Indication For Neoadjuvant Chemotherapy Research Articles

Validation of the targeted axillary dissection technique in the axillary staging of breast cancer after neoadjuvant therapy: Preliminary results

Aim.To study the feasibility and validity of ultrasound-guided pre-chemotherapy marking of metastatic axillary lymph nodes followed by targeted axillary dissection (TAD), in breast cancer patients undergoing neoadjuvant chemotherapy (NACT). Material and methodProspective diagnostic test study conducted between January 2016 and March 2018. Patients with breast cancer and indication for NACT, cN1 or cN2 axillary staging, were included. A clip was placed in the affected lymph node prior to NACT. A sentinel lymph-node biopsy (SLNB) and a clipped lymph-node biopsy (BCLIP) were conducted, followed by axillary lymph node dissection (ALND). Location rate (LR) and negative predictive value (NPV) were evaluated, taking SLNB, BCLIP and their combination (TAD) as evaluated tests and metastatic involvement in the ALND specimen as the gold standard. ResultsTwenty-three patients were included in the study. Sentinel lymph node could only be detected in 19 cases (LR = 80.61%), whereas BCLIP was successful in 22 (LR = 95.65%). The sentinel lymph node coincided with the marked lymph node in 14 patients (60.9%). We found a NPV for the SLNB of 0.85 (95%CI: 0.61–1.0), whereas for TAD it was 1.00 (95%CI: 0.74–1.0). ConclusionTAD is a feasible test for axillary restaging after NACT, with a higher success rate than SLNB.

Current decisions on neoadjuvant chemotherapy for early breast cancer: Experts’ experiences in the Netherlands

PurposeTo evaluate the opinion of surgical and medical oncologists on neoadjuvant chemotherapy (NAC) for early breast cancer. MethodsSurgical and medical oncologists (N = 292) participating in breast cancer care in the Netherlands were invited for a 20-question survey on the influence of patient, disease, and management related factors on their decisions towards NAC. ResultsA total of 138 surgical and medical oncologists from 64 out of 89 different Dutch hospitals completed the survey. NAC was recommended for locally advanced breast cancer (94%) and for downstaging to enable breast conserving surgery (BCS) (75%). Despite willingness to downstage, 64% of clinicians routinely recommended NAC when systemic therapy was indicated preoperatively. Reported reasons to refrain from NAC are comorbidities (68%), age >70 years (52%), and WHO-performance status ≥2 (93%). Opinions on NAC and surgical management were inconclusive; while 75% recommends NAC to enable BCS, some stated that BCS after NAC increases the risk of a non-radical resection (21%), surgical complications (9%) and recurrence of disease (5%). ConclusionThis article emphasizes the need for more consensus among specialists on the indications for NAC in early BC patients. Unambiguous and evidence-based treatment information could improve doctor-patient communication, supporting the patient in chemotherapy timing decision-making.

Outcome of neoadjuvant chemotherapy in “locally advanced/borderline resectable” gallbladder cancer: the need to define indications

BackgroundStudies evaluating neo-adjuvant chemotherapy (NACT) exclusively in gallbladder cancer (GBC) are few and there are no randomized trials on the subject. Locally advanced GBC and indications for NACT in GBC are not yet clearly defined. MethodsWe analysed 160 consecutive GBC patients who received NACT based on clinico-radiologic criteria suggesting high-risk disease (TMH Criteria) from January 2010 to February 2016. ResultsOn initial assessment, 140 (87.5%) patients had T3/T4 disease and 105 (65%) patients were node positive. Response rate and clinical benefit rate was 52.5% and 70% respectively. Sixty six (41.2%) patients could undergo curative intent resection. With a median follow-up of 33 months, the median OS and EFS of the entire cohort were 13 and 8 months respectively. Patient undergoing curative surgery had a statistically superior OS (49 vs. 7 months; p = 0.0001) and EFS (25 months vs. 5 months; p = 0.0001) compared to those who did not. ConclusionLocally advanced GBC remains a disease with poor prognosis. Chemotherapy with neoadjuvant intent in locally advanced/borderline resectable GBC showed good response rates. This resulted in curative surgical resection or disease stabilisation in significant proportion of patients. Patients who undergo definitive surgery after favourable response to NACT experience good survival.

