Final Surgical Margins Research Articles

Intraductal carcinoma of the breast: pathologic features associated with local recurrence in patients treated with breast-conserving therapy.

Local excision and radiation therapy is a standard treatment option for duct carcinoma in situ (DCIS) of the breast. There is no consensus regarding the significant histologic features associated with recurrence. The authors studied a large group of patients with mammographically detected DCIS treated with breast-conserving therapy to explore DCIS volume relationships, DCIS features, specimen characteristics, and the effect of patient age at diagnosis. Thirteen patients (10%) developed a recurrent carcinoma in the ipsilateral breast, resulting in 5- and 10-year actuarial recurrence rates of 8.9% and 10.3%, respectively. Local recurrences were identified as a true recurrence/marginal miss (TR/MM) in nine patients, and elsewhere in the breast in four patients. The notable features associated with TR/MM recurrences on univariate analysis included patient age less than 45 years old, six or more slides with DCIS, no microscopic calcifications within DCIS ducts, and five or more DCIS ducts or terminal duct lobular units (TDLUs) with cancerization of lobules (COL) within 0.42 cm of the final surgical margin. DCIS tumor size, nuclear grade, amount of central necrosis, and margin status were not associated with outcome. Multivariate analysis found that the absence of microcalcifications within DCIS ducts, patient age, number of slides with DCIS or TDLUs with COL, and the number of DCIS ducts or TDLUs with COL within 0.42 cm of the final margin were related significantly to TR/MM recurrence. Patients with a total of six or more slides with DCIS, or who have 11 or more DCIS ducts or TDLUs with COL near the final margin are at increased risk of having a substantial volume of residual DCIS in the adjacent unexcised breast. These results suggest that the volume of DCIS in the specimen, and the volume of DCIS near the margin are associated with local recurrence. These features can be used to identify those patients with a higher chance of local recurrence.

Internal mammary node irradiation neither decreases distant metastases nor improves survival in stage I and II breast cancer

Purpose: To compare outcome for ipsilateral breast tumor recurrence (IBTR), or regional node recurrence, initial and subsequent distant metastases, and overall and cause-specific survival in women treated with conservative surgery and radiation based on whether or not radiation was targeted to the internal mammary nodes (IMN). Methods and Materials: From 1979–1994, 1383 women with Stage I–II breast cancer underwent wide excision, axillary node dissection with ≥10 nodes removed, and radiation. Median follow-up was 6 years; median age was 55 years. A total of 114 women had radiation targeted to the IMN with deep tangents and 1269 did not. Women who received IMN treatment were more often axillary node–positive (40% vs. 25%, p = 0.002), had central or inner quadrant tumors (61% vs. 40%, p = 0.001), and had T2 tumors (47% vs. 31%, p = 0.001). All axillary node–positive women received adjuvant chemotherapy and/or tamoxifen. For axillary node–negative women, 13% of the IMN treatment group received adjuvant systemic therapy compared to 37% of the no treatment group ( p = 0.001). Radiation was directed to the breast only in 97% of the axillary node–negative women who had IMN treatment and 99% of the no IMN treatment group. For axillary node–positive women, 98% of the IMN-treated group had radiation to the breast and supraclavicular nodes ± a posterior axillary field compared to 77% of the no IMN treatment group ( p = 0.001). There were no significant differences between the two groups for median age, menopausal status, histology, final surgical margin, estrogen and progesterone receptor status, or the number of positive nodes. Results: There were no significant differences in the 5- and 10-year cumulative incidence of an IBTR, regional node recurrence, initial or total distant metastases for the two groups. Similarly 5- and 10-year actuarial overall and cause-specific survival were not significantly different. However, subset analysis revealed a statistically significant increase in initial (29% vs. 15% at 10 yr, p = 0.002) and total (30% vs. 17% at 10 yr, p = 0.01) distant metastases and a significant decrease in cause-specific survival (76% vs. 89% at 10 yr, p = 0.02) for postmenopausal women who received IMN treatment. These findings could not be attributed to differences in the use of systemic therapy or the number of positive nodes. Axillary node–positive patients did not experience a significant decrease in initial (36% vs. 22% at 10 yr, p = 0.21) or total distant metastases (37% vs. 28% at 10 yr, p = 0.62) or a significant improvement in cause-specific survival (72% vs. 76% at 10 yr, p = 0.76) with IMN treatment regardless of whether the tumor was lateral or medial/central in location. IMN treatment was not associated with an increase in non–breast cancer deaths during this period of observation. Conclusions: This retrospective series was unable to identify a significant benefit for IMN irradiation in terms of distant metastases or cause-specific survival for the entire patient population, and in particular, for patients with positive axillary nodes and medially located lesions. The results of the proposed or ongoing prospective randomized trials will further address this controversial issue.

Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients.

The prognosis of patients with chordoma of the sacrum and mobile spine has been reported to be dismal and attributable in the majority of cases to intralesional surgery. The purpose of this study was to evaluate the clinical outcome of these patients using modern surgical principles aimed at complete resection and to identify prognostic factors. The clinical and morphologic features, type of surgery, and follow-up of 39 consecutive patients with chordoma were reviewed and analyzed statistically. Thirty sacral and 9 mobile spine chordomas (size range, 3-20 cm; mean, 8 cm) occurring in 22 women and 17 men (median age, 55 years) were analyzed. The preoperative morphologic diagnosis was based on fine-needle aspiration (FNA) biopsy, core needle biopsy, or incisional biopsy. The final surgical margins were wide in 23 patients and marginal or intralesional in 16. The mean follow-up was 8.1 years (range, 0.1-23 years). Seventeen patients (44%) developed local recurrences and 11 patients (28%) developed metastases. The estimated 5-, 10-, 15-, and 20-year survival rates were 84%, 64%, 52%, and 52%, respectively. Local recurrence was associated significantly with an increased risk of metastasis and tumor-related death (P < 0.001). New surgical techniques have improved local control and survival of patients with sacral or spinal chordoma significantly and have decreased progressive neurologic deterioration. Larger tumor size, performance of an invasive morphologic diagnostic procedure outside of the tumor center, inadequate surgical margins, microscopic tumor necrosis, Ki-67 > 5%, and local recurrence were found to be adverse prognostic factors. FNA is the preferred method for establishing the preoperative morphologic diagnosis of chordoma.

Breast conserving therapy in breast cancer patients presenting with nipple discharge

Purpose: To retrospectively review the outcome of conservatively treated breast cancer patients who present with nipple discharge at initial diagnosis. Methods and Materials: The charts of 1097 patients undergoing conservative surgery and radiation therapy between January 1970 and December 1990 were reviewed. All patient data, including clinical, pathologic, treatment, and outcome variables were entered onto a computerized database. For the current study, specific attention was directed to the initial presenting symptoms and patients were divided into two groups: those presenting at initial diagnosis with nipple discharge (D/C-YES, n = 17), and those presenting without nipple discharge (D/C-NO, n = 1080). Results: As of August 1998, with a median follow-up of 12 years, the 10-year actuarial survival, distant metastasis-free survival, and breast relapse-free survival rates for the overall population were 73%, 78%, and 83%, respectively. Although the D/C-YES and D/C-NO groups were well balanced with respect to the majority of clinical factors, the D/C-YES patients had a higher percentage of DCIS histology (7.3% vs 1.2%, p < 0.01), were less likely to undergo reexcision (12% vs 35%), and were more frequently under age 40 (35% vs 12%) than the D/C-NO patients. Over the time span of this study, status of the final surgical margin was indeterminate in the majority of cases. Local relapses occurred in 6 of the 17 patients in the D/C-YES group, resulting in a 10-year actuarial breast relapse-free survival rate of 50%, which was signifcantly lower than the 10-year breast relapse-free survival rate of 86% in the D/C-NO population. Among the patients presenting with nipple discharge, those with sacrifice of the nipple areolar complex had a lower local relapse rate than those patients who had conservation of the nipple areolar complex (20% vs 42%), although this difference did not reach statistical significance. Conclusions: Although patients presenting with nipple discharge may be suitable candidates for radiation therapy, local relapse rates were higher than those presenting without nipple discharge. The limitations of the study and implications regarding breast conserving management in patients presenting with nipple discharge are discussed.

