Hosam A. Kader

The prognostic significance of the percentage of positive/dissected axillary lymph nodes in breast cancer recurrence and survival in patients with one to three positive axillary lymph nodes

Adjuvant therapy for women with T1–T2 breast carcinoma and 1–3 positive lymph nodes is controversial due to discrepancies in reported baseline locoregional recurrence (LRR) risks. This inconsistency has been attributed to variations in lymph node staging techniques, which have yielded different numbers of dissected lymph nodes. The current study evaluated the prognostic impact of the percentage of positive/dissected lymph nodes on recurrence and survival in women with one to three positive lymph nodes.

Patients With T1 to T2 Breast Cancer With One to Three Positive Nodes Have Higher Local and Regional Recurrence Risks Compared With Node-Negative Patients After Breast-Conserving Surgery and Whole-Breast Radiotherapy

PURPOSE To evaluate locoregional recurrence according to nodal status in women with T1 to T2 breast cancer and zero to three positive nodes (0-3N+) treated with breast-conserving surgery (BCS). METHODS AND MATERIALS The study subjects comprised 5,688 women referred to the British Columbia Cancer Agency between 1989 and 1999 with pT1 to T2, 0-3N+, M0 breast cancer, who underwent breast-conserving surgery with clear margins and radiotherapy (RT) of the whole breast. The 10-year Kaplan-Meier local, regional, and locoregional recurrence (LR, RR, and LRR, respectively) were compared between the N0 (n = 4,433) and 1-3N+ (n = 1,255) cohorts. The LRR was also examined in patients with one to three positive nodes (1-3N+) treated with and without nodal RT. Multivariate analysis was performed using Cox regression modeling. RESULTS Median follow-up was 8.6 years. Systemic therapy was used in 97% of 1-3N+ and 41% of N0 patients. Nodal RT was used in 35% of 1-3N+ patients. The 10-year recurrence rates in N0 and 1-3N+ cohorts were as follows: LR 5.1% vs. 5.8% (p = 0.04); RR 2.3% vs. 6.1% (p < 0.001), and LRR 6.7% vs. 10.1% (p < 0.001). Among 817 1-3N+ patients treated without nodal RT, 10-year LRR were 13.8% with age <50 years, 20.3% with Grade III, and 23.4% with estrogen receptor (ER)-negative disease. On multivariate analysis, 1-3N+ status was associated with significantly higher LRR (hazard ratio [HR], 1.85; 95% confidence interval, 1.34-2.55, p < 0.001), whereas nodal RT significantly reduced LRR (HR, 0.59; 95% confidence interval, 0.38-0.92, p = 0.02). CONCLUSION Patients with 1-3N+ and young age, Grade III, or ER-negative disease have high LRR risks approximating 15% to 20% despite BCS, whole-breast RT and systemic therapy. These patients may benefit with more comprehensive RT volume encompassing the regional nodes.

The effects of age and comorbidity on treatment and outcomes in women with endometrial cancer.

Background:Although the incidence of endometrial cancer increases with age, the effect of patient age on treatment selection and outcomes is unclear. In addition, although aging is associated with increased prevalence of comorbid conditions, the extent to which comorbidities influence endometrial cancer management is not well documented. Methods:This population-based analysis evaluates the effect of age and comorbidity on endometrial cancer treatment and outcome in a cohort of 401 patients referred to the Vancouver Island Centre, British Columbia Cancer Agency from 1989 to 1996. Treatment and 5-year actuarial overall survival (OS) and disease-free survival (DFS) were compared by age at diagnosis (<65, 65–74, and ≥75 years) and comorbidity index (Charlson score 0–1 and ≥2). Results:Median follow-up time was 7.8 years. In this cohort, 148 (37%), 152 (38%), and 101 (25%) were aged <65, 65–74, and ≥75 years, respectively. Charlson comorbidity scores ≥2 were found in 18% of patients. Distributions of disease stage, tumor characteristics, and surgical therapy were similar across age and comorbidity subgroups. Standard surgery in this cohort comprised hysterectomy without routine lymphadenectomy. In stage Ic disease, the use of postoperative RT declined with advanced age (96%, 97%, and 74% in patients aged <65, 65–74, and ≥75 years, respectively, P = 0.05) and with increased comorbidities (91% and 79% in patients with Charlson score 0–1 and ≥2, respectively, P = 0.07). Among stage Ic patients aged ≥75 years, pelvic/vaginal relapse occurred in 2 of 6 patients treated with hysterectomy alone compared with 0 of 20 patients treated with postoperative radiotherapy (P = 0.006). On multivariable Cox modeling, age at diagnosis, performance status, stage, grade, lymphovascular invasion, surgery, and radiotherapy use, but not Charlson comorbidity score, were significant predictors for overall survival. Conclusions:Although surgical therapy for endometrial cancer was not influenced by age or comorbidities, reduced use of postoperative radiotherapy in stage Ic disease was observed among women with advanced age and high comorbidity index. The associated pelvic/vaginal relapse rates were higher in elderly patients not treated with radiotherapy. Chronologic age alone should not preclude patients from consideration of optimal local therapy.