Pattern of breast cancer blood flow and metabolism, assessed using dual-acquisition 18FDG PET: Correlation with tumor phenotypic features and pathological response to neoadjuvant chemotherapy

Introduction In breast cancer, early changes in tumor glucose metabolism and blood flow (BF) have been evaluated separately and are proposed to monitor tumor response to neoadjuvant chemotherapy (NAC). This study used a single 18FDG dual-acquisitions PET exam to simultaneously assess these imaging features and to answer two questions: (i) Do tumor blood flow (BF) and tumor metabolism correlated with the same pre-therapy tumor phenotypic features? (ii) Are early changes in tumor BF and metabolism in response to NAC comparable or complementary in the ability to predict the final pathological response (pCR)? Methods 150 women with breast cancer and an indication for NAC were prospectively included. Women had a baseline PET exam with a 2-min chest-centered dynamic acquisition, started at the time of 18F-FDG injection, followed by a delayed static PET acquisition performed at 90 min. Tumor BF was calculated from the dynamic image using a validated first-pass model, and tumor glucose metabolism (SUVmax) was calculated on the delayed acquisition. This dual-PET acquisition was repeated after the first cycle of NAC to measure early changes in tumor BF (?BF) and SUVmax (?SUVmax). Results A weak correlation was found between baseline tumor SUVmax and BF ( r = 0.22; P = 0.006). A higher baseline SUVmax was associated with all biological markers of tumor aggressiveness, including the Triple Negative Breast Cancer (TNBC) subtype ( P P = 0.002). Mean?SUVmax was −44.6 ± 26.9% and varied significantly depending on the SBR grade, the overexpression of HER2+ and the lack of hormonal receptor expression ( P = 0.04, P P = 0.01, respectively). Mean?BF was −26.9 ± 54.3% and a drastic reduction was only observed in HER2-positive subtypes (−58.7 ± 30.0%), supporting the anti-angiogenic effect of Trastuzumab. Changes in tumor glucose metabolism outperformed changes in BF to predict pCR in all tumor subtypes: the AUC of?SUVmax (ROC curves analyses) were 0.82, 0.65 and 0.90 in the TNBC, HER2-positive and Luminal subtypes, respectively. Conclusion Of the two biological hallmarks of cancer evaluated in this study, the reduction in tumor metabolism was more accurate than the reduction in BF to predict pCR in the different subtypes of breast cancer.

Review of the role of the sentinel node biopsy in neoadjuvant chemotherapy in women with breast cancer and negative or positive axillary node at diagnosis.

The role of the selective sentinel node biopsy (SNB) is increasing in relevance in breast cancer women with indication of neoadjuvant chemotherapy (NAC). The Radiosurgery Working Group of the SEMNIM is aware of the necessity of establishing the need for SNB before or after NAC, and also how to manage patients with axillary node-negative or node-positive. There is sufficient data to assess that the SNB with radioisotope techniques are feasible and safe in all these scenarios. An adequate axilla evaluation prior to surgery and the possibility of marking prior to NAC the nodes infiltrated must be the two main pillars to guarantee the success of the SNB. It has been shown that to incorporate the SNB in breast cancer women with indication of NAC increases the rate of a conservative treatment of the axilla that will be a clear benefit for these patients.

Review of the role of the sentinel node biopsy in neoadjuvant chemotherapy in women with breast cancer and negative or positive axillary node at diagnosis

The role of the selective sentinel node biopsy (SNB) is increasing in relevance in breast cancer women with indication of neoadjuvant chemotherapy (NAC). The Radiosurgery Working Group of the SEMNIM is aware of the necessity of establishing the need for SNB before or after NAC, and also how to manage patients with axillary node-negative or node-positive. There is sufficient data to assess that the SNB with radioisotope techniques is feasible and safe in all these scenarios. An adequate axilla evaluation prior to surgery and the possibility of marking prior to NAC the nodes infiltrated must be the two main pillars to guarantee the success of the SNB. It has been shown that to incorporate the SNB in breast cancer women with indication of NAC increases the rate of a conservative treatment of the axilla that will be a clear benefit for these patients.

