Predictive Factors For Pathologic Response Research Articles

Abstract PO5-02-02: LyKi1: a highly predictive immune-based score of pathological response to chemotherapy in luminal breast cancer

Abstract Background: Identifying which luminal breast cancer (BC) patients will benefit from (neo)adjuvant chemotherapy still remains a challenge. Efficient predictive tests and genomic signatures are still lacking. Because neoadjuvant chemotherapy (NACT) constitutes an in vivo chemotherapy-sensitivity test, we used the pre-treatment core biopsies to identify predictive factors of pathological response in luminal HR+/Her2- BC. Analyses on sTILS and TIL subtypes (CD3, CD4, CD8, CD20) are rare in luminal BC while a predictive value has been reported in TNBC and Her-2 positive BC. Patients and Methods: We performed a retrospective analysis of 211 patients treated with NACT followed by surgery for a T0-T4 luminal (HR+/Her-2-) breast cancer. Association of anthracyclin and taxane was used in 99% of cases. Median age was 48.4 yo (28 – 76). Initial clinical stage was: I: 0.5%, II: 67%; III: 33%. Biopsy analyses were the followings: NST carcinomas: 90%; luminal B: 82%; E&E grade I/II/III: 10%/57%/32%; KI-67 > 20%: 74%. After NACT, RCB 0-1 was observed in 32 cases (15.2%) and pCR in 19 (9.0 %) cases. All pre-therapeutic biopsies were reviewed for pathological factors, blinded to the patients’ outcomes. Clinico-pathological analyses were performed using standard methods. sTILs were estimated on H&E slides. Intratumoral CD3, CD4, CD8 and CD20 infiltrates were carried out by an independent laboratory using a machine learning model for automated and quantitative evaluation based on digital IHC stains. Correlation between sTILs and TIL subtypes were assessed by Spearman’s coefficient. Predictive factors of RCB 0/1 were explored using unconditional logistic regression analysis. After selection on univariate analysis (p< 0.05), multivariate prognostic models were developed using stepwise backward variable elimination process and compared using area under the curve (AUC). Results: sTILs levels ≥ 10% were observed in 15.2% of biopsies. 42 % of tumors had ≥ 10 % CD3-positive cells, 46% for CD4, 38% for CD8, and 8% for CD20. A high level of correlation was observed between these different markers (Spearman’s coefficient ≥ 0.73 for each comparison). By univariate analysis, significant factors (p< 0.05) associated with RCB 0-1 were: age, mitotic index (1 vs 2 vs 3), aneuploidy (1-2 vs 3), differentiation (1-2 vs 3), E&E grade (1-2 vs 3), mitotic count, Ki-67, Magee equation 3, phenotypic group (luminal A vs B), ER, sTILs and each TIL subtype. Age, E&E grade, Ki-67, Magee equation 3, sTILs and all TIL subtypes were selected for multivariate analysis. As TIL subtypes were highly correlated, different predictive models could be performed. The model we selected (called LyKi1) was constructed based on CD8 [OR 2.24 (95%CI 1.55-3.25; p< 10-4)], E&E grade [OR 3.00 (95%CI 1.22-7.42; p=0.017)] and Ki-67 [OR 1.74 (95%CI 1.09-2.76; p=0.019)]. It was highly significantly associated with RCB 0-1, with an AUC value of 0.856 (95%CI 0.756-0.916). For instance, LyKi1 could isolate a group of 30% of patients that achieved RCB 0-1 in 39.7% of cases vs 4.7% for the 70% of patients with lowest LyKi1 scores. pCR rates were 25% and 2%, respectively. Importantly, prediction value of LyKi1 remained very high if restricted to luminal B tumors (AUC 0.817; 95% CI: 0.741-0.894). Ability to predict pCR was also very high (AUC 0.837 (95%CI: 0.750-0.924) in this phenotype). Conclusion: This retrospective analysis clearly highlights the important predictive role of sTILs and TIL subpopulations for the response to an anthracyclin-taxane based regimen in a neoadjuvant setting for luminal breast cancer. Within this cohort, LyKi1 score (combining CD8, grade and Ki-67) has a very high value to predict pathological response to NACT in luminal breast cancer. Importantly, such score has to be validated in a multicentric prospective cohort and investigated in adjuvant setting. Citation Format: Marc Debled, Hugo Deboissy, Coralie Cantarel, Chloé Delfour, Léonie Alran, Marion Fournier, Nathalie Quenel-Tueux, Valérie Velasco, Foucault Chammings, Véronique Brouste, Monica Arnedos, Gaétan MacGrogan. LyKi1: a highly predictive immune-based score of pathological response to chemotherapy in luminal breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-02.

