RENATA RODRIGUES DA CUNHA COLOMBO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
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conferenceObject Expression of ERCC1 protein (excision repair cross complementing group 1) in patients with invasive carcinoma of the uterine cervix (CC) undergoing definitive chemoradiation (CR)(2012) CAIRES, Inacelli Queiroz de Souza; CAIRES-LIMA, Rafael; COLOMBO, Renata; RAMOS, Clarissa C. A.; MACHADO, Karime Kalil; SIQUEIRA, Sheila Aparecida Coelho; CARVALHO, Heloisa de Andrade; FUKUSHIMA, Julia Tizue; ADRA, Thais Rodrigues; HOFF, Paulo M.; ESTEVEZ-DIZ, Maria Del PilarBackground: CC is the leading cause of cancer death among women in developing countries. ERCC1 protein participates in DNA repair through the nucleotide excision repair pathway, involved in resistance to platinum-based chemotherapy. Its value as a predictive marker of tumor response to treatment, progression or death is still unknown. We evaluated ERCC1 protein expression and clinical variables as a predictive marker of progression-free survival (PFS) and overall survival (OS) in patients (pts) with CC submitted to CR. Methods: Retrospective data analysis of pts with histological diagnosis of CC, treated with CR between 2004-2009. Platinum-based chemotherapy was administered weekly (x6) concurrent to external beam radiotherapy (EBRT) to the pelvis (39.6 – 45.0 Gy), parametrial boost (14.0 – 20.0 Gy) when indicated and high-dose rate brachytherapy (HDR) (28.0 – 30.0 Gy). ERCC1 expression was assessed by immunohistochemistry (IHC). Results: We analyzed 75 pts, median age was 55 years (range 24-76), the performance status (PS) was 0 or 1 at baseline in 50 pts (66%) and 63 had squamous histology (84%). Thirty-two were stage IIB (43%) and 19 were IIIB (25%). Sixty-five patients received cisplatin 40mg/m2/w (87%) and 9, carboplatin AUC2/w (12%), median of 6 cycles (range 2-9). Median RT and HDR doses were 59.4 Gy (range 40.4 to 60.3) and 28.0 Gy (range 14.0 – 37.5), respectively. Thirty-two pts were available by ERCC1 IHC and all expressed the marker. Median PFS and OS were 35.5 (95% CI – 13.8 - 57.6) and 81 (95% CI- 21.2 - 140.8) months, respectively. In multivariate analysis, receiving < 6 chemotherapy cycles and baseline Hb <10.0 were correlated with disease progression and death, HR 0.302; p 0.011 (95% CI- 0.012-0.762) and HR 0.6; p 0.00 (95% CI- 0.474 – 0.760), respectively. PS at baseline did not correlate with PFS or OS, HR 0.985; p 0.614 (95% CI 0.930 – 1.044). Conclusions: In this population, since all pts expressed the protein, ERCC1 expression couldn't discriminate patients who most benefit from CR. Interestingly, a minimum of 6 chemotherapy cycles and a baseline Hb ≥ 10.0 seem to have a prognostic value.- Induction Chemotherapy for Locally Advanced Esophageal Cancer(2020) HARADA, Guilherme; BONADIO, Renata Rodrigues da Cunha Colombo; ARAUJO, Frederico Cantarino Cordeiro de; VICTOR, Carolina Ribeiro; SALLUM, Rubens Antonio Aissar; RIBEIRO JUNIOR, Ulysses; CECCONELLO, Ivan; TAKEDA, Flavio Roberto; CASTRIA, Tiago Biachi deBackground Concurrent chemoradiotherapy followed by surgery is the standard treatment for locally advanced esophageal cancer (EC), and the role of induction chemotherapy (IC) remains unclear. We aimed to study if the addition of IC to standard treatment increases the rate of pathologic complete response (pCR). Methods We assembled a retrospective analysis of patients (pts) diagnosed with locally advanced EC and treated with preoperative chemoradiotherapy followed by esophagectomy (CRT+S), preceded or not by IC, between 2009 and 2017. Patients' characteristics, tumor variables, and treatment outcomes were evaluated. The Kaplan-Meier method was used to estimate overall survival and the Cox proportional hazard model to evaluate prognostic factors. Results One hundred and three patients were studied, with a median age of 62 years (range 37-84). Seventy-five patients (73%) were male, 67 (65%) had squamous cell carcinoma, and 31 (30%) had adenocarcinoma. Forty-three patients (41.7%) received IC followed by CRT+S (IC+CRT+S). The most frequent IC consisted of paclitaxel and platinum chemotherapy (90%), and the median number of cycles was 2. All patients received CRT+S. Concurrent chemotherapy was a combination of paclitaxel and platinum in 94 patients (91%). There was no statistically significant difference in pCR between the IC group and the standard CRT+S group. The pCR was 41.9% and 46.7% in the IC+CRT+S and CRT+S groups (p = 0.628), respectively. In the multivariate analysis, pCR was an independent prognostic factor for time to treatment failure (TTF) (HR 0.35, p = 0.021), but not for overall survival (OS) (p = 0.863). The factor that significantly affected OS in the multivariate analysis was positive lymph node (HR 5.9, 95%, p = 0.026). Conclusions Our data suggest that the addition of IC to standard CRT + S does not increase the pCR rate in locally advanced EC. No difference in OS was observed between pts. that received or not IC. Regardless of the treatment received, pts. achieving a pCR presented improved TTF.
