Milena Perez Mak

Palliative chemotherapy outcomes in patients with ECOG-PS higher than 1

Purpose Although patients with incurable disease and Eastern Cooperative Oncology Group performance status (ECOG-PS ≥ 2) are underrepresented in clinical trials, they are frequently offered palliative chemotherapy (pCT) in daily clinical practice in order to improve symptoms and quality of life. In this case-control retrospective analysis, our goal was to identify factors associated with poorer survival and lack of benefit of pCT in this population. Patients and methods We evaluated 2,514 patients who died between August 2011 and July 2012 in an academic cancer care institution and its hospice. A total of 301 patients with solid tumours and ECOG-PS ≥ 2 at prescription of pCT were selected for this case-control retrospective analysis. Cases were defined as patients who survived less than 90 days after the first cycle of first line pCT, and controls were those who had a longer survival. Results 142 cases and 159 controls were included. Cases were more likely to experience grade ≥ 3 toxicity (43% versus 28%; p = 0.005), die of toxicity (16% versus 6%; p < 0.001) and not be offered best supportive care (BSC) only (47% versus 71%; p < 0.001). Median overall survival was 204 among controls and 34 days in cases (hazard ratio = 0.177; 95%, confidence interval = 0.015–0.033, p < 0.001). Logistic regression analysis identified ECOG-PS > 2 (odds ratio (OR) = 2.3, p = 0.044) and serum creatinine (sCr) > 1 mg/dL (OR = 11.2, p < 0.001) as independent predictors of 90-day mortality. Conclusions The independent predictors of short survival (less than 3 months) after initiation of pCT in this population were ECOG-PS > 2 and elevated sCr. Therefore, patient selection is crucial, as pCT may be deleterious in ECOG-PS ≥ 2 pts.

Malignancy-Related Hypercalcemia in Advanced Solid Tumors: Survival Outcomes

Purpose Malignancy-related hypercalcemia (MRH) is associated with a dismal prognosis. The widespread use of bisphosphonates (BPs), availability of more effective drugs in cancer treatment, and improvement in supportive care might have attenuated its impact. Patients and Methods To assess overall survival (OS) of patients with MRH in a contemporary setting, we conducted a retrospective analysis of 306 patients with solid cancer hospitalized for symptomatic hypercalcemia. A multivariable Cox proportional hazards regression model was performed to evaluate possible prognostic factors associated with MRH. Results All patients had serum ionized calcium > 5.5 mg/dL or total Ca > 10.5 mg/dL. Median age was 57 years, and the majority had squamous cell carcinoma (62%) and Eastern Cooperative Oncology Group performance status > 1 (96%). Head and neck was the most frequent primary site (28%). Forty-five percent had no previous chemotherapy (CT), and subsequent CT was administered to 32%. Eighty-three percent received BP with no survival gain. Median OS was 40 (95% CI, 33 to 47) days. Patients with a performance status > 2, altered mental status, C-reactive protein > 30 mg/L, albumin < 2.5 g/dL, or body mass index < 18 kg/m2 had significantly poorer survival in a univariable analysis, and longer OS was related to treatment-naive patients, subsequent CT, and breast primary site. In the multivariable analysis, subsequent CT led to a median OS improvement of 144 versus 25 days (hazard ratio, 0.24; 95% CI, 0.14 to 0.40; P < .001). Conclusion In a contemporary setting, MRH remains a marker of poor prognosis. Patients treated with CT had better survival, which suggests that appropriate treatment of selected patients might alter the course of this syndrome.

MicroRNA expression in saliva in locally advanced oral and oropharyngeal squamous cell carcinoma

