PD-L1 expression complements CALGB prognostic scoring system in malignant pleural mesothelioma.

Background: Programmed death ligand-1 (PD-L1) expression is a predictive biomarker in patients with lung cancer, but its role in malignant pleural mesothelioma (MPM) remains unclear. Evidence suggests that higher PD-L1 expression is correlated with worse survival. CALGB is the main scoring system used to predict the benefit of chemotherapy treatment. This study aimed to determine the prognostic value of PD-L1 expression and its addition to CALGB scoring system in patients with MPM. Methods: In this retrospective analysis, we evaluated samples with confirmed locally advanced or metastatic MPM. PD-L1 Tumor Proportional Score (TPS) was determined by immunohistochemistry at diagnosis. Results: 73 patients were included in this study. A cutoff value of 15 was set for a high or low PD-L1 TPS. In total, 71.2% (n=52) and 28.8% (n=21) of individuals harbored low or high PD-L1 expression, respectively. PD-L1High was associated with worse median progression-free Survival (mPFS) [4.9 vs. 10.8 months; HR 2.724, 95% CI (1.44-5.14); p = 0.002] and Overall Survival (OS) [6.0 vs. 20.9 months; HR 6.87, 95% CI (3.4-8.7); p<0.001] compared to patients with PD-L1Low. Multivariate analysis confirmed that PD-L1 expression was an independent factor for PFS and OS in patients with MPM and CALGB score of 5-6. Conclusion: PD-L1 addition to CALGB scale improves its prognostic estimation of MPM survival and should be considered in future research.

Efficacy and safety of pembrolizumab monotherapy in patients with advanced thyroid cancer in the phase 2 KEYNOTE-158 study.

BACKGROUND: The authors report results from the thyroid carcinoma cohort of the multicohort phase 2 KEYNOTE-158 study (NCT02628067), which evaluated pembrolizumab monotherapy in patients with previously treated cancers. METHODS: Eligible patients had histologically and/or cytologically confirmed papillary or follicular thyroid carcinoma, failure of or intolerance to prior therapy, and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Patients received pembrolizumab (200 mg) every 3 weeks for up to 35 cycles. The primary end point was objective response rate (ORR) per RECIST v1.1 by independent central review. RESULTS: A total of 103 patients were enrolled and received pembrolizumab. Median duration from first dose to data cutoff (October 5, 2020) was 49.4 (range, 43.9-54.9) months. ORR was 6.8% (95% confidence interval [CI], 2.8%-13.5%), and median duration of response was 18.4 (range, 4.2-47.2+) months. ORR was 8.7% (95% CI, 2.4%-20.8%) among patients with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥1 (n = 46) and 5.7% (95% CI, 1.2%-15.7%) among patients with PD-L1 CPS <1 (n = 53). Median overall survival and progression-free survival were 34.5 (95% CI, 21.2 to not reached) and 4.2 (95% CI, 3.9-6.2) months, respectively. Treatment-related adverse events occurred in 69.9% of patients (grade 3-5, 14.6%). CONCLUSIONS: Pembrolizumab demonstrated manageable toxicity and durable antitumor activity in a small subset of patients with advanced thyroid cancer. These results provide evidence of modest antitumor activity in this setting regardless of tumor PD-L1 expression. Future studies evaluating immune checkpoint inhibitors in patients with differentiated thyroid cancer should focus on biomarker-driven patient selection or combination of immune checkpoint inhibitors with other agents, in order to achieve higher response rates than observed in this study.

Impact of the Discordance Between Scales of Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium in Patients' Prognosis With Metastatic Renal Cancer.

Background: In Mexico, about 30% of renal cancer patients are diagnosed in a metastatic state. Despite the recent advances in the treatment of cancer, metastatic renal cancer is still an incurable illness. Thus, identifying prognostic factors helps improve prognosis accuracy and survival prediction for patients. Methods: In this study, we retrospectively analyzed 26 patients with histological diagnosis of renal cell carcinoma, including clear cell and other subtypes in stage IV (metastatic), recurrent or unresectable disease. We performed a multivariate analysis of overall survival regarding the congruity between prognostic scales. Results: Our results showed a significant difference in favor of patients with congruity between scales for progression-free survival (18.9 vs. 3.1 months; P = 0.048) and a tendency towards better overall survival in patients with the congruity of both scales compared to the discordant patients (112 vs. 32 months; P = 0.99). Conclusion: This study highlights the discordance between Memorial Sloan-Kettering Cancer Center and International Metastatic Renal Cell Carcinoma Database Consortium scales, which was associated with worse prognosis with a significant difference in progression-free survival but not in overall survival.

