Atilla Soran

The Effect on Tumor Response of Adding Sequential Preoperative Docetaxel to Preoperative Doxorubicin and Cyclophosphamide: Preliminary Results From National Surgical Adjuvant Breast and Bowel Project Protocol B-27

PURPOSE The National Surgical Adjuvant Breast and Bowel Project Protocol B-27 was designed to determine the effect of adding docetaxel after four cycles of preoperative doxorubicin and cyclophosphamide (AC) on clinical and pathological response rates and on disease-free and overall survival of women with operable breast cancer. PATIENTS AND METHODS Women (N = 2,411) with operable primary breast cancer were randomly assigned to receive either four cycles of preoperative AC followed by surgery (group I), or four cycles of AC followed by four cycles of docetaxel, followed by surgery (group II), or four cycles of AC followed by surgery and then four cycles of docetaxel (group III). Clinical and pathologic tumor responses to preoperative therapy were assessed. RESULTS Mean tumor size (4.5 cm) and other key characteristics were evenly balanced among the three treatment arms. Grade 4 toxicity was observed in 10.3% of 2,400 patients during AC treatment, and in 23.4% of 1584 patients during docetaxel treatment. Compared to preoperative AC alone, preoperative AC followed by docetaxel increased the clinical complete response rate (40.1% v 63.6%; P <.001), the overall clinical response rate (85.5% v 90.7%; P <.001), the pathologic complete response rate (13.7% v 26.1%; P <.001), and the proportion of patients with negative nodes (50.8% v 58.2%; P <.001). Pathologic primary breast tumor response was a significant predictor of pathologic nodal status (P <.001). CONCLUSION The addition of four cycles of preoperative docetaxel after four cycles of preoperative AC significantly increased clinical and pathologic response rates for operable breast cancer.

Sequential Preoperative or Postoperative Docetaxel Added to Preoperative Doxorubicin Plus Cyclophosphamide for Operable Breast Cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27

PURPOSE This study was designed to determine the effect of adding docetaxel (T) to preoperative doxorubicin and cyclophosphamide (AC) on breast cancer response rates and disease-free survival (DFS) and overall survival (OS). PATIENTS AND METHODS Women with operable breast cancer (N = 2,411) were randomly assigned to receive preoperative AC followed by surgery, AC followed by T and surgery, or AC followed by surgery and then T. Tamoxifen was initiated concurrently with chemotherapy. Median time on study for 2,404 patients with follow-up was 77.9 months. RESULTS Addition of T to AC did not significantly impact DFS or OS. There were trends toward improved DFS with addition of T. The addition of T reduced the incidence of local recurrences as first events (P = .0034). Preoperative T, but not postoperative T, significantly improved DFS in patients who had a clinical partial response after AC (hazard ratio [HR] = 0.71; 95% CI, 0.55 to 0.91; P = .007). Pathologic complete response, which was doubled by addition of preoperative T, was a significant predictor of OS regardless of treatment (HR = 0.33; 95% CI, 0.23 to 0.47; P < .0001). Pathologic nodal status after chemotherapy was a significant predictor of OS (P < .0001). CONCLUSION The addition of preoperative or postoperative T after preoperative AC did not significantly affect OS, slightly improved DFS, and decreased the incidence of local recurrences. The sample size of this study was not sufficient to yield significance for the moderate DFS improvement. Concurrent use of tamoxifen may have limited the impact of adding T.

Paclitaxel After Doxorubicin Plus Cyclophosphamide As Adjuvant Chemotherapy for Node-Positive Breast Cancer: Results From NSABP B-28

PURPOSE The primary aim of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 was to determine whether four cycles of adjuvant paclitaxel (PTX) after four cycles of adjuvant doxorubicin/cyclophosphamide (AC) will prolong disease-free survival (DFS) and overall survival (OS) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes. PATIENTS AND METHODS Between August 1995 and May 1998, 3,060 patients were randomly assigned (AC, 1,529; AC followed by PTX [AC --> PTX], 1,531). Patients > or = 50 years and those younger than 50 years with estrogen receptor (ER) or progesterone receptor (PR) -positive tumors also received tamoxifen for 5 years, starting with the first dose of AC. Postlumpectomy radiotherapy was mandated. Postmastectomy or regional radiotherapy was prohibited. Median follow-up is 64.6 months. RESULTS The addition of PTX to AC significantly reduced the hazard for DFS event by 17% (relative risk [RR], 0.83; 95% CI, 0.72 to 0.95; P = .006). Five-year DFS was 76% +/- 2% for patients randomly assigned to AC --> PTX compared with 72% +/- 2% for those randomly assigned to AC. Improvement in OS was small and not statistically significant (RR, 0.93; 95% CI, 0.78 to 1.12; P = .46). Five-year OS was 85% +/- 2% for both groups. Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction (for DFS, P = .30 and P = .44, respectively). Toxicity with the AC --> PTX regimen was acceptable for the adjuvant setting. CONCLUSION The addition of PTX to AC resulted in significant improvement in DFS but no significant improvement in OS with acceptable toxicity. No significant interaction between treatment effect and receptor status or tamoxifen administration was observed.