- Everolimus plus anastrozole for female adnexal tumor of probable Wolffian origin (FATWO) with STK11 mutation(2021) ESTEVEZ-DIZ, Maria De Pilar; BONADIO, Renata Colombo; CARVALHO, Filomena Marino; CARVALHO, Jesus PaulaFemale adnexal tumor of probable Wolffian origin (FATWO) are a rare type of cancer that originates from Wolffian duct remnants. Due to its rarity, no standard systemic treatment is established for cases of recurrent or metastatic disease. Previous literature reported the use of platinum-based chemotherapy and c-Kit tyrosine kinase inhibitors for FATWO cases with c-Kit positive expression. Currently, however, the broader availability of next-generation sequencing (NGS) tests allows a better molecular characterization of rare cancer such as FATWO and a possibility for the use of personalized, targeted therapy. Previous case series that performed NGS for FATWO patients described the presence of STK11 mutations in a considerable number of cases, representing a potential target in this population. To our knowledge, we describe here the first case report of a patient with FATWO and STK11 mutation exhibiting a considerable and durable response after treatment with an mTOR inhibitor plus endocrine therapy.
- Quality of life of locally advanced cervical cancer patients after neoadjuvant chemotherapy followed by chemoradiation versus chemoradiation alone (CIRCE trial): a randomized phase II trial(2020) ARRUDA, Fernanda Nunes de; COSTA, Samantha da; BONADIO, Renata; DORNELLAS, Abraao; PEREIRA, Daniela; BOCK, Geertruida H. de; DIZ, Maria Del Pilar EstevezObjective The CIRCE trial (NCT 01973101) investigated the efficacy, safety, and quality of life of the addition of neoadjuvant chemotherapy with cisplatin and gemcitabine to standard chemoradiation for locally advanced cervical cancer (stages IIB-IVA). The impact of both treatment arms on quality of life is reported in the present study. Methods Patients completed the European Organization of Research and Treatment of Cancer questionnaire QLQ-C30 and CX24 before treatment and at 3, 6, 9, and 12 months after treatment. Linear mixed models were fitted to analyze differences in quality of life over time and between groups. Differences in mean quality of life scales >10 points and p<0.05 were considered clinically relevant and statistically significant, respectively. Inclusion criteria were: (1) histological diagnosis of locally advanced invasive carcinoma of the uterine cervix, International Federation of Gynecology and Obstetrics stages IIB-IVA; (2) signed informed consent to participate in the CIRCE trial; and (3) answered at least one quality of life questionnaire. Excluded were patients who did not complete any quality of life questionnaire. Relevant exclusion criteria for the CIRCE trial included Eastern Cooperative Oncology Group performance status >2 and peripheral neuropathy >2. Mann-Whitney U tests were performed to assess differences between groups in quality of life at baseline. To evaluate differences between treatment arms, linear mixed models were fitted using the transformed quality of life scores as a dependent variable and time of follow-up and study arm as factors. Results A total of 107 patients were enrolled (n=55 neoadjuvant chemotherapy arm; n=52 chemoradiation arm). Quality of life compliance rates were higher for the chemoradiation group at every assessment time (ranging from 75-86.5% in the chemoradiation arm vs 55-81.8% in the neoadjuvant chemotherapy arm). For quality of life results at baseline, no statistically significant difference between the groups was seen. For both groups, most scales showed improvements over time, except for worsening of the summary score, sexual enjoyment, peripheral neuropathy, and menopausal symptoms. For chemoradiation, body image was lower (p<0.001) and patients presented more lymphedema (p<0.001) and sexual worry (p<0.001) at 12 months compared with baseline. Comparing study arms, neoadjuvant chemotherapy showed significantly lower scores in the menopausal symptoms scale (p=0.03) and higher scores for sexual/vaginal functioning (p=0.01). At 12 months, clinical differences were seen only for body image and menopausal symptoms scale, with neoadjuvant chemotherapy presenting better body image scores and a lower burden of menopausal symptoms. Conclusion After treatment for locally advanced cervical cancer, patients improved in most quality of life aspects. However, worsening was observed in sexual enjoyment, peripheral neuropathy, and menopausal symptoms. To improve patients' quality of life, efforts should be made to prevent and treat these long term effects of locally advanced cervical cancer treatment.
