Relapse after chemotherapy treatment depends on the cancer initiating cells (CICs). PEDF (Pigmented Epithelium Derived Factor) is an anti-angiogenic, neurotrophic and self-renewal regulator molecule, also involved in CICs biology. Acute and chronic exposition of colon cancer cell lines to CT/CTE PEDF-derived peptides decreased drug-resistance to conventional colorectal cancer treatments, such as oxaliplatin or irinotecan. We confirmed a reduction in the irinotecan and oxaliplatin IC50 doses for all tested tumour cell lines. After xenograft transplantation, CT/CTE treatments also produced a reduction in resistance to conventional chemotherapy treatments as in culture-assays. Metastatic capacity of these treated cell lines was also depleted. The PEDF signaling pathway could be a future therapeutic tool for use as an adjuvant therapy that decreases IC50 dosis, adverse effects and treatment costs. This pathway could also be involved in an increase of the time relapse in patients, decreased tumourigenicity, and decreased capacity to produce metastasis.
e20565 Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer. Prognosis is generally poor, with a median overall survival (mOS) of approximately 12 months. MPM appears to be directly linked to immunosuppressive mechanisms, leading to use of checkpoint inhibitors for patients with this disease. Methods: We performed a retrospective chart review of patients with MPM at our institution between January 2015 to December 2020. All patients were over 18 years at the time of diagnosis of mesothelioma, a total of 8 patients were retrieved from the pathology database of The American British Cowdray Medical Center. The clinical-pathologic features collected were sex, age, performance status, risk factors, pTNM stage (AJCC 8th edition), histology type, sintomatology of onset, metastases sites and treatment. Clinical response rate and other outcomes were assessed. Descriptive statistics were used to describe a patient's demographic and disease characteristics. Results: 8 patients, aged 49 to 71 years (median of 65) at diagnosis of MPM were treated in our center. Both sex presented 4 patients in total. An identifiable risk factor was recorded in 4 patients (2 with asbesto exposure and 2 with heavy smoking). 7 patients (87.5%) had PS 0 or 1, the remaining has PS 2. The clinical stage at diagnosis was unresectable in 7 patients. 3 patients were assessed with PD-L1 expression (SP263 or 22C3), only one with expression of 20%. All patients received at least one scheme of chemotherapy prior to receiving immunotherapy, 25% received bevacizumab/platinum/anti-folate agents. Checkpoint inhibitors were introduced as a second line in 20% and in 80% has a third or more lines. Pembrolizumab was used in 20% and Nivolumab in 80%. The tumor responses with immunotherapy were as follows: partial response 12.5%, stable disease 75% and progressive disease 12.5%. Median progression-free survival of the first line treatment was 18.9 months (4.6-33.6 months), and for the line with checkpoint inhibitors was 11.2 weeks (7-21.2). In the full cohort, mOS was 37.0 months (95% CI:14.5-39.6). According to histology, the mOS for epithelioid-type was 36.6 months and for biphasic-type was 14.6 months (p = 0.42). mOS was 37.0 months for the group with immunotherapy and 15.0 months for those with standard chemotherapy (p = 0.14). The most frequently reported immune mediated adverse events were hypothyroidism and colitis (each one with one patient). Conclusions: In this real-world analysis, mOS was superior to those obtained in the MAPS2 trial (mOS 11.9 months), despite the fact that 80% of the population that received immunotherapy was in third or more lines. Limitations include limited numbers of patients, retrospective review, single institution, and inclusión of many heavily pretreated patients. Also molecular and immunohistochemical results such as PD-L1 status were only available on a limited number of patients.
e22517 Background: there are few reported series n women with breast cancer (BC) and COVID-19, a better prognosis has been observed, with a lower rate of hospitalization and mortality than other neoplasms. Methods: We conducted a restrospective, non-experimental, observational, single center, study with a sample of 69 patients with BC who had presented COVID-19, in the period between March 2020 to August 2021. Clinicopathological characteristics of patients with BC were compared between severe and non-severe covid 19 groups, as well as hospitalized and non-hospitalized patients. An analysis of possible risk factors associated with severe disease and hospitalization was performed. Results: 69 cases were reported, median age 52y, mean BMI 25.2, ECOG 0-1: 97%. Smoking history in 24%, diabetes and hypertension were the most frequent comorbidities. The most frequent histology was ductal carcinoma in 80.6%, 73.8% showed ER + and 69.3% PR +, HER2 was overexpressed in 9.2%. The early stages predominated, I 22 (31.3%), II 25 (37.3%), III in 12 (17.9%) and IV in 6 (9%). The most frequents symptoms of COVID-19 were fatigue 70.1%, fever 65.7%, cough 59.7%, headache 56.7%, hyposmia 47.8%, dysgeusia 38.8%. A total of 53 (76.8%) mild cases, 14 (20.3) severe cases and 2 (2.9%) critical cases were registered. The 89.9% (62 patients) were treated as an outpatient basis, while 7 (10.1%) required hospitalization. Active treatment (< 45 days) at the time of COVID-19 was hormonal therapy 36 (50.7%), chemotherapy 11 (16.4%), anti-HER2 in 3 (4.5%), immunotherapy in 1.5%, targeted treatment in 4 (6.0%), surgery in 7 (10.4%) and radiotherapy in 1 (1.5%) patient. When comparing the severe and non-severe groups, as well as hospitalized versus non-hospitalized, we observed no difference between the clinicopathological characteristics. Then, we serch for possible risk factors, in wich, surgery in a period of less than 3 months increases the risk of severity OR 1,297 (95% CI 1,112-1,514), the risk of hospitalization increased in the triple negative subgroup OR 1,143 (95% CI, 1,035- 1,262), surgery less than 3 months OR 1,116 (1,014-1,229) and chemotherapy less than 45 days OR 1,217 (95% CI, 1,024-1,447). Conclusions: In patients with BC, the prevalence of severe or critical COVID-19 was 23% and the hospitalizacion rate 10%. No patient died from this infection. The clinical and pathological characteristics of BC do not appear to increase the risk of severe COVID-19 or the rate of hospitalization. Surgery performed in a period of less than 3 months is marginally associated with an increased risk of severe disease. Chemotherapy, targeted therapy, and immunotherapy do not modify the risk of severe disease; however, higher Ki 67, triple negative subgroup, surgery and chemotherapy showed a slight increase in risk of hospitalization.
