Microscopic Surgical Margins Research Articles

Malignant phyllodes tumor of the breast: treatment and prognosis.

Surgery remains the mainstay of the treatment in patients with malignant phyllodes tumor of the breast (MPTB); however, the extent of surgery (breast conserving surgery [BCS] versus mastectomy) and the role of adjuvant radiotherapy have been controversial. We report a single institution's experience with MPTB. We discuss controversial therapeutic aspects of this rare tumor. Seventy patients with MPTB treated primarily with surgery were evaluated. The mean age was 50years (21-76), and the mean size of the tumor was 6cm. Thirty-four (48.6%) patients were treated with total mastectomy, and 36 (51.4%) were treated with BCS (lumpectomy or wide local excision). Microscopic surgical margins were free of tumor in all cases. In 64 (91.4%) patients, margins were ≥1cm. Remaining 6 (8.6%) patients treated with BCS margins were <1cm and subsequently radiotherapy was performed. Among 70 patients, 58 (82.9%) had no evidence of disease (NED) after 5years. The extent of surgery was not significantly related to the 5-year NED survival rates (82.4% in patients who underwent mastectomy and 83.3% in patients who underwent BCS only or BCS with adjuvant irradiation). The 5-year NED survival rates in BCS (tumor-free margin ≥1cm) and BCS with irradiation (tumor-free margin <1cm) groups were identical (83.3%). Our data support the potential use of BCS in patients with MPTB. Mastectomy is indicated only if tumor-free margins cannot be obtained by BCS. Adjuvant radiotherapy may be considered if tumor-free margins are <1cm.

Desmoid Tumor of the Rectus Abdominis Muscle in a Postpartum Patient

Desmoid Tumor of the Rectus Abdominis Muscle in a Postpartum Patient

Influence of prognostic factors in pediatric high-grade osteosarcoma survival.

9572 Background: Some others prognostic factors are interrelated with the well-known prognostic factors in high-grade Osteosarcoma (HGO), this can result in poor survival and should be considered for appropriate clinical decision making. Methods: Retrospective, longitudinal and clinical study was performed from Jan/1991-Dec/1998, 58 patients younger than 18 years with extremity HGO and no prior chemotherapy treatment were included. All received CDDP, DOX, CFA and VP-16. Prognostic-factors and Cox analysis with odds-ratio (OR) and p<0.05 were calculated. Outcome variables were age, histologic patterns (HP), primary site, tumor size (TS), metastatic disease, soft-tissue involvement (STI), histological response (HR) assessed by Huvos-grades and disease-free survival (DFS). Results: Median age was 12 years (5-18y) with 18 patients (31%) younger than 10 years. Skeletal site (SS) distribution was 59% distal femur, 17% proximal humerus, 14% proximal tibia, 7% fibula and 3% proximal femur. 18 patients (31%) had pulmonary metastases and 3 patients (5%) had multifocal disease at diagnosis. There were 74% osteoblastic tumors, 14% osteoblastic and chondroblastic, and 5% chondroblastic. 15 patients had an amputation procedure and 33 patients undergoing limb salvage of which 5 patients (15%) had eventual local recurrence. The more significant associated prognostic factors (APF) for local recurrence were STI at diagnosis (OR=6), grade-II HR (OR=2.8), grade-III HR (OR=10), TS (p0.0350) and chondroblastic-HP (p0.0089). For amputation procedures were SS (p0.0018) and have microscopic surgical margins (MSM) p0.0075. For development of metastatic disease were TS (p0.0008), MSM (p0.000), pulmonary metastases at diagnosis (p0.000), SS (p0.000) and chondroblastic-HP (p0.000). For death by tumor activity was poor in HR (p0.0013) and TS (p0.0278). 5-years DFS without APF was 68% Vs 43% with APF (p0.021). Conclusions: APF play a very important roll in Osteosarcoma prognosis and should be considered for appropriate clinical decisions making.

