Genomic profiling in GIST: Implications in clinical outcome and future challenges.

Gastrointestinal Stromal Tumors (GIST) are the most frequent mesenchymal neoplasia of the digestive tract. Genomic alterations in KIT, PDFGRA, SDH, and BRAF genes are essential in GIST oncogenesis. Therefore, the mutations in these genes have demonstrated clinical implications. Tumors with deletions in KIT-exon 11 or duplications in exon 9 are associated with a worse prognosis. In contrast, KIT-exon 11 substitutions and duplications are associated with a better clinical outcome. Moreover, mutations in Kit exon 9 and 11 are actionable, due to their response to imatinib, while mutations in PDGFRA respond to sunitinib and/or avapritinib. Although, molecular testing on tissue samples is effective; it is invasive, requires adequate amounts of tissue, and a long experimental process is needed for results. In contrast, liquid biopsy has been proposed as a simple and non-invasive method to test biomarkers in cancer. The most common molecule analyzed by liquid biopsy is circulating tumor DNA (ctDNA). GISTs ctDNA testing has been demonstrated to be effective in identifying known and novel KIT mutations that were not detected using traditional tissue DNA testing and have been useful in determining progression risk and response to TKI therapy. This allows the clinician to have an accurate picture of the genetic changes of the tumor over time. In this work, we aimed to discuss the implications of mutational testing in clinical outcomes, the methods to test ctDNA and the future challenges in the establishment of alternatives of personalized medicine.

Persistent high levels of carcinoembryonic antigen after tumor resection are associated with poorer survival outcomes in patients with resected colon cancer.

BACKGROUND: Interindividual survival and recurrence rates in cases of locoregional colon cancer following surgical resection are highly variable. The aim of the present study was to determine whether elevated pre-operative and post-operative CEA values are useful prognostic biomarkers for patients with stage I-III colon cancer who underwent surgery with curative intent. METHODS: We conducted a retrospective study in patients with histologically confirmed stage I-III primary colonic adenocarcinoma who underwent radical surgical resection at Mexico's National Cancer Institute, between January 2008 and January 2020. We determined pre-operative and post-operative CEA and analyzed the association of scores with poorer survival outcomes in patients with resected colon cancer, considering overall survival (OS) and disease-free survival (DFS). RESULTS: We included 640 patients with stage I-III colon cancer. Pre-operative CEA levels were in the normal range in 460 patients (group A) and above the reference value in the other 180. Of the latter, 134 presented normalized CEA levels after surgery, but 46 (group C) continued to show CEA levels above the reference values after surgery. Therefore, propensity score matching (PSM) was carried out to reduce the bias. Patients were adjusted at a 1:1:1 ratio with 46 in each group, to match the number in the smallest group. Median follow- up was 46.4 months (range, 4.9-147.4 months). Median DFS was significantly shorter in Group C: 55.5 months (95% CI 39.6-71.3) than in the other two groups [Group A: 77.1 months (95% CI 72.6-81.6). Group B: 75.7 months (95% CI 66.8-84.5) (p-value < 0.001)]. Overall survival was also significantly worse in group C [57.1 (95% CI 37.8-76.3) months] than in group A [82.8 (95% CI 78.6-86.9 months] and group B [87.1 (95% CI 79.6-94.5 months] (p-value = 0.002). To identify whether change in CEA levels operative and post-surgery was an independent prognostic factor for survival outcomes, a Cox proportional hazard model was applied. In multivariate analysis, change in CEA level was a statistically significant, independent prognostic factor for overall survival (p-value = 0.031). CONCLUSIONS: When assessed collectively, pre-operative and post-operative CEA values are useful biomarkers for predicting survival outcomes in patients with resected colon cancer. Prognoses are worse for patients with elevated pre-operative and post-surgical CEA values, but similar in patients with normal post-surgical values, regardless of their pre-surgery values.

Progress in Metabolic Studies of Gastric Cancer and Therapeutic Implications.

BACKGROUND: Worldwide, gastric cancer is ranked the fifth malignancy in incidence and the third malignancy in mortality. Gastric cancer causes an altered metabolism that can be therapeutically exploited. OBJECTIVE: The objective of this study is to provide an overview of the significant metabolic alterations caused by gastric cancer and propose a blockade. METHODS: A comprehensive and up-to-date review of descriptive and experimental publications on the metabolic alterations caused by gastric cancer and their blockade. This is not a systematic review. RESULTS: Gastric cancer causes high rates of glycolysis and glutaminolysis. There are increased rates of de novo fatty acid synthesis and cholesterol synthesis. Moreover, gastric cancer causes high rates of lipid turnover via fatty acid ß-oxidation. Preclinical data indicate that the individual blockade of these pathways via enzyme targeting leads to antitumor effects in vitro and in vivo. Nevertheless, there is no data on the simultaneous blockade of these five pathways, which is critical as tumors show metabolic flexibility in response to the availability of nutrients. This means tumors may activate alternate routes when one or more are inhibited. We hypothesize there is a need to simultaneously block them to avoid or decrease the metabolic flexibility that may lead to treatment resistance. CONCLUSION: There is a need to explore the preclinical efficacy and feasibility of combined metabolic therapy targeting the pathways of glucose, glutamine, fatty acid synthesis, cholesterol synthesis, and fatty acid oxidation. This may have therapeutical implications because we have clinically available drugs that target these pathways in gastric cancer.