- Effectiveness and toxicity of adjuvant chemotherapy in patients with non-small cell lung cancer(2021) HARADA, Guilherme; NEFFA, Maria Fernanda Batistuzzo Vicentini; BONADIO, Renata Colombo; MENDOZA, Elizabeth Zambrano; CAPARICA, Rafael; LAURICELLA, Leticia Leone; TAKAGAKI, Teresa Yae; ROITBERG, Felipe Santa Rosa; TERRA, Ricardo Mingarini; JR, Gilberto De CastroObjective: Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods: This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results: The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin- vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin- vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions: These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.
- Predictors of in-hospital mortality after unplanned admissions among adults with cancer aged 80 years and older(2022) NETO, F. Lazar; HIDALGO FILHO, C. M. T.; ROCHA, J. W. D.; SOBOTTKA, V. P.; STANGLER, L. T. B.; BENFATTI, G.; GUEDES, H.; CLARO, M. Z.; BONADIO, R. C.; DIZ, M. D. P. E.; HOFF, P. M.
conferenceObject Prospective study of biomarkers in squamous cell carcinoma of the anal canal (SCCAC) and their influence on treatment outcomes: Five-year long-term results.(2020) MONIZ, Camila Motta Venchiarutti; RIECHELMANN, Rachel Pimenta; BRAGHIROLI, Maria Ignez; RIBEIRO, Suilane Coelho; RIVELLI, Thomas Giollo; BARIANI, Giovanni M.; CHEN, Andre Tsin Chih; NAHAS, Caio; BONADIO, Renata Colombo; ORTEGA, Cinthia; FRANCO, Rejane; MEIRELES, Sibele; PEREIRA, Allan Andresson Lima; SABBAGA, Jorge; COUDRY, Renata A.; HOFF, Paulo Marcelo- A matched case-control study of the prognosis of early breast cancer in patients with Li-Fraumeni syndrome (BREAST TP53)(2023) PETRY, Vanessa; BONADIO, Renata Colombo; TESTA, Laura; COHN, Daniela JBH.; CAGNACCI, Allyne; CAMPOS, Roberta G.; FRAGOSO, Maria Candida Bv; ESTEVEZ-DIZ, Maria del PilarIntroduction: Breast cancer (BC) is the most common type of cancer in premenopausal women with germline TP53 pathogenic variants (mTP53) (Li Fraumeni syndrome -LFS). However, little is known about the BC prognosis in these patients. This study analyzed the BC-related oncologic outcomes of patients with LFS.Methods: We evaluated a cohort of LFS patients with BC in comparison with a control cohort of BC patients with no pathogenic variant in a hereditary cancer panel. The primary endpoint was recurrence-free survival (RFS). Due to the risk of second malignancies in LFS, only locoregional and distant recurrences were considered events for RFS. Secondary endpoints included rates of contralateral BC, overall survival (OS), and breast cancer-specific survival (BCSS).Results: Forty-one patients were evaluated in the mTP53 group and 82 in the control group. Median age at BC diagnosis was 40 and 41 years, respectively. The mTP53 group received less adjuvant radiotherapy than the control group (63.4% vs 93.9%, P < 0.001). Other relevant baseline characteristics and treatment received were similar between groups. 5y-RFS rates were 79.4% in the mTP53 versus 93.6% in the control group (HR 2.43, 95% CI 0.74-8.01, P = 0.143); and were not impacted by the use of adjuvant radiotherapy. 5y-BCSS rates were 92.2% and 98.6%, respectively (HR 1.87, IC95% 0.25-13.48, P = 0.534).Conclusions: Our results showed no statistically significant difference in BC-related RFS and BCSS between pa-tients with mTP53 and a control group with no pathogenic variant. Larger multicentric studies are warranted to confirm these results.
