Does local recurrence affect the rate of distant metastases and survival in patients with early-stage breast carcinoma treated with breast-conserving therapy?

BACKGROUND: The purpose of the current analysis was to evaluate the impact of local recurrence (LR) on the development of distant metastases (DM), overall survival (OS), and cause specific survival (CSS) in patients with early-stage breast carcinoma who underwent conservative surgery (CS) and received postoperative radiotherapy (RT). METHODS: Between 1980 and 1995, 1169 patients underwent CS and received RT. All patients were followed for > 1 year and had < or = 4 lymph nodes involved with disease. The median duration of follow-up was 7.7 years. A Cox proportional hazards model was performed to evaluate the effect of LR on the development of DM and CSS. A matched-pair analysis that controlled for multiple prognostic factors also was performed comparing the outcomes of patients with and without LR. RESULTS: The LR rate was 11% at 12 years. For the entire population, LR led to poorer OS and CSS rates at 12 years compared with local control (LC) (71% vs. 81% [P = 0.001] and 69% vs. 88% [P < 0.001], respectively). In a Cox multiple regression model, LR was a significant predictor of disease specific mortality. The hazard ratio (HR) associated with LR was 2.69 for mortality and 2.67 for DM (P < 0.001 and P < 0.001, respectively). The median time from surgery to the development of DM was 3.8 years for patients without LR compared with 4.7 years for patients with LR. Patients who developed LR also had two peaks in the rate of DM (at 2.5 years and at 6.5 years) compared to only one peak (at 1.5 years) for patients who did not develop LR. The impact of LR on DM still was evident in patients with small tumors (< or = 2.0 cm; P < 0.001), negative lymph nodes (P = 0.004), or both (P < 0.001). Recurrent disease that developed outside of the surgical bed region had no negative effect on survival. In the matched-pair analysis (controlling for age, tumor size, grade, number of positive lymph nodes, and estrogen receptor status), LR remained the most significant predictor of mortality (HR: mortality, 5.86; DM, 6.43). CONCLUSIONS: The current results suggest that LR may be responsible for an increase in DM and disease specific mortality in patients who undergo CS and receive RT. This suggestion is reinforced by the distinct difference seen in the time distribution of DM after LR developed and by the fact that recurrent disease that originated outside of the surgical bed did not affect OS. These data reinforce the necessity to insure optimal LC in patients who are treated with breast-conserving therapy.     

Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation

BACKGROUND: Lobular carcinoma in situ (LCIS) is a known risk factor for the development of invasive breast carcinoma. However, little is known regarding the impact of LCIS in association with an invasive carcinoma on the risk of an ipsilateral breast tumor recurrence (IBTR) in patients who are treated with conservative surgery (CS) and radiation therapy (RT). The purpose of this study was to examine the influence of LCIS on the local recurrence rate in patients with early stage breast carcinoma after breast-conserving therapy. METHODS: Between 1979 and 1995, 1274 patients with Stage I or Stage II invasive breast carcinoma were treated with CS and RT. The median follow-up time was 6.3 years. RESULTS: LCIS was present in 65 of 1274 patients (5%) in the study population. LCIS was more likely to be associated with an invasive lobular carcinoma (30 of 59 patients; 51%) than with invasive ductal carcinoma (26 of 1125 patients; 2%). Ipsilateral breast tumor recurrence (IBTR) occurred in 57 of 1209 patients (5%) without LCIS compared with 10 of 65 patients (15%) with LCIS (P = 0.001). The 10-year cumulative incidence rate of IBTR was 6% in women without LCIS compared with 29% in women with LCIS (P = 0.0003). In both groups, the majority of recurrences were invasive. The 10-year cumulative incidence rate of IBTR in patients who received tamoxifen was 8% when LCIS was present compared with 6% when LCIS was absent (P = 0.46). Subsets of patients in which the presence of LCIS was associated with an increased risk of breast recurrence included tumor size < 2 cm (T1), age < 50 years, invasive ductal carcinoma, negative lymph node status, and the absence of any adjuvant systemic treatment (chemotherapy or hormonal therapy) (P < 0.001). LCIS margin status, invasive lobular carcinoma histology, T2 tumor size, and positive axillary lymph nodes were not associated with an increased risk of breast recurrence in these women. CONCLUSIONS: The authors conclude that the presence of LCIS significantly increases the risk of an ipsilateral breast tumor recurrence in certain subsets of patients who are treated with breast-conserving therapy. The risk of local recurrence appears to be modified by the use of tamoxifen. Further studies are needed to address this issue.     