WHEN IS CT-BASED POSTOPERATIVE SEROMA MOST USEFUL TO PLAN PARTIAL BREAST RADIOTHERAPY? EVALUATION OF CLINICAL FACTORS AFFECTING SEROMA VOLUME AND CLARITY

PURPOSE To evaluate the effect of the time from surgery and other clinical factors on seroma volume and clarity and establish the optimal time to use the computed tomography (CT)-based seroma to plan partial breast irradiation (PBI). METHODS AND MATERIALS A total of 205 women with early-stage breast cancer underwent planning CT after breast-conserving surgery. One radiation oncologist contoured the seroma volume and scored the seroma clarity, using a standardized Seroma Clarity Score scale, from 0 (not detectable) to 5 (clearest). Univariate and multivariate analyses were performed to evaluate the associations between the seroma characteristics and the interval from surgery and other clinical factors. RESULTS The mean interval from surgery to CT was 84 days (standard deviation 59). During postoperative Weeks 3-8, the mean seroma volume decreased from 47 to 30 cm(3), stabilized during Weeks 9-14 (mean 21) and was involuted beyond 14 weeks (mean 9 cm(3)). The mean seroma clarity score was 3.4 at Weeks 3-8, 2.5 at Weeks 9-14, and 1.6 after 14 weeks. The seroma clarity was greater in patients aged >or=70 years. The seroma volume and clarity correlated significantly with the volume of excised breast tissue but not with the maximal tumor diameter, surgical re-excision, or chemotherapy use. CONCLUSION The optimal time to obtain the planning CT scan for PBI is within 8 weeks after surgery. During Weeks 9-14, the seroma might remain adequately defined in some patients; however, after 14 weeks, alternate strategies are needed to identify the PBI target. The lack of correlation between the seroma volume and tumor size suggests that the CT-based seroma should not be the sole guide for PBI target volume definition.

A positive margin is not always an indication for radiotherapy after mastectomy in early breast cancer

