Significant Prognostic Factors For Recurrence Research Articles

HER2 overexpression is associated with shorter disease-free survival (DFS) following neoadjuvant systemic therapy (NST) of primary breast cancer (PBC) patients with gemcitabine (G), epirubicin (E) and docetaxel (Doc)

11087 Background: To evaluate prognostic factors for disease-free survival (DFS) following NST with G, E and Doc of patients with PBC. Methods: From 1/02 to 12/04 113 patients with T2–4 N0–2 M0 PBC received either six cycles of GEDoc (G 800 mg/m2 day (d) 1+8, E 60–90 mg/m2 d 1, Doc 60–75 mg/m2 d 1 every three weeks; 63 patients) or five cycles of GE (1,250 mg/m2 d 1, E 90–100 mg/m2 d 1 every two weeks) sequentially followed by four cycles of Doc (80–100 mg/m2 d 1every two weeks) with prophylactic filgrastim. 71% of tumours were hormone receptor positive, 24% HER2 positive (3+ by immunohistochemistry), 46% grade 3. 28 patients (25%) achieved a pathologic complete response (pCR) defined as no invasive tumour residue in the removed breast tissue at surgery. 9 of these patients had non-invasive cancer residues in the breast, one patient showed persisting axillary lymph node involvement. Results: With a median follow up of 3.2 years there is no statistically significant difference in DFS, distant DFS (DDFS) and overall survival (OS) rates between patients with and without pCR (DFS 79 versus (vs) 81 %, p=0,61; DDFS 82 vs 84 %, p=0.69; OS 86 vs 91%, p=0.33). In a Cox proportional hazards model HER2 3+ before NST (hazard ratio (HR)= 4.7; 95% confidence interval (CI) 1.9 - 11.3; p=0.0006), positive hormone receptors before NST (HR=0.27; 95% CI 0.11 - 0.65; p=0.003) and clinically nodal involvement before NST (HR=3.3; 95% CI 1.2–9.1; p=0.02) were statistically significant prognostic factors for recurrence whereas tumour size and grade before NST, the achievement of pCR, nodal status at surgery and response after 6 weeks of NST did not reach statistical significance. Thus far, in multivariate analysis only Her2 3+ before NST retained its prognostic significance (HR= 2.8; 95% CI 1.03 - 7.5, p=0.04). Conclusions: With a median follow-up of 3.2 years in multivariate analysis only HER2 3+ is associated with shorter DFS following NST containing G, E and Doc for PBC. Thus far, there is no statistically significant prognostic value for pCR. No significant financial relationships to disclose.

Tumor Invasion of Lymph Node Capsules in Patients with Dukes C Colorectal Adenocarcinoma

The objective of this study was to investigate the correlation between the microscopic findings of positive lymph nodes, especially focusing on capsular invasion, and the outcome after curative surgical resection of colorectal cancer. We analyzed 480 positive lymph nodes from 155 consecutive patients with Stage III colorectal cancer to determine the frequency and significance of lymph node capsular invasion. Recurrence-free and cancer-specific survival rates were assessed in the patients with and without lymph node capsular invasion. Between April 1995 and December 2000, 406 consecutive patients with primary colorectal cancer underwent curative resection. Regional lymph node metastases were present in 155 cases (38.2 percent). During the median follow-up period of 4.8 years, 41 patients (26.5 percent) developed recurrent disease and 28 patients died of cancer. Lymph node capsular invasion was detected in one or more lymph nodes from 75 cases (48.3 percent). The five-year recurrence-free rate was 56.1 percent in this group, whereas in the 80 patients without lymph node capsular invasion the rate was 88 percent (P<0.01). Features that were associated with recurrent disease were greater number of positive lymph nodes, venous invasion in primary tumor, infiltrative growth pattern of intranodal tumor, and presence of lymph node capsular invasion. Multivariate analysis identified lymph node capsular invasion as the only significant prognostic factor for recurrence. In multivariate analysis with regard to survival, lymph node capsular invasion, venous invasion, and number of positive nodes remained as significant prognostic factors. Lymph node capsular invasion, determined by routine hematoxylin-eosin staining, is a potent prognostic factor in Stage III colorectal cancer.