Abstract S2-07: Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): Follow-up of a prospective multi-institutional cohort

Abstract Background Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer has no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), after NAC, is aimed to select patient who should be safely spared of an axillary lymphadenectomy (ALND).GANEA 2 is a French prospective multi institutional trial, aimed to assess SLND after NAC. Objective To assess the risk of relapse for patients without previous axillary node involvement treated with NAC followed with a SLND without a systematic lymphadenectomy. Patients and Method Inclusion: FIGO stage T1-T3 infiltrating breast carcinoma, indication of NAC. Exclusion: inflammatory cancer, local relapse, contra-indication to NAC, NAC interrupted due to progressive disease. Design: indication to plan a NAC, axillary sonography with fine needle cytology before NAC to select patients without lymph node involvement, SLND after NAC. ALND was mandatory in case of SLN involvement (macro or micro-metastasis) or SLND failure. Follow-up was scheduled with a medical visit / 6 months with axillary assessment and a mammography each year. Follow-up results are updated every 6 months. Pathological analysis were carried out according to standard methods and classified according to the last American Joint Committee staging system. Studied parameters were SLND detection rate, pathological results on breast specimen and nodes, rate of relapse (axilla, breast, metastasis), and survival. Results From July 2010 to February 2014, 587 patients were enrolled, from 17 institutions, and experienced breast tumor surgery and a SLND after NAC. Each patient experienced breast surgery. A breast tumour pathological complete response was found in 21.3% (125/587). SLND rate was 97% (570/587), with a median number of 2 sentinel nodes (1-9). Patients with a sentinel detection failure (n=17) experienced a systematic lymphadenectomy, without any involvement (n=13), a micro-metastasis (n=2) and a macro-metastasis (n=2). A total of 140 patients had at least one sentinel node involved: macro-metastasis (n=86), micro-metastasis (n=54). A lymphadenectomy was performed in 128 cases: metastasis free (n=100), macro-metastasis (n=17), micro-metastasis (n=11). A total of 430 patients had a SLN metastasis free (75% ;430/570). A not mandatory lymphadenectomy was performed (n=14): metastasis free (n=11), macro-metastasis (n=2) and micro-metastasis (n=1). 17 patients were lost to follow-up. A total of 399 patients without sentinel node involvement were followed 2.3 years (from 0.5 to 5.6 yrs). At 3 years overall survival was 97.8% [94.9-99.1], disease free survival was 94.8% [91.0-97.1%]. Six patients died. Fifteen patients experienced a relapse: 8 metastasis, 4 homolateral breast, 2 controlateral breast, 1 homolateral axillary relapse. Conclusion This is the most important series of patients followed 2.3 years after SLND without axillary lymphadenectomy after NAC for an advanced breast cancer, showing acceptable results. The current series validate the safety of this conservative strategies avoiding systematic lymphadenectomy to patients without initially involved axillary node treated with NAC. Citation Format: Classe J-M, Loaec C, Alran S, Paillocher N, Tunon-Lara C, Gimbergues P, Faure-Virelizier C, Chauvet M-P, Lasry S, Dupre P-F, Verhaeghe J-L, De Blaye P, Gutowski M, Barranger E, Lecuru F, Lefevre Lacoeuille C, Loussert L, Lambaudie E, Ferron G, Campion L. Sentinel node detection after neoadjuvant chemotherapy in patient without previous axillary node involvement (GANEA 2 trial): Follow-up of a prospective multi-institutional cohort [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr S2-07.

A phase II trial of neoadjuvant chemotherapy with GSL (GEM+TS-1+LV) for marginally resectable pancreatic cancer.