OBJECTIVE Postoperative radiotherapy is frequently employed among breast cancer patients with positive surgical margins after mastectomy but there is little evidence to support this practice. This study examined relapse and survival among women with node-negative breast cancer and positive surgical margins after mastectomy. METHODS Among 2570 women diagnosed between 1989 and 1998 and referred to the British Columbia Cancer Agency with pathologic (p)T1-2, pN0 invasive breast cancer treated with mastectomy, 94 had positive surgical margins and formed the study cohort. Women with more established indications for postmastectomy radiotherapy (PMRT) including T3-4 tumors or node-positive disease were excluded. Demographic, tumor, and treatment factors; relapse patterns; and Kaplan-Meier 8-year locoregional relapse-free, breast cancer-specific, and overall survival rates were compared between women who were treated with (n = 41) and without (n = 53) PMRT. RESULTS Median follow-up time was 7.7 years. The distributions of age, histologic grade, lymphovascular invasion (LVI), estrogen receptor status, and number of axillary nodes removed were similar between the two treatment groups. Six local chest wall recurrences (6.4%), 4 regional recurrences (4.3%), and 11 distant recurrences (11.7%) were identified. Local relapse rates were 2.4% vs. 9.4% (p = 0.23), and regional relapse rates were 2.4% vs. 5.7% (p = 0.63), with and without PMRT, respectively. Trends for higher cumulative locoregional relapse (LRR) rates without PMRT were identified in the presence of age <==50 years (LRR 20% without vs. 0% with PMRT), T2 tumor size (19.2% vs. 6.9%), grade III disease (23.1% vs. 6.7%), and LVI (16.7% vs. 9.1%). Statistical significance was not demonstrated in these differences (p > 0.10), possibly because of the small number of events. In patients with age >50 years, T1 tumors, grade I/II disease, and absence of LVI, no locoregional relapse occurred even with positive margins. PMRT did not improve distant relapse, 8-year breast cancer-specific and overall survival rates. CONCLUSION This study suggests that not all patients with node-negative breast cancer with positive margins after mastectomy require radiotherapy. Locoregional failure rates approximating 20% were observed in women with positive margins plus at least one of the following factors: age <==50 years, T2 tumor size, grade III histology, or LVI. The absolute and relative improvements in locoregional control with radiotherapy in these situations support the judicious, but not routine, use of PMRT for positive margins after mastectomy in patients with node-negative breast cancer.

3D Ultrasound Can Contribute to Planning CT to Define the Target for Partial Breast Radiotherapy

PURPOSE The role of three-dimensional breast ultrasound (3D US) in planning partial breast radiotherapy (PBRT) is unknown. This study evaluated the accuracy of coregistration of 3D US to planning computerized tomography (CT) images, the seroma contouring consistency of radiation oncologists using the two imaging modalities and the clinical situations in which US was associated with improved contouring consistency compared to CT. MATERIALS AND METHODS Twenty consecutive women with early-stage breast cancer were enrolled prospectively after breast-conserving surgery. Subjects underwent 3D US at CT simulation for adjuvant RT. Three radiation oncologists independently contoured the seroma on separate CT and 3D US image sets. Seroma clarity, seroma volumes, and interobserver contouring consistency were compared between the imaging modalities. Associations between clinical characteristics and seroma clarity were examined using Pearson correlation statistics. RESULTS 3D US and CT coregistration was accurate to within 2 mm or less in 19/20 (95%) cases. CT seroma clarity was reduced with dense breast parenchyma (p = 0.035), small seroma volume (p < 0.001), and small volume of excised breast tissue (p = 0.01). US seroma clarity was not affected by these factors (p = NS). US was associated with improved interobserver consistency compared with CT in 8/20 (40%) cases. Of these 8 cases, 7 had low CT seroma clarity scores and 4 had heterogeneously to extremely dense breast parenchyma. CONCLUSION 3D US can be a useful adjunct to CT in planning PBRT. Radiation oncologists were able to use US images to contour the seroma target, with improved interobserver consistency compared with CT in cases with dense breast parenchyma and poor CT seroma clarity.

Outcomes in patients with primary breast cancer and a subsequent diagnosis of endometrial cancer : Comparison of cohorts treated with and without tamoxifen

The study compared tumor characteristics and survival in women with breast cancer who subsequently developed endometrial cancer with or without a history of tamoxifen use.

Endoscopic response predicts for survival and organ preservation after primary chemoradiotherapy for esophageal cancer