The Outcome of Patients on Dialysis With Upper Urinary Tract Transitional Cell Carcinoma

Transitional cell carcinoma is the most common upper urinary tract cancer in Taiwanese patients on dialysis. It is a unique finding compared with Western countries. Unfortunately, the long-term outcomes of patients with upper urinary tract transitional cell carcinoma on dialysis are largely unknown. This study presents clinical outcome of patients on dialysis with upper urinary tract transitional cell carcinoma. We retrospectively reviewed the medical records of all patients with upper urinary tract transitional cell carcinoma who had end stage renal disease and underwent dialysis. Traditional prognostic factors including age, sex, tumor grade, stage and tumor location were analyzed with respect to disease recurrence and survival. A total of 73 patients were included in this study. The major complaints were painless gross hematuria and urethral bloody discharge. Disease relapsed in 40 (54.8%) patients at average time of 15 months (2 to 92). Univariate analysis failed to identify significant prognostic factors for recurrence. The average duration between primary and contralateral metachronous upper urinary tract transitional cell carcinoma recurrence was 36 months (range 5 to 96). Patients on dialysis with upper urinary tract transitional cell carcinoma who had previous or concurrent bladder tumor, or who had a history of recurrent bladder tumor, had high contralateral upper urinary tract transitional cell carcinoma recurrence. (p = 0.038) The statistically significant prognostic factor for disease-free survival was pT stage (p = 0.041). Patients on dialysis with painless gross hematuria or bloody urethral discharge must undergo detail urinary system evaluation. Since patients with upper urinary tract transitional cell carcinoma on dialysis have a high recurrence rate and metachronous or even multiple, early synchronous tumor characteristics that may be missed by imaging, total urinary tract exenteration is a recommended therapeutic option.

The impact of age on long-term outcome in patients with endometrial cancer treated with postoperative radiation

Purpose. Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. Age has been associated with worse outcome in univariate analysis. However, the patterns of failure and associated risk factors in older patients remain unclear. We reviewed our institution's experience to assess the effect of age in a population of endometrial cancer patients treated with surgery and adjuvant radiation therapy. Methods. From 1992–2002, 243 endometrial cancer patients underwent a total abdominal hysterectomy and adjuvant radiation. Forty-nine patients with stage I–II (occult) endometrial adenocarcinoma (no clear cell or serous papillary) were treated postoperatively with vaginal intracavitary high-dose rate (HDR) brachytherapy alone using Iridium-192 (median dose 30 Gy) to a median length of 4 cm. Forty-eight patients with stage I–III endometrial adenocarcinoma (no clear cell or papillary serous) were treated with postoperative pelvic RT (median dose 45 Gy) and intracavitary HDR brachytherapy (median dose 20 Gy). One hundred forty-six patients underwent postoperative whole abdomino-pelvic irradiation (WAPI) secondary to unfavorable histology (clear cell or serous papillary) or two of the following: deep myometrial invasion, grade 3, or FIGO stage III. Age was analyzed as a continuous and a categorical variable. The age of 63 year split the age group using various statistical analyses. Results. Median follow-up of all patients was 4.2 years. Patients grouped by age of ≤63 years or older had similar FIGO stage ( P = 0.5), grade ( P = 0.09), treatment modality ( P = 0.7), and lymphovascular space invasion (LVSI) ( P = 0.6). Twenty-five percent (60/243) of patients developed recurrence. Of these failures, 15% (15/102) were age ≤63 years and 32% (45/141) were age >63 years at diagnosis ( P = 0.02). For all patients, the 5-year event-free survival (EFS), cause specific survival (CSS), and overall survival (OS) were 64%, 82%, and 72%, respectively. Five-year EFS for patients age ≤63 years and >63 years was 76% vs. 55% ( P < 0.001). Five-year OS for age ≤63 years and >63 years was 85% vs. 63% ( P < 0.001). Five-year CSS for age ≤63 years and >63 years was 91% vs. 75% ( P = 0.003). Various factors were analyzed to determine an association with age. Older patients with stage III–IVA had significantly more failures than patients less than age 63 ( P = 0.002). Older patients (>63 years) were found to have serous papillary histology (28%) more often than younger patients (15%) ( P = 0.02). Greater depth of invasion was associated with older age ( P = 0.01). On univariate analysis, older age ( P = 0.003), LVSI ( P = 0.002), FIGO stage ( P < 0.001), grade ( P < 0.001), and depth of invasion ( P = 0.03) predicted for failure. On Cox multivariate analysis, older age ( P = 0.006, HR 2.83), higher FIGO stage ( P = 0.001, HR 1.96), and higher grade ( P = 0.002, HR 2.66) were significant prognostic factors for recurrence. No difference was seen between the two age groups from date of surgery and start of radiation. The duration of therapy was not different between the two groups. Conclusions. Older endometrial cancer (age >63 years) patients have a significantly decreased overall survival, cause-specific survival, and greater risk of recurrence following postoperative RT independent of other prognostic factors and/or treatment technique. The impact of treatment-related variables did not alter the age-related outcome.