Childhood and adolescent thyroid carcinoma

OBJECTIVES: This analysis was performed to evaluate the influence of clinical and treatment factors on local tumor control, control of distant metastasis, survival, and complications in children and adolescents with thyroid carcinoma. METHODS: The records of 56 children and adolescents with papillary and follicular carcinoma of the thyroid were reviewed. They ranged in age from 4 to 20 years. There were 43 females and 13 males. At diagnosis, 15 (27%) patients had disease confined to the thyroid, 34 (60%) had additional lymph node metastasis to the neck or upper mediastinum, and 7 (13%) also had lung metastasis. Treatment consisted of a total thyroidectomy in 48 patients, a subtotal thyroidectomy in 4 patients, and a lobectomy in 4 patients. All 56 patients received postoperative thyroid hormone suppressive therapy. (131)I was administered to 82% (46 of 56) of patients after their initial surgery. RESULTS: The overall survival rate was 98% with a follow-up of 0.6-30.7 years (with a median follow-up of 11.0 years). The one death that occurred in this patient population was the result of a congenital heart defect and was unrelated to thyroid carcinoma. The 10-year progression-free survival rate was 61%. Nineteen patients (34%) experienced a recurrence of their thyroid carcinoma. The time to first recurrence of disease ranged from 8 months to 14.8 years (mean, 5.3 years). None of those with disease confined to the thyroid developed recurrent disease. The recurrence rate was 50% (17 of 34) in patients with lymph node metastasis and 29% (2 of 7) in patients with lung metastasis (P = 0.02). Tumor characteristics were evaluated for time to first recurrence utilizing the logistic likelihood ratio test to predict disease recurrence. Thyroid capsule invasion (P = 0.02), soft tissue invasion (P = 0.03), positive margins (P = 0.006), and tumor location at diagnosis (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02) were significant for developing recurrent disease. Patients younger than 15 years old at diagnosis were more likely to have more extensive tumor at diagnosis than patients who were 15 years and older (thyroid only vs. thyroid and lymph nodes vs. thyroid, lymph nodes, and lung metastasis, P = 0.02). CONCLUSION: Carcinoma of the thyroid in children and adolescents has little risk of mortality but a high risk of recurrence. Younger patients present with a more advanced stage of disease and are more likely to have disease recurrence. Total thyroidectomy and lymph node dissection, followed by postoperative (131)I therapy, thyroid hormone replacement (suppressive) administration, and diligent surveillance are warranted.     

Is the benefit of postmastectomy irradiation limited to patients with four or more positive nodes, as recommended in international consensus reports? A subgroup analysis of the DBCG 82 b&c randomized trials.

BACKGROUND AND AIM: Numerous consensus reports recommend that postmastectomy radiotherapy (RT) in addition to systemic therapy is indicated in high-risk patients with 4+ positive nodes, but not in patients with 1-3 positive nodes. A subgroup analysis of the DBCG 82 b&c trials was performed to evaluate the loco-regional recurrence rate and survival in relation to number of positive nodes. MATERIALS AND METHODS: In the DBCG 82 b&c trials 3083 pre- and postmenopausal high-risk women were randomized to postoperative RT in addition to adjuvant systemic therapy. Since many patients had relatively few lymph nodes removed (median 7), the present analysis was limited to 1152 node positive patients with 8 or more nodes removed. RESULTS: The overall 15-year survival rate in the subgroup was 39% and 29% (p=0.015) after RT and no RT, respectively. RT reduced the 15-year loco-regional failure rate from 51% to 10% (p<0.001) in 4+ positive node patients and from 27% to 4% (p<0.001) in patients with 1-3 positive nodes. Similarly, the 15-year survival benefit after RT was significantly improved in both patients with 1-3 positive nodes (57% vs 48%, p=0.03) and in patients with 4+ positive nodes (21% vs 12%, p=0.03). CONCLUSION: The survival benefit after postmastectomy RT was substantial and similar in patients with 1-3 and 4+ positive lymph nodes. Furthermore, it was not strictly associated with the risk of loco-regional recurrence, which was most pronounced in patients with 4+ positive nodes. The indication for RT seems therefore to be at least equally beneficial in patients with 1-3 positive nodes, and future consensus should be modified accordingly.     

The role of postoperative radiotherapy in node negative breast cancer patients with pT3-T4 disease.

