Adjuvant Therapy Decisions Research Articles

Prognosis in cancer

Prognostication is inherent in essentially all decision making in cancer care. The clinician is usually silently integrating factors about the patient's cancer diagnosis with considerations about the efficacy, toxicity, and risks of treatment all in the context of the patient's age, overall health, and comorbidities. This paradigm is especially apparent when making adjuvant therapy decisions and balancing the risk of recurrence with the statistical risk reduction of treatment and coexisting patient's health issues.

Effect of Hospital Type and Volume on Lymph Node Evaluation for Gastric and Pancreatic Cancer

For gastric and pancreatic cancer, regional lymph node evaluation is important to accurately stage disease in a patient and may be associated with improved survival. We hypothesized that National Comprehensive Cancer Network (NCCN), National Cancer Institute (NCI)-designated institutions, and high-volume hospitals examine more lymph nodes for gastric and pancreatic malignant neoplasms than do low-volume centers and community hospitals. Volume-outcome study. Academic research. Using the National Cancer Data Base (January 1, 2003, to December 31, 2004), patients were identified who underwent resection for gastric (n = 3088) and pancreatic (n = 1130 [pancreaticoduodenectomy only]) cancer. Multivariable logistic regression analysis was used to assess the effect of hospital type and volume on nodal evaluation (>or=15 nodes). Only 23.2% of patients with gastric cancer and 16.4% of patients with pancreatic cancer in the United States underwent evaluation of at least 15 lymph nodes. Patients undergoing surgery had more lymph nodes examined at NCCN-NCI hospitals than at community hospitals (median, 12 vs 6 for gastric cancer and 9 vs 6 for pancreatic cancer; P < .001). Patients at highest-volume hospitals had more lymph nodes examined than patients at low-volume hospitals (median, 10 vs 6 for gastric cancer and 8 vs 6 for pancreatic cancer; P < .001). On multivariable analysis, patients undergoing surgery at NCCN-NCI and high-volume hospitals were more likely to have at least 15 lymph nodes evaluated compared with patients undergoing surgery at community hospitals and low-volume centers (P < .001 and P =.02, respectively). Nodal examination is important for staging, adjuvant therapy decision making, and clinical trial stratification. Moreover, differences in nodal evaluation may contribute to improved long-term outcomes at NCCN-NCI centers and high-volume hospitals for patients with gastric and pancreatic cancer.

Application of immunohistochemistry to breast lesions.

Abstract Context.—Immunohistochemistry has an expanding role in mammary pathology that has been facilitated by a growing list of available antibodies and a better understanding of biology. Objective.—To explore the key role of immunohistochemistry in guiding adjuvant therapy decisions and sentinel node staging in breast cancer, as well as the role of immunohistochemistry as an aid to distinguishing usual ductal hyperplasia from atypical ductal hyperplasia/low-grade carcinoma in situ; subtyping a carcinoma as ductal or lobular, basal or luminal; ruling out microinvasion in extensive intraductal carcinoma; distinguishing invasive carcinoma from mimics; and establishing that a metastatic carcinoma of unknown primary site has originated in the breast. Data Sources.—Current literature is reviewed, including clinical and pathologic journals. Conclusions.—As new, targeted treatments for breast cancer are developed, pathologists can expect additional immunohistochemistry applications in the future.

Application of Immunohistochemistry to Breast Lesions

Immunohistochemistry has an expanding role in mammary pathology that has been facilitated by a growing list of available antibodies and a better understanding of biology. To explore the key role of immunohistochemistry in guiding adjuvant therapy decisions and sentinel node staging in breast cancer, as well as the role of immunohistochemistry as an aid to distinguishing usual ductal hyperplasia from atypical ductal hyperplasia/low-grade carcinoma in situ; subtyping a carcinoma as ductal or lobular, basal or luminal; ruling out microinvasion in extensive intraductal carcinoma; distinguishing invasive carcinoma from mimics; and establishing that a metastatic carcinoma of unknown primary site has originated in the breast. Current literature is reviewed, including clinical and pathologic journals. As new, targeted treatments for breast cancer are developed, pathologists can expect additional immunohistochemistry applications in the future.