Health-related quality of life in patients treated with pembrolizumab for microsatellite instability-high/mismatch repair-deficient advanced solid tumours: Results from the KEYNOTE-158 study.

BACKGROUND: In the KEYNOTE-158 study (NCT02628067), pembrolizumab showed a high objective response rate and durable clinical benefit for patients with previously treated, unresectable/metastatic microsatellite instability-high (MSI-H)/mismatch repair‒deficient (dMMR) non-colorectal solid tumours. We present health-related quality of life (HRQoL) results from the MSI-H/dMMR population (cohort K). PATIENTS AND METHODS: Eligible patients had previously treated MSI-H/dMMR advanced non-colorectal solid tumours, measurable disease per RECIST v1.1, and ECOG performance status ≤1. Patients received pembrolizumab 200 mg Q3W for 35 cycles (2 years). The EORTC Quality of Life Questionnaire (QLQ-C30) and EQ-5D-3L were administered at baseline, at regular intervals throughout treatment, and 30 days after treatment discontinuation. Prespecified analyses (exploratory endpoints) included the magnitude of change from baseline to post-baseline timepoints in all patients and by the best overall response for QLQ-C30 global health status (GHS)/QoL, QLQ-C30 functional/symptom scales/items, and EQ-5D-3L visual analogue scale (VAS) score. RESULTS: At data cutoff (October 5, 2020), 351 patients were enrolled, of whom 311 and 315 completed baseline QLQ-C30 and EQ-5D-3L questionnaires, respectively. QLQ-C30 GHS/QoL scores improved from baseline to week 9 (mean [95% CI] change, 3.07 [0.19-5.94]), then remained stable or improved by week 111, with greater improvements observed in patients with a best response of complete response (CR) or partial response (PR) (10.85 [6.36-15.35]). Patients with CR/PR showed improvements in physical (5.58 [1.91-9.25]), role (9.88 [3.80-15.97]), emotional (5.62 [1.56-9.68]), and social (8.33 [2.70-13.97]) functioning, and stable cognitive functioning (1.74 [-1.45 to 4.94]). CONCLUSIONS: Pembrolizumab generally improved or preserved HRQoL in patients with previously treated MSI-H/dMMR advanced non-colorectal solid tumours.

Impact of Testicular Germ Cell Tumor Laterality on Recurrence-Free Survival in the Mexican Population.

BACKGROUND: To date, the prognostic value of laterality for testicular germ cell tumors remains unknown. Herein, we describe this prognostic factor in the Mexican population. METHODS: A retrospective single-center study that included 37 patients with primary testicular germ cell tumors was conducted. Primary outcome was recurrence-free survival (RFS) at 2 years. Secondary outcomes were RFS by histology, progression-free survival by laterality, and 2-year overall survival. RESULTS: Thirty-seven patients were included, of which five showed relapses. By laterality, the 2-year RFS rate was 100% for left tumors and 77.3% for right tumors, with a trend toward statistical significance (P = 0.058). By histology, the RFS rate was higher for seminomas than non-seminomas (89% vs. 83%, respectively) without this difference being statistically significant. Progression-free survival was higher for right tumors than left tumors (91% vs. 80%, respectively) but without reaching statistical significance. The overall survival rate for the entire cohort was 94.5%. CONCLUSIONS: Our study shows that patients with primary germ cell tumors of the right testicle have a higher risk of recurrence than those with primary germ cell tumors of the left testicle, with a trend toward statistical significance.

Prevalence and Molecular Profile of Breast Carcinoma Using Immunohistochemistry Markers in Mexican Women.

