Local-regional Recurrence Rate Research Articles

Does the revised TNM staging system for lung cancer better estimate actuarial rates of local/regional recurrence after surgery?

7072 Background: The International Association for the Study of Lung Cancer (IASLC) recently recommended changes to the TNM classification of lung cancers. For early-stage disease, increasing tumor size and nodal status are of primary prognostic relevance for overall survival. However, the ability of the old and the new staging system to predict the risk of local/regional recurrence (LRR) has not been evaluated. Therefore, we examined whether the proposed changes in AJCC 7 would refine the risk of LRR in patients who undergo surgery for early-stage NSCLC. Methods: The medical records and pertinent radiographs for all patients who underwent surgery for early-stage (N0-N1) NSCLC at Duke between 1995 and 2005 were reviewed. Patients undergoing suboptimal surgery (sublobar resections, positive margins), or those who received any preoperative therapy or postoperative radiation therapy were excluded. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered a LRR. Stage was assigned based on both AJCC 6 and AJCC 7. Actuarial rates of LRR were estimated using the Kaplan-Meier method. Results: Of 975 patients who underwent surgery during the time interval, 741 were eligible for this analysis. Surgery consisted of lobectomy in 91% (n=672) and pneumonectomy in 9% (n=69) of patients. 82% (n=605) of patients were pathologic N0 (pN0) and 18% (n=136) were pN1. Adjuvant chemotherapy was administered to 7% (n=52). Median follow-up was 35 months. Conversion from AJCC 6 to AJCC 7 resulted in 25% stage migration (upstaging in 15%; downstaging in 10%). For all patients, the 5-year actuarial risk of LRR was 20% (95% CI 17%-24%). 5-year rates of LRR for stage IA, IB, IIA, and IIB disease using AJCC 6 were 12%, 26%, 40%, and 27%, respectively. Using AJCC 7, corresponding rates were 12%, 21%, 34%, and 38%, respectively. Conclusions: The risk of LRR increases monotonically with stage in the new AJCC 7 system, but not for the older AJCC 6 system. Thus, the newer staging system is better in predicting the risk of LRR. This information will be valuable when designing future studies of postoperative RT. No significant financial relationships to disclose.

A multinational pooled analysis of 434 cases of stage I non-small cell lung cancer (NSCLC) treated with volumetrically image-guided (VIGRT) stereotactic lung radiotherapy (SBRT): Results from the Elekta Collaborative Lung Research Group.

7015 Background: Published lung SBRT outcomes/dose response data for inoperable NSCLC come from small phase I-II studies or larger datasets not requiring image-guided radiotherapy (IGRT) or volumetric prescriptions. This entire cohort of SBRT patients had daily online cone-beamCT. Methods: 434 cases of stage I (T1-2N0M0) NSCLC were treated with SBRT via VIGRT at 1 of 5 institutions from 1998-2009. Median age was 74y(42-92); 53% male, 47% female. Median FEV1 was 1.4L(65% predicted); median DLCO was 9.8 ml/min/mmHg(54% predicted). 62% of tumors were biopsy-proven; 84% of cases were staged with CT and PET. Clinical stage was IA in 76%, IB in 22%, locally recurrent in 1%. Median max tumor dimension was 2.4 cm (0.9-8.5cm). Histologies were: 41% adenocarcinoma, 34% squamous, 12% large cell, 13% NSCLC NOS. 8%, 51%, and 42% were grades 1, 2, 3. Median volumetric prescription dose (PD) was 54Gy (20-64Gy) delivered in median of 3 fractions(fx) (1-15fx) over 8d (1-27d). Median biological equivalent PD (BED10) was 132Gy (60-180Gy), equal to 2-Gy fx equivalent (FE) of 110Gy (50-150Gy). Corresponding GTV and PTV mean doses (2-GyFE) were 157Gy and 137Gy. Mean follow-up = 1.3y (0.1-7.3y). Results: 2-y KM rates of local recurrence (LR), regional recurrence (RR) and distant metastasis (DM) were 8%, 13%, and 26%. 2y overall survival (OS) and cause-specific survival (CSS) were 58% and 84%. No statistically significant differences in LR, RR, DM, OS or CSS were identified for biopsied vs. non-biopsied tumors. On univariate analysis, stage (IA 5% v IB 16%, p=0.002), GTV max dimension (<2.7cm 4% v ≥2.7cm 12%, p=0.006), and 2GyFE PD (<88Gy 17% v ≥88Gy 5%, p<0.001) predicted LR. GTV (<115Gy 32% v ≥115Gy 4%, p<0.001) and PTV (<105Gy 24% v ≥105Gy 4%, p<0.001) 2GyFE mean doses also predicted LR. Cox multiple regression confirmed the relationship between PD and LR, independent of GTV size (p=0.01). Conclusions: This is the first Lung SBRT dataset of patients treated uniformly with daily online VIGRT and resulted in excellent local control for stage I NSCLC. A 2-GyFE dose of 88 Gy (BED10 105 Gy) predicted superior local control. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Elekta