Overall Survival and Cause-Specific Mortality of Patients With Stage T1a,bN0M0 Breast Carcinoma

With mammographic screening, the frequency of diagnosis of stage T1a,bN0M0 breast cancer has increased. Prognosis after locoregional therapy and benefit from adjuvant systemic therapy are poorly defined. We reviewed T1a,bN0M0 breast cancer cases registered in the Surveillance, Epidemiology, and End Results (SEER) Program to investigate the impact of prognostic factors on breast cancer-specific (BCSM) and non-breast cancer-related mortality. We identified T1a,bN0M0 breast cancer cases registered in the SEER Program from 1988 to 2001, and used the Kaplan-Meier product limit method to describe overall survival (OS). We estimated the probabilities of death resulting from breast cancer and from other causes, and analyzed associations of patient and tumor characteristics with OS, BCSM, and non-breast cancer-related mortality using the log-rank test, Cox proportional hazards models, and a competing-risk model. We constructed nomograms to assist physicians in adjuvant therapy decision making. We identified 51,246 T1a,bN0M0 cases. Median follow-up was 64 months (range, 1 to 167 months). Median age at diagnosis was 65 years (range, 20 to 101 years). Ten-year probabilities of all-cause mortality and BCSM were 24% and 4%, respectively. Characteristics associated with increased probability of BCSM included age younger than 50 years at diagnosis, high tumor grade, estrogen receptor-negative status, progesterone receptor-negative status, and fewer than six nodes removed at axillary dissection. The constructed nomograms allow a comparison of predicted breast cancer-specific survival and non-breast cancer-specific survival in individual patients. Overall, the prognosis of patients with T1a,bN0M0 breast cancer is excellent. However, subgroups of patients who are at higher risk of BCSM and who should be considered for adjuvant systemic therapy can be identified.

Impact of a Commercial Reference Laboratory Test Recurrence Score on Decision Making in Early-Stage Breast Cancer

To investigate whether recurrence score (RS) as determined using a commercial reference laboratory test influences clinicians' treatment recommendations and eventual treatment in patients with early-stage breast cancer. A retrospective analysis was performed on 74 patients from a community-based oncology practice with estrogen receptor (ER) -positive, lymph node (LN) -negative stage I or II breast cancer for which RS was obtained. Demographic and pathology information was extracted from medical records. Ten-year relapse-free survival was calculated using Adjuvant! Online. Treatment recommendations before the RS knowledge were compared with treatment recommendations after RS knowledge and to the treatment eventually administered. A weak correlation was found between RS and both patient age and tumor size, modest correlation between RS and tumor grade, and modest correlation between RS and 10-year recurrence as determined by Adjuvant! Online. For 21% and 25% of patients, knowledge of the RS changed the clinicians' treatment recommendations and eventual treatment, respectively. The decision to change from hormone therapy to chemotherapy (with or without hormone therapy) was generally associated with high RS (high distant recurrence risk as determined by the commercial reference laboratory test), whereas the decision to change from chemotherapy to hormone therapy was generally associated with low RS (low distant recurrence risk as determined by the commercial reference laboratory test). Knowledge of the RS changed treatment recommendations and eventual treatment in patients with ER-positive/LN-negative early-stage breast cancer. Use of genomic-based prognosis may result in more accurate estimates of true recurrence risk than currently possible with commonly used prognostic factors (such as patient age, tumor size, and tumor grade) alone and thus lead to an increase in appropriate adjuvant therapy decision making.

The value of video-assisted mediastinoscopy in pulmonary metastasectomy

To assess the role of video-assisted mediastinoscopy (VAM) in identifying involved mediastinal lymph nodes in patients undergoing pulmonary metastasectomy. Over a 4-year period (2002-2005) a retrospective study was carried out in 57 patients (44 men, 13 women, mean age 59 years) undergoing isolated, unilateral or bilateral metastasectomy. Following staging CT scan, VAM was performed prior to open thoracotomy, median sternotomy or VATS resection of the metastasis. Follow-up was complete in all patients. Fifty-seven patients underwent 62 operations for metastatic disease. The majority had colorectal cancer (39) followed by renal (11), sarcoma (9), liver (2) and miscellaneous (8). Six patients (10.5%) had positive mediastinal nodes on VAM. There was no perioperative morbidity or mortality. At a median follow-up of 25 months, 63 patients (68.5%) were still alive. Mediastinal lymph node involvement has been reported to occur in up to 14% of patients with pulmonary metastasis. In our study, 10% of patients treated for pulmonary metastasis had positive nodal disease at metastasectomy. We believe our results confirm that VAM can be safely performed and may have a role in more accurate staging of metastatic disease and influence the decision for post-resection adjuvant therapy.