PURPOSE To determine the role of endoscopic surveillance in predicting organ preservation and survival after primary chemoradiotherapy (CRT) for esophageal cancer. MATERIALS AND METHODS Fifty-six consecutive patients with nonmetastatic esophageal cancer were treated with primary CRT between May 1993 and April 1999 with curative intent and subsequent surveillance with endoscopy and CT scans. Patients with residual disease on endoscopy and/or CT 6 weeks after CRT were considered for immediate esophagectomy. The remaining patients continued endoscopic surveillance and were considered for esophagectomy only when local relapse was detected. Five-year survival was estimated using the Kaplan-Meier method, and univariate and multivariate analyses were performed to identify significant factors associated with disease-specific survival. RESULTS With a median follow-up of 62 months, the 5-year overall and disease-specific survival was 30% (95% confidence interval [CI]: 17%-43%) and 37% (95% CI: 22%-50%), respectively. Fourteen of 24 (58%) patients who survived more than 2 years did not require an esophagectomy. On univariate analysis, favorable prognostic factors for disease-specific survival were female gender (p = 0.026), CT-defined N(0) status (p = 0.027), and negative endoscopy at 6 weeks after CRT (p < 0.0001). On multivariate analysis, N(0) status and negative endoscopy after CRT remained significant (p = 0.03 and p < 0.0001, respectively) for disease-specific survival. On multivariate analysis for overall survival, female gender and negative endoscopy were significant (p = 0.35 and p < 0.001, respectively). The hazard ratios for disease-specific survival with positive nodal status and positive endoscopy were 2.44 (95% CI: 1.14-5.3) and 5.18 (95% CI: 2.3-11.6), respectively. CONCLUSIONS Endoscopic response after primary CRT for esophageal cancer was the most significant predictive factor for overall and disease-specific survival. Regular endoscopic surveillance after CRT achieved survival rates comparable to other strategies and successfully preserved the esophagus in the majority of patients who survived more than 2 years.

Treatment Outcomes of Locally Advanced Oropharyngeal Cancer: A Comparison Between Combined Modality Radio-Chemotherapy and Two Variants of Single Modality Altered Fractionation Radiotherapy

PURPOSE To compare outcomes in patients with locally advanced oropharyngeal cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT). METHODS AND MATERIALS Subjects were 321 consecutive patients with newly diagnosed oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and December 2005 at the BC Cancer Agency with RT-CT (n = 157), AccRT (n = 57), or HypoRT (n = 107). Outcomes examined were disease-specific survival (DSS), locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate of hospitalization for acute complications. RESULTS Median follow-up was 3.4 years. Three-year Kaplan-Meier DSS with RT-CT, AccRT, and HypoRT were 80%, 81%, and 74%, respectively (p = 0.219). Cox regression analysis identified treatment modality as a significant factor affecting DSS (p = 0.038). Compared with RT-CT, the hazard ratio (HR) for DSS was 1.0 with AccRT and 2.0 with HypoRT (p = 0.021). Kaplan-Meier pairwise comparisons found no significant difference in LRC and OS between RT-CT and AccRT. HypoRT was associated with significantly lower LRC (p = 0.005) and OS (p = 0.008) compared with RT-CT. There were significant differences in the rates of G-tube use (p < 0.001) and of hospitalization (p = 0.036) among the three treatment groups, with the most frequent rates observed in the RT-CT group. CONCLUSIONS In patients with locally advanced oropharyngeal cancer, AccRT conferred DSS, LRC, and OS comparable to that of RT-CT. Patients treated with RT-CT experienced higher rates of treatment-related acute toxicities. HypoRT was associated with the least favorable outcomes.

Locally Advanced Malignant Myoepithelioma of the Parotid Gland Treated With Radiotherapy: A Case Study and Review of the Bc Cancer Agency Experience.

Objectives: Malignant myoepithelioma of salivary glands is a rare neoplasm; most arise in the parotid gland and minor salivary glands of the palate. Surgery has been the mainstay of treatment. Methods: This is case report of a patient treated with primary radical radiotherapy and retrospective review of institutional experience. Results: An 87-year-old man with locoregionally advanced malignant myoepithelioma of the parotid gland received radiotherapy alone with complete clinical response and sustained 39 months of posttreatment. Between 1981 and 2012, 15 cases of malignant myoepithelioma of the parotid were seen. Thirteen patients received surgical excision and adjuvant radiotherapy. At a median follow-up of 47 months, 12 patients were alive without recurrence, 2 died without recurrence, and 1 died with metastatic myoepithelioma. Conclusions: Durable locoregional disease control and disease-free-survival was achieved in the majority of patients. The case reported suggests radiation therapy may be an effective treatment option for inoperable cases.