The Effect of Radiotherapy on Local Regional Recurrence among Patients with Pathologic Complete Response to Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer.

Abstract Background: Radiotherapy has been shown to reduce local recurrence rates of breast cancer after treatment with surgery and adjuvant chemotherapy. Indications for postmastectomy radiation have historically been based on pathology, but indications for radiation in the setting of pathologic complete response (pCR) to neoadjuvant chemotherapy are not well defined. The aim of this study was to evaluate the rates of local regional recurrence (LRR) among patients with pCR to neoadjuvant chemotherapy followed by surgery with or without radiation (XRT).Patients and Methods: The case histories of 337 patients with locally advanced breast cancer treated with neoadjuvant chemotherapy, surgery with or without radiation from October 1997 to December 2006 were analyzed. Median age at diagnosis was 50.6 years (range: 25-84). The clinical stage at diagnosis was I in 3 (1%), IIA in 105 (31%), IIB in 94 (28%), and III in 135 (40%) patients. All patients received preoperative systemic therapy with a doxorubicin-based regimen (92%) or a single-agent taxane regimen (7%) or CMF (1%). A total of 272 patients received radiation following surgery and 65 did not receive any radiation. Median follow-up time was 40 months among all patients. The Kaplan-Meier method and log rank test were used to evaluate LRR rates and overall survival among both groups.Results: Patients treated with neoadjuvant chemotherapy followed by surgery and XRT had a lower incidence of LRR at 3 years with 24 cases of local recurrence among 272 patients who received XRT compared with 12 cases of local recurrence among the 65 patients who did not receive XRT (8.9% v 18.5%, P=0.02). Radiation also reduced local regional recurrence at 3 years among a subset of patients with clinical stage T2N1 disease (4.9% v 28.6%, P=0.03). There was no difference in overall survival or disease free survival among patients who received XRT compared to patients who did not receive XRT. There were 62 (18%) patients who achieved a pCR to neoadjuvant chemotherapy. Among patients with a pathologic complete response, radiation appeared to reduce the risk of LRR compared to patients who did not receive XRT (7.4% v 25%, P=0.17).Conclusion: Radiotherapy significantly reduced local regional recurrence rate among patients with locally advanced breast cancer treated with neoadjuvant chemotherapy and surgery. Of particular interest, patients who achieve a pathologic complete response to neoadjuvant chemotherapy still had high LRR rates and may benefit from radiotherapy by lowering the risk of local regional recurrence. Further studies on the significance of LRR and overall survival among these patients are needed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4114.

Is Accelerated Partial Breast Irradiation Appropriate Adjuvant Therapy for Patients with Ductal Carcinoma In-Situ?