AIMS: To evaluate the role of postmastectomy radiotherapy (PMRT) in patients with pT3-T4N0M0 breast cancer. METHODS: 156 patients with T3-T4N0M0 breast cancer were retrospectively analyzed. RESULTS: Locoregional recurrences were seen in 17 of 156 patients with a median time for development of 27 months (5.7-248.7 months). Two of 9 patients who were not treated with post-operative radiation therapy had locoregional recurrence as compared with 16 of 147 patients receiving radiotherapy. In multivariate analysis, presence of locoregional recurrence was the only significant prognostic factor for overall survival (18% vs. 86%, p<0.001, RR=9.05). The patients with a median number of dissected lymph nodes >or=10 had a significantly better locoregional disease free survival rate as compared with patients with dissected lymph nodes <10 (90% vs. 78%, p=0.04). Chest wall recurrences were clearly higher in patients without chest wall RT since 5 of 49 patients without RT had recurrences in the chest wall region while only 4 of 107 who received chest wall RT had recurrence. However receiving RT to peripherical lymphatic regions had no additional effect on reducing recurrences in these regions (5% vs. 4%). CONCLUSIONS: Due to the lack of phase III randomized trials directly addressing the role of postmastectomy radiotherapy in these stages, our series suggest that postmastectomy radiotherapy to the ipsilateral chest wall is recommended for patients with PT3N0 and T4N0 breast cancer. The need for irradiating axillary or supraclavicular region shall be neglected in patients who undergo sufficient axillary sampling.     

Positive surgical margins and ipsilateral breast tumor recurrence predict disease-specific survival after breast-conserving therapy

BACKGROUND: The current study identified determinants of systemic recurrence and disease-specific survival (DSS) in patients with early-stage breast carcinoma treated with breast-conserving surgery and radiation therapy (breast-conserving therapy, or BCT). METHODS: The study population consisted of 1,043 consecutive women with Stages I or II breast carcinoma who underwent BCT between 1970 and 1994. Clinical and pathologic characteristics evaluated included age, tumor size, tumor grade, estrogen and progesterone receptor status, surgical margins, axillary lymph node involvement, and use of adjuvant therapy. RESULTS: At a median follow-up time of 8.4 years, 127 patients (12%) had developed an ipsilateral breast tumor recurrence (IBTR), and 184 patients (18%) had developed a systemic recurrence. On multivariate logistic regression analysis, tumor size greater than 2 cm, positive lymph nodes, lack of adjuvant tamoxifen therapy, and positive margins (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.1-12.3; P = 0.034) were predictors of systemic recurrence. When IBTR was added into the model, adjuvant therapy and surgical margins were not independent predictors; however, IBTR was an independent predictor of systemic recurrence (IBTR vs. no IBTR; OR, 6.2; 95% CI, 3.1-12.3; P < 0.001). The 10 year DSS rate after BCT was 87%. On multivariate Cox proportional hazards model analysis, the following factors were independent predictors of poor DSS: tumor size greater than 2 cm (vs. < or = 2 cm; relative risk [RR], 2.3; 95% CI, 1.2-4.3; P = 0.010), negative progesterone receptor status (vs. positive; RR, 2.7; 95% CI, 1.4-5.1; P = 0.003), positive margins (vs. negative; RR, 3.9; 95% CI, 1.4-11.5; P = 0.011), and IBTR (vs. no IBTR; RR, 5.5; 95% CI, 2.8-11.0; P < 0.001). CONCLUSIONS: Positive surgical margins and IBTR are predictors of systemic recurrence and disease-specific survival after BCT. Aggressive local therapy is necessary to ensure adequate surgical margins and to minimize IBTR.     

Lack of benefit of concurrent chemotherapy in patients with cervical cancer and negative lymph nodes by FDG-PET

PURPOSE: To compare the outcome of patients with cervical cancer and negative lymph nodes by fluorodeoxyglucose-positron emission tomography (FDG-PET) treated with irradiation (RT) and concurrent chemotherapy or RT alone. METHODS AND MATERIALS: This was a prospective data registry of 65 patients with cervical cancer and negative lymph nodes by whole-body FDG-PET. The tumor stage was IB2 in 11, IIB in 37, and IIIB in 17 patients. RT alone was administered to 15 and RT with concurrent weekly cisplatin to 50 patients. RESULTS: The 5-year overall survival estimate was 85% with RT and 81% with RT and concurrent chemotherapy (p = 0.91). The corresponding 5-year cause-specific survival estimates were 78% and 74% (p = 0.98). The differences in the sites of recurrence (pelvis vs. distant metastasis) were not statistically significant between the two groups (p = 0.77). A Cox proportional hazards model of survival outcome did not identify chemotherapy, overall treatment time, or radiation dose as statistically significant prognostic factors. Severe complications included one rectovaginal fistula, one rectal stricture requiring colostomy (both in the concurrent chemotherapy group), and one death from chemotherapy-related complications. CONCLUSION: Irradiation with concurrent cisplatin was not advantageous compared with RT alone in patients with negative lymph nodes on FDG-PET.     

