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.

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.

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.

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.

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.

Target volume delineation for partial breast radiotherapy planning: clinical characteristics associated with low interobserver concordance.

PURPOSE: To examine variability in target volume delineation for partial breast radiotherapy planning and evaluate characteristics associated with low interobserver concordance. METHODS AND MATERIALS: Thirty patients who underwent planning CT for adjuvant breast radiotherapy formed the study cohort. Using a standardized scale to score seroma clarity and consensus contouring guidelines, three radiation oncologists independently graded seroma clarity and delineated seroma volumes for each case. Seroma geometric center coordinates, maximum diameters in three axes, and volumes were recorded. Conformity index (CI), the ratio of overlapping volume and encompassing delineated volume, was calculated for each case. Cases with CI

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

BACKGROUND: 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. METHODS: The British Columbia Cancer Agency registry identified 163 women diagnosed with breast cancer between 1989-1999 who received a subsequent diagnosis of endometrial cancer. Of these, 55% (n = 90) had a history of tamoxifen use. Outcomes analyzed were breast cancer-specific survival (BCSS), endometrial cancer-specific survival (ECSS), and overall survival (OS). RESULTS: Median follow-up was 9.4 years. Distributions of age, menopausal status, body mass index, and comorbidities were similar in the tamoxifen-treated and nontamoxifen cohorts. Proportions of aggressive endometrial cancer subtypes including papillary serous, clear cell, and mixed mullerian tumors were higher in the tamoxifen cohort (28% vs14%, P = .03). Distributions of endometrial cancer grade and stage were similar in the 2 groups (P > .05). Hysterectomy and/or oophorectomy were the primary treatments for endometrial cancer in 99% of patients, with comparable pelvic control rates in the tamoxifen and nontamoxifen groups. At 10 years, patients in the tamoxifen group experienced lower BCSS compared with the nontamoxifen group (89% vs 97%, P = .02). No significant differences in ECSS and OS were observed between the 2 groups (ECSS 82% and 82%, P = .85; and OS 69% v. 66%, P = .85). CONCLUSIONS: In patients with breast cancer who developed a subsequent endometrial cancer, tamoxifen-treated patients had higher proportions of aggressive endometrial cancer subtypes, but almost all cases were amenable to surgery, thus resulting in similar endometrial cancer control and survival when compared with nontamoxifen treated patients.

Consistency in seroma contouring for partial breast radiotherapy: impact of guidelines.

PURPOSE: Inconsistencies in contouring target structures can undermine the precision of conformal radiation therapy (RT) planning and compromise the validity of clinical trial results. This study evaluated the impact of guidelines on consistency in target volume contouring for partial breast RT planning. METHODS AND MATERIALS: Guidelines for target volume definition for partial breast radiation therapy (PBRT) planning were developed by members of the steering committee for a pilot trial of PBRT using conformal external beam planning. In phase 1, delineation of the breast seroma in 5 early-stage breast cancer patients was independently performed by a "trained" cohort of four radiation oncologists who were provided with these guidelines and an "untrained" cohort of four radiation oncologists who contoured without guidelines. Using automated planning software, the seroma target volume (STV) was expanded into a clinical target volume (CTV) and planning target volume (PTV) for each oncologist. Means and standard deviations were calculated, and two-tailed t tests were used to assess differences between the "trained" and "untrained" cohorts. In phase 2, all eight radiation oncologists were provided with the same contouring guidelines, and were asked to delineate the seroma in five new cases. Data were again analyzed to evaluate consistency between the two cohorts. RESULTS: The "untrained" cohort contoured larger seroma volumes and had larger CTVs and PTVs compared with the "trained" cohort in three of five cases. When seroma contouring was performed after review of contouring guidelines, the differences in the STVs, CTVs, and PTVs were no longer statistically significant. CONCLUSION: Guidelines can improve consistency among radiation oncologists performing target volume delineation for PBRT planning.