Abstract Introduction: Accelerated partial breast irradiation (APBI) using high-dose rate (HDR) balloon catheter breast brachytherapy following wide segmental resection of the breast has been shown to be equivalent to whole breast irradiation (WB-XRT) in the treatment of stage-I breast carcinoma. Because the majority of all breast cancers recur in the same quadrant as the original tumor, the advantages of this treatment compared with WB-XRT include concentration of radiation in the area where cancer is most likely to recur, shorter treatment duration, and greater patient acceptance. This study examined the rate of local/regional recurrence in patients diagnosed with stage-0 breast cancer, specifically ductal carcinoma in-situ (DCIS), following wide segmental resection of the breast and treatment with APBI using HDR balloon catheter breast brachytherapy.Methods: An IRB-approved, single-institution, retrospective chart review was conducted identifying 40 patients diagnosed with stage-0 breast cancer between March, 2004 and April, 2008 who were treated with wide segmental resection of the breast followed by APBI using HDR MammoSite™ balloon catheter breast brachytherapy. Outcome measures included rates of same-quadrant recurrence, ipsilateral second-primary occurrence, and regional recurrence.Results: Patient age ranged from 44 to 89 years (median = 69 years) with a median follow-up of 40 months (range: 16 to 60 months). All 40 patients had DCIS. One patient of 40 (2.5%) had DCIS with an additional focus of lobular carcinoma in-situ. 29 of 40 patients (72.5%) were estrogen receptor (ER) positive. Of these 29 patients, 17 were also progesterone receptor (PR) positive. One patient (2.5%) at 38 months experienced a local recurrence of DCIS with micro-invasion and a synchronous focus of invasive ductal carcinoma in a separate quadrant. This was subsequently treated with total mastectomy, sentinel lymph node mapping, and axillary lymph node dissection. No other patients experienced local-regional recurrence or ipsilateral primary breast cancer occurrence.Conclusion: Patients with DCIS can be effectively treated with APBI/HDR balloon catheter breast brachytherapy following wide segmental breast resection. The rate of local-regional recurrence was 2.5% at a median follow-up time of 40 months. This is consistent with that of patients with DCIS treated with wide segmental breast resection followed by WB-XRT. Long-term follow-up will be required to assure these rates remain favorable. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2116.

Is There a Role for Intraoperative Radiation Therapy in Patients with Resected Pancreatic Adenocarcinoma?

Is There a Role for Intraoperative Radiation Therapy in Patients with Resected Pancreatic Adenocarcinoma?

Local-regional and distant recurrence rates in skin-sparing mastectomies compared with non-skin-sparing mastectomies.

Abstract Abstract #4138 Background: Although skin-sparing mastectomies (SSMs) are becoming more common, there are few data regarding the local-regional and distant recurrence rates. The aim of this study was to examine the incidence of local-regional recurrence, distant recurrence, and survival in breast cancer patients who underwent SSMs or non-skin-sparing mastectomies (NSSMs) at our institution.&amp;#x2028; Methods: We reviewed records of patients with primary breast carcinoma stage 0 to III who underwent total mastectomies with or without complete axillary dissection at our center from January 2000 to December 2005. After excluding patients with bilateral breast cancer, mastectomies for recurrent breast cancer, and patients with less than two-year follow-up, there were 1623 patients for study. Patient and tumor characteristics were evaluated and comparisons undertaken between the SSM and NSSM groups with univariate and multivariate logistic analyses. Kaplan-Meier curves and log-rank test were used to evaluate the overall and disease-free survival in the two groups.&amp;#x2028; RESULTS: Of the 1623 patients, 465 (28.7%) patients underwent SSM and 1158 (71.3%) underwent NSSM. Patients who underwent NSSM were older (55.6 vs. 48.9, p&amp;lt;0.0001) and had more advanced stage tumor (stage II or high: 48.3% vs. 28%, p&amp;lt;0.0001). Significantly more patients in the NSSM group received systemic chemotherapy (p=0.045), radiation therapy (p&amp;lt;0.0001), and endocrine therapy (p=0.002). At a median follow-up of 24.4 months (range 1.1-95.3), 138 patients (4.6%) had local-regional or distant recurrence. Specifically, 7 patients (1.5%) in the SSM group and 34 patients (2.9%) in the NSSM group had local-regional recurrences (p=0.097). The distant recurrence rate in patients undergoing SSM or NSSM was 14 (3.0%) and 110 (9.5%) patients (p&amp;lt;0.0001) at median follow-up time of 29.2 and 25.4 months, respectively. There is no difference in disease-free survival between the SSM group and NSSM after adjusting for tumor TNM stage and final nodal status at a median follow-up time of 54.3 months and 53.2 months, respectively.&amp;#x2028; CONCLUSIONS: SSM is safe and effective in appropriately selected patients with breast carcinoma. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4138.