TPS516 Background: The impact of neoadjuvant chemotherapy (NAC) for borderline resectable pancreatic cancer is under debate. In this context, a phase II trial of neoadjuvant chemotherapy for marginally resectable pancreatic cancer is undergoing since Jan 2014 (UMIN000012480). In this trial, we employed GSL regimen (Gemcitabine 1000mg/m2, TS-1 80mg/m2, LV 50mg) which have reported favorable results (33% of response rate, 93% of disease control rate and 16.6 months of overall survival) for unresectable pancreatic cancer (Cancer Chemother Pharmacol 2014; 74:911). Methods: The subjects were marginally resectable, pathologically proven pancreatic cancer, which consists of borderline resectable because of arterial attachment (BR-A) and locally advanced or unresectable (LA, UR) with short-segment ( = / < 3cm) arterial abutment based on NCCN guideline 2015. At least two surgeons, two medical oncologists, and one radiologist joined a consensus meeting to decide the indication of NAC and evaluated the efficacy of NAC every month. Patients with CR, PR or SD for 2-6 months underwent curative surgery combined with dissection of the nerve plexus around major arteries. The primary endpoint was R0 resectional rate, and the secondary endpoints were resectional rate, response rate, adverse effect, surgical morbidity, mortality, operative time and hospital stay period. Twenty-four patients are going to be enrolled, and 23 patients have undergone enrollment of NAC at the time of submission of the present abstract. Clinical trial information: 000012480.

Postmastectomy Radiation Therapy

Postmastectomy Radiation Therapy

Neoadjuvant carboplatin and docetaxel in locally advanced triple negative breast cancer: A Hispanic trial.

e12554 Background: To evaluate the impact on efficacy and safety of combination of carboplatin plus docetaxel as neoadjuvant chemotherapy (NACT) for patients with locally advanced triple-negative breast cancer (TNBC), and explore an optimal regimen for TNBC in a Hispanic Cohort. The primary endpoint of the study was pathologic complete response (pCR), with secondary endpoints including clinical response and safety of the combination. Methods: Patients with biopsy confirmed pathological diagnosis of locally advanced invasive breast cancer, triple negative by immunohistochemistry, and with indication for NACT were eligible in this study. A total of thirty five patients (n = 35 ) were enrolled from January 2013 to November 2015 with stage II to III TNBC. Received doxorubicin plus cyclophosphamide once every 3 weeks for four cycles followed by docetaxel 75 mg/m(2) every three weeks for 4 cycles with concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results: Overall, 35 patients were enrolled from January 2013 to August 2015. 33 patients completed chemotherapy as planed while one patient discontinued platinum due to ototoxicity. pCR rate was 50%. All the 35 patients could be evaluated for toxicity according to the NCI-CTC v3.0 criteria. The major toxicities were neutropenia (70 %), nausea (40 %) and vomiting (30%). Grade 3/4 toxicities were low. Ninety four per cent of patients completed six cycles. Conclusions: In locally advanced TNBC, addition of carboplatin to docetaxel regimen in NACT notable increased pCR rates compared with the standard anthracycline plus paclitaxel regimen reported in the literature. This regimen is highly effective, well tolerable and feasible in TNBC.

Patterns of Care in the Administration of Neo-adjuvant Chemotherapy for Breast Cancer. A Population-Based Study

Neo-adjuvant chemotherapy (NAC) is used to facilitate radical surgery for initially irresectable or locally advanced breast cancer. The indication for NAC has been extended to clinically node negative (cN0) patients in whom adjuvant systemic therapy is foreseen. A population-based study was conducted to evaluate the increasing use of NAC, breast conserving surgery (BCS) after NAC and timing of the sentinel node biopsy (SNB). All female breast cancer patients, treated in 10 hospitals in the Eindhoven Cancer Registry area in the Netherlands between January 2003 and June 2012 were included (N = 18,427). In total, 1,402 patients (7.6%) received NAC. The administration increased from 2.5% in 2003 to 13.0% in 2011 (p < 0.001). Use of NAC increased from 0.5% to 2.3% for cT1 tumors, from 2.8% to 27.0% for cT2, from 30.6% to 70.9% for cT3, and from 40.5% to 58.1% for cT4 tumors (p < 0.001). In cN0 patients, use of NAC increased from 1.0% to 4.4% and in clinically node positive patients from 12.0% to 57.5% (p < 0.001). Downsizing of the tumor and BCS are achieved increasingly. In 2011, in three hospitals NAC was administered in <10% of patients, in five hospitals in 10-15% and in two hospitals the proportion of patients receiving NAC was >20% (p < 0.001). Of the 1,402 patients with NAC, 495 patients underwent SNB, 91.5% of whom prior to NAC. In the Netherlands up to one in eight patients receive NAC. The administration of NAC and the percentage of BCS increased over the past decade, especially in cT2 tumors. Considerable hospital variation in the administration of NAC exists.