Retention and Use of Breast Cancer Recurrence Risk Information from Genomic Tests: The Role of Health Literacy

New genomic technology now allows physicians to provide women with individualized and highly accurate breast cancer recurrence risk estimates that are a key factor in adjuvant (after surgery) therapy decisions. Because these genomic tests are so new, little is known about how well patients understand the tests and their results. We interviewed 163 stage I or II breast cancer patients at a routine follow-up appointment. We assessed their health literacy (using the Rapid Estimate of Adult Learning in Medicine) as well as their knowledge of and attitudes towards a genomic test that identifies risk of recurrence in hormone receptor-positive, node-negative breast cancer (the OncoType Dx Recurrence Score). Women with lower health literacy recalled less of the information provided about the recurrence risk test than women with higher health literacy. Health literacy was not related to the amount of additional information women desired. Women with higher health literacy preferred to have a more active role in decisions about the test. Health literacy may affect women's capacity to learn about the new genomic tests as well as their desire for informed participation in their medical care.

Adjuvant treatment of elderly breast cancer patients

Increasing age is the major risk factor for breast cancer. About half of all new breast cancers and more than half of breast cancer deaths in affluent nations occur in women 65 years and older. Endocrine therapy with aromatase inhibitors or tamoxifen is appropriate adjuvant therapy for older women with life expectancies of greater than 5 years and hormone receptor positive tumors. The greatest benefit of adjuvant chemotherapy is in elders with hormone receptor negative, node positive, or high-risk node negative tumors. The effect of co-morbidity on survival must be factored into all adjuvant therapy decisions and newer validated tools can accurately estimate non-breast cancer related survival. Age bias still exists and results in frequent undertreatment of older women and compromised survival. Elders remain under-represented in clinical trials and should be encouraged to participate. Health care providers as well as government leaders and patients need to be educated on cancer in elders.

A computer program designed to assist in NSCLC adjuvant therapy decision making

7230 Background: The goal the computer program, Adjuvant! for NSCLC, is provide the health professional, and the NSCLC patient with information that might be helpful when deciding about adjuvant chemotherapy for completely resected Stage 1 to Stage 3A disease. The 4 elements of this decision are: estimates of prognosis, estimates of the efficacy of adjuvant chemotherapy, estimates of completing mortality, and estimates of toxicity. Methods: Estimates of prognosis are based on an analysis of 17, 130 patients in the SEER registry. Estimates for 5 year disease specific mortality for Stage 1A, 1B, 2A, 2B, and 3A disease are 22%, 37%, 51%, 63%, and 70%. Multivariate analysis justifies using tumor size, histologic grade, and BAC histology for refinement of prognostic estimates for Stage 1 patients. A small subgroup of Stage 1 patients (with tumors &lt; 10mm, low grade, BAC histology) could be identified with a 5 year disease specific mortality risk of &lt;10%. Estimates of the efficacy of chemotherapy were derived from meta-analyses. A proportional risk reduction of 20% is used by the program as the default efficacy estimate for platinum-based therapy. Pop-ups and help files discuss areas of uncertainty and controversy. The user has the option to adjust the default efficacy estimate to the more optimistic efficacy estimates of some of the recent trials, or to take into account some of the uncertainty as to whether adjuvant chemotherapy works as well in Stage 1 disease. SEER data shows the average NSCLC patient has competing mortality rates higher than would be suggested by chronologic age. Regimen specific risks of treatment related toxicity is given by the program. In the over 100 pages of help files there is a detailed discussion of the clinical evidence, adjuvant therapy guidelines, ongoing clinical trials, and corollary areas (radiotherapy, neoadjuvant therapy, biomarkers, etc.) Results: The program projects that for patients with favorable Stage 1 tumors the absolute OS benefit of therapy may be as low as 1% (of the same size as the risk of treatment related mortality), but for patients with Stage 2 and 3A disease the 5 yr OS benefit may be ∼10%. Conclusions: The impact of this tool on physician and patient knowledge about the adjuvant therapy of NSCLC will be presented. [Table: see text]