BACKGROUND: In Mexico, breast cancer is the leading cause of death by malignant tumors in women aged 20 and older. The World Health Organization estimates that 69% of deaths caused by breast cancer occur in developing countries. Little is known about the prevalence of breast carcinoma in Mexico and its molecular subclassification. METHODS: This retrospective cross-sectional study included patients who underwent a mastectomy (single, radical or lumpectomy) or a breast tumor biopsy (core-needle or excisional) from January 2002 to December 2018. The primary purpose of the study was to determine the prevalence and molecular profile of breast in comprehensive cancer center in Mexico and compare our results with those published in the US. This study was approved by our scientific and bioethical committee. RESULTS: The final analysis included 379 patients. The youngest patient was 23 years old and the oldest patient was 89; the mean age at diagnosis was 54.63 years. Patients of 40 years old or younger accounted for 48 of the cases (12.66%) and those older than 40 accounted for 331 of the cases (87.33%). The molecular subclassification showed luminal A subtype in 139 cases (36.67%), luminal B subtype in 143 cases (37.73%), human epidermal growth factor receptor 2-positive carcinomas in 32 cases (8.44%) and triple-negative carcinomas in 65 cases (17.15%). Diabetes mellitus was present in 43 patients (11.34%), hypertension in 78 patients (20.58%), obesity in 82 patients (21.63%) and 66 patients reported being treated with exogenous hormone therapy (17.41%). CONCLUSIONS: Breast carcinoma occurs at an earlier age in Mexican women compared to women in the US. Hormone-positive tumors were found to be more prevalent in older patients, while high-grade tumors were more frequently identified in younger patients.

Association of Carcinoembryonic Antigen Reduction With Progression-free and Overall Survival Improvement in Advanced Non-small-cell Lung Cancer.

BACKGROUND: Non-small cell lung cancer elevates serum carcinoembryonic antigen (CEA). CEA determinations are not recommended currently. This study aims to identify the correlation between reducing serum CEA levels with progression-free survival (PFS) and overall survival. METHODS: This study assessed at baseline and in every scheduled visit serum CEA levels throughout first-line therapy. A sensitivity and specificity analysis identified the best cut-off point and correlated it with progression-free survival and overall survival. Multivariate Cox proportional hazard models were conducted. RESULTS: We assessed 748 patients with elevated serum CEA levels at diagnosis. A ≥20% decrease from baseline was associated with a 2-fold median survival compared with patients with lower decreases (20.5 months vs 9.1 months; hazard ratio, 0.53; 95% confidence interval, 0.44 to -0.64; P < .001). CEA sensitivity and specificity to predict survival was 79.8% and 59.8%, respectively. A ≥10% decrease in CEA concentrations was associated with longer progression-free survival (7.7 months vs 5.9 months; hazard ratio, 0.71; 95% confidence interval, 0.57 to -0.88; P = .001) in those treated with chemotherapy, and in patients under tyrosine kinase inhibitors (11.9 months vs 7.3 months; hazard ratio, 0.63; 95% confidence interval, 0.47 to -0.83; P = .0001) and a ≥20% decrease. CONCLUSION: In patients with metastatic non-small cell lung cancer with an elevated baseline CEA level, the percentage decrease of CEA concentrations above the threshold during the first-line therapy was associated with more prolonged survival and progression-free intervals. Serum CEA determinations are a feasible, noninvasive option for monitoring and prognosis.

Giant Benign Mammary Phyllodes Tumor: Report of a Case and Review of the Literature.

Phyllodes tumor of the breast is an infrequently encountered fibroepithelial neoplasm, which accounts for 0.3-1% of all tumors. Few case reports have described the occurrence of giant phyllodes tumor. To our knowledge, about 20% of phyllodes tumors would be considered giant benign. Complete surgical excision is the standard of care for giant benign phyllodes tumors; axillary lymph node metastasis is rare, and dissection should be limited to patients with pathologic evidence of tumor in the lymph nodes. We report the case of a 40-year-old Mexican woman with giant mammary tumor who underwent a right total mastectomy. The pathology results showed a benign phyllodes tumor 4,857 g in weight and 40.2 × 36.3 × 15 cm in size. We do not suggest adjuvant radiation therapy for patients with benign phyllodes tumors that are widely excised. A review of the pertinent literature was performed.