The number of axillary nodes removed as a predictor of regional recurrence in node negative breast cancer

Purpose To determine if the number of axillary nodes removed is a predictor of recurrence in node negative breast cancer. Materials and methods Five hundred thirty-six patients with T1–T2, N0 invasive breast cancer, treated with lumpectomy and axillary node dissection (AND), were reviewed from January 1, 1986 to December 31, 1992. Patients received radiation to whole breast only, without regional nodal radiation. There was no adjuvant chemotherapy or Tamoxifen given. Patients were grouped according to the number of axillary nodes dissected as follows: 1–5 nodes (91 patients), 6–10 nodes (225 patients) and >10 nodes (220 patients). Hazard ratios and p-values were determined for time to local recurrence, regional recurrence and for disease specific survival. Results Median follow-up was 11.2 years. The overall local recurrence and regional recurrence rates for the three groups were: 1–5 nodes, 9.9% and 8.8%, respectively, 6–10 nodes, 10.2% and 2.2%, respectively, and >10 nodes, 11.8% and 2.7%, respectively. The effect of number of axillary nodes removed was statistically significant only for regional recurrence ( p = 0.017). There was no adverse effect on disease specific survival ( p = 0.363). Conclusion The number of axillary nodes removed predicts only for regional recurrence in node negative breast cancer patients, with less than 6 nodes removed associated with higher regional recurrence. This may have clinical implications with the current practice of sentinel node biopsy (SNB) replacing axillary node dissection in early stage breast cancer.

Locoregional control in locally advanced breast cancer using neoadjuvant chemotherapy followed by breast conservation

539 Background: Neoadjuvant chemotherapy is commonly employed in the treatment of locally advanced breast cancer. However, the difference in local-regional recurrence (LRR) rates between those undergoing BCT and those with mastectomy is not well defined. The purpose of this study was to examine the incidence of LRR in these two groups after neoadjuvant chemotherapy at a single institution. Methods: Under IRB approval, a prospective database was utilized to identify all patients with locally advanced Stage II and III breast cancer undergoing neoadjuvant chemotherapy from 1991 to 2005. Patients presenting with stage IV disease or T4d primary breast cancer were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy by log-rank test and Cox regression analysis was utilized to evaluate individual variables associated with LRR. Results: 236 patients were included, 94 (40%) underwent BCT and 142 (60%) mastectomy. 93/94 (99%) of the BCT and 115/142 (81%) of the mastectomy patients received postoperative radiation. Pathologic complete response (CR) was seen in 60 patients, of which 34 underwent BCT. Those achieving BCT were more likely to have T2 or smaller tumors before treatment (p=0.0053) and smaller tumors post-treatment (p<0.0001) and were more likely to have a pathologic CR (p=0.0035) than those with mastectomy. At a median f/u of 58 months, the rate of LRR was 5% (5/94) in the BCT group and 9% (13/142) in the mastectomy group (p=0.32). Univariate Cox modeling showed ER status (p=0.01), number of positive axillary nodes (p=0.039), post-treatment T stage (p=0.02), tumor size post-treatment (p=0.04) and pathologic stage (p=0.008) were independent predictors of LRR. Pre-treatment T and N stage were not associated with LRR. Five-year overall survival was 90% in the BCT group and 69% in the mastectomy group (p=0.01). Conclusions: In this series of locally advanced breast cancer patients undergoing neoadjuvant chemotherapy, the rate of LRR was very low and was not significantly different between those undergoing BCT as compared to mastectomy. However, overall survival was improved in those achieving BCT, suggesting this may be a surrogate for prognosis. No significant financial relationships to disclose.

Local/regional recurrence following surgery for early-stage lung cancer: A 10-year experience with 975 patients

7542 Background: Surgery, with or without chemotherapy, is the preferred treatment for early-stage NSCLC. The risk of local/regional recurrence (LRR) after resection is not well defined, but generally considered to be small in comparison to the risk of distant recurrence. We herein evaluate the actuarial risk of LRR after surgery for stage I-II disease and assess surgical and pathologic factors affecting this risk. Methods: The medical records and pertinent radiographs of all patients who underwent surgery for pathological T1- 2N0–1 NSCLC at Duke between 1995–2005 were reviewed. Patients receiving preoperative therapy, or with synchronous/prior lung cancers were excluded. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was considered a LRR. Nodal failures were defined as a new or enlarging LN≥1 cm on short axis on CT or hypermetabolic on PET. The actuarial rates of LRR and distant recurrence (assessed independently) were estimated using the Kaplan-Meier method. A univariate and multivariate regression analysis assessed factors associated with LRR. Results: Of 975 patients, 45% were stage IA, 40% IB, and 15% stage II; 79% underwent ≥ lobectomy; 85% had sampling/dissection of mediastinal LNs; 4% had positive margins; 7% received adjuvant chemotherapy; 3% received adjuvant radiation therapy. The 5-year actuarial rate of LRR was 22% and distant recurrence was 31%. LRR was higher for stage IB, IIA, and IIB compared with IA (hazard ratio- 2, 2.6, and 1.9). Sublobar resections were associated with a higher risk of LRR on univariate, but not multivariate, analysis. On multivariate analysis, increasing size, squamous or large cell histology, visceral pleural invasion, stage IIA disease, and lack of nodal sampling were independently associated with a higher rate of LRR. Conclusions: The risk of LRR after surgery for stage I-II NSCLC is ≈22%, and is similar to the risk of distant recurrence. Thus, local control remains an important issue justifying continued clinical research in this area. Postoperative RT, utilizing modest doses and small conformal fields directed to sites most at risk, should be reevaluated. As systemic therapy improves, the relative importance of achieving local control will also increase. No significant financial relationships to disclose.

