Daily localization of partial breast irradiation patients with three-dimensional ultrasound imaging.

PURPOSE: Accurate localization of the lumpectomy cavity during accelerated partial breast radiation (APBR) is essential for daily setup to ensure the prescribed dose encompasses the target and avoids unnecessary irradiation to surrounding normal tissues. Three-dimensional ultrasound (3D-US) allows direct visualization of the lumpectomy cavity without additional radiation exposure. The purpose of this study was to evaluate the feasibility of 3D-US in daily target localization for APBR. MATERIALS AND METHODS: Forty-seven patients with stage I breast cancer who underwent breast conserving surgery were treated with a 2-week course of APBR. Patients with visible lumpectomy cavities on high quality 3D-US images were included in this analysis. Prior to each treatment, X-ray and 3D-US images were acquired and compared to images from simulation to confirm accurate position and determine shifts. Volume change of the lumpectomy cavity was determined daily with 3D-US. RESULTS: A total of 118 images of each modality from 12 eligible patients were analyzed. The average change in cavity volume was 7.8% (range, -24.1% to 14.4%) on 3D-US from simulation to the end-of-treatment. Based on 3D-US, significantly larger shifts were necessary compared to portal films in all three dimensions: anterior/posterior (p = 7E-11), left/right (p = 0.002), and superior/inferior (p = 0.004). CONCLUSION: Given that the lumpectomy cavity is not directly visible via X-ray images, accurate positioning may not be fully achieved by X-ray images. Therefore, when the lumpectomy cavity is visible on US, 3D-US can be considered as an alternative to X-ray imaging during daily positioning for selected patients treated with APBR, thus avoiding additional exposure to ionizing radiation.

A novel schedule of accelerated partial breast radiation using intensity-modulated radiation therapy in elderly patients: survival and toxicity analysis of a prospective clinical trial.

PURPOSE: Several accelerated partial breast radiation (APBR) techniques have been investigated in patients with early-stage breast cancer (BC); however, the optimal treatment delivery techniques remain unclear. We evaluated the feasibility and toxicity of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I BC, using a novel fractionation schedule. MATERIALS AND METHODS: Forty-two patients aged ≥65 years, with stage I BC who underwent breast conserving surgery were enrolled in a phase I/II study evaluating APBR using IMRT. Forty eligible patients received 40 Gy in 4 Gy daily fractions. Patients were assessed for treatment related toxicities, and cosmesis, before APBR, during, and after completion of the treatment. RESULTS: The median age was 73 years, median tumor size 0.8 cm and the median follow-up was 54 months. The 5-year locoregional control was 97.5% and overall survival 90%. Erythema and skin pigmentation was the most common acute adverse event, reported by 27 patients (69%). Twenty-six patients (65%) reported mild pain, rated 1-4/10. This improved at last follow-up to only 2 (15%). Overall the patient and physician reported worst late toxicities were lower than the baseline and at last follow-up, patients and physicians rated cosmesis as excellent/good in 93% and 86 %, respectively. CONCLUSION: In this prospective trial, we observed an excellent rate of tumor control with daily APBR. The acceptable toxicity profile and cosmetic results of this study support the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

Long-term cosmesis following a novel schedule of accelerated partial breast radiation in selected early stage breast cancer: result of a prospective clinical trial.

PURPOSE: There is controversy regarding the cosmetic outcome after accelerated partial breast radiation (APBR). We report the cosmetic outcome from a single-arm prospective clinical trial of APBR delivered using intensity-modulated radiation therapy (IMRT) in elderly patients with stage I breast cancer (BC), using a novel fractionation schedule. MATERIALS AND METHODS: Forty-two patients aged ≥65, with Stage I BC who underwent breast-conserving surgery were enrolled in a phase I/II study evaluating a 2-week course of APBR. Thirty eligible patients received 40 Gy in 4 Gy daily fractions. Cosmetic outcome was assessed subjectively by physician/patient and objectively by using a computer program (BCCT.core) before APBR, during, and after completion of the treatment. RESULTS: The median age was 72 years, the median tumor size was 0.8 cm, and the median follow-up was 50.5 months. The 5-year locoregional control in this cohort was 97% and overall survival 87%. At the last follow-up, patients and physicians rated cosmesis as 'excellent' or 'good' in 100% and 91 %, respectively. The BCCT.core program scored the cosmesis as 'excellent' or 'good' in 87% of the patients at baseline and 81% at the last follow-up. The median V50 (20 Gy) of the whole breast volume (WBV) was 37.2%, with the median WBV V100 (40 Gy) of 10.9%. CONCLUSION: An excellent rate of tumor control was observed in this prospective trial. By using multiple assessment techniques, we are showing acceptable cosmesis, supporting the use of IMRT planned APBR with daily schedule in elderly patients with early stage BC.