Clinico-pathological and treatment-related factors influencing survival in parotid cancer.

One hundred and three patients with primary parotid cancer treated surgically at the Christie Hospital, Manchester (1952-1992), were analysed to assess the influence on survival of prognostic and treatment-related factors. Thirty-seven patients were treated by surgery alone (SG), 66 received post-operative radiation (SG+RT). Median follow-up was 12 years, minimum 5 years. The 10-year disease-specific survival rates for stage I, II and III/IV were 96%, 61% and 17% respectively (P < 0.0001). The various histological types segregated into three survival patterns: low-, intermediate-and high-grade with 10-year survival rates of 93%, 41% and 50% respectively (P < 0.0001). On multivariate analysis, the factors influencing risk of cancer death in order of importance were: tumour size > 4 cm (P < 0.001), presence of nodes (P = 0.001), histology of adenoid cystic carcinoma (P = 0.01), high-tumour grade (P = 0.02) and perineural involvement (P = 0.01). Neither the extent of surgery nor the operator influenced outcome. Overall, adjuvant RT significantly reduced locoregional recurrence (SG+RT 15% vs SG 43%; P = 0.002) but not survival, although on subanalysis, there was a trend to improved survival with large cancers and high-grade tumours. Long-term survival is determined primarily by tumour characteristics, namely clinical stage and grade. Post-operative RT contributes significantly to locoregional control and probably confers some survival advantage in high-risk patients.     

原发肿瘤大小及淋巴结转移状况与非小细胞肺癌术后放疗价值关系

目的 分析影响淋巴结阳性非小细胞肺癌(NSCLC)术后放疗疗效的因素.方法 回顾性分析480例接受根治性手术的N_1～N_2期NSCLC患者,其中267例患者接受了术后化疗,121例接受了术后放疗.根据N分期、原发肿瘤最大径及淋巴结转移度(阳性淋巴结个数占清扫淋巴结总数的百分率)分别分组,分析术后放疗在各组中的应用价值.观察终点为局部无复发生存率(LRFS)及总生存率(OS).采用Kaplan-Meier法及Cox回归分析各临床因素对术后放疗疗效的影响.结果 对于N_2期患者,术后放疗能改善总生存率,淋巴结转移度及原发肿瘤大小均对术后放疗价值有明显影响.根据淋巴结转移度及原发肿瘤直径将N_2期病例分为以下三组:第一组肿瘤直径≤3 cm并且淋巴结转移度≤33%,第二组符合下列条件中一项:肿瘤直径>3 cm或淋巴结转移度>33%,第三组肿瘤直径>3 cm并且淋巴结转移度>33%.三组患者接受术后放疗和未接受术后放疗的5年LRFS分别为55%和60%(χ~2=0.03,P=0.869),42%和50%(χ~2=0.31,P=0.547),62%和52%(χ~2=4.25,P=0.036);5年0s分别为22%和50%(χ~2=1.65,P=0.199),26%和22%(χ~2=0.13,P=0.786),42%和16%(χ~2=15.33,P=0.000).结论 原发肿瘤大小和淋巴结转移度明显影响NSCLC术后放疗疗效,对肿瘤直径>3 cm且淋巴结转移度>33%的N_2期NSCLC,加用术后放疗能提高患者局部控制率及生存率.     

Breast cancer patients with 10 or more involved axillary lymph nodes treated by multimodality therapy: influence of clinical presentation on outcome

PURPOSE: To analyze tumor control and survival for breast cancer patients with 10 or more positive lymph nodes without systemic disease, treated by adjuvant radiation alone or combined-modality therapy. METHODS AND MATERIALS: We reviewed the records of 309 consecutive patients with these characteristics who received locoregional radiotherapy (RT) at our institution. The majority of patients had clinical Stage II or IIIA-B disease (43% and 48%, respectively). The median number of positive axillary lymph nodes was 15 (range, 10-78). Adjuvant therapy consisted of RT alone, with or without chemotherapy, tamoxifen, and/or ovarian castration. RESULTS: The overall 5-year and 10-year disease-free survival (DFS) rates were 20% and 7%, respectively. Median DFS was higher for patients with Stage I-II compared with those with Stage IIIABC (28 vs. 19 months; p = 0.006). Median DFS for patients aged 相似文献   