Importance of lymph node metastases in follicular thyroid cancer.

There are many concepts of risk and prognostic factor analysis for differentiated thyroid cancer. The prognostic role of lymph node metastases in follicular thyroid cancer (FTC), however, is still controversial. We performed a retrospective trial in 186 patients with FTC (124 women, 62 men; mean follow-up 5.5 years) questioning whether lymph node metastases and radical thyroid surgery with neck dissection contribute to the prognosis of FTC. Univariate analysis demonstrated that lymph node metastasesp <0.005), tumor size (p <0.005), tumor stage (p <0.005), distant metastases p = 0.0063), and gender (p = 0.003) are significant prognostic factors for recurrence (Kaplan-Meier). Tumor size (p = 0.004), lymph node metastases p = 0.0478), and distant metastases p = 0.0064) influenced mortality. Age and extent of surgery were not significant for recurrence nor was gender for mortality. Multivariate analysis (Cox regression test) characterized tumor size (p <0.005) and lymph node metastases p = 0.004) as prognostic factors for recurrence of FTC. No significant difference was detected between patients being treated by thyroidectomy when compared to patients treated by thyroidectomy plus neck dissection in relation to recurrence. Our data demonstrate lymph node metastases to be a significant prognostic factor for recurrence of FTC and the patient's survival. We advocate thyroidectomy plus central lymph node dissection as the basic surgical strategy. For T3 and T4 tumors, unilateral modified neck dissection is an all but optional procedure. Whether radical surgery with thyroidectomy plus neck dissection has an impact on survival remains questionable.

Pathologic and Clinical Features Influencing Outcome of Thin Cutaneous Melanoma: Correlation with Newly Proposed Staging System

The incidence of malignant melanoma is increasing. Because of increased awareness, early recognition of malignant melanoma has become more common. In 1997, a new staging system for cutaneous melanoma was proposed, with reclassification of thin melanoma < 1 mm, with and without ulceration. This report evaluates the pathologic and clinical features of thin melanomas influencing recurrence and survival from a tertiary cancer center in an attempt to correlate findings with the proposed staging system. A review of the Roswell Park Cancer Institute tumor registry identified 352 patients with thin cutaneous melanomas (< 1.0 mm) seen during an 18-year period ending August 30, 1998. Overall survival was 93 and 87 per cent at 5 and 10 years, respectively. Disease-free survival was 94 and 93 per cent at 5 and 10 years, respectively. Local recurrence occurred in 3 per cent of patients, regional recurrence in 3 per cent, and metastatic disease in 3 per cent, for an overall recurrence of 7 per cent, with a median follow-up of 118 months. Only the presence of ulceration was a significant prognostic factor for recurrence by both univariate and multivariate analysis. Failure rates (any recurrence) by Clark levels I, II, and III/IV were 3, 5, and 10 per cent, respectively (P = 0.14). Failure rates by tumor thickness (mm), for 0.0-0.24, 0.25-0.49, 0.50-0.74, and 0.75-0.99 were 3, 4, 7, and 10 per cent, respectively (P = 0.49). Ten-year disease-free survival for ulceration versus no ulceration was 40 and 94 per cent, respectively (P < 0.0001). We conclude that thin cutaneous melanoma carries an excellent prognosis with appropriate treatment. Our findings support inclusion of ulceration in a new staging system. Lesions 0.76 to 0.99 mm and Clark level III and IV may warrant close observation as a separate subgroup.