Oral Uracil and Tegafur Plus Leucovorin Compared With Intravenous Fluorouracil and Leucovorin in Stage II and III Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project Protocol C-06

PURPOSE The primary aim of this study was to compare the relative efficacy of oral uracil and tegafur (UFT) plus leucovorin (LV) with the efficacy of weekly intravenous fluorouracil (FU) plus LV in prolonging disease-free survival (DFS) and overall survival (OS) after primary surgery for colon carcinoma. PATIENTS AND METHODS Between February 1997 and March 1999, 1,608 patients with stage II and III carcinoma of the colon were randomly assigned to receive either oral UFT+LV or intravenous FU+LV. RESULTS Of the total patients, 47% had stage II colon cancer, and 53% had stage III colon cancer. Median follow-up time was 62.3 months. The estimated hazard ratio (HR) for OS of patients who received UFT+LV versus that of patients who received FU+LV was 1.014 (95% CI, 0.825 to 1.246). The estimated HR for DFS was 1.004 (95% CI, 0.847 to 1.190). Cox proportional hazards model analyses with regard to age (< 60 v > or = 60 years), stage, or number of involved nodes (none v one to three v > or = four nodes) revealed no interaction with OS or DFS. Toxicity was similar in the two groups. In the UFT+LV arm, 38.2% of patients experienced any grade 3 or 4 toxic event compared with 37.8% of patients in the FU+LV arm. Primary quality-of-life end points did not differ between the two regimens, although convenience of care analysis favored UFT+LV. CONCLUSION UFT+LV achieved similar DFS and OS when compared with an intravenous, weekly, bolus FU+LV regimen. The two regimens were equitoxic and generally well tolerated.

Breast Cancer-Related Lymphedema – What Are the Significant Predictors and How They Affect the Severity of Lymphedema?

Abstract:  According to the American Cancer Society, there are currently 2 million breast cancer (BC) survivors in the USA and 20% of them cope with lymphedema (LE). The primary aim of this study was to determine the predictive factors of BC‐related LE. The secondary aim was to investigate the impact of predictors on the severity of LE. The study design was intended to be a 1:2 matched case–control study. Instead, we stratified on age (±10 years), radiation therapy (y/n), and type of operation (SM/MRM/MRM with tram). Patients who underwent BC surgery between 1990 and 2000 at UPMC Magee‐Womens Hospital were reviewed for LE. Data were collected on 52 women with LE and 104 female controls. Logistic regression was utilized to assess the relationship between risk factors and LE. Ordinal logistic regression was performed to determine the association between risk factors and severity of LE. Severity was defined according to the volume difference between affected and unaffected limbs. Risk factors considered were occupation/hobby (hand use), TNM stage, number of dissected nodes, number of positive nodes, tumor size, infection, allergy, diabetes mellitus, hypertension, hypothyroidism, chronic obstructive pulmonary disease, and body mass index (BMI). LE was mild in 43 patients and was moderate/severe in nine patients. The level of hand use in the control group was categorized as low in 56 (54%), medium in 15 (14%), and high in 33 (32%) patients. The corresponding frequencies were 14 (33%), 6 (14%) and 23 (53%) for patients with mild LE and 3 (33%), 1 (11%), 5 (56%) for patients with moderate/severe LE (p < 0.05). Infection of the operated side arm was reported by two (2%) patients in the control group, 14 (33%) patients with mild LE and five (56%) patients with moderate/severe LE (p < 0.05). The mean BMI was 26.1 kg/m2 (SD 4.9) for the control group, 29.0 kg/m2 (SD 5.9) for the mild LE group and 30.9 kg/m2 (SD 7.5) for patients with moderate/severe LE (p < 0.05). The results of this stratified case–control study demonstrated that the risk and severity of LE was statistically related to infection, BMI, and level of hand use.

Renal Transplantation In Recipients Over The Age Of 60: The Impact of Donor Age

BACKGROUND Kidneys from older donors exhibit a series of changes characterized by glomerular, vascular, and tubular senescence. These changes may be aggravated by atherosclerosis, hypertension, or diabetes, which are highly prevalent in older individuals. METHODS We analyzed the outcome after transplantation in 230 recipients over the age of 60, who received transplants between February 1990 and December 1996. We assessed the 1- and 5-year patient and graft survival, the quality of renal function, tacrolimus levels, the incidence of rejection, and the incidence of delayed graft function, and compared the outcomes in recipients of kidneys from donors over the age of 60 (group 1, n = 40) with those in recipients of kidneys from donors under the age of 60 (group 2, n = 190). There were no differences between the two groups in terms of recipient sex, race, age, and cold ischemia time. Immunosuppression was with tacrolimus and steroids in 61% of cases; in the remainder of the patients, a third agent, either azathioprine, cyclophosphamide (for 1 week), or mycophenolate mofetil was administered as well. The median follow-up was 31.5 months (range: 1-86). RESULTS In recipients over the age of 60 receiving tacrolimus-based immunosuppression, overall patient survival at 1 and 5 years was 90% and 76%, and was not significantly compromised in recipients receiving a kidney from a donor over the age of 60. The overall 1-and 5-year actuarial graft survival was 84% and 64%; in recipients from donors over the age of 60, it was 73% and 52%, whereas in recipients of kidneys from donors under the age of 60, it was 87% and 66% (P<0.05). Most of the effect on graft survival was seen by 1 year. The mean serum creatinine was 2.6+/-2.7 mg/dl, without any difference between the two groups. Although the incidence of delayed graft function was higher in recipients of kidneys from donors over the age of 60, this difference did not reach statistical significance. CONCLUSIONS Although the overall outcomes of transplantation in older recipients remain reasonable, the inferior outcomes with older donor kidneys call into question proposals to utilize older donor kidneys preferentially in older recipients.

