EP.TH.243Western Australian Multicentre review of management of the axilla in breast cancer patients receiving neoadjuvant chemotherapy

Aim De-escalation of treatment in early breast cancer is proposed to reduce morbidity to patients without compromising oncological outcomes. Use of SNB as gold standard in clinically node negative patients is an example of successful implementation. In patients receiving upfront chemotherapy, axillary management is more complex. We reviewed the axillary management of patients undergoing neoadjuvant chemotherapy (NAC) to assess nodal response. Method The MDT records of two centres were reviewed between January 2015 and May 2019 to identify patients receiving NAC. Clinical records were reviewed to collect demographics, radiological and clinicopathological results as well as follow up data. Results 185 patients were identified as suitable, median age 49 (21-79). 49% were clinically node negative on presentation. 32% underwent a SNB prior to NAC; this decreased over the study period from 40.5% to 20.5%. Of the cN0 patients, 24% were upstaged to node positive disease at final surgery. None of these achieved a pCR in the breast. 18% of cN0 patients went straight to ALND, 50% were YpN0. 42% of cN1 patients achieved ypN0. 58% down-staged to ypN0 also achieved pCR in the breast. Only 1 patient with residual disease in axilla achieved pCR in the breast. Conclusion Use of pre-NAC SNB is declining with low rates of upfront ALND in cN0 patients. There is a 42% rate of down-staging axillary disease with NAC. Patients are unlikely to have nodal response without pCR in the breast. There is likely to be a role for targeted axillary dissection in carefully selected patients.

Impact of Neoadjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Population Based Analysis

BACKGROUND AND OBJECTIVES: We examined pathologic complete response (pCR) and pathologic downstaging (pDS) rates after neoadjuvant chemotherapy (NAC) in high-risk upper tract urothelial carcinoma, as well as their predictors. We further sought to determine their effects on overall survival and examine prognosticators of survival after NAC. METHODS: The National Cancer Database was used to identify all patients from 2004 to 2016 with nonmetastatic high grade upper tract urothelial carcinoma who received NAC followed by nephroureterectomy. pCR and pDS rates were examined, and univariate and multivariate logistic regression was performed to identify clinical predictors. Kaplan-Meier and Cox proportional hazard methods were used to estimate overall survival. RESULTS: 309 patients met inclusion criteria. 27 patients (8.74% ) had pCR, and 92 (29.77% ) had pDS. pCR and pDS rates for N+ subgroup were 6.82% and 47.73% respectively, and for N0 subgroup, 9.50% and 22.62%. Female sex (OR 2.94, p = 0.010) was the only predictor of pCR. Node-positive disease (cN1 vs. cN0: OR 6.40, p < 0.001; cN2 vs. cN0: OR 7.46, p < 0.001) was a positive predictor of pDS, and the presence of lymphovascular invasion (LVI) (OR 0.14, p < 0.001) was a negative predictor of pDS. The median OS for all patients was 45.5 months. pCR and pDS were both associated with improved OS, (p < 0.001 for both); median was 99.1 months for both. LVI was the strongest negative prognostic factor for OS (HR 2.85, p < 0.001). CONCLUSIONS: Overall pathological complete response and downstaging rates were 8.74% and 29.77% respectively after multi-agent neoadjuvant chemotherapy. Node-negative and node-positive disease had equivalent rates of complete response, but node-positive disease had a significantly higher rate of downstaging. The presence of LVI was associated with worse overall survival.

Functional Outcomes with Facial Artery Musculo-Mucosal (FAMM) Flap and Dental Implants for Reconstruction of Floor of the Mouth and Tongue Defects in Oncologic Patients