Clinical outcomes for patients with soft tissue sarcoma of the hand

In an earlier report from the current study center regarding surgical treatment for patients with soft tissue sarcoma (STS) of the hand, it was concluded that repeat resection or amputation improves outcomes. Since then, the authors have aggressively sought to achieve negative resection margins, using standard or modified amputations when needed, and performing repeat resections to negative surgical margins when they were not achieved at the time of initial surgery. The current review was conducted to determine whether this approach resulted in better outcomes. A retrospective review of 53 patients with STS of the hand who were treated between 1996 and 2005 was performed. Recurrence-free survival (RFS) and functional outcome of hand-preserving procedures were assessed according to the Musculoskeletal Tumor Society (MSTS) system. The median RFS was not reached at the time of last follow-up. Of 53 patients, 6 (11%) had positive microscopic resection margins. Three patients underwent repeat resection to negative surgical margins, whereas another 3 patients did not. All 3 patients with positive microscopic surgical margins that were not re-excised developed local disease recurrence; 2 patients also developed distant metastases. Two of the 50 patients with negative resection margins developed distant metastases. All 5 patients who developed local and/or distant disease recurrence had deep tumors. The median MSTS score was 29 (interquartile range, 27-30). Patients who underwent more extensive resections, such as double ray amputations, had lower MSTS scores. Suboptimal biopsies and positive resection margins are associated with local and distant disease recurrence in patients with STS. The results of the current study suggest that aggressive surgical treatment can result in better clinical outcomes, and underscore that care must be taken when planning biopsies of hand tumors.

Microvascular reconstruction after resection of soft tissue sarcoma of the leg

Limb-sparing surgery and satisfactory functional outcome is the goal of extremity soft tissue sarcoma (STS) surgery. Tissue defects after tumour excision are often extensive, and microvascular reconstruction is frequently required. Seventy-three patients with STS of the leg requiring microvascular reconstruction were treated between 1985 and 2006. Radiotherapy was delivered if the microscopic surgical margin was less than 2.5 cm. Mean follow-up was 65.9 months. Seventy-five free flaps were performed, with a success rate of 95 per cent. One patient died within a month of surgery. Five-year local recurrence-free survival was 82 per cent, metastasis-free survival 59 per cent, disease-free survival 56 per cent and disease-specific overall survival 70 per cent. Fifty-five (75 per cent) of the 73 patients were able to walk normally or had only minor walking impairment. Without microvascular reconstruction, amputation would have been necessary in most patients. Microvascular reconstruction is safe and reliable in lower extremity STS reconstruction.

Six month follow up on a series of patients treated with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation.

Abstract Abstract #5149 Purpose: Phase IV prospective post market study to evaluate the safety and device performance of electronic brachytherapy treatment using the Xoft Axxent System as adjuvant therapy for early stage breast cancer.&amp;#x2028; Methods and Materials: 44 patients were enrolled between April 2007 and March 2008, and 13 patients have completed 6 months of follow up to date. Patients were eligible if they were older than 50 years, had completely resected DCIS (&amp;lt;2.0cm) or invasive ductal carcinoma (&amp;lt;2.0cm), and microscopic surgical margins of at least 1mm. The balloon applicator was placed in a closed cavity and a balloon surface to skin distance of at least 7mm was required for treatment. The radiation treatment (RT) consisted of delivering 3.4 Gy/fraction twice a day for 10 total fractions. The primary endpoint was the successful delivery of the prescribed RT. Secondary endpoint was adverse device related events.&amp;#x2028; Results: Thirteen of the forty-four patients that were enrolled and treated on this study have been followed a minimum of 6 months. The three month follow-up included cosmesis evaluation using the Harvard Cosmesis Scale, and adverse events. The three month cosmesis evaluated by physicians' showed 100% of the patients rated with excellent to good cosmesis. Related adverse events reported through three months included a total of fifteen CTC v3 Grade One AEs. Events included erythema, itching, induration, skin firmness, rash/ desquamation, fatigue. Of these events 90% were resolved. The six month cosmesis physician evaluations showed 82% of the patients had excellent to good cosmesis. Twelve of the 13 patients rated the appearance of their breast, in addition to the physician assessment, and 12 out of 12 rated their appearance good to excellent, one patient did not select any rating. Adverse events reported at six months were a total of three new CTC v3 Grade One. These AEs included occurrences of induration, skin firmness, and hyperpigmentation. A patient satisfaction survey at 6 months follow-up was completed by the patients. Certain survey questions required an answer using a scale of 0-6 for the ratings, where six was the best score. The patients' mean overall rating of satisfaction with the study participation was 5.55 out of 6 (min 3, max 6), satisfied with the radiation treatment was rated 5.54 out of 6 (min 3, max 6). All 13 patients, 100%, stated they would recommend this treatment to a friend.&amp;#x2028; Conclusion: This report provides an early look at the experience of using electronic brachytherapy as a means for intracavitary partial breast radiotherapy. The first cohort has reached a minimum of 6 months of follow up and the results appear promising. Additional patient follow up will be presented at the meeting. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5149.