Clinical significance of repeat sextant biopsies in prostate cancer patients

Objectives Six random systematic core biopsies (SRSCB) of the prostate is considered by many to represent the standard method of detecting prostate cancer. We sought to evaluate the sensitivity of the transrectal ultrasound (TRU)S-guided needle biopsies in 89 consecutive patients with a history of biopsy-proven prostate cancer. These patients underwent repeat biopsy prior to enrollment in an ongoing, randomized protocol. We also compared the clinical and pathological features of patients with SRSCB-documented prostate carcinoma and negative repeat-sextant biopsy. Methods Our study population consisted of 89 patients enrolled in our randomized, prospective study assessing the effect of androgen deprivation therapy in combination with radical prostatectomy for clinically localized prostate cancer. A comparison was made of the patients' rebiopsy results with initial biopsy. Patients having either a positive or negative rebiopsy were analyzed with respect to grade, T stage, prostate-specific antigen (PSA), PSA density (PSAD), organ-confined rate, and final surgical margin status. Results Repeat sextant biopsy was positive for prostate cancer in 71 (80%) patients and negative in 18 (20%) patients. There was no significant difference between patients with a negative or positive rebiopsy with respect to PSA or PSAD. There was a trend toward greater prostate volumes in the negative-rebiopsy group ( P = 0.08) and lower clinical stage in the negative rebiopsy ( P = 0.025) group. In patients with a negative repeat biopsy, the organ-confined (OC) rate was 77% (14/18 patients), as compared to the positiverebiopsy group of 56% (40/71 patients) ( P = 0.08). Similarly, the margin-positive rate in the negative-rebiopsy group was 17% (3/18 patients), as compared to the positive-rebiopsy group who had a marginpositive rate of 44% (31/71 patients) ( P = 0.03). Conclusions In patients with clinically localized disease, the sensitivity of SRSCB in detecting carcinoma is 80%. The results of this study highlight the potential sampling error of the SRSCB and the implication of a negative rebiopsy in patients with clinically significant prostate cancer.

Prognostic factors affecting outcome in lower gingival carcinoma.

Squamous cell carcinoma of the lower gingiva is a rare lesion that frequently invades the mandible. To determine the factors that affect local disease control and overall survival, a retrospective review of 155 previously untreated patients was performed. Primary lesions larger than 3 cm (P = .021) and persistently disease-positive surgical margins (P = .027) were found to be associated with decreased local control rates. Survival was adversely affected by advanced T stage (P = .001), positive initial and final surgical margins (P = .004), mandibular invasion (P = .014), and cervical metastases (P<.001). Extent of mandibular resection, tumor extension beyond the lower gingiva, recent dental extractions in the region of the primary, perineural invasion, and histologic grade did not affect local control or survival. Although lower gingival carcinoma tends to involve the mandible, our findings indicate that tumor size is more important than mandibular invasion in predicting local disease control. Larger tumors that have a greater propensity for local recurrence and poorer survival require a more extensive surgical resection.

Factors associated with a positive reexcision after excisional biopsy for invasive breast cancer

Breast-conserving therapy followed by adjuvant radiotherapy represents an alternative to mastectomy as a treatment for invasive breast cancer. When excisional biopsy has been performed outside the parent institution, reexcision is often performed, with tumor being identified in 32% to 62% of the subsequent specimens. We analyzed not only the factors associated with a positive reexcision but also those factors associated with final surgical margins that are positive for tumor. Between 1978 and 1991, 956 female patients with American Joint Committee on Cancer clinical stage I or II breast cancer were treated with breast-conserving therapy where a total of 420 patients underwent reexcision after an initial excisional biopsy. Several factors were analyzed to determine their association with a positive reexcision, the status of the final surgical margin, and the nature of the disease present within the reexcision specimen. Factors that correlated with a positive reexcision in both univariate and multivariate analysis were clinical tumor size, method of detection, the pathologic status of the axillary lymph nodes, and the histologic appearance. Those factors associated with finding invasive disease at the time of reexcision were clinical tumor size, clinical presentation, and nodal status. The single factor associated with finding residual in situ disease at the time of reexcision was histologic appearance of the primary tumor. A final positive margin was associated with method of tumor detection, age of the patient, and the presence of axillary lymph node metastases. The most significant factors associated with a positive reexcision are clinical tumor size, method of tumor detection, pathologic nodal status, and histologic appearance. Patients with larger tumors or those that are detected by physical examination, as well as invasive lobular carcinomas, may require a more generous initial resection to achieve negative surgical margins and avoid the likelihood of reexcision.