Long‐term outcomes for patients with limited stage follicular lymphoma

BACKGROUND:

Given the indolent behavior of follicular lymphoma (FL), it is controversial whether limited stage FL can be cured using radiotherapy (RT). Furthermore, the optimal RT field size is unclear. The authors of this report investigated the long‐term outcomes of patients with limited stage FL who received RT alone and studied the impact of reducing the RT field size from involved regional RT (IRRT) to involved node RT with margins up to 5 cm (INRT≤5 cm).

METHODS:

Eligible patients had limited stage, grade 1 through 3A FL diagnosed between 1986 and 2006 and treated were with curative‐intent RT alone. IRRT encompassed the involved lymph node group plus ≥1 adjacent, uninvolved lymph node group(s). INRT≤5 cm covered the involved lymph node(s) with margins ≤5 cm.

RESULTS:

In total, 237 patients were identified (median follow‐up, 7.3 years) and included 48% men, 54% aged >60 years, stage IA disease in 76% of patients, elevated lactate dehydrogenase (LDH) in 7% of patients, grade 3A tumors in 12% of patients, and lymph node size ≥5 cm in 19% of patients. The 2 RT groups were IRRT (142 patients; 60%) and INRT≤5 cm (95 patients; 40%). At 10 years, the progression‐free survival (PFS) rate was 49%, and the overall survival (OS) rate was 66%. Only 2 patients developed recurrent disease beyond 10 years. The most common pattern of first failure was a distant recurrence only, which developed in 38% of patients who received IRRT and in 32% of patients who received INRT≤5 cm. After INRT≤5 cm, 1% of patients had a regional‐only recurrence. Significant risk factors for PFS were lymph nodes ≥5 cm (P = .008) and male gender (P = .042). Risk factors for OS were age >60 years (P < .001), elevated LDH (P = .007), lymph nodes ≥5 cm (P = .016), and grade 3A tumors (P = .036). RT field size did not have an impact on PFS or OS.

CONCLUSIONS:

Disease recurrence after 10 years was uncommon in patients who had limited stage FL, suggesting that a cure is possible. Reducing RT fields to INRT≤5 cm did not compromise long‐term outcomes. Cancer 2010. © 2010 American Cancer Society.     

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.     

Basal-like型乳腺癌临床特征与生存分析

目的分析Basal-like型乳腺癌所占比例、临床特征以及生存情况,为Basal-like型乳腺癌临床诊治提供参考依据。方法回顾性分析我院经手术治疗、资料完整、经病理确诊的女性乳腺癌患者171例。Basal-like型乳腺癌的判定采用Nielsen标准。比较Basal-like型乳腺癌与非Basal-like型乳腺癌的临床病理特征、复发转移及生存情况。结果Basal-like型乳腺癌26例,占15.3%。Basal-like型乳腺癌具有组织学分级高（Basal-like型与非Basal-like型乳腺癌组织学分级Ⅲ级的比例分别为：69.23%和3034%,P＜0.001）,淋巴结转移阳性率低（34.62%和58.62%,P=0.023）,淋巴结转移率低（41.38%和65.38%,P=0.038）的特点。与非Basal-like型乳腺癌相比,Basal-like型乳腺癌肺转移发生率较高（15.38%和3.45%,P=0.012）。Basal-like型乳腺癌和非Basal-like型乳腺癌的5年生存率分别为703%和87.9%（P=0.042）,5年无病生存率分别为59.5%和80.3%（P=0.013）。结论本组患者并没有发现回、汉族患者Basal-like型乳腺癌的发病率差别。本组Basal-like型乳腺癌患者具有组织学分级高、淋巴结转移阳性率低、淋巴结转移率低、易于发生肺转移和预后较差的特点。     

Long-term outcomes and clinicopathologic differences of African-American versus white patients treated with breast conservation therapy for early-stage breast cancer