Overall Survival with Cisplatin and 5-Fluorouracil Neoadjuvant Treatment in Patients with Esophageal Cancer: Single-Center Experience

Background: The survival benefit of neoadjuvant chemotherapy in patients undergoing surgery for esophageal cancer is unclear. Patients and Methods: We retrospectively identified 37 patients with resectable esophageal squamous cell carcinoma or adenocarcinoma, who prior to surgery received 2 cycles of chemotherapy, consisting of cisplatin 80 mg/m² as 3-h intravenous infusion on day 1 followed by 5-fluorouracil 1,000 mg/m² as 96-h continuous infusion on days 1–4, separated by a 3-week interval. Surgery was performed 3–5 weeks after the start of the second cycle of chemotherapy. Results: The overall response rate was 30% (all partial responses). All patients underwent surgery, 32 with esophagectomy (29 transhiatal, 3 transthoracic). Median overall survival (OS) in all patients was 23 months, and was longer in responding than in non-responding patients (32 vs. 19 months). 5 patients with locally unresected tumor and 18 patients with microscopic surgical margin involvement (R1) underwent postoperative chemoradiotherapy or radiotherapy. Median OS in patients after radical tumor resection (R0) was comparable with that in patients who underwent R1 resection (25 vs. 23 months). Conclusions: This retrospective analysis suggests that neoadjuvant chemotherapy prolongs survival in patients with esophageal cancer who responded to chemotherapy compared with non-responding patients.

Adjuvant Chemoradiation for Gastric Cancer: Experience in the Chinese Population

Aims The role of adjuvant chemoradiation for gastric cancer after curative R0 gastrectomy was first established by the US Intergroup 0116 study. Although confirmatory studies are in progress, few data are available regarding its application to the Chinese population. We describe our radiotherapy technique and report the treatment results in Hong Kong. Materials and methods This was a single centre retrospective study on 63 Chinese patients who underwent adjuvant chemoradiation for gastric adenocarcinoma between June 2000 and December 2004. The treatment protocol was based on that of the Intergroup study. Computed tomography planned anteroposterior opposing field arrangement and treatment under breath hold at deep inspiration position were adopted. Results In total, 63 patients, mean age 50 years, with gastric cancer stage IB to limited metastatic IV disease were analysed. The median follow-up time was 27.2 months. The relapse-free survival and overall survival at 3 years were 50 and 54%, respectively. The recurrence pattern was dominated by distant failure and only one patient developed isolated locoregional recurrence. Of the 10 patients who had positive microscopic surgical margins after surgery, seven had recurred and died. On multivariate analysis, margin status was the only significant prognosticator for survival. Thirty per cent of patients experienced grade 3 or above acute toxicity (24% haematological, 14% gastrointestinal) and one patient died of neutropenic sepsis. There was one case of grade 3 late toxicity. Conclusions The outcome after adjuvant chemoradiation for gastric cancer seemed to be favourable, with manageable toxicities, in the Chinese population. Locoregional failure was uncommon. Patients with microscopic surgical margin involvement had a very high failure rate despite adjuvant chemoradiation.