Neuroendocrine Tumor of the Common Bile Duct: Case Report.

Carcinoma of the extrahepatic biliary tract accounts for <2% of all cancers. Neuroendocrine tumor of the extrahepatic bile duct is very rare, and there are <200 cases reported since 1959. The preoperative diagnosis is infrequent (5.12%). The definite diagnosis relies on postoperative pathology which utilized immunohistochemistry study on many biomarkers to diagnose the histological subtypes of neuroendocrine neoplasms, such as chromogranin A, synaptophysin, and neuron-specific enolase. When the primary tumor has no metastases, radical removal of the lesion appears as curative treatment. The treatment of the carcinoid syndrome or other functioning syndrome is the first priority. We report a case of a 12-year-old Mexican woman with neuroendocrine tumor of the extrahepatic bile duct (common bile duct neuroendocrine tumor) seen in our hospital. Resection of the common bile duct, cholecystectomy, end to side Roux-en-y hepaticojejunostomy, and portal lymphadenectomy was performed. A review of the pertinent literature was performed. Given the rarity of the disease, treatment principles are based mainly on retrospective series and case reports. We present the eighth case in adolescence in the literature.

Acute Cardiac Tamponade Secondary to Cardiac Vascular-Type Pleomorphic Leiomyosarcoma: Case Report.

Soft tissue sarcomas represent <1% of all neoplasms. Leiomyosarcomas comprise only 5-7% of cases, and only 2% of these are vascular. Vascular leiomyosarcomas are extremely rare and represent only 0.001% of all neoplasms, the venous type being up to 5 times more frequent. Arterial leiomyosarcomas most frequently affect the great vessels, being fatal in most cases. In the reported cases of arterial leiomyosarcomas, the most frequently affected site is the pulmonary artery. We present the clinical case of 2 patients (a 42-year-old woman and a 36-year-old man) with a diagnosis of arterial pleomorphic leiomyosarcoma that conditioned cardiac tamponade as the initial manifestation. As it is an exceptionally rare neoplasm and with few cases reported in the literature, it is important to identify and describe this pathology which, due to the impossibility of offering surgical treatment, represents a therapeutic challenge.

Epithelial-Cadherin Expression Is Associated With Better Recurrence-Free and Overall Survival in Invasive Lobular Breast Cancer in Mexican Women.

BACKGROUND: There are different clinicopathological characteristics that are associated with the prognosis in patients with breast cancer. To date, the prognostic valor of for epithelial cadherin (E cadherin) expression in invasive lobular breast cancer remains unknown. METHODS: A retrospective single-center study that included 207 patients with primary invasive lobular breast cancer was conducted. The primary outcome was to report the correlation of the different clinical pathological characteristics including the expression of epithelial-cadherin (E-cadherin) in invasive lobular breast cancer in Mexican women with recurrence-free survival (RFS) and overall survival (OS). RESULTS: After 11 years of follow-up of patients with invasive lobular breast cancer, RFS was 89.4% and OS of 96.1%. The best prognosis in RFS was in patients with negative nodes 95.2% (P = 0.0001) and OS was 98.6-100% (P = 0.0001). Regarding tumor size, an RFS of 98.3% was observed in those measuring ≤ 2 cm (P = 0.0001) and OS of 99.2% (P = 0.0001). Negative Her2 was related to an RFS of 92.1% (P = 0.0001), and had better OS of 98.3% (P = 0.0001). Ki67 proliferation index ≤ 14% was associated with an RFS of 93.2% (P = 0.005). Negative lymph vascular invasion (LVI) increases the RFS of 91.8% (P = 0.032). The rate of positive expression of E-cadherin was associated with an increase in the RFS of 97.4%, with a mean of 128.6 ± 2.4 months (95% confidence interval (CI): 123.75 - 133.45 months) compared to the absence of expression E-cadherin: signal log ratio (SLR) 68.9%, a mean of 95 ± 6 months (95% CI: 83.28 - 106.88 months), P <0.001. When the OS was analyzed, the presence of E-cadherin expression increased the OS of 100% vs. 86.9% with the absence, P = 0.015. CONCLUSIONS: The prognostic impact of the different clinicopathological characteristics known worldwide was confirmed. Results of the analysis in the presented study indicate that positive expression of E-cadherin correlates with an improvement in OS and RFS in invasive lobular breast cancer in Mexican women.