Évaluation de facteurs prédictifs de réponse pathologique à la radiothérapie néoadjuvante des sarcomes des tissus mous

PurposeConserving surgery combined with radiotherapy in presence of local recurrence risk factors is standard treatment of soft tissue sarcomas, a group of rare and heterogeneous tumours. Radiotherapy is performed before or after surgery. In neoadjuvant setting, late radiation-induced toxicity is reduced and pathological response to radiotherapy could be achieved. A complete pathological response to radiotherapy has recently been shown to predict better survival. Our study aims at identifying predictive factors of pathological response to neoadjuvant radiotherapy (clinical, radiological or histological) of soft tissue sarcomas. Patients and methodsClinical, imaging (MRI: perilesional oedema, necrosis, tumour heterogeneity, vasculonervous relationships) and pathological (pathological subtype, tumour grade, anticipated/obtained resection quality) data were retrospectively collected. Tumour response (imaging and pathological), patient outcome, acute and late radiation-induced toxicity, predictive factors of pathological response to neoadjuvant radiotherapy were studied. The 2-test or exact-Fisher test (qualitative variables) and by Student's t-test or Kruskal-Wallis test (quantitative variables) were used for statistical analysis. ResultsFrom April 2017 to April 2021, neoadjuvant radiotherapy (50Gy in 25 fractions) followed by surgical excision was performed to 36 consecutive patients with liposarcomas (n=17/36), or undifferentiated sarcomas (n=8/36). MRI response was complete in 1 patient, partial in 9 patients (n=9/36, 25%), stable in 21 patients (n=21/36, 58%) or in progression in 5 patients (n=5/36, 14%). Pathological response was observed in 22 patients (61%). No grade 3-4 acute radiation-induced toxicity was observed. Regarding late toxicity, 28% of patients had grade 1–2 oedema (n=10/36), 39% had a grade 1 fibrosis (n=14/36), and 30% grade 1 pain (n=11/36). No predictive factors of response to radiotherapy was statistically significant. ConclusionsNeoadjuvant radiotherapy is well-tolerated. No clinical, radiological or pathological predictive factors was identified for radiotherapy tumour response.

PO-1264 Predictive factors of pathological response to neoadjuvant chemoradiotherapy in rectal cancer

PO-1264 Predictive factors of pathological response to neoadjuvant chemoradiotherapy in rectal cancer

High GP73 Expression Correlates with Poor Response to Neoadjuvant Chemotherapy and Survival in Gastric Cancer: A Tissue Microarray Study.

Golgi protein 73 (GP73) is a type II Golgi transmembrane protein which is overexpressed in several cancers, however, its role in gastric cancer is still unclear. The aim of this study is to investigate if high GP73 expression is associated with pathological tumor response to neoadjuvant chemotherapy and prognosis for patients with gastric cancer. A total of 348 patients with gastric cancer, who had undergone surgery between 1999 and 2011 were retrospectively reviewed, GP73 expression was examined in tumor tissues using tissue microarray and the correlations between its expression and pathological response to neoadjuvant chemotherapy as well as patients prognosis were analyzed. We found that GP73 expression was not associated with clinicopathologic features including tumor size, differentiation and TNM stage. High expression of GP73 was associated with less pathological tumor response to neoadjuvant chemotherapy and poor survival in gastric cancer, multivariate analysis showed GP73 expression was an independent predictive factor for pathological response to neoadjuvant chemotherapy and for prognosis in patients with gastric cancer. Our results suggest that GP73 expression correlates with the effect of neoadjuvant chemotherapy and is a promising biomarker to identify patients with poor prognosis.