Clear cell sarcoma of tendons and aponeuroses: An analysis of 75 cases

9572 Background: Clear cell sarcoma (CCS) of tendons and aponeuroses is a rare malignant tumor that occurs most commonly in the extremities of young adults. Because of the rarity of the disease (1% of all soft tissue sarcomas), most reports about CCS have dealt with a few cases during a long time period. We conducted a multi-institutional study of CCS to clarify the clinical findings and prognostic factors of CCS treated during the era of modern multidisciplinary treatment. Methods: The records of 75 consecutive patients with histologically confirmed CCS treated at the JMOG affiliated institutions between 1980 and 2004 (follow-up; average 44 months) were reviewed. There were 41 men and 34 women with an average age of 36 years (range, 10–71 years). 65 tumors were in the extremities (foot 22, hand 13, thigh 9, others 21) and 10 were in the trunk. The tumor size ranged from 1 to 11 cm (mean, 4 cm). 52 patients presented with localized disease (M0) and 23 with metastatic disease (M1). Results: Surgical excision of the primary tumor was performed in 71 patients (limb-sparing surgery; 56, amputation; 15). Microscopic surgical margin was negative in 60 and positive in 11. 56 patients received chemotherapy (30 with measurable disease) and 17 had radiotherapy. Local recurrence occurred in 16 patients and 48 patients developed metastasis. The 5-year overall survival rate was 47% (M0; 55%, M1; 20%). On univariate analysis, sex (p=0.02), size (p=0.001), depth (p=0.002), TNM stage (p=0.001), IRS group (p=0.001) and surgical margin (p=0.04) were prognostic factors. On multivariate analysis, size (p=0.02) remained to be a significant prognostic factor. Objective response to chemotherapy was observed in 8 (27%) patients. In the group of M0 patients, those who received adjuvant chemotherapy had better prognosis (5-year survival, 65%) than those without chemotherapy (5-year survival, 23%)(p=0.03). Conclusions: The results support the contention that early diagnosis and initial excision with negative surgical margin are essential for favorable outcome of CCS. The role of chemotherapy for CCS should be further investigated. No significant financial relationships to disclose.

SYNOVIAL SARCOMA OF THE EXTREMITIES: PROGNOSTIC FACTORS FOR 20 NONMETASTATIC CASES AND A NEW HISTOLOGIC GRADING SYSTEM WITH PROGNOSTIC SIGNIFICANCE

To evaluate 20 cases of nonmetastatic synovial sarcoma of the extremities regarding prognostic factors, and to propose a histologic grading system with prognostic significance. The cases of 20 patients (14 females and 6 males) with nonmetastatic synovial sarcomas of the extremities treated between 1985 and 1998, were retrospectively evaluated regarding prognostic factors. A histologic grading system with prognostic significance is proposed. The mean follow-up period was 48.4 months (range, 16-116 months). There was local recurrence in 3 cases (15%), microscopic surgical margin being the only prognostic factor identified. Seven patients (35%) died of the disease in a mean postoperative period of 31.7 months (range, 16-53 months), all with pulmonary or brain metastasis. The survival rate was 65% in 48.4 months of follow-up. The unfavorable prognostic factors identified regarding survival were high histologic grade, tumors proximal to the knee or elbow, and spontaneous tumor necrosis over 25%. Local recurrence did not have influence on survival in this study. The presence of mast cells appears to have a positive influence on survival, although statistical significance was not reached (P = 0.07). The oncologic and functional result was good in 6 cases (30%), regular in 7 (35%), and poor in 7 cases (35%).