Fluorouracil, Mitomycin, and Radiotherapy vs Fluorouracil, Cisplatin, and Radiotherapy for Carcinoma of the Anal Canal

Chemoradiation as definitive therapy is the preferred primary therapy for patients with anal canal carcinoma; however, the 5-year disease-free survival rate from concurrent fluorouracil/mitomycin and radiation is only approximately 65%. To compare the efficacy of cisplatin-based (experimental) therapy vs mitomycin-based (standard) therapy in treatment of anal canal carcinoma. US Gastrointestinal Intergroup trial RTOG 98-11, a multicenter, phase 3, randomized controlled trial comparing treatment with fluorouracil plus mitomycin and radiotherapy vs treatment with fluorouracil plus cisplatin and radiotherapy in 682 patients with anal canal carcinoma enrolled between October 31, 1998, and June 27, 2005. Stratifications included sex, clinical nodal status, and tumor diameter. Participants were randomly assigned to 1 of 2 intervention groups: (1) the mitomycin-based group (n = 341), who received fluorouracil (1000 mg/m2 on days 1-4 and 29-32) plus mitomycin (10 mg/m2 on days 1 and 29) and radiotherapy (45-59 Gy) or (2) the cisplatin-based group (n = 341), who received fluorouracil (1000 mg/m2 on days 1-4, 29-32, 57-60, and 85-88) plus cisplatin (75 mg/m2 on days 1, 29, 57, and 85) and radiotherapy (45-59 Gy; start day = day 57). The primary end point was 5-year disease-free survival; secondary end points were overall survival and time to relapse. A total of 644 patients were assessable. The median follow-up for all patients was 2.51 years. Median age was 55 years, 69% were women, 27% had a tumor diameter greater than 5 cm, and 26% had clinically positive nodes. The 5-year disease-free survival rate was 60% (95% confidence interval [CI], 53%-67%) in the mitomycin-based group and 54% (95% CI, 46%-60%) in the cisplatin-based group (P = .17). The 5-year overall survival rate was 75% (95% CI, 67%-81%) in the mitomycin-based group and 70% (95% CI, 63%-76%) in the cisplatin-based group (P = .10). The 5-year local-regional recurrence and distant metastasis rates were 25% (95% CI, 20%-30%) and 15% (95% CI, 10%-20%), respectively, for mitomycin-based treatment and 33% (95% CI, 27%-40%) and 19% (95% CI, 14%-24%), respectively, for cisplatin-based treatment. The cumulative rate of colostomy was significantly better for mitomycin-based than cisplatin-based treatment (10% vs 19%; P = .02). Severe hematologic toxicity was worse with mitomycin-based treatment (P < .001). In this population of patients with anal canal carcinoma, cisplatin-based therapy failed to improve disease-free-survival compared with mitomycin-based therapy, but cisplatin-based therapy resulted in a significantly worse colostomy rate. These findings do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma. clinicaltrials.gov Identifier: NCT00003596.

Impact of mandibular condyle preservation on patterns of failure in head and neck cancer

To determine the role of native condyle preservation in local recurrence after segmental mandibulectomy in patients with head and neck squamous cell carcinoma. Retrospective chart review with main outcome measuring local control of cancer. Between 1994 and 2003, 72 patients (48 men, 24 women) with an average age of 73.5 years without previous treatment underwent segmental mandibulectomy. Fifty-four cases (n = 54) involved the mandible posterior to the mental foramen and are the subject of this review. In 36 patients, the condyle was preserved and mandibular continuity was restored. In 18 patients, condyle and ramus were resected without mandibular reconstruction. Reconstructive modalities included primary closure (3), split-thickness skin graft (3), pedicle flap (19), and free tissue reconstructions (29). Overall local-regional recurrence rate was 22 percent (12 of 54); no recurrences were identified in patients who underwent condylar resection. Recurrences were observed in patients with mandibular reconstruction by both plate and pedicle flap (5 of 9) or (osteo) myocutaneous free flap (7 of 27). Condylar preservation may predispose patients to local recurrence after segmental mandibulectomy. This does not translate into overall reduction in survival.

