LEONARDO GOMES DA FONSECA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
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- Young-age onset colorectal cancer in Brazil: Analysis of incidence, clinical features, and outcomes in a tertiary cancer center(2019) SILVA, Andrea C. B.; VICENTINI, Maria Fernanda B.; MENDOZA, Elizabeth Z.; FUJIKI, Fernanda K.; FONSECA, Leonardo G. da; BRAGHIROLI, Maria Ignez F. M.; HOFF, Paulo M.Background: Recent studies report increasing incidence of colorectal cancer (CRC) in the young-age population, but data concerning clinical behavior, pathologic findings, and prognosis are controversial for this group. Early recognition of CRC in young patients is a challenge and diagnosis at advanced stage is clearly associated with worse outcomes. Materials and methods: We retrospectively reviewed medical records of 5806 patients diagnosed with CRC between January/2011 and November/2016 and identified 781 patients aged less than 50-years-old. Results: We found an absolute increasing in the incidence of CRC in patients <50 years old of 1.88%-2.23% annually, with a relative increasing of 35.3% between 2011 and 2016. Median age was 42 years, 57.4% were female and 20.9% reported family history of CRC. Left-sided tumors were more frequent and the majority of patients were symptomatic. The most common stages at diagnosis were III (34.1%) and IV (37.3%). The median overall survival (OS) for stage IV was 25 months (95% Cl 20.7-29.3) and was not reached for Stages I-III (P < 0.001). Family history of CRC was independently associated with better OS in stage IV(P= 0.02). For stages I-III, wild-type KRAS, family history of CRC, and absence of angiolymphatic invasion were associated with better OS (P.0.02, P=0.01 and P < 0.001, respectively). Conclusions: In our cohort, the incidence of early-onset CRC is increasing over the past years. Young patients were more likely to be diagnosed with metastatic disease, left-sided and/or rectum site and symptoms at presentation. These findings highlight the emerging importance of young-age onset CRC and the need to discuss strategies to early diagnosis.
- Regorafenib in Patients with Antiangiogenic-Naive and Chemotherapy-Refractory Advanced Colorectal Cancer: Results from a Phase IIb Trial(2019) RIECHELMANN, Rachel P.; LEITE, Luiz S.; BARIANI, Giovanni M.; GLASBERG, Joao; RIVELLI, Thomas G.; FONSECA, Leonardo Gomes da; NEBULONI, Daniela R.; I, Maria Braghiroli; QUEIROZ, Marcelo A.; ISEJIMA, Alice M.; KAPPELER, Christian; KIKUCHI, Luciana; HOFF, Paulo M.Background Regorafenib is a multikinase inhibitor with antiangiogenic effects that improves overall survival (OS) in metastatic colorectal cancer (mCRC) after failure of standard therapies. We investigated the efficacy and safety of regorafenib in antiangiogenic therapy-naive chemotherapy-refractory advanced colorectal cancer. Patients and Methods This single-center, single-arm, phase IIb study (NCT02465502) enrolled adults with mCRC whose disease had progressed on, or who were intolerant to, standard therapy, but who were antiangiogenic therapy-naive. Patients received regorafenib 160 mg once daily for 3 weeks per 4-week cycle. The primary endpoint was progression-free survival (PFS) rate at week 8. Results Of 59 treated patients, almost half had received at least four prior lines of therapy. Patients received a median of 86% of the planned dose. The week 8 PFS rate was 53% (95% confidence interval [CI], 39.1-64.3); median PFS was 3.5 months (95% CI, 1.8-3.6). Median OS was 7.4 months (95% CI, 5.3-8.9). Tumor response (RECIST version 1.1) was 2%, and metabolic response rate (criteria from the European Organisation for Research and Treatment of Cancer) was 41%. The most frequently reported regorafenib-related grade >= 3 adverse events were hypertension (36%), hand-foot skin reaction (HFSR, 25%), and hypophosphatemia (24%). There were no regorafenib-related deaths. An exploratory analysis showed that patients with grade >= 2 HFSR had longer OS (10.2 months) with regorafenib treatment versus those with grades 0-1 (5.4 months). Conclusion These findings support the antitumor activity of regorafenib in antiangiogenic-naive patients with chemotherapy-refractory mCRC. Implications for Practice The multikinase inhibitor regorafenib improved overall survival in the phase III CORRECT and CONCUR trials in heavily pretreated patients with treatment-refractory metastatic colorectal cancer (mCRC). Exploratory subgroup analysis from CONCUR suggested that regorafenib treatment prior to targeted therapy (including bevacizumab) may improve outcomes. In this single-center, single-arm phase IIb study, regorafenib demonstrated antitumor activity in 59 antiangiogenic-naive patients with chemotherapy-refractory mCRC. Further studies should assess the efficacy of regorafenib in this patient population, as well as explore the reasons behind improved outcomes among patients who had a metabolic response and those who developed hand-foot skin reaction.