Giant Cornu Cutaneum

A 58-year-old male presented in our department with a large cutaneous horn of the right preauricular area. The lesion had reportedly been present and slowly growing during the last 3 years, reaching a final size of 10.5 × 3 × 1.3 cm. The patient was asymptomatic and reported a history of significant sunlight exposure due to his occupation as a construction worker. There was no history of previous trauma, spontaneous bleeding, or ulceration. A second cutaneous lesion of significant size was noted on the nasal dorsum. The patient underwent surgical excision of the horn and plastic reconstruction with the use of a local flap. Histological examination revealed the presence of a well-differentiated squamous cell carcinoma arising on the basis of underlying actinic keratosis. Microscopic surgical margins were negative. The second lesion, which was simultaneously resected, histologically represented a basal cell carcinoma of the nasal dorsum. http://www.entnet.org/journal/casereports/OTO-18.pdf/

Toxicity and Survival Results of a Phase II Study Investigating the Role of Postoperative Chemo-radioimmunotherapy for Gastric Adenocarcinoma

To investigate the role of postoperative concomitant chemo-radioimmunotherapy in gastric adenocarcinoma patients. 59 patients, who underwent total or subtotal gastrectomy, with lymph node involvement, positive microscopic surgical margins or serosal involvement were included in the study. Radiotherapy started concomitantly with chemotherapy and levamisole. Extended-field radiotherapy was given to gastric bed and regional lymphatics via two anterior-posterior/posterior-anterior fields. A total dose of 45 Gy in 25 fractions with a fraction size of 1.8 Gy was planned. In 28 patients (48%) with positive surgical margins a 10-Gy boost dose was given to the anastomosis site. An adjuvant i.v. bolus of 450 mg/m(2)/day 5-fluorouracil (5-FU) was administered concomitantly during the first 3 days and at the 20th day of irradiation. After completion of radiotherapy, i.v. boluses of 450 mg/m(2)/day 5-FU and 25 mg/m(2)/day rescuvorin were continued for 6 months once a week. Levamisole 40 mg/day orally was started at the 1st day of radiotherapy and also continued for 6 months. Median follow-up was 37 months (7-112 months). Median survival was 23 months. Overall 3- and 5-year survival rates amounted to 35% and 14%, respectively. Median survival of the patients with positive surgical margins was 22 months. The 3- and 5-year locoregional control rates were 59% and 55%, respectively. The most common toxicity was upper gastrointestinal system toxicity, which was observed in 42 patients (71%). Four patients (7%) died on account of early toxic effects, and six (10%) could not complete treatment. Although 48% of the study population involved patients with microscopic residual disease, the survival results as a whole were satisfactory. However, due to high toxicity, radiotherapy must be delivered with the most proper techniques along with adequate nutrition and supportive care.

Radiothérapie adjuvante des sarcomes des tissus mous des membres : analyse du contrôle local en fonction des volumes irradiés et de la dose

To evaluate retrospectively the anatomical definition of target volumes in the treatment of soft tissue sarcomas of the limbs and to study the radiation dose in the local control and toxicity. Seventy-seven patients were consecutively treated for primary soft tissue sarcoma of the extremity with limb sparing surgery and external beam radiotherapy (EBRT) in the same institution. The median follow up was 56 months (17-89 months). Fifty-two patients (67%) had clear microscopic surgical margin (R0 resection), 23 (30%) had histologically positive microscopic margin (R1 resection), 2 had a macroscopic residual disease (R2 resection). An anatomical definition of target volumes has been realised. The mean dose was 50 Gy in 25 or 28 fractions; 23 patients received a boost restricted to the tumor bed: 13 with EBRT, 10 with brachytherapy (BRT). Thirty-four patients had an adjuvant chemotherapy. The overall 5 year local relapse rate was 10%. Seven local relapses were described, five of the high-grade tumours, and five in patients with positive margin. In univariate analysis, quality of surgery shows a significant effect for local control. By using LENT-SOMA scale for late toxicity, a significant difference was found for neurological complications for patients receiving a boost. The results of the series validate the concept of anatomical definition of the initial target volume. A boost should be realised for positive margin tumors and may be for high-grade tumors. Neurological toxicity must be considered for the evaluation of the prescribed dose.