Background: Oral cavity/oropharynx squamous cell carcinoma (OSCC) is a common cancer in the developing world. Most patients (pts) present with inoperable locally advanced disease, which yields low cure and disease-free survival rates. Concurrent high-dose cisplatin chemoradiation (CRT) is the standard treatment for such pts in our institution. Although this regimen provides high response rates, marked toxicity is observed and relapses are frequent. In light of that, candidate markers for appropriate patient selection are needed to improve OSCC outcomes. There is evidence that miRNAs (miRs) play a key role in resistance to chemotherapy and radiotherapy. However, the role of miRNAs in chemoresistance in OSCC remains poorly elucidated. In the present study we analyzed the expression of miRNAs in the saliva of unresectable locally advanced OSCC pts either before or after CRT. Our goal was to identify miRNAs related to long-term response to CRT with concurrent cisplatin, and also to verify whether circulating miRs are contained within exosomes or circulating free in the saliva. Patients/methods: A total of 33 OSCC pts were included in three groups: (1) treatment-naive (N = 16), (2) after treatment failure (disease progression after CRT - N = 7), and (3) disease-free pts for at least 2 years (N = 10). We also studied saliva of eight healthy volunteers. Following a review of studies in the literature that microRNAs associated with chemoradiotherapy in squamous cell carcinoma, the miR-21-5p, miR-15a-5p, miR-200b-3p and miR-296-5p were chosen to be analyzed by qRT-PCR, using LNA™ primers set (Exiqon). The spike-in Sp6 miRNA was added to saliva samples to control of variation in RNA recovery and the miR-16-5p was for normalization of sample-to-sample RNA variation. The Mann-Whitney U and Kruskal Wallis tests were used to compare the sample groups. Results: The miR-296-5p expression was below the detection level in almost all saliva samples and was excluded from further analyses. As compared to the healthy volunteers group, both samples from pts in groups 1 and 3 showed an increased expression of miR-21-5p, miR-15a-5p, miR-200b-3p. Significant reduction of the expression of miR-21-5p and miR-200b-3p (p = 0.01 and 0.08) was observed in group 2 patients, as compared to group 1. Furthermore, the expression of these two miRNAs was higher in group 3 pts compared to group 2 (p = 0.01). Transmission electron microscopic preliminary data of isolated microvesicles exhibited round vesicles measuring 30-60 nm in diameter, compatible with the size of exosomes. Conclusion: Changes in the abundance of circulating miR-21-5p and miR-200b-3p, previously reported as crucial modulators of stemness and Head and Neck SCC progression, may be associated with long-term response to cisplatin-based CRT. Supported by Fundacao de Amparo a Pesquisa (FAPESP 2013/25397-0). Citation Format: Fabyane Oliveira Teixeira Garcia, Vivian Marinelli Constantino, Milena Perez Mak, Gilberto de Castro-Jr, Fatima S. Pasini. MicroRNA expression in saliva in locally advanced oral and oropharyngeal squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 587. doi:10.1158/1538-7445.AM2015-587

Advanced small-cell ovarian carcinoma, hypercalcemic type: a challenging therapeutic entity

Small-cell ovarian carcinoma (SCOC) is a rare and aggressive neoplasia, predominantly affecting young women who are frequently first diagnosed with advanced stage disease. Platinum-based chemotherapy (ChT) can provide high response rates and rapidly ameliorate symptoms in this scenario. However, progression after chemotherapy usually occurs quickly, leading to high mortality rates. In addition, ChT complications, such as tumor lysis syndrome (TLS) can also occur, jeopardizing the patient’s outcome. We present a case of metastatic SCOC in a 47-year-old patient who achieved tumor response after platinum-based chemotherapy and developed TLS, from which she recovered with supportive treatment. After the second ChT cycle, she developed febrile neutropenia and died 8 weeks after the diagnosis of SCOC. Although SCOC is a chemo-sensitive tumor, short-lived responses and frequent chemotherapy complications lead to a dismal prognosis.

Outcomes of sunitinib therapy in patients (pts) with metastatic renal cell carcinoma (mRCC) with poor risk features.

476 Background: Temsirolimus is perceived as the standard of care in pts with mRCC with poor risk features. However, sunitinib (Su) is commonly used in this setting. In this study, we assessed the use of Su in an unselected mRCC population. METHODS Retrospective analysis of 51 pts with mRCC and ≥ 3 poor prognosis features, as determined in the Advanced Renal Cell Carcinoma (ARCC) trial, treated with Su between January 2006 and July 2012. Primary outcome was overall survival (OS). Clinical and laboratory parameters were evaluated, as well as Su-related adverse events (AE). Median time to treatment failure (mTTF) and OS were estimated by Kaplan-Meier methods. On exploratory grounds, univariate, and multivariate analysis using Cox regression model was performed to determine possible prognostic variables. RESULTS Median age was 60 years (26-89). Most had clear cell histology (98%), 19% prior systemic treatment, and 51% prior nephrectomy. 64%, 15%, and 4% had 4, 5, and 6 adverse prognosis factors respectively. 88% had diagnosis to treatment intervals < 1 year and 45% had KPS scores of < 80. A median of 2 cycles (0-12) were administered. 63% received standard regimen of Su (50 mg/d 4 wk on/2 wk off). Reasons for discontinuation were disease progression (63%) and adverse events (21%). Most grade ≥ 3 AE were fatigue (14%), neutropenia (8%), and stomatitis (8%). 17%, 25%, and 14% developed hypothyroidism, hand-foot syndrome (HFS), and hypertension, respectively. Two therapy-related deaths were observed (one febrile neutropenia and one intracranial hemorrhage). Estimated mTTF and mOS of this cohort were 2.4 and 6.6 months, respectively. Multivariate analysis revealed that in a model adjusted for type of Su regimen, KPS, presence of brain metastasis, and occurrence of HFS, only Su-associated hypothyroidism was significantly associated with survival (respectively, odds ratio [OR] = 0.23; 95% CI = 0.07-0.68). CONCLUSIONS Pts with mRCC with poor risk features treated with Su have an OS, TTF and rates of therapy discontinuation due to AE comparable to clinical trial subsets of similar pts. Our data suggest that the development of hypothyroidism in this setting might be useful as a predictor of OS, and this finding should be further investigated.