No abstract

e15176 Background: Few data regard efficacy and safety of FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, fluorouracil bolus of 400 mg/m2 and continuous infusion of 2400 mg/m2 over 46 hours and leucovorin 400 mg/m2) in patients over 65 years with advanced pancreatic adenocarcinoma. Methods: After Ethical Committee approval, consecutive patients age over 65 with biopsy proven pancreatic adenocarcinoma that received at least one cycle of modified dose-attenuated FOLFIRINOX (no bolus FU and reduced dose of at least one agent since first cycle) were selected (São José Hospital database) for a retrospective review for safety, response, and survival. Results: Nineteen consecutive patients were selected from our database. Patients characteristics included 12 (63,1%) males, 7 (36,9 %) females, median age 72,7 (range 66-79). Tumor location was 11 (57,8 %) head of the pancreas, 6 (31,57 %) body and 2 (11 %) in other sites. Grade 3/4 toxicities were reported in 10 patients (52,6 %): nausea/vomiting 1 (5,2 %), diarrhea 1 (5,2 %), fatigue 3 (15,7%), neutropenia 4 (21 %), thrombocytopenia 1 (5,2%) and febrile neutropenia 3 (15,6 %). Elevations in AST and ALT above the upper limit of normality were identified in 5 (26,31%). No deaths reported due to toxicity. Prophylactic granulocyte colony stimulator factor (G-CSF) was given to 14 (73 %). Seventeen patients completed at least four cycles; disease control was obtained in 15 (83, 3 %) with 1 complete response, 5 partial response and 9 stable diseases. Median reductions in doses in the first cycle of chemotherapy by drugs were: oxaliplatin 23,3 % (10%-30%), irinotecan 24,6 % (0%-60%), fluorouracil 20,6% (0%-40%). Median reductions in doses in the fourth cycle of chemotherapy by drugs were: oxaliplatin 20,8 % (0%-42%), irinotecan 24,9 % (0%-75%), fluorouracil 17,6% (0%-40%).With a median follow up of 4.5 months, median overall or progression free survival is not reached. Conclusions: Modified dose-attenuated FOLFIRINOX is a therapeutic option to elderly with advanced pancreatic adenocarcinoma. Although grade 3 and 4 toxicities were reported, they were manageable. Modified attenuated-dose of FOLFIRINOX needs further investigated.

No abstract

e23575 Background: STS include a heterogeneous group of malignancies that arises from or into connective tissues and limbs are the preferential primary sites. An adequate local control with multimodality therapy can be obtained in most cases. An additional approach, that is, the IORT-LK is able to deliver high dose to risky areas for recurrence, minimizing the toxicity to structures around the target. Such an importance is even greater in abdominal sarcomas, because there is some difficulty in removing the whole neoplasia with clear margins. IORT-LK has the advantage of higher Relative Biological Effectiveness (RBE), a mathematical model that measures the potential for tumour double-strand break (radiation effectiveness), that is close to Proton beam and higher than electron beam. Nevertheless, IORT-LK is not free of complications. It has been reported peripheral neuropathy and enteritis, in cases of limb and abdominal STS, respectively. Methods: In this retrospective study from a single Brazilian institution (Hospital Alemão Oswaldo Cruz), we reported 6 patients with histologically confirmed STS, that underwent IORT-LK (Intrabeam - Carl Zeiss). There are 3 male and 3 female patients, with a median age 48 years, and mean of 39 years. The histological subtypes are as follows: fibromyxoid sarcoma, high grade pleomorphic sarcoma, desmoid tumor, chondrosarcoma, dedifferentiated liposarcoma and malignant schwannoma - one subtype for each patient. The primary sites are: inferior limb (3), superior limb (1) and abdomen (2). Results: IORT-LK was administered in doses that ranged from 14 to 15 Gy to the involved area. Two patients, each one with a limb STS, received also neoadjuvant chemotherapy. With a mean follow-up of 30 months, there is no local recurrence among the 6 patients reported. The first patient received the IORT-LK in April, 2017 and the last one in July, 2019. All of them had clinical observation up-to-dated on January, 2020. No serious complications were observed, but one patient had a moderate local infection. Conclusions: The therapy was well tolerated. We must emphasize that dose previously used by Brussiers was slightly superior than ours but with electrons and not Low-Kylovoltage. In his pilot study it was used 17 Gy for treatment of abdominal sarcomas. In sum, we believe that IORT-LK has higher RBE than previous available equipment and can improve local control of STS, mainly those that arise on the extremities. Future studies must be carried out to confirm our initial impression.