Optimal functional outcomes in oncologic patients with squamous cell carcinoma (SCCA) of the tongue and floor of the mouth require good lingual mobility, adequate facial competence, the cheek suction effect and dental rehabilitation with osseointegrated implants. In this study, twenty-two oncologic patients who had been diagnosed with intraoral SCCA affecting the tongue and the floor of the mouth and who had undergone wide resection of the tumor and immediate reconstruction with an inferiorly pedicled FAMM flap and immediate osseointegrated implants were assessed. Lingual mobility, speech articulation, deglutition, implant success rate, mouth opening, and aesthetic results were evaluated. All patients were staged as T2 and the defect size ranged from 3.7 × 2.1 cm to 6.3 × 4.2 cm. A selective neck dissection was performed in all patients as part of their oncologic treatment, either electively or for node positive disease. Thirteen patients (59%) were diagnosed with node positive disease and underwent adjuvant radiotherapy. A total of 101 osseointegrated implants were placed for prosthetic rehabilitation and 8 implants were lost (7.9%), of which 7 received radiotherapy (87.5%). The implant success rate was 92.1%. Mouth opening was reported as normal in 19 patients (86.3%). Tongue tip elevation was reported as excellent in 19 patients (86.3%) and good in 3 patients (13.6%). Lingual protrusion was referred to as excellent in 15 patients (68.2%) and good in 6 patients (27.2%). Lateral excursion was reported as excellent in 14 patients (63.6%) and good in 7 patients (31.8%). In terms of speech articulation, 20 patients reported normal speech (90.9%). Regarding deglutition, 19 patients (86.3%) reported a regular diet while a soft diet was reported by 3 patients (13.7%). Aesthetic results were referred to as excellent in 17 patients (77.3%). FAMM flaps, immediate implants and fixed prostheses enable the functional rehabilitation of oncologic patients, optimizing aesthetics and functional outcomes even in patients undergoing irradiation, thus returning oncologic patients to an excellent quality of life.

Is routine neck dissection warranted at salvage laryngectomy?

Background There is controversy regarding management of the neck at salvage laryngectomy. The aim of this study was to perform an analysis to determine the incidence of occult node positivity in this group and analyse factors affecting it. Method A retrospective analysis of 171 patients who underwent salvage total laryngectomy between 2000 and 2015 for recurrent or residual disease following definitive non-surgical treatment and were clinico-radiologically node negative at the time salvage laryngectomy was carried out. Results A total of 171 patients with laryngeal or hypopharyngeal cancers underwent concurrent neck dissection at laryngectomy. There were 162 patients (94.7 per cent) who underwent bilateral neck dissection, and 9 patients (5.3 per cent) who underwent ipsilateral neck dissection. The occult lateral nodal metastasis rate was 10.5 per cent. Of various factors, initial node positive disease was the only factor predicting occult metastasis on univariable and multivariable analysis (p = 0.001). Conclusion Risk of occult metastasis is high in patients who have node positive disease before starting radiotherapy. This group should be offered elective neck dissection.

Development and validation of an improved pathologic nodal classification system for cutaneous melanoma.

e21563 Background: Given recent therapeutic advances and evolving patterns of lymph node (LN) evaluation for cutaneous melanoma, accurate and precise LN staging is needed to guide adjuvant treatment and future investigations. Current staging was developed primarily for patients undergoing completion LN dissection (CLND) for node-positive disease and do not produce LN classification groups with continuously increasing mortality. Thus, we developed and validated an improved LN classification system for cutaneous melanoma. Methods: Retrospective cohort analysis of 105,785 patients with cutaneous melanoma who underwent surgery from 2004 to 2015 in the National Cancer Database. Extent of LN dissection (sentinel LN biopsy [SLNB] and/or CLND) was available for patients diagnosed 2012 onward. Multivariable models were generated with number of positive LNs modeled using a non-linear restricted cubic spline function. Recursive partitioning analysis (RPA) was used to derive a modified LN classification system based on LN variables independently associated with overall survival (OS). The proposed LN classification system was validated in 85,499 patients from SEER-18. Results: Number of positive LNs (1-2 LN+: hazard ratio [HR] 2.48 per LN, 95% CI, 2.37-2.61, P< 0.001; ≥3 LN+: HR 1.10 per LN, 95% CI, 1.07-1.13, P< 0.001), clinically detected metastases (HR 1.35, 95% CI 1.27-1.42; P< 0.001), and in-transit metastases (HR 1.48; 95% CI 1.34-1.65; P< 0.001) were associated with OS. An RPA-derived LN classification system using these variables demonstrated continuously increasing mortality risk for each proposed LN classification group (HR: 1.83, 2.72, 3.79, 4.56, 6.15, and 8.25 for the proposed N1a-N3b groups, Table, P< 0.001). By contrast, AJCC 8E produced a more haphazard mortality profile (HR: 1.83, 3.81, 2.59, 2.71, 4.51, 3.44, 6.06, 8.15, and 6.90 for N1a-N3c). As a sensitivity analysis, the proposed system continued to accurately predict outcomes when we excluded patients undergoing CLND for microscopic LN metastases. Lastly, we validated this system for OS and cause-specific mortality in SEER-18 ( P< 0.001). Conclusions: A modified and simplified LN classification system can accurately predict mortality in cutaneous melanoma in an era of increasing use of SLNB without CLND and should be considered for future staging systems.[Table: see text]