Long-term outcomes in patients with mucinous, medullary, tubular, and invasive ductal carcinomas after lumpectomy

Background Mucinous, medullary, and tubular carcinomas are uncommon types of breast cancer whose rarity does not permit large single-institution studies or randomized trials to define optimal treatments. In this study, we evaluated the long-term outcomes of breast-conserving therapy (BCT) for these subtypes of breast cancer and compared them with those for invasive ductal carcinoma. Methods In our institutional database of patients who received BCT from 1965 to 1999, 1,643 patients with stage I to II mucinous (61), medullary (37), tubular (60), and invasive ductal (1,485) histologies were identified. The clinical and pathologic features of the 4 groups were evaluated and compared with respect to local-regional recurrence rates, disease-free survival, and overall survival (OS). Results No statistically significant differences were found in the local-regional failure rate among the 4 groups (10.6-year median follow-up). Only patients with tubular carcinoma had better 5- and 10-year OS rates ( P = .013). In multivariable analysis, factors associated with improved OS included age at or below 50 years, negative nodal status, use of chemotherapy or hormonal therapy, and tubular histology. Conclusions BCT for mucinous, medullary, or tubular carcinoma resulted in similar local-regional failure rates to that for invasive ductal carcinoma. Tubular carcinoma patients had the most favorable OS. BCT is an appropriate treatment strategy for early-stage mucinous, medullary, and tubular carcinomas.

Postmastectomy Radiation Improves the Outcome of Patients With Locally Advanced Breast Cancer Who Achieve a Pathologic Complete Response to Neoadjuvant Chemotherapy

The aim of this study was to investigate the role of postmastectomy radiation therapy in women with breast cancer who achieved a pathologic complete response (pCR) to neoadjuvant chemotherapy. We retrospectively identified 226 patients treated at our institution who achieved a pCR at surgery after receiving neoadjuvant chemotherapy. Of these, the 106 patients without inflammatory breast cancer who were treated with mastectomy were analyzed. The patients' clinical stages at diagnosis were I in 2%, II in 31%, IIIA in 30%, IIIB in 25%, and IIIC in 11% (American Joint Committee on Cancer 2003 system). Of the patients, 92% received anthracycline-based chemotherapy, and 38% also received a taxane. A total of 72 patients received postmastectomy radiation therapy, and 34 did not. The actuarial rates of local-regional recurrence (LRR) and survival of the two groups were compared using the log-rank test. The median follow-up of surviving patients was 62 months. Use of radiation therapy did not affect the 10-year rates of LRR for patients with Stage I or II disease (the 10-year LRR rates were 0% for both groups). However, the 10-year LRR rate for patients with Stage III disease was significantly improved with radiation therapy (7.3% +/- 3.5% with vs. 33.3% +/- 15.7% without; p = 0.040). Within this cohort, use of radiation therapy was also associated with improved disease-specific and overall survival. Postmastectomy radiation therapy provides a significant clinical benefit for breast cancer patients who present with clinical Stage III disease and achieve a pCR after neoadjuvant chemotherapy.

1–37 Breast Conservation Surgery Achieving ≥ 2 mm Tumor-Free Margins Results in Decreased Local-Regional Recurrence Rates

1–37 Breast Conservation Surgery Achieving ≥ 2 mm Tumor-Free Margins Results in Decreased Local-Regional Recurrence Rates

Local-regional recurrence after surgery without postoperative irradiation for carcinomas of the major salivary glands: Implications for adjuvant therapy