Intergluteal Cleft Eccrine Porocarcinoma with Metastasis to Inguinal Region and Lung: Case Report and Review of the Literature.

Eccrine porocarcinoma (EPC) is an infrequent cutaneous neoplasm, and was described in 1963 by Pinkus and Mehregan. It is a rare type of skin tumor (0.005-0.01% of all skin tumors). Less than 300 cases have been described in the entire world medical literature. To our knowledge, no case of intergluteal cleft EPC has been reported in the literature in English and Spanish to date, so this would be the first reported case of such pathology. Metastatic EPC is less frequent, since only <10% of metastatic type have been reported and the rest as localized disease. The primary treatment of choice is surgical wide local excision of the tumor with histological confirmation of tumor-free margins. Prognosis is difficult to determine because of the rarity of EPC and the variations in natural history. There are no data to support the use of adjuvant chemotherapy or radiotherapy, and there are currently no agreed criteria to define patients at high risk of relapse. We present a 67-year-old man with intergluteal cleft eccrine tumor by biopsy. Metastasis to left inguinal region and lung was reported by contrasted abdominal and chest computed tomography. He started chemotherapy based on etoposide, vincristine, carboplatin. A review of pertinent literature is provided.

Impact of the Type of Analgesic Therapy on Postsurgical Complications of Patients with Kidney Cancer Undergoing Nephrectomy.

BACKGROUND: The treatment of kidney cancer usually involves surgery, and in some cases systemic therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to control postsurgical pain in patients undergoing nephrectomy for renal cancer. Nevertheless, the association between these drugs and adverse postsurgical outcomes, including deterioration of renal function, is not fully established. METHODS: This retrospective cohort study included patients >18 years old with kidney cancer undergoing nephrectomy between January 2006 and January 2018. The primary endpoint was to determine the impact of postsurgical analgesic therapy (NSAIDs vs. acetaminophen) on renal function and postsurgical complications. This study was approved by our scientific and bioethical committee. RESULTS: One hundred patients were included in the final analysis. Clear-cell renal-cell carcinoma was the most frequent histologic subtype. Adequate acute pain control was accomplished in 91% of the patients during hospitalization. Twenty percent of the patients presented postsurgical complications. Bleeding-related complications were the most frequent (9%), followed by surgical-site infection (6%) and acute renal injury (6%). The administration of NSAIDs was not related to any postsurgical complication in comparison with the use of acetaminophen (21.3 vs. 17.9%, respectively). The length of hospital stay did not differ between patients treated with NSAIDs and those treated with acetaminophen (the average stay was 4 days for both groups, p = 0.32). CONCLUSION: The use of NSAIDs was not related to acute kidney injury, postsurgical complications, or prolonged hospital stay in patients with renal cancer undergoing nephrectomy.

Epidemiological Profile of Patients of Aged 65 Years and Over in a University Private Hospital.

OBJECTIVES: An increase in life expectancy is predicted for the general population and, by 2050, about one billion people will be older than 65 years. The Global Cancer Incidence, Mortality and Prevalence database estimates that 1.2 million people of this age will have cancer; this number represents 58% of new cases in the American population. This represents a challenge for diagnosis and treatment, given that some older people have multiple comorbidities and disabilities. MATERIALS AND METHODS: This was a retrospective descriptive study of 204 patients aged 65 years and over. All had a solid tumor that was diagnosed in a private hospital from January 2015 to December 2017. RESULTS: The median age was 72.2 years; the most frequent age group (48.5% of patients) was 65-75 years, and only a small percentage (4.4%) were aged > 85 years. The most common type of cancer was lung cancer (22.5%), followed by colorectal and urinary cancer. Most patients received cancer treatment after the disease diagnosis. CONCLUSION: There are no epidemiological studies of the older oncology population in Mexico. We believe it is necessary to perform larger studies to understand this population and to undertake actions to facilitate greater attention to patient diagnosis, treatment, and alleviation.