A 14-Year Retrospective Review of Angiosarcoma

Angiosarcoma is a rare vascular malignancy, and there are few published data to guide chemotherapy treatment decisions. We present a retrospective analysis of angiosarcoma encompassing all anatomic sites of disease presenting to a single institution over a 14-year period. Characteristics at presentation and prognostic factors are reviewed. For patients with unresectable disease, progression-free survival with various chemotherapy regimens is described. Pathological confirmation of all cases was performed before they were included in this analysis. One hundred twenty-five patients with angiosarcoma were seen and treated between January 1, 1990 and December 31, 2003. Angiosarcoma showed marked variation by anatomic site regarding gender ratio, median age at diagnosis, overall survival, and response to chemotherapy. Overall 5-year survival was 31% for angiosarcoma. Superficial depth and negative microscopic surgical margins correlated with longer overall survival, but tumor size did not reach significance as a prognostic factor. For unresectable angiosarcoma, doxorubicin based regimens yielded progression-free survival of 3.7-5.4 months. Paclitaxel achieved a progression-free survival of 6.8 months for scalp angiosarcoma and 2.8 months for sites below the clavicle. Angiosarcoma is an aggressive malignancy characterized by biologic heterogeneity at different anatomic sites and relative sensitivity to paclitaxel and doxorubicin.

Breast-conserving surgery following radiation therapy of 50 Gy in Stages I and II carcinoma of the breast: The experience at one institute in Japan

This study evaluated the results of breast-conserving therapy experienced in one institute. A total of 217 breasts in 215 patients with clinical stages I and II breast cancer undergoing breast-conserving therapy between August 1991 and December 1999 were included. The actuarial 5-year local recurrence-free survival, disease-free survival and overall survival rates were 97.4%, 88.5% and 92.5%, respectively. Microscopic margins were negative in 176 (81.1%) of the total breasts and positive in 41 (18.9%). There were no differences in the age at operation, tumor size, clinical stage, lymph node status, estrogen receptor status, or distance from tumor to nipple between patients with positive surgical margins and with negative surgical margins. During the follow-up period, local recurrence occurred in seven patients. Local recurrence was significantly less frequent in patients with surgical margin-negative tumors than those with surgical margin-positive tumors, and also in ER-positive tumors than ER-negative or ER-unknown tumors. There was no difference in overall survival between patients with and without breast-recurrence. Using multivariate analysis, the surgical margin was determined to be an independent predictive factor for local recurrence in the conserved breast. Nodal status and ER status were independent prognostic factors, but local recurrence did not have an independent negative impact on survival. We conclude that microscopic surgical margin is the most important factor associated with local recurrence in the conserved breast among patients treated with breast-conserving surgery and radiation therapy of 50 Gy. Local recurrence however, has no adverse effect on survival of patients.

Adjuvant radiotherapy for margin-positive high-grade soft tissue sarcoma of the extremity

Purpose: Adjuvant radiotherapy (RT) has been shown to improve local control in patients with soft tissue sarcoma of the extremities (STS). The specific impact of adjuvant radiation on patients with positive margins, however, has not been clearly defined. The purpose of this study was to determine if adjuvant RT improves local control in patients with high-grade STS who had positive margins of resection. Methods and Materials: Between 8/82 and 2/97, 110 adult patients with primary high-grade STS of an extremity underwent limb sparing surgery and were found to have a histologically positive microscopic surgical margin. Ninety-one (83%) received RT and 19 (17%) had no RT. The two groups were balanced with regard to size, site, location, and tumor depth. Adjuvant RT was delivered with brachytherapy (BRT) alone in 34 patients, external beam radiotherapy (EBRT) alone in 33 patients, or BRT+EBRT in 24 patients. The BRT dose was 45 Gy when used alone and 15–20 Gy when used as a boost. The EBRT dose was 60–70 Gy when used alone and 45–50 Gy when given with BRT. The median follow-up time was 41 months (range, 3–186 months). Results: The overall 5 year local control rate was 71%. This rate was significantly higher in the RT group compared to the no RT group (74% vs. 56%, respectively) ( p = 0.01). On univariate analysis, lower extremity site and proximal location were also found to be predictors of improved local control ( p = 0.03 and 0.03, respectively). However, only proximal location and the use of RT retained their significance as predictors of improved local control on multivariate analysis ( p = 0.003 and 0.01, respectively). The overall 5-year distant relapse-free survival, disease-free survival, and overall survival rates were 54%, 44%, and 53%, respectively. No statistical differences were found in these survival rates between RT and no RT groups. Conclusion: Based on this study, adjuvant radiotherapy seems to improve local control in patients with high-grade STS of the extremity with positive margins. However, local recurrence still occurs in a substantial proportion of patients, mandating further need for improvement.