HER2 comparison with novel 3-gene marker sets for risk prediction of distant recurrence of breast carcinoma

20009 Background: The risk of distant recurrence in patients with invasive breast carcinoma (BrCa) is predicted imperfectly by currently used factors (e.g. nuclear grade, hormone receptor status), complicating adjuvant therapy decisions. In an effort to discover biomarkers for recurrence, we retrospectively analyzed BrCa recurrence and tumor gene amplification. Multi-gene marker sets were evaluated for predictive significance and accuracy. Because studies of HER2 as a suitable biomarker report positive and negative results, we compared our marker sets with HER2. Methods: 229 of 723 BrCa patients met inclusion criteria: invasive ductal carcinoma, no isolated local recurrence, minimum 4 years follow-up, and archived specimens adequate for fluorescent in situ hybridization (FISH) assay. Study endpoint was recurrence, or non-recurrence throughout follow-up. FISH was performed on formalin-fixed paraffin sections with probes for previously identified genomic regions. Signals were counted with a Metasystems workstation, and used in a “Prognostic Index” (PI) to categorize recurrence risk. One-sided Fisher’s exact test was used to assess increased incidence of distant recurrence in relation to PI and HER2, and increased incidence of HER2 amplification in relation to PI. Results: Two separate 3-gene marker sets were obtained that predict clinical outcome for hormone receptor + (HR+) and hormone receptor − (HR−) tumors. In HR+ samples a PI based upon regions surrounding CYP24, PDCP6IP, and BIRC5 was the best predictor of recurrence, while for HR- specimens the PI was based on the NR1D1, SMARCE1, and BIRC5 regions. The PIs are significantly associated with recurrence of HR+ and HR− tumors (OR = 9.52, 95% CI &gt; 2.12, p = 0.0024; and OR = 12.3, 95% CI &gt; 1.45, p = 0.0188, respectively). However, tumor HER2 amplification was not prognostic for recurrence (OR = 1.76, 95% CI &gt; 0.77, p = 0.1395). Furthermore, there was no significant association of PI with HER2 status (OR = 1.56, CI &gt; 0.57, p = 0.862). Conclusions: Prognostic Indices based on copy numbers of two 3-gene marker sets significantly predict clinical outcome of stage I-III invasive ductal carcinoma. HER2 amplification, included in our previous whole genome survey but not present in our final marker sets, had no prognostic value. [Table: see text]

Validation of a nomogram for predicting disease‐specific survival after an R0 resection for gastric carcinoma

A statistical model for predicting disease-specific survival in patients with gastric carcinoma, based on a single U.S. institution experience, was tested for validity in a sample of patients treated at different institutions. The authors analysed 459 patients from the Dutch Gastric Cancer trial that compared limited (D1) with extended (D2) lymph node dissection. The discrimination ability of the nomogram with respect to 5 and 9-year disease-specific survival probabilities was superior to that of the American Joint Committee on Cancer (AJCC) staging system. There was considerable heterogeneity of risk within many of the AJCC stages. Calibration plots suggested that predicted probabilities from the nomogram corresponded closely to actual disease-specific survival. The gastric carcinoma nomogram performed well when applied to patients treated in a large number of institutions. The nomogram provided predictions that discriminated better than the AJCC staging system, regardless of the extent of lymph node dissection. Patient counseling and adjuvant therapy decision-making should benefit from use of the nomogram.