To determine factors predictive of local-regional recurrence (LRR) after surgery alone for carcinomas of the major salivary glands in an attempt to evaluate the potential role of postoperative radiation therapy. Between 1960 and 2004, 207 patients with carcinomas of the major salivary glands were treated with definitive surgery without postoperative radiation therapy. Histology was: 67 mucoepidermoid (32%), 50 adenoid cystic (24%), 34 acinic cell (16%), 23 malignant mixed (11%), 16 adenocarcinoma (8%), 6 oncocytic (3%), 6 myoepithelial (3%), and 5 other (2%). Distribution of pathologic T-stage was: 54 T1 (26%), 83 T2 (40%), 46 T3 (22%), and 24 T4 (12%). Sixty patients (29%) had microscopically positive margins. Median follow-up was 6.1 years (range, 0.5-18.7 years). The 5-year and 10-year estimates of local-regional control were 86% and 74%, respectively. A Cox proportional hazard model identified pathologic lymph node metastasis (hazard ratio [HR], 4.8; p = 0.001), high histologic grade (HR, 4.2; p = 0.003), positive margins (HR, 2.6; p = 0.03), and T3-4 disease (HR, 2.0; p = 0.04) as independent predictors of LRR. The presence of any one of these factors was associated with 10-year local-regional control rates of 37% to 63%. Lymph node metastasis, high tumor grade, positive margins, and T3-4 stage predict for significant rates of LRR after surgery for carcinomas of the major salivary glands. Postoperative radiation therapy should be considered for patients with these disease characteristics.

2011: The Number of Axillary Nodes Removed as a Predictor of Regional Recurrence in Node Negative Breast Cancer

To determine if the number of axillary nodes removed is a predictor of recurrence in node negative breast cancer. Five hundred thirty-six patients with T1-T2, N0 invasive breast cancer, treated with lumpectomy and axillary node dissection (AND), were reviewed from January 1, 1986 to December 31, 1992 at the London Regional Cancer Program. Patients received radiation to whole breast only, without regional nodal radiation. There was no adjuvant chemotherapy or Tamoxifen given. Patients were grouped according to the number of axillary nodes dissected as follows: 1–5 nodes (91 patients), 6–10 nodes (225 patients) and >10 nodes (220 patients). Hazard ratios and p-values were determined for time to local recurrence, regional recurrence and for disease specific survival. Median follow-up was 11.2 years. The overall local recurrence and regional recurrence rates for the three groups were: 1–5 nodes, 9.9% and 8.8% respectively, 6–10 nodes, 10.2% and 2.2% respectively, and >10 nodes, 11.8% and 2.7% respectively. The effect of number of axillary nodes removed was statistically significant only for regional recurrence (p=0.017). There was no adverse effect on disease specific survival (p=0.363). The number of axillary nodes removed predicts only for regional recurrence in node negative breast cancer patients, with <6 nodes removed associated with higher regional recurrence. This may have clinical implications with the current practice of sentinal node biopsy (SNB) replacing axillary node dissection in early stage breast cancer.

Outcomes of breast-conservation therapy for invasive lobular carcinoma are equivalent to those for invasive ductal carcinoma

Background Breast-conservation therapy (BCT), including wide local excision and postoperative irradiation, is considered standard treatment for early-stage invasive ductal carcinoma (IDC). The use of BCT in patients with invasive lobular carcinoma (ILC) has been questioned because of concerns regarding ipsilateral breast recurrence and risk of bilateral breast cancer. We evaluated our institutional experience with BCT and compared treatment outcomes for ILC with those for IDC. Methods A review of our BCT database revealed 84 patients with ILC and 1,126 with IDC with stage I or II disease treated with BCT and radiation between 1976 and 1999. We evaluated local-regional recurrence, disease-specific survival, and contralateral breast cancer rates in both groups. Results The 5- and 10-year local-regional recurrence rates for the ILC group were 1% and 7%, respectively, and 4% and 9%, respectively, for the IDC group ( P = .70). There were no significant differences in the 5- and 10-year disease-specific survival rates between the groups. Contralateral breast cancer occurred in 11.3% of patients with IDC and 11.9% of patients with ILC. Conclusions BCT achieves similar local-regional control and survival outcomes in selected patients with ILC or IDC. Breast-conservation therapy is an appropriate treatment strategy for patients with early-stage invasive lobular carcinoma.

