Indolent histology, female sex and fludarabine + rituximab significantly correlated with frequency of NNI but multivariate analysis picked fludarabine + rituximab followed by female gender as the only two independent variables predictive of NNI.
INTRODUCTION: The typical presentation of patients with low grade lymphoma consists of disseminated lymphadenopathy, absence of constitutional symptoms, normal LDH, low Ki-67 and PET scan with low SUVs (i.e. <14). We have identified a subset of atypical cases who present with one or more clinically aggressive features. We have named these cases clinically discordant indolent histologies (CDIH). The goal of this study is to identify these cases with CDIH in order to determine if their prognosis and clinical behavior are different from those with the typical low grade NHL presentation. METHODS: We defined CDIH as any follicular grade 1-2, grade 3-A or small lymphocytic lymphoma (SLL) who meet at least one or more of the following conditions: constitutional symptoms, unexplained LDH elevation, PET SUV >14, Ki67 >30%, unusual areas of involvement for indolent NHL (bone, pleura, CNS, soft tissue, lung), necrotic areas seen in CT scan or discrete space occupying lesions in liver or spleen. We analyzed their failure free survival (FFS), overall survival (OS), rate of transformation to a high grade histology and correlation with FLIPI-2 prognostic score. RESULTS: A total of 97 cases (86 follicular, 11 SLL) with a median follow up of 56 months were identified from our data base. Of these 97 cases, 46 met the criteria for CDIH. Figure 1 shows the FFS of cases with CDIH as contrasted with 51 without CDIH. As is evident from Figure 1, those with CDIH not only had a higher relapse rate but also showed a trend for earlier relapses (within 3 years), reminiscent of high grade NHLs. Figure 2 depicts the OS of CDIH cases which is significantly inferior. We also analyzed the risk of transformation. The rate of transformation of CDIH was 5/46 (11%) in contrast to 0/51 with non CDIH (p=.02). All episodes of transformation occurred early, between 6 to 35 months from diagnosis. In order to determine if there was an underlying lymphoma of high grade histology at diagnosis, 8 cases with CDIH underwent a second biopsy of a site suspected of harboring an aggressive NHL because of findings such as SUV of ≥14. None of the 8 cases showed evidence of a high grade NHL in the second biopsy. In nearly all (94/97=97%) treatment included rituximab in combination with chemo and 80% of these were given maintenance. Management consisted of: Treatment A (n=55)-non-doxorubicin regimens, mostly fludara or bendamustine based; Treatment B (n=19)-R-CHOP; Treatment C (n=23)-R-CHOP x 6 followed by fludara based regimen (FND) x 4. The latter was used primarily for CDIH. Of the 46 cases of CDIH, 31 were treated with a doxorubicin-rituximab combination (either Treatment B or C). Their OS at 8 years was 98 % vs 62% for those who received a non- doxorubicin regimen (Treatment A), p=0.014. Of 40 cases without CDIH who received Treatment A, only 1 has relapsed. FLIPI-2 prognostic score correlated poorly with CDIH: of 23 with high risk score, 12 had CDIH and of 7 with low risk, 3 were CDIH. CONCLUSIONS: 1-Cases with CDIH have less favorable OS, FFS, and higher rate of transformation to a higher grade histology. 2-In spite of the fact that CDIH histologically is identical to an indolent NHL, it functionally behaves as an aggressive NHL with frequent early relapses. 3-FLIPI-2 prognostic score correlates poorly with CDIH. This is not surprising since FLIPI-2 score doesn't include B symptoms and LDH. 4-Confirmatory biopsies to rule out co-existing high grade NHL at diagnosis are not useful or recommended. 5-Those without CDIH do very well when treated with a non-doxorubicin regimen such as a fludarabine-rituximab containing combination while CDIH cases appear to fare better when treated with a doxorubicin-rituximab containing regimen. These conclusions have to be interpreted in light of the retrospective nature of the study. Disclosures No relevant conflicts of interest to declare.
Background: Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with improved disease free survival (DFS) and overall survival (OS). The Residual Cancer Burden Score (RCB) method is a useful tool that predicts DFS and OS after NAC. We present the results of pts with either triple negative or HER2 positive breast cancer treated with a novel NAC. Methods: 34 pts with localized breast cancer >1 cm with HER2+ (N = 19) or triple negative breast cancer (TNBC) (N = 15) were treated with this novel regimen consisting first of TEC (docetaxel 75 mg/m2, epirubicin 80 mg/m2, and cyclophosphamide 500 mg/m2) + PEG Filgrastim x 4 cycles. Following the 4th course, TNBC patients received 4 additional TEC cycles if they achieved CR by MRI, or were switched to a non cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they had < CR. HER2+ pts received TEC x4 followed by docetaxel + trastuzumab x 4. RCB score was used to measure pathologic response. Pretreament PET scan was done and repeated after course 1 in order to correlate with RCB. Results: Median age was 56 (58 for Her2+ and 49 for TNBC). RCB = 0 (pCR) was achieved in 76%, while only 1 responded poorly (RCB = 3). There was no significant difference in the pCR rate between Her2+ and TNBC patients (74% vs 80% respectively), but there was a difference in the rate of pCR without DCIS and invasive cancer between these two (see table, p = 0.034). Pts with SUV drop > 5% after 1st TEC had 84% pCR while none with < 5% achieved pCR (p = 0.001). Comparison of our results with other NAC regimens reported in the literature is summarized in the table below: ProtocolpCR (no invasive)pCR(no invasive and no DCIS)RCB 0-1Auxilio Cancer Center HER2+/TNBC74%/80%37%/73%79%/80%I-Spy trial 1 HER2+/TNBC45%/35%N/A61%/40%GeparQuinto HER2+/TNBCN/A45%/38.4%N/ANSABP B-40 TNBC51%N/AN/ANeoAltto HER2+47%N/AN/ANeoSphere HER2+39%N/AN/AMDACC FEC+trastuzumab HER2+60%N/AN/A Conclusions: This novel chemotherapy approach results in a high pCR rate and RCB 0-1, which have been associated with improved clinical outcomes. Early PET can predict pCR. Although sample size is modest, results are encouraging and deserve further evaluation. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-17.
Gastric cancer is the second cause of cancer death with approximately 800,000 annual new cases reported worldwide. The incidence of gastric adenocarcinoma has progressively increased, while 5-year survival rates of 20% have remained unchanged for several decades. New strategies for early detection and treatment remain a significant unmet medical need. Advances in our understanding of signal transduction mechanisms have led to novel treatment approaches in a variety of tumors. Over-expression of the HER2/NEU gene is associated with aggressive behavior and poor prognosis in breast cancer, and this has made the Her2/neu protein a target for directed therapy. Several reports indicate that there are ethnic differences in the clinical behavior of gastric cancer, but the reasons for this observation are not clearly understood. We have investigated potential differences in the expression of selected signal transduction proteins (Her2/neu, EGF-R, Cyclin D1 and p-Stat3) in gastric cancers from 100 Puerto Rican and 95 Caucasian patients. Puerto Rican patients had higher disease stages at presentation (Stage IV disease was observed in 44% of Puerto Ricans and in 18% of Caucasians). The majority of tumors in both populations showed over-expression of p-Stat3 but there were no statistical significant differences between the two groups. Her2/neu was over-expressed in the tumors of both patient populations but at higher HHS Public Access
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