Final analysis of overall survival (OS) and relapse-free-survival (RFS) in the intergroup S1404 phase III randomized trial comparing either high-dose interferon (HDI) or ipilimumab to pembrolizumab in patients with high-risk resected melanoma.

9501 Background: We assessed whether or not adjuvant pembrolizumab given over 1 year would improve OS and RFS in comparison to high dose ipilimumab (ipi10) or HDI - the two FDA-approved adjuvant treatments for high risk resected melanoma at the time of study design. Methods: Patients age 18 or greater with resected stages IIIA(N2), B, C and IV were eligible. Patients with CNS metastasis were excluded. At entry, patients must have had complete staging and adequate surgery to render them free of melanoma including completion lymph node dissection for those with sentinel node positive disease. Prior therapy with PD-1 blockade, ipilimumab or interferon was not allowed. Two treatment arms were assigned based on stratification by stage, PD-L1 status (positive vs. negative vs. unknown), and intended control arm (HDI vs. Ipi10). Patients enrolled between 10/2015 and 8/2017 were randomized 1:1 to either the control arm [(1) interferon alfa-2b 20 MU/m2 IV days 1-5, weeks 1-4, followed by 10 MU/m2/d SC days 1, 3, and 5, weeks 5-52 (n=190), or (2) ipilimumab 10 mg/kg IV q3w for 4 doses, then q12w for up to 3 years (n=465)], or the experimental arm [pembrolizumab 200 mg IV q3w for 52 weeks (n=648)]. The study had three primary comparisons: 1) RFS among all patients, 2) OS among all patients, 3) OS among patients with PD-L1+ baseline biopsies. Results: 1,426 patients were screened and 1,345 patients were randomized with 11%, 49%, 34%, and 6% AJCC7 stage IIIA(N2), IIIB, IIIC and IV, respectively. This final analysis was performed per-protocol 3.5 years from the date the last patient was randomized, with 512 RFS and 199 OS events. The pembrolizumab group had a statistically significant improvement in RFS compared to the control group (pooled HDI and ipi10) with HR 0.740 (99.618% CI, 0.571 to 0.958). There was no statistically signifcant improvement in OS in the 1,303 eligible randomized overall patient population with HR 0.837 (96.3% CI, 0.622 to 1.297), or among the 1,070 (82%) patients with PD-L1 positive baseline biopsies with HR 0.883 (97.8% CI, 0.604 to 1.291). Gr 3/4/5 event rates were as follows: HDI 69/9/0%, ipi10 43/5/0.5% and pembrolizumab 17/2/0.3%. Conclusions: Pembrolizumab improves RFS but not OS compared to HDI or ipi10 in the adjuvant treatment of patients with high-risk resected melanoma. Pembrolizumab is a better tolerated adjuvant treatment regimen than HDI or Ipi10. Support: NIH/NCI NCTN grants CA180888, CA180819, CA180820, CA180863; and in part by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Editorial Acknowledgement: With special thanks to Elad Sharon, MD, MPH, and Larissa Korde, MD, MPH. National Cancer Institute, Investigational Drug Branch, for their contributions to this trial, as well as Nageatte Ibrahim, MD, and Sama Ahsan, MD Merck. Clinical trial information: NCT02506153.