Access to Care in Vermont: Factors Linked With Time to Chemotherapy for Women With Breast Cancer-A Retrospective Cohort Study.

PURPOSE: In the rural United States, there are multiple potential barriers to the timely initiation of chemotherapy. The goal of this study was to identify factors associated with delays in the time from initial diagnosis to first systemic therapy (TTC) among women with breast cancer in Vermont. METHODS: Using data from the Vermont Cancer Registry, we explored TTC for 702 female Vermont residents diagnosed with stage I to III breast cancer between 2006 and 2010 who received adjuvant chemotherapy. Multivariable linear regression was used to evaluate the associations between TTC and patient, tumor, treatment, and geographic variables. RESULTS: Mean TTC was 10.2 weeks. Longer drive time (P < .001), more invasive surgery (P = .01), and breast reconstruction (P < .001) were each associated with longer TTC. Each additional 15 minutes of drive time was associated with a 0.34-week (95% CI, 0.22 to 0.46 weeks) increase in TTC. Participants age younger than 65 years whose primary payer was Medicare (n = 27) had significantly longer average TTC, by 2.37 weeks (P = .001), compared with those with private or military insurance. There was also substantial variation in TTC across hospitals (P < .001). CONCLUSION: Most female patients with stage I to III breast cancer in Vermont are receiving adjuvant chemotherapy within the National Comprehensive Cancer Network-recommended timeframe; however, improvements remain needed for certain subgroups. Novel approaches for women with long drive times need to be developed and evaluated in the community. Variation in TTC by hospital, even after adjusting for patient, tumor, and treatment factors, also suggests opportunities for process improvement.

Inactivation of nuclear GSK3ß by Ser(389) phosphorylation promotes lymphocyte fitness during DNA double-strand break response.

Variable, diversity and joining (V(D)J) recombination and immunoglobulin class switch recombination (CSR) are key processes in adaptive immune responses that naturally generate DNA double-strand breaks (DSBs) and trigger a DNA repair response. It is unclear whether this response is associated with distinct survival signals that protect T and B cells. Glycogen synthase kinase 3ß (GSK3ß) is a constitutively active kinase known to promote cell death. Here we show that phosphorylation of GSK3ß on Ser(389) by p38 MAPK (mitogen-activated protein kinase) is induced selectively by DSBs through ATM (ataxia telangiectasia mutated) as a unique mechanism to attenuate the activity of nuclear GSK3ß and promote survival of cells undergoing DSBs. Inability to inactivate GSK3ß through Ser(389) phosphorylation in Ser(389)Ala knockin mice causes a decrease in the fitness of cells undergoing V(D)J recombination and CSR. Preselection-Tcrß repertoire is impaired and antigen-specific IgG antibody responses following immunization are blunted in Ser(389)GSK3ß knockin mice. Thus, GSK3ß emerges as an important modulator of the adaptive immune response.

Hormone therapy and radiotherapy for early prostate cancer: a utility-adjusted number needed to treat (NNT) analysis.

PURPOSE: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term (< or =6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. METHODS AND MATERIALS: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. RESULTS: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. CONCLUSIONS: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment.

Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: toxicity and clinical outcome.