Correlation Between MIB1-Determined Tumor Growth Fraction and Incidence of Tumor Recurrence in Early Ovarian Carcinomas

Purpose: The decision concerning adjuvant therapy remains difficult in patients with very early stage ovarian carcinomas [Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) Ia/b]. Therefore, we compared the MIB1-determined tumor growth fraction in archival tumor tissue with tumor recurrence and outcome of disease, and in relationship to other stages and clinical and morphological findings. Patients and Methods: Ninety-two patients were followed in early stages of ovarian carcinomas (FIGO I and II) with no tumor residuals and were analyzed for tumor recurrences and long-term overall survival (mean 6.0 years, median 5.5). Fifty-eight patients had stage I tumors, among these were 38 in the sub-stages Ia/b. Tumor growth fraction (MIB1) in tissues from primary surgery was compared with the status of patients and disease, histology, and immunohistochemistry for carcinoembryonic antigen (CEA), CA125, CA153, steroid hormone receptors, and angiogenesis (chi-square test, Kaplan–Meier and discriminant analyses). Results: Tumor-associated deaths occurred in 27 cases, tumor recurrences occurred in 35 cases. In contrast to the advanced stages of disease, the MIB1-determined tumor growth fraction outweighed all other parameters in the prediction of the course of disease (p < 0.001), followed by tumor grading (p = 0.001) and FIGO-substages (p = 0.026) in this retrospective study. Particularly in the very early stages, MIB1 predicted tumor recurrences in 84% of the cases (p < 0.001). Recurrences were not observed below a tumor growth fraction of 10% but prevailed in cases of more than 15%. Conclusion: Our data suggest MIB1 as an interesting additional tool for the decision of adjuvant therapy in patients with very early stages of ovarian carcinomas, which should be tested in prospective trials.

Le prélèvement du ganglion sentinelle dans le cancer du sein : aspects techniques et résultats

Sentinel lymph node biopsy for breast cancer has been introduced in the mid-1990s and it has now been performed on thousands of patients. Although this procedure has not been validated by randomised clinical trials, it has been rapidly adopted around the world by surgical specialists in clinical practice as a diagnostic procedure instead of the axillary lymph node dissection. The critical issue in sentinel lymph node biopsy is the false negative results which could expose the patients to axillary recurrence and lead to understaging and incorrect adjuvant therapy decisions. The current problem is to perfect the procedure for an optimal use in routine reducing this risk of false negative results. This false negative rate declines sharply when the technique is performed in selected patients by experienced surgeons using a combined detection. In this article, we review the technical aspects and results of the sentinel lymph node biopsy in breast cancer and discuss the recommendations for the optimal clinical practice.

Value of systematic mediastinal lymph node dissection during pulmonary metastasectomy

Background. Systematic mediastinal lymph node dissection is the accepted standard when curative resection of bronchial carcinoma is performed. However, mediastinal lymph node dissection is not routinely performed with pulmonary metastasectomy, in which only enlarged or suspicious lymph nodes are removed. The incidence of malignant infiltration of mediastinal lymph nodes in patients with pulmonary metastases is not known. Methods. Sixty-three patients who underwent 71 resections through a thoracotomy for pulmonary metastases of different primary tumors were studied prospectively. Selected patients showed no evidence of tumor progression or extrathoracic metastases and pulmonary metastasectomy was planned with curative intent. All patients underwent preoperative helical computed tomography (CT) scanning. Only patients with no evidence of suspicious mediastinal lymph nodes on the CT scan (less than 1 cm in the short axis) were included in this study. A mediastinal lymph node dissection was performed routinely with metastasectomy. Results. In 9 patients (14.3%) at least one mediastinal lymph node revealed malignant cells in accordance with the resected metastases. When compared with the preoperative CT scan, additional pulmonary metastases were detected in 16.9% of performed operations. There was a trend toward an improved survival rate in patients without involvement of the mediastinal lymph nodes. The number of pulmonary metastases had no influence on survival. Conclusions. On a patient-by-patient basis, the frequency of misdiagnosed mediastinal lymph node metastases is about the same as compared with non–small cell bronchial carcinomas. Systematic mediastinal lymph node dissection reveals a significant number of patients, who otherwise are assumed free of residual tumor. The knowledge of metastases to mediastinal lymph nodes after complete resection of pulmonary metastases could influence the decision for adjuvant therapy in selected cases.