Outcomes of Patients With Metastatic Anal Cancer According to HIV Infection: A Multicenter Study by the Latin American Gastrointestinal Oncology Group (SLAGO).

BACKGROUND: HIV-positive patients are underrepresented in clinical trials of metastatic squamous cell carcinoma of the anal canal (mSCCA). We aimed to compare the clinical outcomes of mSCCA patients according to HIV infection. METHODS: This was a retrospective multicenter cohort study of consecutive patients with mSCCA. All HIV-positive patients received antiretroviral therapy. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and response rate (RR). RESULTS: From January 2005 to December 2019, 113 patients were included: 20 (17.6%) had HIV infection. HIV-positive patients were younger at diagnosis and more frequently male, and 20% (n = 8) received exclusively best supportive care in comparison with 8.6% of HIV-negative patients (P = .13). Both groups were similar in terms of Eastern Cooperative Oncology Group (ECOG) performance status, pattern of metastatic disease, and type of first-line chemotherapy. Five (25%) HIV-positive and 36 (38.7%) HIV-negative patients received second-line therapies (P = .24). RR and median PFS in first-line were similar between the groups: 35% and 30.1% (P = .78) and 4.9 and 5.3 months (P = .85) for patients with and without HIV infection, respectively. At a median follow-up of 26 months, median OS was 11.3 months (95% confidence interval [CI] 10.1 to 26.4) for HIV-infected patients versus 14.6 months (95% CI 11.1 to 18.1) for HIV-negative patients (P = .92). In the univariate analysis for OS, only ECOG performance status was significant. CONCLUSION: HIV-positive mSCCA patients under antiretroviral therapy have oncological outcomes similar to those of HIV-negative patients. These patients should be included in trials of mSCCA.

Carcinoma epidermoide puro-combinado de vesícula biliar / Gallbladder epidermoid carcinoma

Background: Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age. Aim: To report the features of 15 patients with gallbladder epidermoid carcinoma. Material and Methods: Review of medical records of patients with gallbladder cancer in an oncology service. Results: Of 207 patients with gallbladder cancer, 15patients aged 53-72years, 93% women had an epidermoid component in their cancer. Forty percent were diabetic and 33% had cholelithiasis. All had locoregional extension of the tumor. A cholecystectomy was done in nine patients (using open surgery in six). In six patients, only a biopsy was done. Median survival was 4.2 months. Conclusions: Gallbladder epidermoid carcinoma is uncommon and has a bad prognosis.

[Gallbladder epidermoid carcinoma]. / Carcinoma epidermoide puro-combinado de vesícula biliar.

BACKGROUND: Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age. AIM: To report the features of 15 patients with gallbladder epidermoid carcinoma. MATERIAL AND METHODS: Review of medical records of patients with gallbladder cancer in an oncology service. RESULTS: Of 207 patients with gallbladder cancer, 15patients aged 53-72years, 93% women had an epidermoid component in their cancer. Forty percent were diabetic and 33% had cholelithiasis. All had locoregional extension of the tumor. A cholecystectomy was done in nine patients (using open surgery in six). In six patients, only a biopsy was done. Median survival was 4.2 months. CONCLUSIONS: Gallbladder epidermoid carcinoma is uncommon and has a bad prognosis.

Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015 / Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.

[Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology]. / Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015.

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.

Gastric cancer in young people under 30 years of age: worse prognosis, or delay in diagnosis?

BACKGROUND: Gastric cancer is an aggressive disease with nonspecific early symptoms. Its incidence and prognosis in young patients has shown considerable variability. PURPOSE OF THE STUDY: Our objective was to retrospectively study patients from our institution aged <30 years with gastric carcinoma. The study was undertaken to describe the experience of gastric cancer in this population, and to demonstrate its specific clinical and pathological characteristics. MATERIALS AND METHODS: We reviewed the cases of histologically confirmed gastric cancer between 1985 and 2006 at the Instituto Nacional de Cancerología of Mexico (INCan); emphasis in our review was placed on clinical presentation, diagnostic and therapeutic intervention, pathology, and the results. RESULTS: Thirty cases of gastric carcinoma were reviewed. The patients' median age was 27 years (range, 18-30 years) and the male:female ratio was 1:1. CONCLUSION: Gastric cancer exhibits different behavior in patients aged, 30 years, but delay in diagnosis and the tumor's behavior appear to be the most important factors in prognosis of the disease.

Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study.

BACKGROUND: A frequent manifestation of advanced NSCLC is malnutrition, even though there are many studies which relate it with a poor survival, its relation with toxicity has not yet been consistently reported. The aim of this study was to associate malnutrition and albumin serum levels with the occurrence of chemotherapy-induced toxicity in cisplatin plus paclitaxel chemotherapy-treated NSCLC. METHODS: We prospectively evaluated 100 stage IV NSCLC patients treated with paclitaxel (175 mg/m2) and cisplatin (80 mg/m2). Malnutrition was assessed using SGA prior treatment. Neutrophil Lymphocyte Ratio (NLR) and the Platelet Lymphocyte Ratio (PLR) were used to determine the presence of systemic inflammatory response (SIR) and were related to the development of toxicity. Toxicity was graded according to NCI CTCAE version 3.0 after two chemotherapy cycles. RESULTS: Median age was 58 +/- 10 years, 51% of patients were malnourished, 50% had albumin < or =3.0 mg/mL. NLR > or = 5 was associated with basal hypoalbuminemia (mean ranks, 55.7 vs. 39 p = 0.006), ECOG = 2 (47.2 vs. 55.4 p = 0.026) and PLR > or = 150 were significantly related with a basal body mass index < or =20 (56.6 vs. 43.5; p = 0.02) and hypoalbuminemia (58.9 vs. 41.3; p = 0.02). Main toxicities observed after 2 cycles of chemotherapy were alopecia (84%), nausea (49%), neuropathy (46%), anemia (33%), lymphopenia (31%), and leukopenia (30%). Patients malnourished and with hypoalbuminemia developed more chemotherapy-induced toxicity overall when compared with those without malnutrition (31 vs 22; p = 0.02) and normal albumin (mean ranks, 62 vs 43; p = 0.002), respectively. Hypoalbuminemia was associated with anemia (56 vs 47; p = 0.05), fatigue (58 vs 46; p = 0.01), and appetite loss (57.1 vs 46.7; p = 0.004) compared with normal albumin. PLR > or = 150 was related with the development of toxicity grade III/IV (59.27 vs. 47.03 p = 0.008) and anemia (37.9 vs 53.8 p = 0.004). CONCLUSION: SIR parameters were associated with malnutrition, weight loss and hypoalbuminemia. Chemotherapy-induced toxicity in NSCLC patients treated with paclitaxel and cisplatin was associated with malnutrition and hypoalbuminemia. Early nutritional assessment and support might confer beneficial effects.

[The first Mexican consensus of endometrial cancer. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México]. / Primer consenso Mexicano de cancer de endometrio.

INTRODUCTION: Endometrial cancer (EC) is the second most common gynecologic malignancy worldwide in the peri and postmenopausal period. Most often for the endometrioid variety. In early clinical stages long-term survival is greater than 80%, while in advanced stages it is less than 50%. In our country there is not a standard management between institutions. GICOM collaborative group under the auspice of different institutions have made the following consensus in order to make recommendations for the management of patients with this type of neoplasm. MATERIAL AND METHODS: The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of four days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. RESULTS: Screening should be performed women at high risk (diabetics, family history of inherited colon cancer, Lynch S. type II). Endometrial thickness in postmenopausal patients is best evaluated by transvaginal US, a thickness greater than or equal to 5 mm must be evaluated. Women taking tamoxifen should be monitored using this method. Abnormal bleeding in the usual main symptom, all post menopausal women with vaginal bleeding should be evaluated. Diagnosis is made by histerescopy-guided biopsy. Magnetic resonance is the best image method as preoperative evaluation. Frozen section evaluates histologic grade, myometrial invasion, cervical and adnexal involvement. Total abdominal hysterectomy, bilateral salpingo oophorectomy, pelvic and para-aortic lymphadenectomy should be performed except in endometrial histology grades 1 and 2, less than 50% invasion of the myometrium without evidence of disease out of the uterus. Omentectomy should be done in histologies other than endometriod. Surgery should be always performed by a Gynecologic Oncologist or Surgical Oncologist, laparoscopy is an alternative, especially in patients with hypertension and diabetes for being less morbid. Adjuvant treatment after surgery includes radiation therapy to the pelvis, brachytherapy, and chemotherapy. Patients with Stages III and IV should have surgery with intention to achieve optimal cytoreduction because of the impact on survival (51 m vs. 14 m), the treatment of recurrence can be with surgery depending on the pattern of relapse, systemic chemotherapy or hormonal therapy. Follow-up of patients is basically clinical in a regular basis. CONCLUSIONS: Screening programme is only for high risk patients. Multidisciplinary treatment impacts on survival and local control of the disease, including surgery, radiation therapy and chemotherapy, hormonal treatment is reserved to selected cases of recurrence. This is the first attempt of a Mexican Collaborative Group in Gynecology to give recommendations is a special type of neoplasm.