PURPOSE: To assess survival, local control, and toxicity of intensity modulated radiation therapy (IMRT) in squamous cell carcinoma of the anal canal. METHODS AND MATERIALS: Seventeen patients were treated with nine-field IMRT plans. Thirteen received concurrent 5-fluorouracil and mitomycin C, whereas 1 patient received 5-fluorouracil alone. Seven patients were planned with three-dimensional anteroposterior/posterior-anterior (AP/PA) fields for dosimetric comparison to IMRT. RESULTS: Compared with AP/PA, IMRT reduced the mean and threshold doses to small bowel, bladder, and genitalia. Treatment was well tolerated, with no Grade > or =3 acute nonhematologic toxicity. There were no treatment breaks attributable to gastrointestinal or skin toxicity. Of patients who received mitomycin C, 38% experienced Grade 4 hematologic toxicity. IMRT did not afford bone marrow sparing, possibly resulting from the clinical decision to prescribe 45 Gy to the whole pelvis in most patients, vs. the Radiation Therapy Oncology Group-recommended 30.6 Gy whole pelvic dose. Three of 17 patients, who did not achieve a complete response, proceeded to an abdominoperineal resection and colostomy. At a median follow-up of 20.3 months, there were no other local failures. Two-year overall survival, disease-free survival, and colostomy-free survival are: 91%, 65%, and 82% respectively. CONCLUSIONS: In this hypothesis-generating analysis, the acute toxicity and clinical outcome with IMRT in the treatment of anal cancer is encouraging. Compared with historical controls, local control is not compromised despite efforts to increase conformality and reduce normal structure dose.

Concomitant radiation therapy and paclitaxel for unresectable locally advanced breast cancer: results from two consecutive phase I/II trials.

PURPOSE: The management of unresectable locally advanced breast cancer (ULABC) remains a major challenge because of the necessity both to treat local disease and to prevent distant disease. Two consecutive Phase I/II trials of concomitant chemotherapy and radiation (CRT) were performed to attempt to address both local and distant disease control in ULABC. This analysis focuses on rates of locoregional control and radiation-associated acute and late complications. METHODS AND MATERIALS: Thirty-three patients with unresectable locally advanced or inflammatory breast cancers (T4N0-3M0-1) or locally recurrent disease were treated with CRT on two consecutive Phase I/II trials. Radiotherapy consisted of 60-70 Gy to the breast or chest wall and 60 Gy to draining lymphatics in a week-on/week-off (WO/WO) schedule. Chemotherapy consisted of either continuous infusion or bolus paclitaxel +/- vinorelbine. A subset analysis of 16 patients with nonmetastatic ULABC Stage IIIB-C (T4N0-3M0) was performed. Among this cohort, 13 patients (81%) underwent planned mastectomy after CRT. RESULTS: Of the 16 patients with Stage IIIB-C disease, acute toxicity included moist desquamation (n = 8) and Grade 3-4 neutropenia (n = 3). Late toxicity included breast reconstruction loss, decreased range of arm motion, lymphedema, and skin toxicity, although none was life-threatening. Of 15 assessable patients, 14 had a clinical response, 7 had a pathologic complete response (pCR) including 6 of 13 patients undergoing mastectomy. With a median follow-up for living patients of 43.8 months, the 4-year actuarial locoregional control, disease-free survival, and overall survival were 83%, 33%, and 56% respectively. CONCLUSIONS: Concurrent WO/WO radiation therapy and paclitaxel +/- vinorelbine is effective locoregional therapy for ULABC with an acceptable toxicity profile. Further investigation of concurrent chemoradiotherapy in ULABC is warranted.

Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome.