BACKGROUND: African-American (AA) and white patients with early-stage disease who were treated with breast conservation therapy (BCT) were examined to detect differences in clinicopathologic features and outcomes as a function of race. METHODS: Clinical data from the charts of 2164 white and 207 AA patients treated with BCT, and p53 expression status on 444 patients (from an existing tissue database), were analyzed to detect differences between the 2 cohorts. RESULTS: The median follow-up was 7 years. There were no differences in the method of tumor detection, lymph nodes excised, surgical margin status, or chemotherapy/radiotherapy delivered, reflecting similar screening and treatment policies for AA women in the study community. Despite this, AA patient presented at a younger age, with higher T and N classifications, and more estrogen and progesterone negative and "triple negative" tumors (all P values < .016). Tumors in AA patients were p53 positive more often than tumors in white patients (P= .0003). At 10 years, AA patients had a higher rate of distant metastasis (20% vs 17%; P= .042), lymph node recurrence (6% vs 2%; P= .004), and breast recurrence (17% vs 13%; P= .036). There was no difference in overall survival between the 2 groups. On multivariate analysis, only lymph node recurrence (risk ratio of 3.140; 95% confidence interval, 1.396-7.063 [P= .0057]) remained significantly higher among AA women. CONCLUSIONS: In this cohort of uniformly treated patients, the authors found the expected clinicopathologic differences, but race was not found to be an independent predictor of local recurrence for AA patients when other confounding variables were taken into account in the multivariate model. These findings suggest that BCT is a reasonable option for appropriately selected AA patients. To the authors' knowledge, this is the largest study addressing outcomes after BCT for AA women published to date.     

Percent positive axillary lymph node metastasis predicts survival in patients with non-metastatic breast cancer

PURPOSE: We retrospectively evaluated the impact of percent positive axillary nodal involvement on the therapeutic outcomes in patients with non-metastatic breast cancer receiving postmastectomy radiotherapy and chemotherapy. MATERIALS AND METHODS: Between January 1994 and December 2002, the medical records of 939 eligible non metastatic breast carcinoma patients were analyzed. Chest wall radiotherapy was indicated in case of positive surgical margin, tumor size equal or more than 4 cm, skin-fascia invasion. Lymphatic irradiation was applied for more than three metastatic axillary lymph nodes, incomplete axillary dissection (<10 lymph nodes), extracapsular extension or perinodal fat tissue invasion. A total dose of 50 Gy was given to chest wall and lymph node regions with 2 Gy daily fractions. Statistical analyses were performed by Kaplan-Meier method, Log-rank test and Cox's regression analysis. RESULTS: The median follow-up for all patients alive was 62 months. The 5-year overall survival (OS) and disease-free survival (DFS) for entire cohort were 81%, and 65%, respectively. Univariate analysis for OS revealed significance for tumour size (< or =5 cm vs. >5 cm, p<0.001), metastatic nodal involvement (0 vs. 1-3 vs. >4 LN, p<0.001), percent positive nodal involvement ([metastatic nodes/total nodes removed] x 100; 0 vs. < or =25% vs. 26-50% vs. >50%, p<0.001), surgical margin status (negative vs. positive, p=0.05), and hormonal treatment (present vs. absent, p=0.03). DFS had similarly significance for age (< or =40 years vs. >40 years, p=0.006), tumour size (0.02), metastatic nodal involvement (p<0.001), percent positive nodal involvement (p<0.001), and perinodal invasion (present vs. absent, p=0.01). Multivariate analysis revealed significance for tumour size, percent positive nodal involvement, hormonal treatment, and surgical margin status for OS. Age and percent positive nodal involvement were found to be significant for DFS. CONCLUSION: Percent positive nodal involvement was found to be a significant prognostic factor for survival in all end-points.     

Improving local control with breast-conserving therapy: a 27-year single-institution experience

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.     

Involvement of three or more lymph nodes predicts poor prognosis in submucosal gastric carcinoma

BACKGROUND: Multivariate analyses has shown that the status of lymph node metastasis and the depth of tumor penetration through the gastric wall are the most important prognostic factors in patients with advanced gastric carcinoma after curative operation. A clinicopathological study was carried out to clarify a simple and optimal prognostic indicator for early gastric cancer. METHODS: Retrospective analyses of 982 patients with early gastric cancer (562 with mucosal [M] and 420 with submucosal [SM] tumor) treated by gastrectomy with D2 lymph node dissection were performed. RESULTS: The incidence of lymph node metastasis from M and SM tumors was 2.5% (14/562) and 20.2% (85/420), respectively. There were no apparent prognostic indicators in patients with M tumors. In patients with SM tumors, the cancer-specific 5-year survival of those with lymph node metastasis was significantly lower than that of those without such metastasis (77.6% vs 98.2%; P < 0.001). An sharp decrease in survival was seen between patients with two positive nodes and those with three positive nodes, and the cancer-specific 5-year survival rate of patients with three or more metastatic lymph nodes was significantly lower than that of those with one or two nodes (P < 0.001; univariate analysis). Multivariate analysis revealed that the involvement of three or more lymph nodes was the sole independent prognostic determinant (P = 0.016); the level of nodal metastasis was not an independent prognostic factor (P = 0.384). All patients with N2 lymph node echelons (according to the Japanese Research Society for Gastric Cancer classification of the draining lymph nodes of the stomach) in the group with one or two positive nodes survived for more than 5 years. CONCLUSION: The sole independent prognostic factor in SM gastric cancer is the involvement of three or more metastatic lymph nodes. We suggest that this simple prognostic indicator for the follow-up of early gastric cancer, and this could lead to potentially effective adjuvant chemotherapy.     