Primary treatment of cystosarcoma phyllodes of the breast.

Cystosarcoma phyllodes is a rare sarcoma of the breast. Although surgical removal is the mainstay of treatment, the extent of surgery required (excision vs. mastectomy) and the need for additional local therapy, such as radiotherapy, are unclear. The current study evaluated the rate of local and distant failure, as well as potential prognostic factors, to better define appropriate treatment strategies. One hundred one patients treated primarily for cystosarcoma phyllodes of the breast were evaluated. These tumors were classified histologically into benign (58%), indeterminate (12%), and malignant (30%) based on well defined criteria. Stromal overgrowth (29%) was considered separately. Surgery was comprised of local excision with breast conservation (47%) or mastectomy (53%). Microscopic surgical margins were negative in 99% of cases. Six patients received adjuvant radiotherapy. Overall survival for the 101 patients was 88%, 79%, and 62% at 5, 10, and 15 years, respectively. For patients with nonmalignant (benign or indeterminate) and malignant cystosarcoma phyllodes, the overall survival was 91% and 82%, respectively, at 5 years, and 79% and 42%, respectively, at 10 years. Similar rates were observed based on the presence or absence of stromal overgrowth. Local recurrence occurred in 4 patients, with an actuarial 10-year rate of 8%. Eight patients developed distant metastases, with an actuarial 10-year rate of 13%. Multivariate analysis using Cox proportional hazards regression revealed stromal overgrowth to be the only independent predictor of distant failure. Local failure in this group of largely margin negative patients with cystosarcoma phyllodes of the breast was low, showing that breast-conserving surgery with appropriate margins is the preferred primary therapy. The current study data do not support the use of adjuvant radiotherapy for patients with adequately resected disease. Patients with stromal overgrowth, particularly when the tumor size was > 5 cm, were found to have a high rate of distant failure; such patients merit consideration of a trial that examines the efficacy of systemic therapy.

Surgical margin and breast recurrence after breast-conserving therapy.

A total of 161 patients with clinical stage I and II breast cancer received breast-conserving therapy between August 1991 and December 1997, and local recurrence occurred in five patients. The actuarial local control 5 years after breast-conserving surgery was 96.6%. We studied microscopic surgical margins of resected specimens in patients with breast-conserving surgery to determine whether the surgical margin was a risk factor for local recurrence in the conserved breast. Microscopic margins were negative in 125 (78%) of 161 patients and positive in 36 (22%). There were no differences between patients with positive surgical margins and those with negative surgical margins in age at operation, tumor size, clinical stage, lymph node status, estrogen receptor status, or distance from tumor to nipple. Local control was significantly better in the surgical margin-negative patients than in the surgical margin-positive patients. We conclude that microscopic surgical margin is a risk factor for local recurrence in the conserved breast.

Modified staging system for extremity soft tissue sarcomas.

