; 0.99-1.13 (non-Hispanic blacks), 1.08; 1.02-1.13 (Hispanics), and 1.05; 1.00-1.10 (Asian/others). Females had higher odds of delayed diagnosis (1.09; 1.06-1.13) than males. Descending ORs were measured for successively lower to highest socioeconomic status (SES) quintiles (OR 4:5=1.08; 1.03-1.14, OR 3:5=1.13; 1.08-1.19, OR 2:5=1.18; 1.12- 1.24, and OR 1:5=1.21; 1.14-1.28). CONCLUSIONS Younger and older than age 50-74; females; Hispanic ethnicity; bowel segment contrasts (right/left, proximal/distal, cecum plus appendix/distal), and lower SES were independent predictors of delayed diagnosis. Low SES was the most robust predictor of delayed diagnosis, independent of other covariates. Approximately 77% of delayed diagnoses were in non-Hispanic whites and Asian/others. These findings illustrate the value of a community SES index for targeting egalitarian colorectal cancer screening.

Lymph Node Counts as an Indicator of Quality at the Hospital Level in Colorectal Surgery

BACKGROUND Substantial evidence suggests that the number of lymph nodes examined in colorectal cancer (CRC) is a powerful predictor of outcomes. However, the lymph node count as a benchmark of quality in CRC is controversial. We sought to examine the impact of lymph node counts on disease-specific survival (DSS) of CRC patients at the hospital level. STUDY DESIGN This study used data obtained between 1994 and 2003 from Region 5 of the California Cancer Registry. Hospitals in Region 5 of the California Cancer Registry were stratified according to the median number of nodes examined and grouped according to the median number of nodes examined, <7, 7 to 9, and ≥10. These hospital groups were then evaluated for the frequency of meeting the 12-node threshold, frequency of positive lymph nodes, and DSS at the hospital level. RESULTS Median number of nodes examined in group A was 4 (mean 5.6, SD 5.9), in group B was 8 (mean 9.7, SD 8.5), and in group C was 10 (mean 11.3, SD 9.2). In group A, 13.7%, in group B 32.8%, and in group C, 42.8% met the 12-node threshold. The frequency of N1 and N2 disease for group A was 20.7% and 9.1%, 19. 7% and 11.1% for group B, and 20.1% and 11.3% for group C (p = 0.12). Five-year DSS was 72.7% for group A, 73.7% for group B, and 76.7% for group C (p = 0.002). DSS survival of N0 patients for group A was 78.6%, 81.5% for group B, and 85.1% for group C (p < 0.0001). There was no statistically significant difference in DSS for N1 (p = 0.18) or N2 (p = 0.90) between the 3 groups. CONCLUSIONS Lymph node counts can have value as a benchmark of surgical/pathologic quality in node-negative CRC. These results question the value of lymph node counts as a benchmark of surgical/pathologic quality for node-positive CRC.

Size of Extranodal Extension on Sentinel Lymph Node Dissection in the American College of Surgeons Oncology Group Z0011 Trial Era

IMPORTANCE Based on the American College of Surgeons Oncology Group Z0011 trial exclusion criteria, patients with T1N0 or T2N0 breast cancer with 1 or 2 positive sentinel lymph nodes (SLNs) are recommended to undergo axillary lymph node dissection if extranodal extension (ENE) is present. OBJECTIVE To determine the effect of ENE size on residual axillary nodal burden, disease recurrence, and survival in patients meeting Z0011 criteria. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study between January 1, 2000, and December 31, 2012, at a single tertiary cancer center. Patients had T1 or T2 breast cancer with 1 or 2 positive SLNs. The ENE was classified as 2 mm or smaller or as larger than 2 mm. MAIN OUTCOMES AND MEASURES Nodal burden, disease recurrence, and overall survival. RESULTS Of 208 patients, 149 (71.6%) had no ENE, 21 (10.1%) had ENE 2 mm or smaller, and 38 (18.3%) had ENE larger than 2 mm on SLN dissection. The median follow-up time was 60 months (range, 1-158 months). The mean (SD) total number of positive lymph nodes differed significantly for the group with no ENE (1.72 [1.39]) vs the group with ENE 2 mm or smaller (3.22 [2.09]; P < .001) and vs the group with ENE larger than 2 mm (4.26 [5.01]; P < .001). Similar patterns were observed for mean (SD) nonsentinel lymph node metastases: 0.48 (1.30) for no ENE vs 1.91 (2.07) with ENE 2 mm or smaller (P = .02) and vs 2.95 (4.95) with ENE larger than 2 mm (P < .001). For the group without ENE vs the group with ENE 2 mm or smaller, there were no significant differences in recurrence (distant recurrence, 4 patients [2.7%] vs 1 patient [4.8%], respectively; P = .62) or in mortality (18 patients [12.1%] vs 4 patients [19.1%], respectively; P = .48). For the group without ENE vs the group with ENE larger than 2 mm, there were no significant differences in recurrence (distant recurrence, 4 patients [2.7%] vs 4 patients [10.5%], respectively; P = .19) or in mortality (18 patients [12.1%] vs 9 patients [23.7%], respectively; P = .07). CONCLUSIONS AND RELEVANCE Presence of ENE on SLN dissection is associated with N2 disease. Despite increased nodal burden, patients with 1 or 2 positive SLNs and ENE 2 mm or smaller demonstrated recurrence and survival rates similar to those of patients without ENE. Reporting of ENE size should be standardized and required.

The prevalence of overweight and obesity in a breast clinic population: Consideration for weight loss as a therapeutic intervention

BACKGROUND Obesity is an important risk factor for breast cancer and weight loss may be associated with a decreased risk for breast cancer and its recurrence. We evaluated the prevalence of overweight, obesity, and obesity-related co-morbidities in a breast health clinic population to determine the potential need for weight loss intervention. METHODS A retrospective review was conducted of sequential patients seen at a breast health clinic from July 1 to December 31, 2011. Body mass index (BMI), reason for visit (breast cancer diagnosis, high risk for breast cancer, or benign condition), and presence of obesity-related co-morbidities were recorded. RESULTS The 302 patients who met inclusion criteria had a median age of 52 years (10-91) and median BMI of 26 kg/m(2) (15.4-56.5). Overall, 36.8% of patients had a BMI between 18.5-24.9 kg/m(2); 32.1%, 25-29.9 kg/m(2); 14.2%, 30-34.9 kg/m(2); 8.3%, 35-39.9 kg/m(2); and 4.3%, ≥ 40 kg/m(2). Overweight or obesity (BMI ≥ 25 kg/m(2)) occurred in 64.2% of breast cancer, 65.0% of high-risk, and 57.1% of benign patients (P value not significant). Criteria for bariatric surgery (BMI 35-39.9 kg/m(2) with ≥ 1 obesity-related co-morbidity or BMI ≥ 40 kg/m(2)) were met in 8.2% of breast cancer, 16.7% of high-risk, and 11.5% of benign patients (P value not significant). CONCLUSIONS Regardless of diagnosis, a significant proportion of patients visiting the breast health clinic meet criteria for weight loss intervention, including bariatric surgery. Weight management represents an underutilized therapeutic modality that could potentially decrease the risk of breast cancer and its recurrence, and improve overall prognosis.