Lymphocytic Count and Ratio as Predictive Factors for Pathological Response after Neoadjuvant Therapy in Patients with Rectal Cancer

AbstractBackground: To evaluate results of pre-operative Complete Blood Count (CBC), with special emphasis on lymphocytic count and ratio as predictive factors for rectal cancer response to neoadjuvant chemoradiotherapy and prediction of complete pathological response.The Aim of the Study: Is to evaluate results of pre-operative complete blood count, with special emphasis on lymphocytic count and lymphocyte ratio as predictive factors of rectal cancer response to neoadjuvant chemoradiotherapy.Patients and Methods: This research studied the associa-tion between CBC results of patients with stage II or III Locally Advanced Rectal Cancer (LARC) before neoadjuvant therapy and the pathological response found in the specimen after standard surgical management. Patients were divided into two groups; Group I included patients with complete pathological response and Group II included patients with no or partial pathological response to study the predictive factors for complete pathological response.Results: A total of 36 patients (20 females and 16 males) were included. Mean age was 56.40±11.18 years. 19 patients (52.7%) underwent low anterior resections and 17 patients (47.2%) underwent abdomino-perineal resections. Lymphocytic count and ratio were significant predictive factors for the pathological response of the tumor to neoadjuvant therapy (p=0.011 and 0.048, respectively). Comparison between Group I and Group II showed that lymphocytic count and ratio were significant predictive factors for patients in Group I compared to Group II (p=0.001 and p=0.049, respectively).Conclusions: Lymphocytic count and ratio can play an important role as predictive factors for pathological response to neoadjuvant therapy in patients with LARC and also as predictive factors for complete pathological response. Further multicenter studies with larger number of patients are needed.

EP-1275: Patients with locally advanced rectal cancer (larc): predictive factors of pathological response

EP-1275: Patients with locally advanced rectal cancer (larc): predictive factors of pathological response

Predictive Factors of Pathologic Response in Patients With Localized Pancreatic Cancer Treated With Induction Chemotherapy and Stereotactic Body Radiation Therapy

Predictive Factors of Pathologic Response in Patients With Localized Pancreatic Cancer Treated With Induction Chemotherapy and Stereotactic Body Radiation Therapy

Carbonic anhydrase 9 is associated with chemosensitivity and prognosis in breast cancer patients treated with taxane and anthracycline.

BackgroundNeoadjuvant chemotherapy (NAC) is one of the standard care regimens for patients with resectable early-stage breast cancer. It would be advantageous to determine the chemosensitivity of tumors before initiating NAC. One of the parameters potentially compromising such chemosensitivity would be a hypoxic microenvironment of cancer cells. The aim of this study was thus to clarify the correlation between expression of the hypoxic marker carbonic anhydrase-9 (CA9) and chemosensitivity to NAC as well as prognosis of breast cancer patients.MethodsA total of 102 patients with resectable early-stage breast cancer was treated with NAC consisting of FEC (5-fluorouracil, epirubicin, and cyclophosphamide) followed by weekly paclitaxel before surgery. Core needle biopsy (CNB) specimens and resected tumors were obtained from all patients before and after NAC, respectively. Chemosensitivity to NAC and the prognostic potential of CA9 expression were evaluated by immunohistochemistry.ResultsCA9 positivity was detected in the CNB specimens from 47 (46%) of 102 patients. The CA9 expression in CNB specimens was significantly correlated with pathological response, lymph node metastasis, and lymph-vascular invasion. Multivariate analysis revealed that the CA9 expression in CNB specimens was an independent predictive factor for pathological response. The Kaplan-Meier survival curve revealed a significant negative correlation (p = 0.013) between the disease-free survival (DFS) and the CA 9 expression in resected tissues after NAC. Multivariate regression analyses indicated that the CA9 expression in resected tissues was an independent prognostic factor for DFS.ConclusionsCA9 expression in CNB specimens is a useful marker for predicting chemosensitivity, and CA9 expression in resected tissue is prognostic of DFS in patients with resectable early-stage breast cancer treated by sequential FEC and weekly paclitaxel prior to resection.

The relationship between Lin28 and the chemotherapy response of gastric cancer

ObjectiveThe aim of the study reported here was to identify whether a stem cell biomarker, Lin28, may predict the pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer.MethodsThe study enrolled 47 patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and March 2012. Cancer tissue was biopsied by gastroscopy and Lin28 expression in the tissue was measured by immunohistochemistry. Statistical analyses were performed to identify the relationship between Lin28 expression and tumor regression grade.ResultsOf the 47 cases, pathologic nonresponse was observed in 29 (61.7%) and pathologic response in 18 (38.3%). Receiver-operating characteristic curve analysis showed that the histoscore of Lin28 expression with 0.325 as a cutoff value could differentiate between pathologic response and nonresponse. Multivariable analysis showed that Lin28 expression was an independent predictive factor for pathologic response to neoadjuvant chemotherapy (P = 0.006).ConclusionLin28 expression was associated with pathologic tumor response in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. This may suggest that Lin28 can serve as a predictive biomarker for neoadjuvant chemotherapy in patients with gastric cancer.