Malignant salivary tumors--analysis of prognostic factors and survival.

A group of 113 patients with malignant salivary gland tumors was retrospectively reviewed to analyze the association of clinical and histologic factors with survival. These factors were patient sex and age, tumor site, clinical stage, histologic diagnosis, tumor grade, and whether or not final surgical margins were clear. There were 57 parotid, 40 minor salivary, and 16 submandibular gland cancers. The histologic groups were mucoepidermoid carcinoma (49 patients), adenoid cystic carcinoma (31), adenocarcinoma not otherwise specified (18), acinic cell carcinoma (7), malignant mixed tumor (5), squamous cell carcinoma (2), and undifferentiated carcinoma (1). Univariate analysis of clinical factors showed that age and clinical stage significantly influenced survival. At 10 yr the predicted cumulative survival rates for Stage I, II, III, and IV tumors were 74%, 56%, 32%, and 10%, respectively. Tumor grade was the only significant histologic factor. This was most obviously reflected among patients with mucoepidermoid carcinomas. Cumulative survival at 5 yr was 94% for those with low-grade tumors and 26% for high-grade tumors. By multivariate analysis, clinical stage, age, and tumor grade remained highly significant. Analysis of patients with only Stage I and II disease demonstrated that the significant factors were patient age, tumor site, tumor grade, and whether or not surgical clearance was achieved. These results suggest that clinical stage should not be the exclusive determinant of the extent of surgery and that the selection of patients, for adjuvant therapy may be improved by an awareness of these prognostic factors.

Perioperative blood transfusions are associated with increased rates of recurrence and decreased survival in patients with high-grade soft-tissue sarcomas of the extremities.

One hundred fifty-six patients with high-grade soft-tissue sarcomas of the extremities treated on prospective randomized trials were analyzed to determine the impact of perioperative blood transfusions on tumor recurrence and patient survival. A significant increase in the incidence of tumor recurrence and decrease in survival were associated with the receipt of blood transfusions at the time of definitive surgical therapy of the sarcoma. Actuarial 5-year continuous disease-free survival was 70% in patients who had not been transfused compared to 48% in patients who received one or more transfusions (P = .007). Overall 5-year survival was also substantially decreased in patients receiving transfusions (85% compared to 63%; P = .0035). A direct relationship existed between the number of transfusions administered and the decrease in disease-free and overall survival; the larger the number of transfusions the worse the prognosis (P less than .0001 and P = .0001, respectively). A large number of other prognostic factors were included in the analysis including the age, sex, race of the patient, histology of the primary lesion, anatomic site of the primary lesion, final surgical margins, size of the tumor, type of surgery required, the use of chemotherapy, actual time in the operating room under anesthesia, the exact anesthetic agent used, and the individual surgeon who performed the operation. Accounting for all of these factors a strong association continued to exist between the receipt of blood transfusion and poor patient prognosis. We have previously shown that adjuvant chemotherapy is of benefit to patients with high-grade extremity sarcomas, and 132 (84.6%) of 156 patients in this series received chemotherapy. In patients receiving chemotherapy, blood transfusions were associated with increased recurrence (P less than .0001) and decreased survival (P = .0001). The only other significant independent prognostic variable in these patients was the size of the primary tumor. An analysis of all patients, stratified for tumor size, revealed an impact of transfusions on increasing recurrence (P = .007) and decreasing survival (P = .016). An analysis of the subpopulation of patients with large tumors (greater than 150 mL) gave the same results (P = .03 and .015, respectively). It thus appears that the receipt of blood transfusions is associated with increased tumor recurrence and decreased survival in patients with high-grade soft-tissue sarcomas of the extremities.(ABSTRACT TRUNCATED AT 400 WORDS)