The establishment of a universally acceptable staging system for soft tissue sarcomas has been hampered by the low incidence, various grading systems, and lack of consensus regarding the value of different prognostic factors. We aimed to evaluate prognostic factors in patients with extremity soft tissue sarcomas and to test the validity of the AJCC/UICC staging system. Prospectively collected data from 316 previously untreated patients with primary extremity soft tissue sarcomas treated at a single institution between 1989 and 1995 were studied. The influence of clinical and pathological factors on local recurrence, distant metastasis, and disease-specific survival was analyzed by univariate and multivariate techniques. Large tumor size and high histological grade were independent adverse prognostic factors for distant metastasis. Large size, high grade, and positive microscopic surgical margins were independent adverse prognostic factors, and liposarcoma histology was an independent favorable prognostic factor for disease-specific survival. Within each histological grade, there was a progressive decline in survival with increasing tumor size, as reflected by an almost linear increase in hazard ratios. Similarly, there was a progressive fall in survival with increasing grade within each size group (<5 cm, 5 to 10 cm, 10 to 15 cm, and > 15 cm). AJCC staging did not correlate well with prognosis. Survival for intermediate-grade tumors smaller than 5 cm (stage IIA) was better than that for low-grade tumors larger than 5 cm (stage IB) (86% vs. 73%). Survival for high-grade tumors smaller than 5 cm (stage IIIA) was better than that for intermediate-grade tumors larger than 5 cm (stage IIB) (72% vs. 57%). A modified staging system was formulated based on the additive influence of size and grade on the estimated hazard ratios for disease-specific survival, as follows: stage IA, G1T1; stage IB, G1T2 or G2T1; stage IIA, G1T3 or G2T2 or G3T1; stage IIB, G1T4 or G2T3 or G3T2; stage IIIA, G2T4 or G3T3; stage IIIB, G3T4; and stage IV, M1 (G1, G2, G3 = low, intermediate, and high grade; T1, T2, T3, T4 = tumor size < 5 cm, 5-10 cm, 10-15 cm, and > 15 cm, respectively). The 5-year disease-specific survivals of stages IA, IB, IIA, IIB, IIIA, and IIIB were 100%, 83%, 74%, 61%, 39%, and 18%, respectively. The 5-year disease-specific survival for stages I, II, III, and IV were 90%, 67%, 31%, and 6% respectively. The survival difference between each stage was statistically significant (P < .001). Histological grade and tumor size are equally important determinants of distant metastases and survival. The AJCC/UICC staging system is based primarily on the grade of the tumor, with size used to subgroup each stage. A staging system for extremity soft tissue sarcomas with equal emphasis on grade and size is proposed that correlates extremely well with prognosis.

Conservation treatment intensified with tamoxifen and CAF chemotherapy for subareolar breast cancers.

Formerly, patients with subareolar breast cancers have not been good candidates for breast-conservation treatment (BCT) in Japan. However, recently it was reported that patients with subareolar cancers were good candidates for this treatment. In order to improve both cosmetic results and survival rates, we performed BCT for 27 patients with subareolar breast cancers following pre-operative CAF chemotherapy and tamoxifen administration. From August 1989 to June 1998, we performed BCT for 200 out of 206 patients who visited our hospital with the desire of breast-conservation. Of these patients, 27 presented with tumors within 2 cm of the nipple areolar complex. For 26 of these 27 patients, breast-conserving surgery was performed following two to four times of CAF chemotherapy, and another one patient did not undertake any surgical resection. Following the surgery, patients were treated with radiation therapy to the intact breast and ipsilateral axilla to a total dose of 4,400 cGy with electron conedown to a total dose of 5,300 cGy. Their primary tumors were at T4bN0 in 1 case, T2N1b in 5 cases, T2N0 in 18 cases, and T1cN0 in 3 cases. Tamoxifen was administered to all the patients. CAF chemotherapy was performed six times for stage I patients, and eight times for stage II patients in total. For one patient with direct tumor invasion to the nipple, intraarterial infusion chemotherapy was performed following radiation therapy and CAF chemotherapy, without any surgical resection. For another 26 patients, breast-conserving surgery was performed, and 5 of them underwent lumpectomy under local anesthesia on an outpatient basis. For these 26 patients, the microscopic surgical margin was positive for 8 patients, close for 6 patients, negative for 10 patients, and unknown for 2 patients. All patients are alive with no evidence of disease after a follow-up of approximately 47 months on average, and all of their cosmetic results are estimated as excellent or good. It is concluded that BCT intensified with preoperative CAF chemotherapy and tamoxifen for subareolar breast cancers is a satisfying treatment modality in terms of both cosmetic results and survival rates.