Introduction: Next Generation Sequencing (NGS) is a key tool since it unreveals genetic alterations (GA) with potential for targeted-therapy, frequently, not detected for conventional methods done previously. Nevertheless, avaiability of these drugs is a major concern and, additionally, oncologists are challenged to deal with such a huge amount of findings whose clinical significance and sensibility to those drugs are, many times, uncertain. Is broadly unknown, except for isolated initiatives, the correlated clinical outcomes of targeted-therapy guided by NGS. Methods: In this retrospective study, we describe clinical outcomes of 34 pts with advanced solid tumors (tu) treated in a single Cancer Center in Brazil according to therapies guided by NGS. All tests were performed using Illumina HiSeqs of Foundation Medicine (FM). The f/u was obtained from our electronic charts. Results: From apr/14 to oct/17, 34 pts were identified, 13M/21F, mean 58y/o. Histologies were: 7 NSCLC, 10 mCRC, 3 pancreatic, 3 breast and 11 varied. In 26 / 34 pts (76%), druggable GA were identified and 17 (50%) were treated with NGS-guided therapies - 14 with TKi and 3 with immunotherapy (imm). Importantly, 8/ 17 pts (47%) experienced clinical benefit (DE, PR, CR) by RECIST 1.1 (1 melanoma, 1 colon, 6 lung adeno). Seven (41%) had PD in the first control in 4-8w (mCRC treated with cobimetinib because of TP53 G12D; mCRC-trastuzumab-HER2 R678Q; breast-olaparibe-BRCA-2 T431fs*20; breast-EVE-PIK3CA E545K; endometrium-EVE-PIK3CA C604R/PIK3CA E81K and PTEN R233*/PTEN S229; mCRC-trastuzumab+lapatinib-HER2 amplification V777L; HCC-EVE-IKBKE amplification and PTEN loss exon 2-9), 1 had just started the therapy (BRCA-2 mutated pancreatic adeno with olaparib) and 1 died before restaging (HER2-mut mCRC treated with chemo+trastuzumab). The DoR was better in those with anti-ALK (3 pts, 18 mo) and anti-EGFR (1 pt, 6 mo ongoing response) and in those with TMB-I/high treated with imm (1 melanoma with TMB27 and 2 lung adeno with TMB 18 and 8). Amongst the 10 pts with evaluable TMB values, 6 were TMB-I/high and, in those, was found a high frequency of mutations: mean of 7). Curiously, 1 pt with mCRC with Kras G12V mutation treated with Trametinib, according to FM recommendations, experienced SD for 12 mo. Finally, 7 pts had samples tested by local companies using other methods (IHC, FISH, PCR) and in 5 (14% of all 34) it did not identified the GA observed by NGS. Conclusion: NGS identified a significant amount of GA otherwise not detected by conventional tools, changed management and resulted in improved clinical benefit, especially for those with lung adeno treated by anti-ALK/EGFR and those with TMB-I/high treated by imm. Addionally, this study suggests that tu with higher amount of GA in NGS are prone to harbor TMB-I/high and also confirms the low responsiveness of solid tumors to EVE even with driver-mutations in the PI3K-Akt-mTor pathway. Citation Format: Marcos Andre Costa, Marcelo Santos, Roberto Abramoff, Renata D'alpino, Carlos Teixeira, Ariel Kann, Jacques Tabacof, Riad Younes. Clinical outcomes of pts with advanced solid tumors treated according to NGS guided-therapy in a Brazilian cancer center [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2601.

No abstract

e19261 Background: MDTB have emerged as a valuable forum to address questions related to patient management. There is a general data lack of its overall benefit by attending physicians. However, few reports describe numerical impact on patient care of this tailor-made and shared model of medical decision. Methods: We describe, in this prospectively-collected study, data from a Cancer Center (HAOC) regarding multiple weekly, 1h-long discussions, as part of MDTB (GU, neuro-oncology GI, thorax, HN, breast, gyneco, melanoma/sarcoma and palliative care). Only newly-diagnosed or on-treatment challenging cancer cases were included. Attendees (onco, surgeons, RT, paths and radiologists) pooled their expertise to warrant quality and maximize resources. The primary endpoint was change in the medical planning. In our institution, further adherence to MDTB recommendations are left totally at physician discretion. Results: From Oct/17 to Feb/19, 413 cases were discussed (60% female), mean of 2.9 cases/MDTB, but GI (3.8), thorax (3.7) and breast (2.94) were above the median. Mean was 13.4 doctors/MDTB - more in breast (16.5), GI (15.8) and uro (15.1). Mean of oncologist/MDTB in general was 6.1, but 8.1 in GI, 7.8 thorax, breast 6.8 and 6.7 uro. Mean of surgeons/MDTB in general was 3.5, but 6.2 in breast, 5.8 uro and 5.5 GI. 100% of all had at least 1 oncologist and uro/GI/breast had at least 1 surgeon in 100% of them. In 50% (uro), 44% (neuro), 23.5% (breast), 6.4% (thorax) and 3.7% (GI) had at least 1 physician of 5 major areas. Oncologists engaged with more cases: 80.4% (thorax), 70.6% (uro), 59.6% (GI), 56.5% (HN). Prostate (38.2%), metastasis (neuro, 28.9%), colorectal (18.2%), lung adenoCA (43.5%), mouth (30.4%), ductal carcinoma (35.8%) were the more frequently discussed per system. In 25.7%, MDTB changed original medical planning. By site: GI (35,6%), thorax (24,7%), breast (22,6%), neuro (21,7%), uro (17,7%) and HN (17,4%). Oncologists were responsible more in thorax (73,9%) and less in breast (33%) and surgeons more in breast (50%) and less in GI (33%). Adherence to NCCN guidelines was total. Finally, but not measurable, a sizeable number of cases requires significant weekly time-effort. Conclusions: This study confirms MDTB leading role in cancer care, highlighting the importance of teamwork for more precise patient care. We point out that it led to substantial practice-changing in our institution, reinforcing its importance in a scenario which doctors are confronted with increasing complexities in patient management.

Distant metastases generally indicate disseminated disease and the standard treatment for these patients is palliative chemotherapy. Retrospective series showed that selected patients with metastatic lung cancer and a solitary extrathoracic disease could be effectively treated with curative intention by resection of both primary tumor and the single site of metastatic disease. According to current data, adrenalectomy might be considered as an alternative option for patients with isolated adrenal metastases. Significant morbidity and mortality may be happened by these procedures, and a cautious analysis of pros and cons should be discussed with the patient. We present a review of the literature and updated recommendations focusing lung cancer with solitary adrenal metastasis.