P-0082 - Routine Use of Perioperative Chemotherapy for Resectable Gastroesophageal Cancer

Methods: Patients diagnosed with locally advanced gastric cancer were treated with perioperative chemotherapy and surgery in our institution. Perioperative chemotherapy schedules were selected by the oncologists according to each patient’s baseline characteristics and comorbidities. We obtained available clinical, radiological, surgical and pathological data for all patients analyzed. The primary end point was the complete resection (R0) rate. Secondary end points were disease-free survival (DFS), overall survival (OS), toxicity, radiological response rate, pathological response rate and downstaging rate. We also looked for prognostic and predictive factors for DFS, overall survival (OS), pathological complete response rate and the R0 rate. The study got the approval of the local Research Ethics Committee. Kaplan-Meier method and long-rank test were apply to univariate survival analysis. Multivariate analysis was performed. Cox regression and multiple linear regression analysis was applied when required. Results: Forty patients were found eligible for this retrospective analysis. The median follow-up period was 19 months (range 5.7-54.8). At diagnosis, 52.5% of patients were classified as stage II and 47.5% were stage III. The most common chemotherapy schedule used was a combination of epirubicin, cisplatin and capecitabine. Forty percent of patients completed three preoperative cycles and three postoperative cycles. A tolerable toxicity related to chemotherapy was found without any chemotherapy toxicity–related deaths. Thirty-nine patients underwent surgery: 80% reached a complete resection (R0), down-staging was detected in 57.5% and 17.5% had a pathologically complete response. The median time of disease-free survival was 34.05 months (IC95% 25.6-42.4) and the median time of overall survival was 39.01 months (IC95% 30.8-47.1). Pathological response, radiological response, perineural invasion and resection type were related to better disease-free survival (p0.001, p < 0.001, p0.001 and p < 0.001 respectively) and better overall survival (p0.001, p0.024, p < 0.001 and p0.002 respectively). However, the statistical significance was lost in the multivariate analysis. Predictive factors for pathological complete response in the univariate analysis were: vomiting at diagnosis (p0.0005), the presence of comorbidities (p0.0016) and radiological response (p0.004). Only the presence of comorbidities maintained statistical significance after the multiple linear regression analysis (p0.024). The resection type could be predicted by the chemotherapy schedule used (p0.014) and the clinical response (p0.048); these factors maintained significance after the multiple linear regression with p values of 0.029 and 0.025, respectively. Conclusion: Our results support that perioperative chemotherapy for locally advanced gastric cancer can be safely delivered in daily clinical practice, obtaining an improvement of the pathologic response and the complete resection of gastric cancer. We found that the presence of comorbidities were independent predictive factors for the pathologic response, while the chemotherapy schedule and the clinical response could independently predict a complete resection.

P-0190 - Predictors of Pathologic Response and Oncologic Outcome in Patients Submitted to Chemoradiation for Locally Advanced Rectal Cancer

Background: Neoadjuvant chemoradiotherapy (CRT) followed by surgery is standard of care treatment for locally advanced rectal cancer (LARC). Pathological response (PR) may play a role in local control and patient's outcome, but it is still not possible to anticipate before therapy who will respond. The goal of this study was to evaluate clinical parameters as predictive factors for PR, and the survival of patients treated with neoadjuvant CRT and surgery for LARC, stratified according to response to CRT.