Locoregional recurrence risks in elderly breast cancer patients treated with mastectomy without adjuvant radiotherapy.

This study examined tumour and treatment characteristics in elderly women treated with mastectomy without radiotherapy and compared their outcomes to younger counterparts. Data were analysed for 2362 women aged 50 years and older referred to the British Columbia Cancer Agency, Canada between 1989 and 1997. The women had invasive T1-4, N0-N3, M0 breast cancer treated with mastectomy without adjuvant radiotherapy. Clinical characteristics and patient outcomes were compared between two age cohorts: 50-69 (n = 1423) and 70+ years (n = 939). Median follow-up was 8.3 years. Tumours > 5 cm were present in 5% of women aged 50-69 and 3.5% of women aged 70+, respectively. The distribution of nodal stage was similar in the two age cohorts but older women were more likely to have fewer axillary nodes removed (P = 0.009). Fewer women aged 70+ had grade III histology (P = 0.002) and estrogen receptor (ER)-negative status (P < 0.001). The rates of systemic therapy use were comparable in the two age groups. With tumours > 5 cm, locoregional recurrence (LRR) were 13.7% and 30.0% in women aged 50-69 and 70+, respectively. With 1-3 positive nodes (N+), LRR were 14.8% and 13.0% in women aged 50-69 and 70+. In the presence of 4 N+, LRR were 16.8% and 30.8% in women aged 50-69 and 70+. On multivariate analysis, age was not significantly associated with LRR (P = 0.62). Independent prognostic factors for LRR were grade III histology, lymphovascular invasion and positive nodal status. This study suggests that despite more favourable tumour characteristics and comparable systemic therapy use, women aged 70+ years have similar or higher postmastectomy LRR risks compared to younger women. Chronologic age alone should not preclude these women from consideration of adjuvant radiotherapy.

Lymphovascular invasion is associated with reduced locoregional control and survival in women with node-negative breast cancer treated with mastectomy and systemic therapy.

BACKGROUND: The impact of lymphovascular invasion (LVI) on postmastectomy locoregional relapse (LRR) and its use in guiding locoregional therapy in node-negative breast cancer are unclear. This study evaluates the association of LVI with relapse and survival in a cohort of women with early-stage breast cancer. STUDY DESIGN: The study cohort comprised 763 women with pT1-2, pN0 breast cancer referred from 1989 to 1999 and treated with mastectomy and adjuvant systemic therapy without radiotherapy. Kaplan-Meier LRR, distant relapse, and overall survival rates at 7 years were compared between patients with and without LVI. Cox regression analyses were performed to evaluate the prognostic significance of LVI for relapse and survival. RESULTS: Median followup was 7.0 years (range 0.34 to 14.9 years). LVI was present in 210 (27.5%) patients. In log-rank comparisons of Kaplan-Meier curves stratified by LVI status, LVI-positive disease was associated with significantly higher risks of LRR (p = 0.006), distant relapse (p = 0.04), and lower overall survival (p = 0.02). In the multivariable Cox regression analysis, LVI was significantly associated with LRR (relative risk [RR] = 2.32; 95% CI, 1.26-4.27; p = 0.007), distance relapse (RR = 1.53; 95% CI, 1.00-2.35; p = 0.05), and overall survival (RR = 1.46; 95% CI, 1.04-2.07; p = 0.03). In patients with one of the following characteristics: age younger than 50 years, premenopausal status, grade III histology, or estrogen receptor-negative disease, 7-year LRR risks increased threefold from 3% to 5% when LVI was absent, to 15% to 20% in the presence of LVI. CONCLUSIONS: LVI is an adverse prognostic factor for relapse and survival in node-negative patients treated with mastectomy and systemic therapy. LVI, in combination with age older than 50 years, premenopausal status, grade III histology, or estrogen receptor-negative disease, identified patient subsets with 7-year LRR risks of approximately 15% to 20%. Prospective research is required to define the role of adjuvant radiotherapy in these patients.