e12630 Background: The current standard of treatment for locally advanced and early HER2+ breast cancer is the use of neoadjuvant chemotherapy (NAC) in combination with trastuzumab and pertuzumab. Mexican reports about its efficacy and predictive factors leading to pathological complete response (pCR) are scarce and few statistics are known. Methods: We performed a retrospective review of medical records of locally advanced and early HER2+ breast cancer patients who were treated with NAC in association with pertuzumab and trastuzumab. pCR was defined as the absence of residual invasive cancer cells in the breast and lymph nodes (ypT0/ypN0). Other histopathological features included Tumor type, estrogen, and progesterone receptor expression, HER2 status and Ki67. Clinical data included age, body mass index and number of metastatic nodes. Results: Thirty-five patients with early or locally advanced HER2+ breast cancer diagnosed and treated in a Comprehensive Cancer Center between January 2014 to June 2020 were included. The median age in the population was 47 years (range 28-79) with 20 patients under 50 years (57% of the total population). 40% of the patients were classified as overweight or obese at the time of diagnosis. The predominant histology was infiltrating ductal carcinoma (91%). The most frequent clinical stages were IIA, (34.2%) IIB (31.4%) and IIIA (22.8%). The population included patients with N0 (21.7%), N1 (56.5%), N2 (13%) and N3 (8.7%). Most tumors were larger than 2 centimeters at the time of diagnosis. T1 (17.4%), T2 (60.9%), T3 (17.4%) and T4 (4.3%). Most of the patients (77%) had a high proliferation index (Ki67 > 20). A total of 12 patients (34.3%) were hormone receptor (HR) negative and the rest (65.7%) were categorized as Triple Positive. The chemotherapy schemes used for NAC treatment were AC/THP (57.5%), THP (22.8%), TCHP (17.1%) and FEC/THP (2.7%) pCR was achieved in 60% of the patients. Patients with HR (-) achieved a pCR in 83% of the cases (10/12 patients) against 47.8% (11/23 patients) of the triple positive population. The Odds ratio (OR) for residual disease was 6.6 (95%CI 1.17-37.02) in the HR+ population. HR-/HER2+ tumors (p = 0.49) were independent predictors of pCR at multivariate logistic regression. No other variables including Ki67, BMI, age, tumor size, type of chemotherapy administered, and lymph node status were statistically significant. Conclusions: In this Mexican population there is a significant difference between the percentage of patients who achieve pCR in relation to the status of hormone receptors, favoring those patients with hormone receptor negative tumors. Nevertheless, most of the population achieves this benefit regardless of their hormone status, as HER2+ tumors showed sensitivity to chemotherapy and to the humanized anti-HER2 therapies. No other clinical or pathological variables were associated with pCR.
e21593 Background: Non-Small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for most of all cancer-related morbidity and deaths in the World. Recent Evidence shows that inflammatory response is associated with a poor prognostic in several cancers. Evaluating these markers is of great importance to classify patients of solid tumors including NSCLC. Inflammatory markers like, Glasgow Prognostic Score (GPS), Lung Immune prognostic index (LIPI) and C-Reactive Protein (CRP) have been associated with poor prognosis in patients treated with immune checkpoint inhibitors. Neutrophil to Lymphocyte Ratio (NLR) is a biomarker for the general immune response to various stress stimuli in peripheral blood. It can be easily determined, inexpensive and can correlate with poor outcomes. Methods: A review of medical records was performed including patients from January 2013 to December 2018. The clinical characteristics were described, analyzed and the NLR and the LIPI were calculated. Categorical variables were analyzed with Chi-square test and the correlation was analyzed with the Pearson correlation coefficient. Variables were included in the construction of survival models through Cox multivariate regression using statistical software: STATA SE ver11.0 (StataCorp LLC Texas,USA). Results: A total of 175 patients with complete medical record and pathology samples were included. Around half of patients were female. The mean age was 69 years ± 11 years. The most frequent histology was Adenocarcinoma in 87%, Epidermoid 10% and others 3%. The most frequent mutations were KRAS 25%, EGFR 22% and ALK 1%. PDL-1 > 1% was determined in 20% of patients. Clinical stage IV was found in 58% of the cases followed by Clinical Stage I, II and III with 25%, 9%, 8% respectively. The NLR > 4 is associated with a worse prognosis in Stage I and II HR = 5.4 (95% CI 1.73 - 17.17, p = 0.004). LIPI > 2 had predictive capacity for progression in Stage IV HR = 8.2 (IC 95 % 2.39-23.4, p = < 0.001). Conclusions: NLR > 4 showed prognostic value for recurrence in early clinical stages. LIPI score > 2 resulted in higher risk for progression in metastatic stages. Determination of these indexes has the potential as a readily available prognostic indicator for patients.
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