56. The role of external irradiation in postoperative treatment of soft tissue sarcomas – last decade of gliwice experience

Aim of the study was to evaluate the role of postoperative external irradiation in the treatment of patients with high risk of local relapse of soft tissue sarcomas, as well as to evaluate the long-term results of this combined treatment. Data charts of the 77 patients with STS treated by surgery and postoperative external beam radiotherapy in Institute of Oncology in Gliwice during the period 1990–1999 has been reviewed. Extremity was the most frequent tumour site (75%), followed by trunk (10%), pelvis (7%), head and neck (4%) and retroperitoneal space (4%). Histological types included liposarcoma (27%), MFH (23%), fibrosarcoma (22%), neurosarcoma (12%), synovial sarcoma (8%) and others (8%). Only in 52% of patients the grade of the tumour was evaluated (G1–12 pts, G2–14 pts, G3–14 pts). Only 23 patients (30%) was treated by chemotherapy after local treatment. In majority patients were primary operated at general surgery departments, outside the reference centre with technique typical for benign tumours. Because of non-radical first surgical treatment and large number of early local recurrences in a whole group over 140 operations has been undertaken. Surgical margins were proven by histological procedures only in 29% of the patients. Long term OS, DFS and LC rates have been 64%, 56% and 69% respectively. Distant metastases have occurred in 30% of pts. during the first 2 years of observation. Prognostic factors have been evaluated in both univariate and multivariate analysis. The most important positive prognostic factors were as follows: radical surgical treatment and concomitant chemo-radiotherapy. The first, often proven or suspected as non-radical, tumour excision is the most important and probably independent negative prognostic factor for tumour cure and patient survival. For such clinical situations secondary surgical approach as a wide excision is recommended. Because of a large number of cases in analysed material with single or multiple local relapses decision of adjuvant therapy has to be considered individually. It seems that in such clinical situation, postoperative radiotherapy or aggressive radio-chemotherapy in cases with no clinically detected local relapse gives the best chance for survival. The long time of anamnesis, several surgical treatments of tumour relapses with no sarcoma policy stress the need to establish the general national rules for diagnosis and adjuvant treatment of soft tissue sarcomas.

A decision analysis of the effect of avoiding axillary lymph node dissection in low risk women with invasive breast carcinoma

Evidence that avoiding axillary lymph node dissection (AxD) strikes an appropriate balance between morbidity and recurrence risk in patients with invasive breast carcinoma generally is anecdotal and without a formally quantified basis. The current study presents a decision analysis of the difference in 5-year disease free survival (DFS) rate between treatment scenarios with and without routine AxD. To derive quantitative estimates of the effect of avoiding AxD on 5-year DFS, the authors examined outcomes for women undergoing 2 treatment scenarios: AxD or no AxD with adjuvant therapy decisions based on risk factors in the primary tumor. Eligible patients belonged to 2 lymph node metastases risk groups: low (patients without palpable lymph nodes and lymphatic or vascular invasion [LVI] negative tumors < or = 0.5 cm in greatest dimension) and moderate (patients with mammographically detected, LVI negative tumors, between 0.6-2.0 cm in greatest dimension or patients with palpable LVI negative tumors between 0.6-1.0 cm in greatest dimension with nonpalpable lymph nodes). Along with observed data regarding treatment and recurrence, the authors employed estimates of the efficacy of chemotherapy, tamoxifen, and regional radiation therapy derived from published randomized trials to estimate the 5-year DFS rate for treatment scenarios with and without AxD. Patients in the low risk group had a 5% risk of lymph node metastases. In these women, eliminating AxD and treating no patients with chemotherapy and/or tamoxifen resulted in a < 1% decrease in the 5-year DFS rate. Patients in the moderate risk group had a 10% risk of lymph node metastases. Eliminating AxD and treating only those women with Grade 3 tumors > 1 cm in greatest dimension with chemotherapy and/or tamoxifen resulted in a 1.8% decrease in the 5-year DFS rate. However, if all patients in this group were treated with chemotherapy and/or tamoxifen and no AxD, the 5-year DFS rate increased by 2.7%. In patients with a low risk of lymph node metastases, it was estimated that eliminating AxD may result in only minimal changes in the estimated 5-year DFS rate.