Role of clinical variables for predicting pathologic response to neoadjuvant chemoradiation in locally advanced rectal cancer.

e14691 Background: pathologic response to neoadjuvant chemoradiation is a strong prognostic factor for rectal cancer. Some studies have suggesting a wait and see approach for rectal cancer after clinical complete response to chemoradiation. In this study, we tried to identify clinical predictive factors of pathologic response to neoadjuvant chemoradiation. Methods: we retrospectively reviewed data of 129 patients from a prospective database, treated between January, 2008 and December, 2012. Patients with mid and low rectal adenocarcinoma, clinically staged (MRI) as T3,T4 any N or any T, N+, received pre-operative chemoradiation, which consists in 5040 cGy, concomitant to 5-FU-based chemotherapy. All patients were operated, by radical TME procedures. The clinical variables analyzed were: age, gender, distance from dentate line, cT stage, cN stage, pre-treatment CEA level, NIH toxicity during chemoradiation, endoscopic assessment of response, and interval between the end of radiation and surgery. We investigate associations between these variables with complete pathological response (cPR) and “good” pathological response (gPR), defined as ypT0orT1 N0. Results: the rate of cPR was 20.2%. The rate of gPR was 31.8%. For predicting cPR, only the endoscopic assessment of response showed significant association with cPR. Among 18 patients with complete endoscopic response, 8 (44.4%) confirmed cPR after resection. Among 93 patients with endoscopic findings suggesting residual disease, 14 (15.1%) presented cPR (p=0.008). 55.6% (10/18) of patients with complete endoscopic response still have microscopic residual disease in the resected specimen. For predicting gPR, only the cN staging was significantly associated with ypT0orT1 N0 (23.9% of gPR among cN+ patients against 41.3% among cN0 patients; p=0.038). Conclusions: clinical tools are very poor for predicting pathological response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinomas. Despite endoscopic assessment of response by retoscopy have showed significant association with cPR, the predictive value was weak.

Pathologic and Oncologic Outcomes in Locally Advanced Gastric Cancer with Neoadjuvant Chemotherapy or Chemoradiotherapy

PurposeAlthough neoadjuvant therapy has been accepted as a treatment option in locally-advanced gastric cancer, its prognostic value has been difficult to evaluate.Materials and MethodsSeventy-four gastric cancer patients who underwent gastrectomy after neoadjuvant treatment were divided into two groups according to the pathologic response: favorable (ypT0) and others (ypT1-4). The clinicopathologic characteristics, predictive factors for pathologic response, and oncologic outcome were evaluated.ResultsEleven patients (14.8%) demonstrated ypT0 and the remaining 63 patients (85.2%) were ypT1-4. Chemoradiotherapy (CCRTx) rather than chemotherapy (CTx) was the only predictive factor for a favorable pathologic response. Chemotherapeutic factors and tumor marker levels did not predict pathologic response. The 1-, 2-, and 3-year disease-free survivals were 83.4%, 70%, and 52.2%. The 1-, 3-, 5-year overall survivals were 88.5%, 67.5%, and 51.2%, respectively. Although a complete pathologic response (ypT0N0M0) was achieved in 7 patients, 28.6% of them demonstrated recurrence of the tumor within 6 months after curative surgery.ConclusionCCRTx rather than CTx appears to be more effective for achieving good pathologic response. Although favorable pathologic response has been achieved after neoadjuvant treatment, the survival benefit remains controversial.

Preoperative chemoradiation with nimotuzumab and capecitabine in patients with locally advanced rectal cancer: A phase II study.

e14049 Background: To evaluate the efficacy and safety of preoperative chemoradiation with Nimotuzumab(a humanized monoclonal antibody that targets and binds to the epidermal growth factor receptor)and capecitabine in the patients with locally advanced rectal cancer. Methods: Twelve patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50 Gy/25 fractions. Concurrent therapy consisted of Nimotuzumab 400 mg/m2,1 week before radiotherapy, and then Nimotuzumab 400 mg/m2/week for 5 weeks, and capecitabine 1,650 mg/m2/day for 5 days a week (weekdays only) from the first day during radiotherapy. Three weeks after the end of chemoradiation, 1 cycle chemotherapy with oxaliplatin and capecitabine(XELOX) was performed. Oxaliplatin 130mg/m2, Day1 and capecitabine 1000 mg/m2, bid, from Day 1 to Day 14. Postoperative chemotherapy after surgery followed by preoperative CRT was in all patients, The same dosage of XELOX was started within 3 to 4 weeks after surgery, repeated every 3 weeks for 6 cycles. Total mesorectal excision was performed within 6 ~ 8 weeks. The pathologic response was evaluated as study endpoint, and an additional KRAS mutation analysis was performed. Results: In total, 9 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 33.3% (3/9), and 3 patients (33.3%) showed near total regression of tumor. Grade 3 toxicities was diarrhea (2/12, 16.7 %), No grade 4 toxicity was observed. KRAS mutations were found in 2 of 12 patients (16.7%) who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Conclusions: Preoperative chemoradiation with Nimotuzumab and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.

Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: A ten-year follow up of 257 patients treated at a single institution

ObjectiveTo report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma. Methods257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates. Results44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35).7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122months [1–282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3–87.5] and 80.9% CI [76.3–85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively). ConclusionsPreoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery.

Preoperative Chemoradiation With Cetuximab, Irinotecan, and Capecitabine in Patients With Locally Advanced Resectable Rectal Cancer: A Multicenter Phase II Study

To evaluate the efficacy and safety of preoperative chemoradiation with cetuximab, irinotecan, and capecitabine in patients with rectal cancer. Forty patients with locally advanced, nonmetastatic, and mid- to lower rectal cancer were enrolled. Radiotherapy was delivered at a dose of 50.4 Gy/28 fractions. Concurrent chemotherapy consisted of an initial dose of cetuximab of 400 mg/m(2) 1 week before radiotherapy, and then cetuximab 250 mg/m(2)/week, irinotecan 40 mg/m(2)/week for 5 consecutive weeks and capecitabine 1,650 mg/m(2)/day for 5 days a week (weekdays only) from the first day during radiotherapy. Total mesorectal excision was performed within 6 ± 2 weeks. The pathologic responses and survival outcomes were evaluated as study endpoints, and an additional KRAS mutation analysis was performed. In total, 39 patients completed their planned preoperative chemoradiation and underwent R0 resection. The pathologic complete response rate was 23.1% (9/39), and 3 patients (7.7%) showed near total regression of tumor. The 3-year disease-free and overall survival rates were 80.0% and 94.7%, respectively. Grade 3/4 toxicities included leukopenia (4, 10.3%), neutropenia (2, 5.1%), anemia (1, 2.6%), diarrhea (2, 5.1%), fatigue (1, 2.6%), skin rash (1, 2.6%), and ileus (1, 2.6%). KRAS mutations were found in 5 (13.2%) of 38 patients who had available tissue for testing. Clinical outcomes were not significantly correlated with KRAS mutation status. Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study.

Neoadjuvant chemotherapy (NCT) in 466 patients for operable breast cancer: Predictive factors for pathological response.

648 Background: In a new database harbouringthe patients of several prospective phase II neoadjuvant trials (fec 50-100, net, tncf, taxotere/tncf, taxotere alone), the predictive value of tumour factors (SBR grade, RH, Her2, Ki-67 and cycline D1) was studied in 466 women with stage II-III operable breast cancer treated between 1991 and 2006. Methods: Median age of the patients was 48 years [27-76]. Median diameter of the invasive tumour was 40 mm [10-130]. 382 (82%) patients had a canalar, 57 (12.2%) a lobular, 14 (3%) a mixed or invasive carcinoma, 3 (0.6%) neoplasic cells only and 10 (2.2%) another carcinoma. Before chemotherapy, 32.8% were grade III SBR, 60% were RH+ and 10% were Her2+. For 36% of the tumours, the Ki-67 was ≤ 20% and for 16% of the tumours, the cyclin D1 was ≤ 20%. The median number of NCT courses was 6 [1-8] followed by a surgery for 98%, a radiotherapy for 93%, an adjuvant chemotherapy (20%) and/or a hormonotherapy (56%). Results: Overall response rate was 71% (17% complete). The complete pathological response (pCR) rate was 16.7% according to Chevallier's classification. On 455 patients operated, 324 (71%) had a conservative surgery. On 390 patients with an axillary dissection, 195 (50%) had involved nodes (median number :2 [1-20]). After a median follow-up of 121 months, DFS and actuarial survival at 120 months were 61.9% and 69.7%, respectively. Concerning the predictive value of the tumour factors, the pCR according to Chevallier's classification was threefold more frequent for Her-2-positive patients (p=1.7.10−3) and for RH negative patients (p=10−7) ; and elevenfold more frequent for SBR III patients (p=5.4.10− 7). Moreover, the pCR was twofold more frequent when Ki-67 was > 20% (p=0.012). There was no significant correlation between the cyclin D1 and the pCR. Using a multivariate analysis, these four factors remain predictive in the following order (from stongest to weakest): RH, Her2, SBR grade and Ki-67. Conclusions: SBR grade, RH, Her2 and Ki-67 were strong predictive factors of the pathological complete response. No significant financial relationships to disclose.