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 > or =75 years) and comorbidity index (Charlson score 0-1 and > or =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 > or =75 years, respectively. Charlson comorbidity scores > or =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 > or =75 years, respectively, P = 0.05) and with increased comorbidities (91% and 79% in patients with Charlson score 0-1 and > or =2, respectively, P = 0.07). Among stage Ic patients aged > or =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.

Selecting breast cancer patients with T1-T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy.

PURPOSE: To define the individual factors and combinations of factors associated with increased risk of locoregional recurrence (LRR) that may justify postmastectomy radiotherapy (PMRT) in patients with T1-T2 breast cancer and one to three positive nodes. METHODS AND MATERIALS: The study cohort comprised 821 women referred to the British Columbia Cancer Agency between 1989 and 1997 with pathologic T1-T2 breast cancer and one to three positive nodes treated with mastectomy without adjuvant RT. The 10-year Kaplan-Meier estimates of isolated LRR and LRR with or without simultaneous distant recurrence (LRR +/- SDR) were analyzed according to age, histologic findings, tumor location, size, and grade, lymphovascular invasion status, estrogen receptor (ER) status, margin status, number of positive nodes, number of nodes removed, percentage of positive nodes, and systemic therapy use. Multivariate analyses were performed using Cox proportional hazards modeling. A risk classification model was developed using combinations of the statistically significant factors identified on multivariate analysis. RESULTS: The median follow-up was 7.7 years. Systemic therapy was used in 94% of patients. Overall, the 10-year Kaplan-Meier isolated LRR and LRR +/- SDR rate was 12.7% and 15.9%, respectively. Without PMRT, a 10-year LRR risk of >20% was identified in women with one to three positive nodes plus at least one of the following factors: age <45 years, Stage T2, histologic Grade 3, ER-negative disease, medial location, more than one positive node, or >25% of nodes positive (all p < 0.05 on univariate analysis). On multivariate analysis, age <45 years, >25% of nodes positive, medial tumor location, and ER-negative status were statistically significant predictors of isolated LRR and LRR +/- SDR. In the classification model, the first split was according to age (<45 years vs. >/=45 years), with 29.3% vs. 13.7% developing LRR +/- SDR (p < 0.0001). Of 123 women <45 years, the presence of >25% of nodes positive was associated with a risk of LRR +/- SDR of 58.0% compared with 23.8% for those with 45 years, the presence of >25% of nodes positive also conferred a greater LRR +/- SDR risk (26.7%) compared with women with 45 years with 25% of nodes positive, a medial tumor location, and ER-negative status were statistically significant independent factors associated with greater LRR, meriting consideration and discussion of PMRT. Combinations of these factors further augmented the LRR risk, warranting recommendation of PMRT to optimize locoregional control and potentially improve survival. The absence of high-risk factors identifies women who may reasonably be spared the morbidity of PMRT.

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.

BACKGROUND: 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. METHODS: The study cohort was comprised of 542 women with pathologic T1-T2 breast carcinoma who had 1-3 positive lymph nodes and who had undergone mastectomy and received adjuvant systemic therapy without radiotherapy. Ten-year Kaplan-Meier (KM) LRR, distant recurrence (DR), and overall survival (OS) rates stratified by the number of positive lymph nodes, the number of dissected lymph nodes, and the percentage of positive lymph nodes were examined using different cut-off levels. Multivariate analysis was performed to evaluate the prognostic significance of the percentage of positive lymph nodes in disease recurrence and survival. RESULTS: The median follow-up was 7.5 years. LRR, DR, and OS rates correlated significantly with the number of positive lymph nodes and the percentage of positive lymph nodes, but not with the number of dissected lymph nodes. The cut-off level at which the most significant difference in LRR was observed was 25% positive lymph nodes (the 10-year KM LRR rates were 13.9% and 36.7% in women with < or = 25% and > 25% positive lymph nodes, respectively; P < 0.0001). Higher DR rates and lower OS rates were observed among patients who had > 25% positive lymph nodes compared with patients who had < or = 25% positive lymph nodes (DR: 53.0% vs. 30.3%, respectively; P < 0.0001; OS: 43.4% vs. 62.6%, respectively; P < 0.0001). In the multivariate analysis, the percentage of positive lymph nodes and the histologic grade were significant, independent factors associated with LRR, DR, and OS. CONCLUSIONS: The presence of > 25% positive lymph nodes was an adverse prognostic factor in patients with 1-3 positive nodes and may be used to identify patients at high risks of postmastectomy locoregional and distant recurrence who may benefit with adjuvant radiotherapy and more aggressive systemic therapy regimens.