A decision analysis of the effect of avoiding axillary lymph node dissection in low risk women with invasive breast carcinoma

BACKGROUND Evidence that avoiding axillary lymph node dissection (AxD) strikes an appropriate balance between morbidity and recurrence risk in patients with invasive breast carcinoma generally is anecdotal and without a formally quantified basis. The current study presents a decision analysis of the difference in 5-year disease free survival (DFS) rate between treatment scenarios with and without routine AxD. METHODS To derive quantitative estimates of the effect of avoiding AxD on 5-year DFS, the authors examined outcomes for women undergoing 2 treatment scenarios: AxD or no AxD with adjuvant therapy decisions based on risk factors in the primary tumor. Eligible patients belonged to 2 lymph node metastases risk groups: low (patients without palpable lymph nodes and lymphatic or vascular invasion [LVI] negative tumors ≤ 0.5 cm in greatest dimension) and moderate (patients with mammographically detected, LVI negative tumors, between 0.6-2.0 cm in greatest dimension or patients with palpable LVI negative tumors between 0.6-1.0 cm in greatest dimension with nonpalpable lymph nodes). Along with observed data regarding treatment and recurrence, the authors employed estimates of the efficacy of chemotherapy, tamoxifen, and regional radiation therapy derived from published randomized trials to estimate the 5-year DFS rate for treatment scenarios with and without AxD. RESULTS Patients in the low risk group had a 5% risk of lymph node metastases. In these women, eliminating AxD and treating no patients with chemotherapy and/or tamoxifen resulted in a < 1% decrease in the 5-year DFS rate. Patients in the moderate risk group had a 10% risk of lymph node metastases. Eliminating AxD and treating only those women with Grade 3 tumors > 1 cm in greatest dimension with chemotherapy and/or tamoxifen resulted in a 1.8% decrease in the 5-year DFS rate. However, if all patients in this group were treated with chemotherapy and/or tamoxifen and no AxD, the 5-year DFS rate increased by 2.7%. CONCLUSIONS In patients with a low risk of lymph node metastases, it was estimated that eliminating AxD may result in only minimal changes in the estimated 5-year DFS rate. Cancer 2000;88:1852–62. © 2000 American Cancer Society.

Close Vaginal Margins as a Prognostic Factor after Radical Hysterectomy

From 1965 to 1995, at the University of Miami/Jackson Memorial Medical Center, 1223 patients with stage IA2, IB, or IIA cervical cancer have undergone a radical hysterectomy. The charts of these patients were reviewed retrospectively for pathology reports showing positive or close surgical margins. Fifty-one of these cases had final pathology results interpreted as close vaginal margins (CVM), which we define as tumor less than or equal to 0.5 cm from the vaginal margins of resection. All slides of blocks with close vaginal margins were found and reviewed by a single pathologist. Twenty-eight (54.9%) had parametrial involvement or positive lymph nodes and received adjuvant radiation therapy (RT). Of the remaining 23 cases, only 6 had other high risk factors, tumor greater than 4 cm, poorly differentiated, greater than 50% invasion, or lymphovascular space involvement. Sixteen of 23 received radiation. The 5-year survival was significantly greater with RT, 81.3%, than without RT, 28.6% (P< 0.05). The recurrence rate was also decreased from 85.7 to 12.5% (P< 0.01). Although present in less than 2% of radical hysterectomy specimens, CVM without other high risk factors may be an important prognostic variable that should be considered when making adjuvant therapy decisions.

Breast Cancer in Identical Twins with Different Clinical Course

: Recent discussions have questioned the need or benefit of radical axillary lymphadenectomy for some patients as part of treatment for breast carcinoma. An evaluation of the need for discontinuous lymphadenectomy is presented with proposal to eliminate lymphadenectomy in the breast-conserving therapy of some patients. From 1977 through 1993, 101 breasts in 95 patients with breast carcinoma were treated by breast conservation without radical axillary lymphadenectomy. At median follow-up of 76 months, only four patients (4.0% of cancers) had occurrence of axillary disease requiring invasive evaluation of delayed clinically positive axillae. One of the four patients had negative nodes. Two patients had positive lymph nodes without recurrent disease in the ipsilateral breast or distant metastasis. The fourth patient had distant metastasis, and a positive fine-needle aspiration biopsy of an axillary lymph node was sufficient for diagnosis. Discontinuous radical axillary lymphadenectomy was neither technically different nor more difficult that primary lymphadenectomy. Some breast cancer patients may forego surgical evaluation of the axilla as part of their breast conservation therapy without compromise in adjuvant therapy decisions or detriment in outcome. The authors strongly recommend large prospective, clinical studies be performed in the near future.