Is a change in patient-reported dysphagia after induction chemotherapy in locally advanced esophageal cancer a predictive factor for pathological response to neoadjuvant chemoradiation?

In patients with locally advanced esophageal cancer, only those responding to the treatment ultimately benefit from preoperative chemoradiation. We investigated whether changes in subjective dysphagia or eating restrictions after two cycles of induction chemotherapy can predict histopathological tumor response observed after chemoradiation. In addition, we examined general long-term quality of life (QoL) and, in particular, eating restrictions after esophagectomy. Patients with resectable, locally advanced squamous cell- or adenocarcinoma of the esophagus were treated with two cycles of chemotherapy followed by chemoradiation and surgery. They were asked to complete the EORTC oesophageal-specific QoL module (EORTC QLQ-OES24), and linear analogue self-assessment QoL indicators, before and during neoadjuvant therapy and quarterly until 1 year postoperatively. A median change of at least eight points was considered as clinically meaningful. Clinically meaningful improvements in the median scores for dysphagia and eating restrictions were found during induction chemotherapy. These improvements were not associated with a histopathological response observed after chemoradiation, but enhanced treatment compliance. Postoperatively, dysphagia scores remained low at 1 year, while eating restrictions persisted more frequently in patients with extended transthoracic resection compared to those with limited transhiatal resection. The improvement of dysphagia and eating restrictions after induction chemotherapy did not predict tumor response observed after chemoradiation. One year after esophagectomy, dysphagia was a minor problem, and global QoL was rather good. Eating restrictions persisted depending on the surgical technique used.

Clinical Factors Predicting Pathologic Response after Preoperative Concurrent Chemoradiation for Rectal Cancer

Clinical Factors Predicting Pathologic Response after Preoperative Concurrent Chemoradiation for Rectal Cancer

Complete pathological response of colorectal liver metastases after neoadjuvant chemotherapy: myth or reality?

4063 Background: A complete clinical response (CCR) of colorectal liver metastases (CLM) following chemotherapy has been shown unrelated to the real disappearance of active tumor. By contrast, a complete pathological response (PCR) could be more clinically relevant, but has not been explored. The aim of this study was to evaluate the incidence and outcome as well as predictive factors of PCR, in patients resected from CLM after neoadjuvant chemotherapy. Methods: In our institution 791 consecutive patients with CLM underwent liver resection after neoadjuvant chemotherapy. CCR was defined as the disappearance of all lesions after chemotherapy, and PCR was defined as the total necrosis of all metastases on the resection specimen. Both were selected from a prospective database. Patients with and without PCR were compared, survivals were determined and predictive factors for PCR were analyzed using a multivariate risk model. Results: There were 0.4% CCR (3/791) and 4% PCR (31/791). Among the 31 patients with PCR, the median number of CLM was 2.0 (range 1–13) with a maximum diameter = 3 cm for most cases (73%) at diagnosis. Ten patients (32%) had extrahepatic metastases. Compared to patients without PCR, patients with PCR were younger (p&lt; 0.05) and had a smaller maximum tumor size (p=0.007). Rate of objective response was higher (81% vs. 52%; p=0.002) and last chemotherapy regimen contained more frequently oxaliplatin than irinotecan (p=0.05). Number of chemotherapy cycles and treatment lines were not different. At multivariate analysis, 4 predictive factors of PCR were identified: age = 60 yrs, maximum size at diagnosis = 3 cm, CEA = 40 ng/ml at diagnosis and achievement of an objective response. The probability of PCR ranged from 0.2% when all were absent to 33.8% when all were present. PCR strongly impacted overall survival (OS) that was 69% and 62% at 5 and 10 years with a disease-free survival (DFS) of 42% for both. Conclusions: PCR concerns overall 4% of patients receiving neoadjuvant chemotherapy allowing for surgery, but as much as one third of those aged less than 60 years, developing response on liver metastases smaller than 3 cm, with low CEA values. Uncommon high survival rates are observed in this setting. PCR more than CCR is a reality and strongly impacts patient outcome. No significant financial relationships to disclose.