Improved biochemical outcome with adjuvant radiotherapy after radical prostatectomy for prostate cancer with poor pathologic features

PURPOSE: The indications for adjuvant external beam radiotherapy (EBRT) after radical prostatectomy (RP) are poorly defined. We performed a retrospective comparison of our institution's experience treating prostate cancer with RP vs. RP followed by adjuvant EBRT. METHODS AND MATERIALS: Between 1987 and 1998, 617 patients with clinical Stage T1-T2N0M0 prostate cancer underwent RP. Patients who underwent preoperative androgen deprivation and those with positive lymph nodes were excluded. Of the 617 patients, 34 (5.5%) with an undetectable postoperative prostate-specific antigen (PSA) level underwent adjuvant prostatic fossa RT at a median of 0.25 year (range, 0.1-0.6) postoperatively because of poor pathologic features. The median total dose was 59.4 Gy (range, 50.4-66.6 Gy) in 1.8-2.0-Gy fractions. These 34 RP+RT patients were compared with the remaining 583 RP patients. Biochemical failure was defined as any postoperative PSA level > or =0.1 ng/mL and any postoperative PSA level > or =0.3 ng/mL (at least 30 days after surgery). Administration of androgen deprivation was also scored as biochemical failure when applying either definition. The median clinical follow-up was 8.2 years (range, 0.1-11.2 years) for RP and 8.4 years (range, 0.3-13.8 years) for RP+RT. RESULTS: Radical prostatectomy + radiation therapy patients had a greater pathologic Gleason score (mean, 7.3 vs. 6.5; p < 0.01) and pathologic T stage (median, T3a vs. T2c; p < 0.01). Age (median, 65.7 years) and pretreatment PSA level (median, 7.9 ng/mL) were similar between the treatment groups. Extracapsular extension was present in 72% of RP+RT patients vs. 27% of RP patients (p < 0.01). The RP+RT patients were more likely to have seminal vesicle invasion (29% vs. 9%, p < 0.01) and positive margins (73% vs. 36%, p < 0.01). Despite these poor pathologic features, the 5-year biochemical control (BC) rate (PSA <0.1 ng/mL) was 57% for RP+RT and 47% for RP (p = 0.28). For patients with extracapsular extension, the 5-year BC rate was 52% for RP+RT vs. 30% for RP (p < 0.01). The 5-year BC rate for patients with seminal vesicle invasion was 60% for RP+RT vs. 18% for RP (p < 0.01). For those with positive margins, the 5-year BC rate was 64% for RP+RT vs. 27% for RP (p < 0.01). The use of adjuvant RT remained statistically significant on multivariate analysis when applying either biochemical failure definition. Adjuvant RT also remained statistically significant when including the postoperative PSA level (>30 days after surgery) in the multivariate analyses. In addition, 99 (17%) of the 583 RP patients required salvage prostatic fossa RT (median dose, 59.4 Gy) at a median interval of 1.3 years after surgery (range, 0.1-8.4) for a palpable recurrence (n = 10) or a detectable/rising postoperative PSA level (n = 89). The median PSA level before salvage RT was 0.8 ng/mL (mean, 3.2 ng/mL). The 5-year and 8-year BC rate, using the PSA <0.1 ng/mL definition, from the date of salvage RT was 41% and 35%, respectively. The 5-year and 8-year BC rate, using the PSA <0.3 ng/mL definition, was 46% and 36%, respectively. The 8-year local recurrence rate after salvage RT was 4%. CONCLUSION: Adjuvant RT demonstrated improved efficacy against prostate cancer. For patients with poor pathologic features (extracapsular extension, seminal vesicle invasion, positive margins), adjuvant RT improved the biochemical outcome independent of other prognostic factors.     