A new histological therapeutic classification system to predict eradicated and residual lymph nodes in breast cancer after neoadjuvant chemotherapy.

The indication for neoadjuvant chemotherapy (NAC) has recently broadened to include its use in the treatment of initial stage breast cancer. Axillary lymph node metastasis after NAC in breast cancer is a poor prognostic factor. Thus, the prediction of lymph node metastasis is important to estimate the prognosis of breast cancer patients after NAC. Therefore, we focused on residual carcinoma patterns of primary breast tumors after NAC and examined the correlation between the patterns and lymph node metastasis. In this study, we examined 50 breast cancer specimens and associated dissected lymph nodes after NAC. We divided 40 cases into an eradicated lymph node group and a residual lymph node group to analyze residual carcinoma patterns of primary breast tumors. Residual carcinoma patterns were classified according to the cell density of carcinoma cells: dense, focal/nested and sporadic/in-situ. There were significant differences in residual carcinoma patterns (P<0.01) among the three pattern groups. There was a high incidence of dense patterns in the residual lymph node group and a high incidence of sporadic/in-situ patterns in the eradicated lymph node group. Analysis of residual carcinoma patterns of primary breast tumors and clinicopathological factors demonstrated that there were significant differences in tumor reduced ratio on CT (P<0.001), primary tumor area before NAC (P<0.01), primary tumor area after NAC (P<0.00001), intrinsic subtype (P<0.01), Ki-67 labeling index (P<0.01), histological grade (P<0.05) and mitotic count (P<0.01) between the dense and non-dense groups. Therefore, our results suggest that the residual carcinoma pattern is useful for predicting eradicated or residual lymph nodes and the malignant potential in breast cancer after NAC.