PURPOSE: To assess the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) in pancreatic and bile duct (cholangiocarcinoma) malignancies. METHODS AND MATERIALS: Twenty-five patients with pancreatic and bile duct cancer were treated with IMRT. Twenty-three received concurrent 5-fluoruracil. One patient with a pancreatic primitive neuroectodermal tumor received concurrent etoposide and ifosfamide. Eight patients had resected tumors, and 17 had unresectable primary (n = 14) or recurrent (n = 3) tumors. Six patients underwent treatment planning with conventional three-dimensional four-field techniques for dosimetric comparison with IMRT. RESULTS: Compared with conventional RT, IMRT reduced the mean dose to the liver, kidneys, stomach, and small bowel. IMRT was well tolerated, with 80% experiencing Grade 2 or less acute upper GI toxicity. At a median follow-up of 10.2 months, no resected patients had local failure, and only 1 of 10 assessable patients with unresectable cancer had local progression. The median survival and distant metastasis-free survival of the 24 patients with adenocarcinoma was 13.4 and 7.3 months, respectively. Grade 4 late liver toxicity occurred in 1 patient surviving >5 years. The remainder of the assessable patients experienced no (n = 9) or Grade 1 (n = 4) late toxicity. CONCLUSION: In this hypothesis-generating analysis, the acute and chronic toxicity profile with IMRT in the treatment of pancreatic and bile duct cancer was encouraging. Local control was not compromised, despite efforts to increase conformality and avoid doses to normal structures. Distant failure remains a major obstacle in pancreatic cancer.

Efficacy of Breast Conservation Therapy in Early Stage Bilateral Breast Cancer.

The purpose of this study was to evaluate the outcome of patients with bilateral breast cancer as compared to unilateral breast cancer treated with breast conservation therapy. Sixty patients with bilateral breast cancer (BBC) and 1,080 unilateral breast cancer (UBC) patients treated with breast conservation therapy from 1977 to 1994 were analyzed for outcome. Of the 60 bilateral patients, 44 were metachronous bilateral breast cancer patients (MBBC) and 16 were synchronous bilateral breast cancer patients (SBBC). The majority of patients received lumpectomy, axillary node dissection, and localized radiation therapy. Median tumor size was 1.4 cm for BBC and 1.5 cm for UBC patients. Median total dose to the tumor bed was 60 Gy for both unilateral and bilateral patients. Of the 44 MBBC patients, 14 received breast conservation for both the first and second lesions, while 30 received breast conservation for only the second metachronous lesion. Thus 58 lesions in 44 patients were treated with breast conservation therapy. Of the SBBC patients, 13 of 16 patients received breast-conserving therapy for both breasts, while 3 received a mastectomy for the second synchronous primary. Median follow-up was 50 months for SBBC patients, 45 months for MBBC patients, and 52 months for UBC patients. Local control and survival were analyzed in patients with SBBC, MBBC, and UBC. The interval to development of local recurrence and survival were calculated from the time of development of the second breast lesion in patients with MBBC. No differences were found for survival and failure-free survival in patients with SBBC, MBBC, or UBC. Five-year overall survival by lifetable analysis was 76% for SBBC, 78% for MBBC, and 87% for UBC patients (p = 0.32 by log-rank analysis). The 5-year failure-free survival was 79% for SBBC, 73% for MBBC, and 85% for UBC patients (p = 0.28 by log-rank analysis). No significant differences were seen for median age, tumor size, pathologic node status, tamoxifen use, chemotherapy use, or median total radiation dose for SBBC, MBBC, or UBC patients. A significant difference was found in the incidence of family history of breast cancer in patients with unilateral versus bilateral breast cancer (p = 0.028 by chi-square analysis). However, there was no difference in outcome of patients by family history of breast cancer. The local control was identical in both BBC and UBC patients, with a local failure rate of 3%. Therefore, breast conservation therapy in local-regional, early stage breast cancer is a rational and efficacious treatment modality for patients with SBBC, MBBC, and UBC.

Defining negative margins in DCIS patients treated with breast conservation therapy: The University of Chicago experience.