- Neoadjuvant Chemotherapy With Cisplatin and Gemcitabine Followed by Chemoradiation Versus Chemoradiation for Locally Advanced Cervical Cancer: A Randomized Phase II Trial(2019) COSTA, Samantha Cabral S. da; BONADIO, Renata Colombo; GABRIELLI, Flavia Carolina G.; ARANHA, Andrea S.; GENTA, Maria Luiza N. Dias; MIRANDA, Vanessa C.; FREITAS, Daniela de; ABDO FILHO, Elias; FERREIRA, Patricia A. O.; MACHADO, Karime K.; SCARANTI, Mariana; CARVALHO, Heloisa de A.; ESTEVEZ-DIZ, Maria Del PilarPURPOSE Although chemoradiation therapy (CRT) with cisplatin remains the standard treatment of patients with locally advanced cervical cancer (LACC), 40% of patients present with disease recurrence. Additional treatment strategies are required to improve outcomes. We conducted a trial to evaluate the efficacy and safety of neoadjuvant chemotherapy (NAC) with cisplatin and gemcitabine followed by CRT. METHODS In this phase II trial, patients with LACC (International Federation of Gynecology and Obstetrics stage IIB to IVA or with positive lymph nodes) were randomly assigned to three cycles of NAC with cisplatin and gemcitabine followed by standard CRT with weekly cisplatin plus pelvic radiotherapy or to standard CRT alone. The primary end point was 3-year progression-free survival (PFS). Secondary end points were response rate, 3-year locoregional control, 3-year overall survival (OS), safety, and quality of life. RESULTS From 107 patients enrolled in the trial, 55 were randomly assigned to the NAC arm and 52 to the CRT-alone arm. The majority of patients had squamous cell carcinoma (87.8%). After a median follow-up of 31.7 months, NAC was associated with an inferior PFS, with 3-year PFS rates of 40.9% v 60.4% in the CRT arm (hazard ratio, 1.84; 95% CI, 1.04 to 3.26; P = .033). NAC also was associated with a lower OS (3-year OS rate, 60.7% v 86.8%; hazard ratio, 2.79; 95% CI, 1.29 to 6.01; P = .006). After treatment completion, complete response rates were 56.3% in the NAC arm and 80.3% in the CRT arm (P = .008). Toxicities were similar in both arms, with the exception of hypomagnesemia and neuropathy being more common with NAC. CONCLUSION This study shows that the addition of NAC consisting of cisplatin and gemcitabine to standard CRT is not superior and is possibly inferior to CRT alone for the treatment of LACC. (C) 2019 by American Society of Clinical Oncology
- Real-world evidence on first-line treatment for metastatic renal cell carcinoma with non-clear cell and sarcomatoid histologies: are sunitinib and pazopanib interchangeable?(2019) BONADIO, Renata Colombo; VELHO, Pedro Isaacsson; MARTA, Guilherme Nader; NARDA, Mirella; SOUZA, Manoel Carlos La; MUNIZ, David Q. B.; BEZERRA, Regis O. F.; BISPO, Raisa K. A.; FARAJ, Sheila F.; BASTOS, Diogo A.; DZIK, CarlosIntroduction: Non-clear cell renal cell carcinoma (nccRCC) and sarcomatoid renal cell carcinoma (sRCC) are underrepresented in clinical trials. Treatment approaches are frequently extrapolated from data of clear cell renal cell carcinoma, in which pazopanib is non-inferior to sunitinib. We aim to compare the effectiveness of first-line sunitinib and pazopanib for nccRCC and sRCC. Methods: We evaluated a retrospective cohort of patients with metastatic nccRCC and sRCC treated with first-line sunitinib or pazopanib at an academic cancer centre. Overall survival (OS), progression-free survival (PFS) and response rate were measured. Kaplan-Meier and log-rank analyses were used for time-to-event data. Cox regression was used for prognostic factors. Results: Fifty-three patients were included; 16 (30.1%) treated with sunitinib and 37 (69.9%) with pazopanib. Forty-six (86.8%) patients had nccRCC and 7 (13.2%) had sRCC. The majority had intermediate or poor International Metastatic Renal-Cell Carcinoma Database Consortium risk (93%). Median PFS was 6.6 months with sunitinib and 4.9 months with pazopanib (HR 1.75; P = 0.078). Treatment with pazopanib was associated with inferior OS in comparison with sunitinib (median OS: 30.4 months versus 8.7 months; HR 2.71, 95% CI 1.31-5.58, P = 0.007). These results were confirmed in subgroup analysis of patients with papillary, chromophobe and MiT family translocation histologies (median OS: 38.7 months versus 14.7 months; HR 3.16, 95% CI 1.20-8.29, P = 0.019). Unclassified and sarcomatoid histologies had inferior OS (median: 6.9 and 1.1 months, respectively) regardless of the treatment used. Conclusion: In this patient cohort, pazopanib was associated with inferior OS in comparison with sunitinib for metastatic nccRCC. Larger trials are ideally warranted to confirm these results.