Nodal basin recurrence following lymph node dissection for melanoma: implications for adjuvant radiotherapy

PURPOSE: To analyze patterns of failure in malignant melanoma patients with lymph node involvement who underwent complete lymph node dissection (LND) of the nodal basin. To determine prognostic factors predictive of local recurrence in the lymph node basin in order to select patients who may benefit from adjuvant radiotherapy. METHODS AND MATERIALS: A retrospective analysis of 338 patients undergoing complete LND for melanoma between 1970 and 1996 who had pathologically involved lymph nodes was performed. Mean follow-up from the time of LND was 54 months (range: 12-306 months). Lymph node basins dissected included the neck (56 patients), axilla (160 patients), and groin (122 patients). Two hundred fifty-three patients (75%) underwent therapeutic LND for clinically involved nodes, while 85 patients (25%) had elective dissections. Forty-four percent of patients received adjuvant systemic therapy. No patients received adjuvant radiotherapy to the lymph node basin. RESULTS: Overall and disease-specific survival for all patients at 10 years was 30% and 36%, respectively. Overall nodal basin recurrence was 30% at 10 years. Mean time to nodal basin recurrence was 12 months (range: 2-78 months). Site of nodal involvement was prognostic with 43%, 28%, and 23% nodal basin recurrence at 10 years with cervical, axillary, and inguinal involvement, respectively (p = 0.008). Extracapsular extension (ECE) led to a 10-year nodal basin failure rate of 63% vs. 23% without ECE (p < 0.0001). Patients undergoing a therapeutic dissection for clinically involved nodes had a 36% failure rate in the nodal basin at 10 years, compared to 16% for patients found to have involved nodes after elective dissection (p = 0.002). Lymph nodes larger than 6 cm led to a failure rate of 80% compared to 42% for nodes 3-6 cm and 24% for nodes less than 3 cm (p < 0.001). The number of lymph nodes involved also predicted for nodal basin failure with 25%, 46%, and 63% failure rates at 10 years for 1-3, 4-10, and > 10 nodes involved (p = 0.0001). There was no significant difference in nodal basin control in patients with synchronous or metachronous lymph node metastases, nor in patients receiving or not receiving adjuvant systemic therapy. Nodal basin failure was predictive of distant metastasis with 87% of patients with nodal basin recurrence developing distant disease compared to 54% of patients without nodal failure (p < 0.0001). On multivariate analysis, number of positive nodes and type of dissection (elective vs. therapeutic) were significant predictors of overall and disease-specific survival. Size of the largest lymph node was also predictive of disease-specific survival. Site of nodal involvement and ECE were significant predictors of nodal basin failure. CONCLUSIONS: Malignant melanoma patients with nodal involvement have a significant risk of nodal basin failure after LND if they have cervical involvement, ECE, >3 positive lymph nodes, clinically involved nodes, or any node larger than 3 cm. Patients with these risk factors should be considered for adjuvant radiotherapy to the lymph node basin to reduce the incidence of nodal basin recurrence. Patients with nodal basin failure are at higher risk of developing distant metastases.     

Impact of race on outcome after definitive radiotherapy for squamous cell carcinoma of the head and neck

BACKGROUND: The objective of the current study was to evaluate the impact of race (black vs. white) on the outcome of patients with invasive squamous cell carcinoma of the head and neck. METHODS: Between 1983 and 1997, 686 patients completed definitive, twice-daily radiotherapy (RT) alone or combined with a planned neck dissection; no patients received adjuvant chemotherapy. The minimum follow-up was 2 years, and median follow-up was 7 years for living patients. No patients were lost to follow-up. Fifty-five patients were black (8%). RESULTS: Although the two groups had similar 5-year local-regional control rates (black patients vs. white patients: 70% vs. 76%, respectively; P = 0.275), black patients had double the risk for distant recurrence compared with white patients (27% vs. 13%; P = 0.012). The 5-year cause-specific and absolute survival rates were lower for black patients (52% vs. 74% [P = 0.001] and 29% vs. 52% [P < 0.001], respectively). Multivariate analyses revealed that race was an independent predictor of freedom from distant metastasis (P = 0.013), cause-specific survival (P = 0.005), and absolute survival (P < 0.001). CONCLUSIONS: Although equal local-regional control rates can be achieved in black patients and white patients with squamous cell carcinoma of the head and neck, the risk of distant recurrence was significantly higher in black patients and resulted in decreased survival. Reevaluation of current strategies for pretreatment metastatic work-ups and development of more effective systemic therapy will be key to improving the survival disparity in this group.