Abstract P1-14-20: HER2 and estrogen receptor status drive decisions regarding the use of neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NC) is widely utilized to facilitate breast-conserving surgery and is considered equivalent to adjuvant chemotherapy with regard to recurrence-free and overall survival. However, controversy exists about specific indications for NC and its effects on other outcomes, particularly related to surgery in the breast and axilla. Limited data are available about specific recommendations of breast cancer-focused clinical investigators (CI). Methods: A 139-item survey was sent in May 2015 to 94 US-based surgical (S) and medical oncology (MO) CI from a proprietary database to assess their usual practice patterns. A modest honorarium was provided. Results: The assessment was completed by 59 CI (28 S and 31 MO; 63% of those sent the survey). Most (86%) recommend NC to patients with estrogen receptor-negative/HER2-negative (ER-/HER2-) and HER2-positive (HER2+) tumors larger than 2 cm or with biopsy-proven axillary node involvement. For such patients with HER2+ tumors, MO routinely (98%) use pertuzumab (P) with trastuzumab (T) combined with NC — either paclitaxel (14%), docetaxel (7%), docetaxel/carboplatin (55%) or a taxane and doxorubicin (24%). For patients with these higher-risk HER2+ tumors not receiving NC, 52% of MO use P in the adjuvant setting, either during chemotherapy or continuing for a year. There was more heterogeneity and less use of NC in patients with ER-positive (ER+)/HER2- tumors, and 48% of MO use genomic profiling (generally the 21-gene Recurrence Score® to facilitate this decision. Globally, for the 36 defined scenarios that were evaluated, S were somewhat more likely to recommend NC (70%) than MO (63%). In terms of axillary management, S typically employ post-NC sentinel node biopsy (SNB; 82%) and only proceed to axillary dissection if the SNB is positive. Conclusions: S and MO CI consider ER and HER2 (with tumor size and axillary node status) essential factors in NC decisions. In 2013, P (in combination with NC/T) became the first agent to receive FDA approval in the neoadjuvant setting in patients with HER2+ tumors, and it is now commonly used in both the adjuvant and neoadjuvant settings. The algorithms generated by this assessment will be helpful in educating community-based physicians, and as a result an online point-of-care tool to facilitate these decisions is being developed and evaluated. Neodajuvant chemotherapy? (%)*Nodal statusTumor size (cm)ER-/HER2+ER+/HER2+ER-/HER2-**ER+/HER2-Biopsy positive: Palpable1.0-2.0Yes: 86Yes: 81Yes: 80Yes: 24No: 7No: 8No: 7No: 39G: 24 2.1-3.0Yes: 93Yes: 92Yes: 88Yes: 36No: 2No: 5No: 5No: 25G: 29 3.1-5.0Yes: 100Yes: 98Yes: 95Yes: 49No: 0No: 2No: 2No: 7G: 29Biopsy positive: Imaging1.0-2.0Yes: 71Yes: 73Yes: 64Yes: 10No: 10No: 12No: 7No: 46G: 27 2.1-3.0Yes: 88Yes: 88Yes: 83Yes: 17No: 2No: 7No: 5No: 29G: 34 3.1-5.0Yes: 98Yes: 98Yes: 93Yes: 37No: 0No: 2No: 2No: 8G: 32Clinically negative1.0-2.0Yes: 22Yes: 15Yes: 20Yes: 2No: 51No: 63No: 46No: 54G: 39 2.1-3.0Yes: 69Yes: 66Yes: 71Yes: 5No: 12No: 17No: 17No: 42G: 46 3.1-5.0Yes: 92Yes: 92Yes: 85Yes: 15No: 3No: 2No: 5No: 15G: 49* Remaining responses = no preference between neoadjuvant and adjuvant chemotherapy; ** BRCA-negative; G = genomic assay ordered Citation Format: Love N, Blackwell KL, Mamounas EP, Moss J, Ziel K. HER2 and estrogen receptor status drive decisions regarding the use of neoadjuvant chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-20.

Identification of Biomarkers Including 18FDG-PET/CT for Early Prediction of Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

To investigate the value of the metabolic tumor response assessed with (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), compared with clinicobiologic markers to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in women with triple-negative breast cancer (TNBC). Fifty consecutive women with TNBC and an indication for NAC were prospectively included. Different pretreatment clinical, biologic, and pathologic biomarkers, including SBR grade, the Ki-67 proliferation index, androgen receptor expression, EGF receptor (EGFR), and cytokeratin 5/6 staining, were assessed. Tumor glucose metabolism at baseline and its change after the first cycle of NAC (ΔSUVmax) were assessed using FDG-PET. The pCR rate was 42%. High Ki-67 proliferation index (P = 0.016), negative EGFR status (P = 0.042), and high ΔSUVmax (P = 0.002) were significantly associated with pCR. In multivariate logistic regression, both negative EGFR status (OR, 6.4; P = 0.043) and high ΔSUVmax (OR, 7.1; P = 0.014) were independent predictors of pCR. Using a threshold at -50%, tumor ΔSUVmax predicted pCR with a negative, a positive predictive value, and an accuracy of 79%, 70%, and 75%, respectively. Combining a low ΔSUVmax and positive EGFR status could predict non-pCR with an accuracy of 92%. It is important to define the chemosensitivity of TNBC to NAC early. Combining EGFR status and the metabolic response assessed with FDG-PET can help the physician to early predict the probability of achieving pCR or not. Given these results, the interest of response-guided tailoring of the chemotherapy might be tested in multicenter trials. Clin Cancer Res; 21(24); 5460-8. ©2015 AACR.