Management of ductal carcinoma in situ (DCIS) has been evolving and the majority of women are now being treated with breast-conserving surgery and radiation therapy (i.e. breast conservation therapy [BCT]). Controversies still exist regarding the histologic features and margin status that are associated with local recurrence. The goal of this study was to review our institution's experience in patients diagnosed with DCIS and treated with BCT to determine pathologic features that can predict local recurrence, with particular emphasis on the final surgical margin status. We analyzed 103 consecutive patients with DCIS who were treated with BCT between 1986 and 2000. The slides were reviewed to determine the final margin status, type of DCIS, size of DCIS, nuclear grade, presence of necrosis and calcification, and volume of excised specimen. Margins were considered positive when DCIS touched or was transected at an inked margin. Negative margins were further categorized as close (less than 1 mm), 1--5 mm, and more than 5 mm. The size of the DCIS was determined based on either the maximal dimension on a slide or from the number of consecutive slides containing DCIS. Morphology and immunohistochemical profiles of the recurrent DCIS cases were compared with original DCIS. All patients were treated uniformly with external beam radiation therapy to the entire breast (median dose 46 Gy) with a boost to the tumor bed (median dose 14 Gy). The median follow-up was 63 months (range 7--191 months). The actuarial 5-year local control rate was 89%. The median time to local recurrence was 55 months. There were 13 local recurrences, of which 9 recurred as pure DCIS and 4 as invasive ductal carcinomas. Univariate analysis showed a significant association with local recurrence for positive margin (p=0.008), high nuclear grade (p=0.02), and young age at diagnosis (p=0.03). If margins were negative, the 5-year local control was 93%, as compared to 69% if margins were positive. A multivariate analysis showed that early age at diagnosis, positive margin status, and high nuclear grade were independently associated with local recurrence. The morphology and immunohistochemical stains of all nine recurrent DCIS were similar to those of the original DCIS. Breast conservation can be achieved with excellent local control by obtaining microscopically negative margins as strictly defined by DCIS not touching the inked surgical margins, and postoperative radiation that includes boost therapy to the tumor bed.

Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?

BACKGROUND: There are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor-free axillary lymph nodes on disease-free survival (DFS) in two distinct patient populations. METHODS: Eight hundred thirty-three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast-conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1-3 lymph nodes examined, Group 2 had 4-9 lymph nodes examined, Group 3 had 10-20 lymph nodes examined, and Group 4 had >20 lymph nodes examined. RESULTS: In the mastectomy cohort, with a median follow-up of 153 months, the 10-year DFS rate was 70%, 65%, 79%, and 81% for Groups 1-4, respectively. On multivariate analysis, pathologic tumor size (P<0.001) and the number of lymph nodes examined (P=0.010) were significant predictors for long-term DFS. In the breast-conservation cohort, with a median follow-up of 53 months, the 5-year DFS rate was 90%, 91%, 92%, and 95% for Groups 1-4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P=0.003) and tumor size (P=0.035). CONCLUSIONS: The recovery of <10 lymph nodes in lymph node-negative patients who underwent mastectomy resulted in a 10-15% decreased long-term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast-conservation therapy, which included radiation.

Mammographically detected breast cancers and the risk of axillary lymph node involvement: is it just the tumor size?

PURPOSE: In early breast cancer the knowledge of the risk of axillary node involvement is important in determining local as well as systemic therapy. Because of the increased acceptance of mammography, there has been an increase in the diagnosis of small, mammographically detected tumors. The objective of this study is to determine whether mammographically detected breast cancers have a lower risk of axillary node involvement compared to those detected clinically. PATIENTS AND METHODS: From our patient database of stage I and II breast cancer we identified 980 patients with tumors < or = 2 cm whom had axillary node dissection. Four hundred thirty-five (44%) patients presented with abnormal mammograms without clinically palpable tumors; 545 (56%) patients had clinically detected tumors. The median size of the mammographically detected tumors is 1.0 cm, and the median size of the clinically detected tumors is 1.5 cm. The median age of the patients with mammographically detected tumors is 61 (range: 29-87) compared to 53 (range: 27-88) in those with palpable tumors. RESULTS: Fourteen percent of the patients with mammographically detected tumors had positive axillary nodes compared to 26% of those with clinically detected tumors. Eight percent of patients with mammographically detected tumors had a single positive, while the clinically detected tumors 11% had a single positive node. Thirteen percent of patients with < or = 1 cm tumors and 25% with tumors 1.1 cm to 2 cm had positive axillary nodes. Because the smaller size of the mammographically detected tumors could explain the lower proportion of positive axillary nodes, we analyzed separately the < or = 1 cm tumors. In the group of < or = 1 cm tumors, 9% had positive axillary nodes iftheywere mammographically detected compared to 19% if clinically detected. Four percent had a single positive node while 5% had multiple positive nodes. If the tumors were palpable and < or = 1 cm 9% had a single positive node and 10% had multiple positive nodes. Mammo-graphicallydetected tumors < or = 1 cm had similargrade to clinically detected tumors. In multivariate analysis, method of detection remains a significant variable impacting on the risk of axillary node involvement even in tumors < or = 1 cm. DISCUSSION: The risk of axillary node involvement is lower in mammographically detected tumors compared to clinically detected tumors independent of tumor size or grade. Mammography detects tumors early in their metastatic progression. The majority of the axillary node-positive patients who are mammographically detected have a single positive axillary node. Method of detection may need to be considered when assessing the risk of axillary node involvement and incorporated in the staging.