Conservative treatment for infiltrating breast cancer: Ten years follow-up experience

We retrospectively analyze our experience in conservative treatment for infiltrating advanced breast cancer before implementation of selective sentinel node biopsy, specially focusing on characteristics, incidence, treatment and evolution of local-regional recurrences, disease-free survival time, overall survival and patient's satisfaction. From January 1984 to 31st December 1998, 739 female patients were operated in our institution, diagnosed as having infiltrating breast cancer. One hundred and eighty-eight patients (25.43%) received conservative treatment and they were followed up until December 2003. Average age when diagnosed was 50.42 years old (24-87 years). 53.19% of the patients were premenopausal. After a median follow-up of 129 months (60-198 months), 13 women (6.91%) presented local -regional recurrence and the disease-free time was 48.4 months (8-108 months). Global survival rate was 83.5% and disease free survival rate was 80.85%. The management of choice for early stage (I and II) infiltrating breast cancer is nowadays conservative, with a low local-regional recurrence rate and survival rate that are comparable to radical mastectomy, according to the literature. It's a safe and efficient method that let us preserve the breast with a good esthetical result. In selected cases, when a regional recurrence occurs, a second conservative management is possible with a good control of the disease, although the most widely accepted treatment in these cases is total mastectomy.

Comparison of risk of local-regional recurrence after mastectomy or breast conservation therapy for patients treated with neoadjuvant chemotherapy and radiation stratified according to a prognostic index score

We previously developed a prognostic index that stratified patients treated with breast conservation therapy (BCT) after neoadjuvant chemotherapy into groups with different risks for local-regional recurrence (LRR). The purpose of this study was to compare the rates of LRR as a function of prognostic index score for patients treated with BCT or mastectomy plus radiation after neoadjuvant chemotherapy. We retrospectively analyzed 815 patients treated with neoadjuvant chemotherapy, surgery, and radiation. Patients were assigned an index score from 0 to 4 and given 1 point for the presence of each factor: clinical N2 to N3 disease, lymphovascular invasion, pathologic size>2 cm, and multifocal residual disease. The 10-year LRR rates were very low and similar between the mastectomy and BCT groups for patients with an index score of 0 or 1. For patients with a score of 2, LRR trended lower for those treated with mastectomy vs. BCT (12% vs. 28%, p=0.28). For patients with a score of 3 to 4, LRR was significantly lower for those treated with mastectomy vs. BCT (19% vs. 61%, p=0.009). This analysis suggests that BCT can provide excellent local-regional treatment for the vast majority of patients after neoadjuvant chemotherapy. For the few patients with a score of 3 to 4, LRR was >60% after BCT and was <20% with mastectomy. If these findings are confirmed in larger randomized studies, the prognostic index may be useful in helping to select the type of surgical treatment for patients treated with neoadjuvant chemotherapy, surgery, and radiation.

Breast-Conserving Therapy after Neoadjuvant Chemotherapy: Long-term Results

The purpose of this study was to determine patterns of ipsilateral breast tumor recurrence (IBTR) and local-regional recurrence (LRR) after neoadjuvant chemotherapy and breast-conserving therapy (BCT). A total of 153 breast cancer patients were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy between 1980 and 2002. The clinical stage (American Joint Committee on Cancer [AJCC] 1997) at diagnosis was IIA in 22%, IIB in 28%, IIIA in 39%, and IIIB in 11%. The prechemotherapy T size distribution was less than 2 cm in 5 patients, 2.1-5 cm in 100 patients, and greater than 5.1 cm in 48 patients. Sixty-seven patients (44%) underwent cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy and 86 (56%) underwent Adriamycin-based chemotherapy. Thirty-seven patients (24%) had a complete pathologic response in the breast. All procedures were performed by a single surgeon (G.F.S.). The surgery was local excision alone in 19 patients, local excision and axillary lymph node dissection (ALND) in 130 patients, and ALND alone in 4 patients. Eleven patients had positive surgical margins. Rates of LRR-, IBTR-, and distant metastasis (DM)-free survival were calculated by the Kaplan-Meier method. Patient and pathologic variables were then analyzed in an attempt to identify predictors of clinical outcome. With a median follow-up period of 55 months (range 6-200 months), eight patients developed LRR, five of which were classified as IBTR. Five- and 10-year actuarial rates of LRR-free, IBTR-free, and DM-free survival were 93% and 88%, 96% and 91%, and 70% and 58%, respectively. Pretreatment and pathologic parameters that positively correlated with IBTR were advanced stage (p = 0.03) and margin positivity (p = 0.04). No other clinical factors were predictive of higher recurrence. BCT results in a low rate of IBTR and LRR in appropriately selected patients. Advanced stage at presentation is associated with increased risk of IBTR, although overall recurrence is low. In selected cases, BCT is safe and an effective alternative to mastectomy.