Prognostic Factor For DFS Research Articles

Microanatomic characteristics of melanoma metastases in the sentinel node(s) (SN) predict survival and question the need for complete lymph node dissection (cLND)

8005 Introduction: The SN procedure has become a widely used staging procedure for stage I/II melanoma patients. We previously reported on the high SN+ identification rate with the use of the EORTC MG group pathology protocol (van Akkooi et al., Eur J Cancer: 2006, in press). Because only approximately 20% of SN positive patients have additional non-SN lymph node involvement in the cLND specimen, we have proposed to identify a SN+ patient group, which can be spared a cLND. Therefore further microanatomic analyses of the metastatic SNs has been performed to identify patient/tumor or SN factors which predict DFS and OS as well as additional non-SN nodal positivity. Methods: 262 stage I/II pts were included into the SN database between 10/97 and 5/04. 77 were SN+ (29%). 74 pts had SN material for re-evaluation in this study. Microanatomic analysis categorized a.o. the location of tumor cells; subcapsular, parenchymal (or combined), multifocal or extensive; the Starz classification and the measurement of the amount of tumor load (in mm). Tumor load was quantified by size: <0.1mm (single melanoma cells), 0.1 - 1.0mm, >1.0mm. DFS, OS and additional non-SN positivity was calculated for all the microanatomic analyses. Results: Mean/Median Breslow was 3.5/3.0 (0.8 - 12.0) mm, mean/median FU was 35/30 (6 - 81) months. There were no signif. differences in OS or additional non-SN positivity for the different loc. of involvement. The estimated 5yr OS rates were 100%, 63% and 35% for the different groups of tumor load, <0.1mm, 0.1 - 1.0mm, >1.0mm respectively (Figure)(P=0.03). There were no patients with add. non-SN positivity in the group with involvement <0.1mm. On multivariate analysis the tumor load was the most important prognostic factor for DFS (P=0.005) and OS (P=0.03). DFS, OS and add. non-SN positivity of all other analyses will be presented at the meeting. Conclusions: It is questionable whether SN with onlysingle cells involvement (<0.1mm) should be considered positive. Dist. mets are exceedingly rare (1/16 = 6.3%) and was identical to the SN- patient pop., and non-sentinel node involvement was not observed at all. These patients should probably not undergo add. LND and may not be considered stage III patients. No significant financial relationships to disclose.

Prognostic factors in preoperative radiotherapy for locally advanced rectal cancer

3647 Background: Preoperative radiotherapy and chemoradiotherapy lower the risk of local recurrence and improves survival in stage II and III rectal cancer. Methods: Retrospective clinical study was performed to evaluate 165 patients (33% women and 67% men) with locally advanced rectal adenocarcinoma treated with preoperative radiotherapy or chemoradiotherapy in the period 1998–2002. Tumor extent was evaluated on CT or MRI or TRUS and tumor biopsy was taken during colonoscopy. The median follow up is 21 month. All patients received preoperative external beam radiation to primary tumor, adjacent lymphnodes and presacral region. CT localisation of target volume was used for 3D radiotherapy treatment planning. Patients were treated using linear accelerator with irregularly shaped three-field or four-field technique. Accelerated regimen (25 Gy/5 fraction/1 week) was performed in 14% of patients especially in year 1998–2000 and normofractionated regimen (40–50 Gy/20–25 fractions/4–5 weeks) was performed in 86 % of patients. Chemoradiotherapy with 5-FU was carried out in 22% of patients. Results: Radical resection underwent 85% of patients, inoperable tumor persisted in 7% and distant metastases were detected peroperatively in 8%. The overall survival (OS) rate at 2-years is 84% and at 5-years 60% following radical resection. The important prognostic factor affecting survival are postradiotherapy determined pathological stage (p=0,005), postradiotherapy assessed tumor grade (p< 0,001) and angioinvasion and/or perineural spread (p=0,023). Prognostic factors for DFS were identical with those for OS. Higher local recurrence rate was associated in preradiotherapy assessed T4 tumor (p=0,048) and in presence of angioinvasion and/or perineural spread (0,049). No statistically significant association was found according to age, tumor location, preradiotherapy biopsy evaluated histology grading and tumor downstaging for survival and the local recurrence rate. Conclusions: The best survival rates are obtained in patients with postradiotherapy grade 1 tumors, tumors without angioinvasion and perineural spread and complete remission after preoperative RT. No significant financial relationships to disclose.

Prognostic and predictive value of the urokinase-type plasminogen activator (uPA) and its inhibitors PAI-1 and PAI-2 in operable breast cancer

The present study on the prognostic and predictive value of serine proteases was conducted in 460 early breast cancer patients mostly treated with some kind of adjuvant systemic therapy: 156 received chemotherapy, 141 hormone therapy and 111 a combination of both. Already in univariate analysis PAI-1 was the only proteolytic factor with a significant impact on DFS, which was retained in multivariate analysis (p = 0.020); PAI-2 showed borderline significance in univariate analysis (p = 0.0503) and uPA did not present as a significant prognostic factor for DFS in our patient series. In a separate univariate analysis of DFS on patient subgroups defined by adjuvant systemic therapy, a higher risk of relapse associated with higher uPA and PAI-1 levels was found in the subgroup of patients who did not receive any treatment; this difference did not reach the level of significance, probably due to the small number (n = 52) of patients in this group (HR 1.37; p = 0.71 and HR 2.14; p = 0.321, respectively). A higher risk of relapse was also found in the subgroup of patients treated with adjuvant chemotherapy (HR 1.44; p = 0.381 and HR 2.48; p = 0.003, respectively). In contrast, the bad prognostic impact of high uPA and PAI-1 levels was lost in the subgroup of patients treated with adjuvant hormone therapy (HR 0.79; p = 0.693 and HR 0.26; p = 0.204, respectively). The same observations were made for the uPA/PAI-1 combination. Our study confirmed the prognostic value of serine proteases in early breast cancer. In addition, it pointed to a possible predictive value of these tumor markers for response to adjuvant hormone therapy with tamoxifen, which should be confirmed in further studies.

666 Have histological grade nuclear components (MSBR) of scarff bloom richardson (SBR) a prognostic value for lobular invasive breast carcinoma?

Usually, the SBR histoprognostic grading is not considered appropriate for lobular invasive carcinoma. We previously demonstrated improved prognostic value of a modified SBR grading (MSBR) for invasive ductal carcinoma (IDC), specially when node negative. We did a multivariate analysis of 291 patients with operable, invasive, lobular breast carcinoma, to assess the prognostic value of the SBR/MSBR grading. We applied this MSBR to the studied population. The Cox multivariate analysis showed that the nodal status, clinical tumor size and MSBR were the three most important prognostic factors for DFS, and nodal metastasis, MSBR and progesterone receptor (PR) status for MFS. Indeed, we concluded that SBR grading is relevant for lobular invasive carcinoma, MSBR being more accurate, mainly because it discriminates grade II SBR patients. This result was not surprising as the pattern of ILC implicated a higher proportion of grade II SBR patients (78%), than IDC (55%).