Patient subsets with T1-T2, node-negative breast cancer at high locoregional recurrence risk after mastectomy.

PURPOSE: To identify patient subsets with T1-T2N0 breast cancer at high risk of locoregional recurrence (LRR) who may warrant consideration for postmastectomy radiotherapy. METHODS AND MATERIALS: Data were analyzed for 1505 women referred between 1989 and 1999 with pathologic T1-T2N0M0 breast cancer treated with mastectomy with clear margins and no adjuvant radiotherapy. Logistic regression analysis was performed to identify statistically significant factors associated with LRR. Recursive partitioning was used to develop a classification tree model for LRR given the prognostic variables. RESULTS: The median follow-up was 7.0 years. The 10-year Kaplan-Meier LRR rate was 7.8%. On logistic regression analysis, the statistically significant factors predicting LRR were histologic grade (p <0.0001), lymphovascular invasion (LVI) (p <0.0001), T stage (p = 0.05), and systemic therapy use (p = 0.01). In the recursive partitioning model, the first split in the classification tree was histologic grade. For 972 patients without high-grade histologic features, the 10-year Kaplan-Meier LRR rate was 5.5%. For 533 patients with Grade 3 disease (LRR rate 12.1%), the concomitant presence of LVI was associated with a LRR rate of 21.2% (n = 126). In patients with Grade 3 disease without LVI, T2 tumors conferred a LRR rate of 13.4% (n = 194), which increased to 23.2% for patients who did not receive systemic therapy (n = 63). CONCLUSION: Women with pT1-T2N0 breast cancer experienced a LRR risk of approximately 20% in the presence of Grade 3 disease with LVI or Grade 3 disease, T2 tumors, and no systemic therapy. These subsets of node-negative patients warrant consideration of for postmastectomy radiotherapy.

Adjuvant radiation therapy after breast-conserving surgery in elderly women with early-stage breast cancer: controversy or consensus?

Breast-conservation therapy (BCT), which consists of breast-conserving surgery (BCS) and postoperative radiation therapy (RT), provides similar levels of local control and survival compared with mastectomy. Although the incidence of breast cancer increases with age and the proportion of elderly women in the population continues to increase, clinical trials of BCT have included few women aged > or = 65 years, limiting the ability to establish clear consensus regarding optimal therapy in this population. This article examines the literature on BCT in elderly women with early-stage breast cancer. A systematic search of the Medline and CancerLit databases was conducted to identify articles specifically addressing BCT in elderly women. The outcomes evaluated were local control, disease-free survival, overall survival, and treatment-related toxicities. The lack of consensus in breast-conservation management in elderly patients is highlighted by a paucity of prospective data and numerous retrospective series reporting diverse treatment approaches with conflicting results. The available evidence from BCT trials with and without age subgroup analyses support BCS with postoperative RT as the standard approach associated with the most favorable local control outcomes. A low-risk subset of patients in whom RT may be omitted without compromising local control remains to be defined. Despite these findings, the use of standard therapy significantly decreases with advancing patient age. Although data specifically addressing BCT in elderly patients are limited, age should not preclude consideration of standard treatment strategies to optimize local disease control. Modern clinical trials with representative samples of elderly patients evaluating cancer recurrence and survival as well as functional and quality-of-life outcomes are needed to define optimal breast-conservation management for this important patient population.

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.

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.