Construction of multi-gene classifier for prediction of response to and prognosis after neoadjuvant chemotherapy for estrogen receptor positive breast cancers

The aims of this study were to develop a multi-gene expression-based prediction model for pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) and to evaluate its prognosis prediction for estrogen receptor (ER) positive breast cancers. The training set included the NAC-treated patients (n = 104) with ER+ breast tumors in our hospital and the validation set included the NAC-treated patients (n = 259) with ER+/HER2− breast tumors in the public database (GSE25066). Gene expression in the tumor biopsy specimens obtained before NAC was analyzed with DNA microarray, and the prediction model (MPCP155) for pCR was constructed for the training set by using the genes (155 probes) involved in the metabolic pathways which the pathway analysis identified as being significantly associated with pathological response. With MPCP155, the tumors in the validation set could be classified into low chemo-sensitive (low-CS) (pCR rate = 2.6%) and high-CS (pCR rate = 15.3%; P = 0.0006) groups. Furthermore, the low-CS group showed a significantly better prognosis than the high-CS group (P = 2.0E−6). Moreover, prognosis prediction by MPCP155 was independent of the residual cancer burden score. MPCP155 may be helpful for decision making regarding the indication for neoadjuvant chemotherapy. In addition, MPCP155 was found to be useful for prognosis prediction for NAC-treated patients with ER+/HER2− tumors.

P094. Clinical feasibility of Cerenkov Luminescence Imaging (CLI) for intraoperative assessment of tumour excision margins and sentinel lymph node metastases in breast-conserving surgery

P094. Clinical feasibility of Cerenkov Luminescence Imaging (CLI) for intraoperative assessment of tumour excision margins and sentinel lymph node metastases in breast-conserving surgery

Abstract P2-01-01: Sentinel node surgery after neoadjuvant chemotherapy in patient with axillary node involvement: The French GANEA 2 prospective multi-institutional trial

Abstract Background Half of the patient treated with neoadjuvant chemotherapy (NAC) for a large operable breast cancer has no axillary lymph node involvement at the time of surgery. Sentinel lymph node detection (SLND), performed after NAC, must select patient who should be spared of an axillary lymph node dissection (ALND). The application of SLND for staging the axilla after NAC for patient who initially had a proven axillary lymph node involvement remains controversial because of a low detection rate (DR) and a high false negative rate (FNR). Objective The aim of GANEA 2 trial was to assess the DR and the FNR of SLND after NAC in the particular case of patients with a proven axillary lymph node involvement. Patients and Method GANEA 2 was validated by scientific and ethical national boards. Inclusion criteria: FIGO stage T2-T3 infiltrating breast carcinoma, indication of NAC, surgery (radical or conservative) after NAC and signed consent form, Exclusion criteria: inflammatory cancer, local relapse, previous surgical removal of the tumour, mental disorder, pregnancy or no contraceptive method, contra-indication to NAC, NAC interrupted due to progressive disease. Design: Diagnosis and indication to plan a NAC, control of inclusion and exclusion criteria, consent form signature, axillary sonography with fine needle cytology before NAC to select patients with a proven lymph node involvement. After NAC patients underwent both SLND, with the combined technique Blue dye and radiolabeled colloid, and complementary ALND. Pathological procedure: Pathological analysis, of sentinel and non sentinel nodes, carried out according to standard methods and classified according the last American Joint Committee staging system and Sataloff classification. Studied parameters were detection rate, false negative rate and Sataloff grading on tumor and lymph nodes. We evaluated particularly the likelihood that the FNR in patients with one or more SLN examined was greater than 10%. Patients with no lymph node involvement before NAC underwent only a SLND with an ALND only in the case of SLN macro-metastasis with a rigorous follow up. They are not part of this abstract. Results From July 2010, to February 2014, 242 patients from 19 institutions were enrolled, with a proven axillary lymph node involvement before NAC. After NAC, 1/3 had metastasis free axillary lymph node (80/142). Detection rate was 83.1% (201/242). Half of the patients with a detection failure had an involved ALND. The false negative rate was 14.2% in the whole series but 24.5% in the case of only 1 SLN resected, and 8% in case of more than 1 SLN resected. In case of involved SLN, half of the patients had involved ALND. Considering the node Sataloff scoring, 18 of the 20 false negative cases were grade C or D (n=15 grade C, metastatic disease and therapeutic effect; n = 3 grade D, metastasis and no therapeutic effect). Conclusion Among patients treated by NAC for a large operable breast cancer with proven involved lymph node before NAC, who had only 1 SLN examined, the false negative rate was 24.5%. SLND with the combined technique, provides a FNR of less than 10% only in the case of 2 or more SLN resected. Citation Format: Jean-Marc Classe, Loic Campion, Severine Alran, Christine Tunon de Lara, Pierre Francois Dupre, Christelle Faure, Nicolas Paillocher, Serge Lasry, Marie Pierre Chauvet, Gilles Houvenaeghel, Marian Gutowski, Pascaline De Blaye, Charlotte Ngo, Emmanuel Barranger, Jean Luc Veraeghe, Celine Lefebvre, Jean Francois Rodier, Virginie Bordes, Helene Charitansky, Gwenael Ferron, Pierre Gimbergues. Sentinel node surgery after neoadjuvant chemotherapy in patient with axillary node involvement: The French GANEA 2 prospective multi-institutional trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-01.