- Circulating Tumor DNA Detection in the Management of Anti-EGFR Therapy for Advanced Colorectal Cancer(2019) KNEBEL, Franciele H.; BETTONI, Fabiana; FONSECA, Leonardo G. da; CAMARGO, Anamaria A.; SABBAGA, Jorge; JARDIM, Denis L.Background: Anti-EGFR antibodies are a standard care for advanced KRAS-wild type colorectal cancers. Circulating tumor DNA (ctDNA) monitoring during therapy can detect emergence of KRAS mutant clones and early resistance to therapy. Case Presentation: We describe a 61-years-old man presenting a metastatic and recurrent rectal cancer treated with different chemotherapy regimens. His tumor was KRAS wild-type based on tissue analysis and he was treated sequentially with cetuximab-based chemotherapy, chemotherapy alone and panitumumab-based chemotherapy. We performed sequential analysis of ctDNA using droplet digital PCR (ddPCR) and a commercial assay designed for the detection of frequent KRAS mutations during his clinical follow-up. Prior to the first cetuximab-based chemotherapy ctDNA analysis demonstrated an absence of KRAS mutations. Emergence of KRAS mutations in ctDNA occurred similar to 3 months after treatment initiation and preceded clinical and imaging progression in about 2 months. Fractional abundance of KRAS mutation rapidly increased to 70.7% immediately before a chemotherapy alone regimen was initiated. Interestingly, KRAS mutation abundance decreased significantly during the first two months of chemotherapy, reaching a fractional abundance of 3.0%, despite minimal clinical benefit with this therapy. Re-challenge with a different anti-EGFR antibody was attempted as later line, but high levels of KRAS mutations in ctDNA before therapy correlated with an absence of clinical benefit. Conclusions: The monitoring of resistance mutations in KRAS using ctDNA during the treatment of KRAS wild-type advanced colorectal cancers can detect the emergence of resistant clones prior to clinical progression. Dynamics of resistant clones may alter during periods on and off anti-EGFR antibodies, detecting window of opportunities for a re-challenge with these therapies.
conferenceObject A multicenter international study of sorafenib treatment in patients with hepatocellular carcinoma and chronic kidney disease undergoing hemodialysis(2019) DIAZ-GONZALEZ, Alvaro; SANDUZZI-ZAMPARELLI, Marco; FONSECA, Leonardo Gomes da; COSTANZO, Giovan Giuseppe Di; ALVES, Rogerio; IAVARONE, Massimo; LEAL, Cassia Regina G.; SACCO, Rodolfo; MATILLA, Ana M.; GUERRA, Manuel Hernandez; SOTERAS, Gabriel Alejandro Aballay; MARCUS, Worns; PINTER, Matthias; VARELA, Maria; LADEKARL, Morten; CHAGAS, Aline Lopes; MINGUEZ, Beatriz; RUIZ-TAPIADOR, Juan Ignacio Arenas; GRANITO, Alessandro; SANCHEZ, Yolanda; ROJAS, Angela; LOPE, Carlos Rodriguez De; ALVARES-DA-SILVA, Mario Reis; PASCUAL, Sonia; RIMASSA, Lorenza; LLEDO, Jose Luis; HUERTAS, Carlos; SANGRO, Bruno; GIANNINI, Edoardo Giovanni; DELGADO, Manuel; GOMEZ, Mercedes Vergara; PERELLO, Christie; LUE, Alberto; SALA, Margarita; MOYA, Adolfo Gallego; COLL, Susana; ALSINA, Tania Hernaez; PINERO, Federico; PEREIRA, Gustavo; FRANCA, Alex Vianey Callado; MARIN, Juan; ANDERS, Maria Margarita; MELLO, Vivianne; LOZANO, Maria Del Mar; NAULT, Jean Charles; MENENDEZ, Jose Maria; JUAREZ, Ignacio Garcia; BRUIX, Jordi; REIG, Maria