The natural history of breast carcinoma in the elderly: implications for screening and treatment.

BACKGROUND: The authors evaluated the two indicators of metastatic proclivity (namely, virulence [V; the rate of appearance of distant metastases] and metastagenicity [M; the ultimate likelihood of developing distant metastases]) of breast carcinoma in elderly women. The authors then compared these characteristics with the corresponding characteristics in a cohort of younger women to determine whether breast carcinoma was more indolent in women age > 70 years, as is commonly believed in the medical community. METHODS: The authors examined 2136 women who underwent mastectomy without adjuvant systemic therapy at The University of Chicago Hospitals (Chicago, IL) between 1927 and 1987. The median follow-up period was 12.3 years. Distant disease-free survival (DDFS) was determined for women who did not receive systemic therapy. V and M were obtained from log-linear plots of DDFS. RESULTS: No significant difference in tumor size at presentation was observed among women age < 40 years, women ages 40-70 years, and women age > 70 years (P = 0.86), whereas significantly fewer women age > 70 years presented with positive lymph nodes compared with younger women (P = 0.05). In women with negative lymph node status, there was a higher DDFS rate among patients ages 40-70 years (81% at 10 years) compared with patients age > 70 years (65% at 10 years; P = 0.018). There was no significant age-related difference among women with lymph node-positive disease (P = 0.2). For example, the 10-year DDFS rate for women ages 40-70 years was 33%, compared with 38% for women age > 70 years. Among those with lymph node-negative disease, V was 3% per year for women ages 40-70 years as well as women age > 70 years. Among women with lymph node-negative disease, M was 0.20 for patients ages 40-70 years and 0.35 for patients age > 70 years. In women with positive lymph node status, both V (11% per year vs. 10% per year) and M (0.70 vs. 0.65) were similar in both age groups. CONCLUSIONS: Fewer women age > 70 years had lymph node involvement at presentation. However, when this finding was taken into account, the authors found no evidence that breast carcinoma was more indolent in women age > 70 years. These results support the use of similar diagnostic and therapeutic efforts for elderly women and younger women, with modification for elderly women based only on comorbidity.

Sentinel lymph node versus axillary lymph node dissection for early-stage breast carcinoma: a comparison using a utility-adjusted number needed to treat analysis.

BACKGROUND: The current study was performed to compare the value of sentinel lymph node dissection (SND) and axillary lymph node dissection (AND) in improving the utility-adjusted survival for early-stage breast carcinoma patients. METHODS: A number needed to treat (NNT) analysis was used to compare SND with AND. In the NNT equation, 1/(S(SND) - S(AND)), S is the 5-year utility-adjusted survival. A literature review was performed to estimate 1) the prevalence of axillary lymph node disease for early-stage breast carcinoma, 2) the sensitivity and specificity of SND and AND, 3) the 5-year overall survival as a function of axillary lymph node involvement, 4) the risk of arm lymphedema as a function of the intervention performed, and 5) the utility correction (Uc; impairment of quality of life) for arm lymphedema. RESULTS: The NNT method of analysis favored SND over nearly the entire range of parameters with a sign change to a negative value occurring only as Uc becomes very close to unity. This suggests the superiority of the SND approach. Only when there is minimal loss of utility does AND become favored and then only minimally. CONCLUSIONS: Compared with AND, SND improves the utility-adjusted survival in patients with early-stage breast carcinoma. This finding is quite robust and was found to remain constant over a range of values for utility and lymph node prevalence.