Risk of Pneumonitis with the Use of Different Immune Checkpoint Inhibitors in a Mexican Population.

PURPOSE: The incidence of pneumonitis reported in previous trials in patients with advanced cancer and use of programmed cell death protein 1 (PD-1) immunotherapy inhibitors was 2.7-3.6%. However, none of these trials included Mexican populations. METHODS: This was a retrospective analysis involving 87 patients with advanced cancer who received PD-1 inhibitors as part of their therapy. The primary outcome was the incidence of pneumonitis after using PD-1 inhibitors. The secondary outcomes were major risk factors and radiological patterns of pneumonitis. RESULTS: We found 13 cases of pneumonitis, giving an overall incidence of 15%; three of the cases were high-grade (grade 3). A ground-glass pattern was the major form found by chest computed tomography scans. We did not find any significant risk factor for pneumonitis. CONCLUSION: The incidence of pneumonitis secondary to treatment with PD-1 inhibitors in our Mexican population was 15%, which is 5 times higher than that found in other studies. No risk factor was identified for this increased incidence of drug-induced pneumonitis following the use of PD-1 inhibitors.

Spontaneous regression as a 'burned-out' non-seminomatous testicular germ cell tumor: a case report and literature review.

Testicular germ cell tumors (TGCTs) are the most frequent type of cancer in young adults. An exceptional event is the spontaneous regression (SR) of the primary tumor. Herein, we describe a burned-out non-seminomatous TGCT case and relevant literature review. A 34-year-old male presenting with low back pain was found to have a retroperitoneal mass upon urotomography. During workup, a heterogeneous testicular mass was evident, and its biopsy showed findings that support the diagnosis of spontaneous tumoral regression. The patient underwent unilateral orchiectomy and a chemotherapy protocol was later initiated, with 85% regression of the retroperitoneal metastatic mass. No progression of the primary tumor has been found. The etiology of SR across different cancer types appears to be associated with the host's immune response and an angiogenic disturbance of the tumor microenvironment. The burned-out phenomenon is a rare event that needs further research into its molecular sequencing.

Cancer immunotherapy experience in the Integral Oncology Centre "Diana Laura Riojas de Colosio", Médica Sur Hospital.

INTRODUCTION: The useof immunotherapy in Mexico has been used since 2012 with ipilimumab and since 2015 with nivolumab and pembrolizumab, so it is a matter of necessity to know the experience of these drugs. MATERIAL AND METHODS: An observational, descriptive, cross-sectional, and retrospective study was performed in Médica Sur Hospital, where with dossiers from 2012 to June 2018 patients with metastatic cancer who received immunotherapy with ipilimumab, nivolumab, and pembrolizumab for six months were evaluated, searching as principal outcomes the adverse effects of those drugs and as secondary outcomes the response to treatment. RESULTS: Seventy subjects fulfilled the inclusion criteria for the study, and 42 (60%) were women with an average age of 60.73 ±13.64 years (16-82 years). The pathologies that received immunotherapy were the following: melanoma and lung cancer. The most frequent clinical and laboratory adverse effects were as follows: fatigue - 32 (45.71%), asthaenia - 30 (42%), nausea - 8 (11.4%), diarrhoea - 8 (11.4%), and rash - 7 (10%). The worst adverse effects were respiratory and endocrinological: pneumonitis - 10 (14.28%), hypothyroidism - 4 (5.71%), hyperglycaemia - 1 (1.4%), and hypophysitis - 2 (2.9%). With respect to treatment response: complete response - 8 (11.4%), partial response - 11 (15.71%), stable disease - 33 (47.14%), and disease progression - 19 (27.14%). CONCLUSIONS: The most common adverse effects did not condition the suspension of treatment or increase in intra-hospital stay, but there were some adverse effects that actually had an impact on evolution, hospital stay, and mortality.

Searching for the Culprit: Metastases from a Cancer of Unknown Primary.