Immunohistochemical surrogate markers of breast cancer molecular classes predicts response to neoadjuvant chemotherapy: a single institutional experience with 359 cases.

Complete pathologic response to neoadjuvant chemotherapy (NACT) is predominantly seen in “ERBB2” and “basal‐like” tumors using expression profiling. We hypothesize that a similar response could be predicted using semiquantitative immunohistochemistry for estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2).

Emergent resection for acute sigmoid volvulus: results of 106 consecutive cases.

AbstractINTRODUCTION: After nonoperative decompression of acute sigmoid volvulus, definitive surgery is necessary because of the high risk of recurrence. However, the optimal surgical technique for this purpose has not been determined. METHODS: We studied 106 consecutive patients (mean age, 60.9 (range, 26–93) years) who underwent emergency resection for acute sigmoid volvulus between 1992 and 2000. No patient underwent preoperative decompression techniques, had the bowel prepared, or received on-table lavage. RESULTS: Depending on the patient’s condition and the surgeon’s preference, either primary anastomosis (57 cases) or Hartmann’s procedure (49 cases) was performed. The overall mortality rate was 6.6 percent (7/106). The presence of a gangrenous bowel increased the mortality rate to 11 percent. Wound infections were documented in 8 and 12 cases, intra-abdominal abscess occurred in 1 and 7 cases, and subsequent surgery was required in 6 and 5 patients who underwent primary anastomosis and Hartmann’s procedure, respectively. There were four cases of anastomotic dehiscence (7 percent) and two cases of stoma revisions (4 percent). The median length of stay was eight days for both those who underwent primary anastomosis (range, 3–27 days) and those who underwent Hartmann’s procedure (range, 5–29 days). CONCLUSION: Emergent primary resection of the acute sigmoid volvulus with or without anastomosis is adequate treatment for this emergent surgical problem.

Breast cancer risk factors in Turkish women – a University Hospital based nested case control study

BackgroundBreast cancer has been increased in developing countries, but there are limited data for breast cancer risk factors in these countries. To clarify the risk for breast cancer among the Turkish women, an university hospital based nested case-control study was conducted.MethodsBetween January 2000 and December 2006, a survey was prospectively conducted among women admitted to clinics of Istanbul Medical Faculty for examination and/or treatment by using a questionnaire. Therefore, characteristics of patients diagnosed with breast cancer (n = 1492) were compared with control cases (n = 2167) admitted to hospital for non-neoplastic, non-hormone related diseases.ResultsBreast cancer risk was found to be increased in women with age (≥ 50) [95% confidence interval (CI) 2.42–3.18], induced abortion (95% CI 1.13–1.53), age at first birth (≥ 35) (95% CI 1.62–5.77), body mass index (BMI ≥ 25) (95% CI 1.27–1.68), and a positive family history (95% CI 1.11–1.92). However, decreased breast cancer risk was associated with the duration of education (≥ 13 years) (95% CI 0.62–0.81), presence of spontaneous abortion (95% CI 0.60–0.85), smoking (95% CI 0.61–0.85), breast feeding (95% CI 0.11–0.27), nulliparity (95% CI 0.92–0.98), hormone replacement therapy (HRT) (95% CI 0.26–0.47), and oral contraceptive use (95% CI 0.50–0.69). On multivariable logistic regression analysis, age (≥ 50) years (OR 2.61, 95% CI 2.20–3.11), induced abortion (OR 1.66, 95% CI 1.38–1.99), and oral contraceptive use (OR 0.60, 95% CI 0.48–0.74) were found to be associated with breast cancer risk as statistically significant independent factors.ConclusionThese findings suggest that age and induced abortion were found to be significantly associated with increased breast cancer risk whereas oral contraceptive use was observed to be associated with decreased breast cancer risk among Turkish women in Istanbul.

Predictors of Residual Invasive Disease after Core Needle Biopsy Diagnosis of Ductal Carcinoma In Situ

Abstract:  Core needle biopsy (CNB) is used to sample both mammographically and ultrasound detected breast lesions. A diagnosis of ductal carcinoma in situ (DCIS) by CNB does not ensure the absence of invasive cancer upon surgical excision and as a result an upstaged patient may need to undergo additional surgery for axillary nodal evaluation. This study evaluates the accuracy of CNB in excluding invasive disease and the preoperative features that predict upstaging of DCIS to invasive breast cancer.