Prognostic factors, recurrence, and survival in transitional cell carcinoma of the upper urinary tract: a 30-year experience in 252 patients

Objectives. To review a large single-center experience of patients treated for upper tract transitional cell carcinoma (TCC) with extended follow-up in order to identify patterns of recurrence, assess patient outcomes, and determine the impact of traditional prognostic factors. Methods. We reviewed 252 patients treated surgically for upper tract TCC with a median follow-up of 64 months. Most patients (77%) underwent nephroureterectomy, whereas 17% were treated with a parenchymal sparing approach. Traditional prognostic factors including age, sex, tumor stage, grade, location, and type of surgical treatment were analyzed with respect to disease recurrence and survival. Results. Disease relapse occurred in 67 patients (27%) at a median time of 12.0 months. Recurrences were local in the retroperitoneum (9%), the bladder (51%), remaining upper tract (18%), or distant in the lung, bone, or liver (22%). The 6 patients with local relapse were among the 73 patients with pT3 or pT4 tumors, and all died of TCC at a median time from diagnosis of 37 months. Significant prognostic factors for recurrence by univariate analysis were tumor grade ( P = 0.0014) and stage ( P = 0.0001). On multivariate analysis, only tumor stage ( P = 0.017) and treatment modality ( P = 0.020) were predictors of recurrence. Actuarial 5-year disease-specific survival rates by primary tumor stage were 100% for Ta/cis, 91.7% for T1, 72.6% for T2, and 40.5% for T3. Patients with primary Stage T4 tumors had a median survival of 6 months. Although tumor stage and grade correlated with disease-specific survival on univariate analysis, only patient age ( P = 0.042) and stage ( P = 0.0001) were significant on multivariate analysis with the type of surgical procedure performed approaching significance ( P = 0.0504). Conclusions. Primary tumor stage and surgical procedure performed (radical versus parenchymal sparing) are important predictors of disease recurrence. Patient age and tumor stage were the only predictors of disease-specific survival on multivariate analysis with the type of surgical procedure approaching significance. Radical nephroureterectomy achieves excellent local control even in the setting of locally advanced (pT3 or T4) disease. The major clinical feature in this setting is distant failure, and the development of effective systemic therapy is needed to improve the outcome in these patients.

Neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Prognostic factors for response and survival

Between January 1986 and September 1988, 75 patients with locally advanced cervical carcinoma (International Federation of Gynecology and Obstetrics [FIGO] Stages IB-III) received three courses of neoadjuvant chemotherapy (NAC), including cisplatin, bleomycin, and methotrexate (PBM). Fifteen percent of patients achieved a complete response (CR) and 68% a partial response (PR). Pretreatment characteristics were analyzed for response to NAC. Significantly lower response rates were found in patients with tumor size more than 5 cm in diameter and bilateral parametrial involvement to the pelvic side wall. None of the biological parameters studied was related to chemoresponsiveness. Patients achieving CR or PR had a significantly improved 3-year survival rate compared with those who did not respond. After NAC, radical surgery was possible in all responding patients. The median number of lymph nodes removed was 60. A lower than expected incidence of lymph node metastases was detected. None of the clinical and pathologic features considered was significantly correlated with the lymph node status. Twelve of the 62 operated patients had disease recurrence. Pathologic parametrial involvement and cervical infiltration equal to or deeper than 5 mm were found to be significant prognostic factors for recurrence. A 3-year, disease-free survival of 89%, 73%, and 43% for Stage IB-IIA, IIB, and III, respectively, was found. Among the operated patients these rates increased to 100%, 81%, and 66% for Stage IB-IIA, IIB, and III, respectively. A prospective randomized trial comparing NAC and surgery with radiotherapy alone is in progress.