We report a case of metastases from a cancer of unknown primary whose primary site could not be identified during the appropriate pretreatment evaluation. The patient was a 58-year-old woman with a history of passive smoking and with no history of cancer in the family. Her current condition started with asthenia, adynamia, and pallor, followed by palpitations. An abdominopelvic computed tomography (CT) scan was performed, showing multiple osteolytic lesions distributed in all bone structures and axillary adenopathy on the left side. As part of the approach and given the high suspicion of multiple myeloma, tests were performed. The results were negative for multiple myeloma. A PET-CT scan was performed and showed left axillary adenopathy. The breasts and other organs were not affected. Left axillary lymph node resection revealed breast primary metastatic pleomorphic lobular carcinoma. Due to the metastatic disease (caused by the primary breast cancer), it was decided to start chemotherapy.

Prevalence, Risk Factors, and Survival of Patients with Intrahepatic Cholangiocarcinoma.

PURPOSE: To investigate the prevalence, related risk factors, and survival of intrahepatic cholangiocarcinoma in a Mexican population. MATERIAL AND METHODS: We conducted a cross-sectional study at Medica Sur Hospital in Mexico City with approval of the local research ethics committee. We found cases by reviewing all clinical records of in-patients between October 2005 and January 2016 who had been diagnosed with malignant liver tumors. Clinical characteristics and comorbidities were obtained to evaluate the probable risk factors and the Charlson index. The cases were staged based on the TNM staging system for bile duct tumors used by the American Joint Committee on Cancer and median patient survival rates were calculated using the Kaplan-Meier method. RESULTS: We reviewed 233 cases of hepatic cancer. Amongst these, hepatocellular carcinomas represented 19.3% (n = 45), followed by intrahepatic cholangiocarcinomas, which accounted for 7.7% (n = 18). The median age of patients with intrahepatic cholangiocarcinoma was 63 years, and most of them presented with cholestasis and intrahepatic biliary ductal dilation. Unfortunately, 89% (n = 16) of them were in an advanced stage and 80% had multicentric tumors. Median survival was 286 days among patients with advanced stage tumors (25th-75th interquartile range, 174-645 days). No correlation was found between the presence of comorbidities defined by the Charlson index, and survival. We evaluated the presence of definite and probable risk factors for the development of intrahepatic cholangiocarcinoma, that is, smoking, alcohol consumption, and primary sclerosing cholangitis. DISCUSSION: We found an overall prevalence of intrahepatic cholangiocarcinoma of 7.7%; unfortunately, these patients were diagnosed at advanced stages. Smoking and primary sclerosing cholangitis were the positive risk factors for its development in this population.

Reproducibility of the EGFR immunohistochemistry scores for tumor samples from patients with advanced non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) is overexpressed in >60% of non-small cell lung cancer (NSCLC) cases. In combination with radiotherapy or chemotherapy, first-line treatments with antibodies against EGFR, including cetuximab and necitumumab, have demonstrated benefits by increasing overall survival (OS), particularly in patients who overexpress EGFR. The present study evaluated the interobserver agreement among three senior pathologists, who were blinded to the clinical outcomes and assessed tumor samples from 85 patients with NSCLC using the H-score method. EGFR immunohistochemistry was performed using a qualitative immunohistochemical kit. The reported (mean ± standard deviation) H-scores from each pathologist were 111±102, 127±103 and 128.53±104.03. The patients with average H-scores ≥1, ≥100, ≥200 and between 250-300 were 85.9, 54.1, 28.2 and 12.9, respectively. Patients who had an average H-score >100 had a shorter OS time compared with those with lower scores. Furthermore, patients with EGFR mutations who were treated with EGFR-tyrosine kinase inhibitors (TKIs) and had an average H-score >100 had a longer OS time compared with those with an average H-score <100. The interobserver concordance for the total H-scores were 0.982, 0.980 and 0.988, and for a positive H-score ≥200, the interobserver concordance was 0.773, 0.710 and 0.675, respectively. The determination of EGFR expression by the H-score method is highly reproducible among pathologists and is a prognostic factor associated with a poor OS in all patients. Additionally, the results of the present study suggest that patients with EGFR mutations that are treated with EGFR-TKIs and present with a high H-score have a longer OS time.