Neoadjuvant chemotherapy for colon cancer based on evidence-based medicine

The incidence of colon cancer has been increasing in recent years with the improvement in living standard, and becomes one of the leading causes of cancer-related death. While radical surgery remains the primary choice for colon cancer, neoadjuvant chemotherapy has significantly improved the successful rate of surgery and increased postoperative survival. In addition to traditional chemotherapy with 5-Fu or oxliplatin, molecular targeted drugs lead to a higher response rate and show its dramatic effect on disease-recurrence time. However some side effects such as disease progression during chemotherapy, bleeding or liver toxicity should be concerned. In addition, indications for neoadjuvant chemotherapy do not reach a consensus. In the future, these controversies may be solved based on some large randomized controlled trials.

Indication for neoadjuvant chemotherapy in patients with colorectal liver metastases based on a nomogram that predicts disease-free survival.

The purpose of this study was to validate the Beppu nomogram, which predicts disease-free survival (DFS) after resection of colorectal liver metastases, and to investigate the efficacy of neoadjuvant chemotherapy based on the nomogram-predicted recurrence risk. We retrospectively analyzed 234 patients with colorectal liver metastases who underwent a hepatic resection at eight hospitals between 2005 and 2010. The nomogram c-index of all the patients was 0.59. The observed and the predicted 3-year DFS showed good agreement. When the patients were divided into two groups who received or did not receive pre-hepatectomy chemotherapy (PHC), the c-index of the patients who received PHC was inferior to that of the patients who did not (0.56 and 0.61, respectively). In patients who received PHC, DFS among the quintiles clustered by the nomogram score indicated no significant differences (P = 0.25), unlike in patients who did not receive PHC (P < 0.0001). Surprisingly, in patients with no risk factors for recurrence, neoadjuvant chemotherapy provided significantly lower DFS than no neoadjuvant chemotherapy (3-year DFS: 42.9% vs. 80.0%, P = 0.03). The nomogram validation was shown to be moderately predictive. PHC decreased the performance of the nomogram and might produce no DFS benefit in patients with low recurrent risk.

Predictive testing for DPD deficiency in a patient with familial history of fluoropyrimidine-associated toxicity.

Reduced activity of DPD leads to severe toxicity in cancer patients receiving standard doses of fluoropyrimidines, particularly in the case of combination regimens. We describe a 38-year-old man with a resectable metastasis from hereditary nonpolyposis colorectal cancer, with indication of neoadjuvant chemotherapy and a family history of fluoropyrimidine-associated toxicity. We tested our patient for functional DPYD variants, before any choice of the neoadjuvant regimen, including for the c.496A>G, already described in his mother, and a deep intronic variant c.1129-5923C>G recently reported associated to severe toxicity. Our patient was found to be heterozygous for both c.469A>G and c.1129-5923C>G DPYD variants. We thus offered the most active perioperative regimen, capecitabine, oxaliplatin, irinotecan plus bevacizumab by which we reduced the dosing of capecitabine to 50%. Treatment was well tolerated, with grade 2 diarrhea as the most significant adverse event, and led to a complete pathological response after liver resection. We provide a rationale approach to improve the safety of fluoropirimidine-based therapy in a patient with family history of fluoropyrimidine-associated toxicity.