Prevalence and spectrum of germline pathogenic variants in cancer susceptibility genes among mexican patients with exocrine pancreatic cancer.

BACKGROUND: Although universal germline genetic testing is recommended for patients with exocrine pancreatic cancer (PC), access to genetic testing remains limited in low- and middle-income countries. This study aims to narrow the gap in our understanding of the spectrum of germline pathogenic and likely pathogenic variants (PVs) in cancer susceptibility genes in the Mexican population. METHODS: The landscape of PVs in cancer susceptibility genes was identified by next-generation sequencing multigene panel assays among patients with PC who were enrolled in the Clinical Cancer Genomics Community Research Network prospective registry in Mexico City. RESULTS: From August 2019 to April 2023, 137 patients underwent genetic testing. The median age at diagnosis was 60 years (range 36-85), 58.4 % were women, and 38.7 % were metastatic at diagnosis. The frequency of germline PVs was 16 % (n = 22): ATM 36.4 % (n = 8), CDKN2A/p16INK4A 27.3 % (n = 6), BRCA2 9.1 % (n = 2), PALB2 9.1 % (n = 2), CHEK2 9.1 % (n = 2), TP53 4.5 % (n = 1), and NF1 4.5 % (n = 1). Additionally, 2 carriers of monoallelic germline variants in MUTYH were identified. No significant differences were observed between carriers and non-carriers in terms of family history of pancreatic cancer. CONCLUSIONS: We identified a significant frequency of actionable germline PVs in Mexicans with PC, wherein the majority were in a broad spectrum of genes associated with the homologous recombination DNA repair mechanism. Most pancreatic cancer associated PVs were detected in non-BRCA genes, so our findings support the recommendation of multigene panel testing for genetic cancer risk assessment of Mexican individuals with PC.

Patient Navigation to Improve Early Access to Supportive Care for Patients with Advanced Cancer in Resource-Limited Settings: A Randomized Controlled Trial.

BACKGROUND: The early integration of supportive care in oncology improves patient-centered outcomes. However, data are lacking regarding how to achieve this in resource-limited settings. We studied whether patient navigation increased access to multidisciplinary supportive care among Mexican patients with advanced cancer. MATERIALS AND METHODS: This randomized controlled trial was conducted between August 2017 and April 2018 at a public hospital in Mexico City. Patients aged ≥18 years with metastatic tumors ≤6 weeks from diagnosis were randomized (1:1) to a patient navigation intervention or usual care. Patients randomized to patient navigation received personalized supportive care from a navigator and a multidisciplinary team. Patients randomized to usual care obtained supportive care referrals from treating oncologists. The primary outcome was the implementation of supportive care interventions at 12 weeks. Secondary outcomes included advance directive completion, supportive care needs, and quality of life. RESULTS: One hundred thirty-four patients were randomized: 67 to patient navigation and 67 to usual care. Supportive care interventions were provided to 74% of patients in the patient navigation arm versus 24% in usual care (difference 0.50, 95% confidence interval [CI] 0.34-0.62; p < .0001). In the patient navigation arm, 48% of eligible patients completed advance directives, compared with 0% in usual care (p < .0001). At 12 weeks, patients randomized to patient navigation had less moderate/severe pain (10% vs. 33%; difference 0.23, 95% CI 0.07-0.38; p = .006), without differences in quality of life between arms. CONCLUSION: Patient navigation improves access to early supportive care, advance care planning, and pain for patients with advanced cancer in resource-limited settings. IMPLICATIONS FOR PRACTICE: The early implementation of supportive care in oncology is recommended by international guidelines, but this might be difficult to achieve in resource-limited settings. This randomized clinical trial including 134 Mexican patients with advanced cancer demonstrates that a multidisciplinary patient navigation intervention can improve the early access to supportive and palliative care interventions, increase advance care planning, and reduce symptoms compared with usual oncologist-guided care alone. These results demonstrate that patient navigation represents a potentially useful solution to achieve the adequate implementation of supportive and palliative care in resource-limited settings globally.

Systemic therapy for non-serous ovarian carcinoma.

Ovarian cancer is one of the top ten most common cancers in women around the world, with high-grade serous epithelial cancer being the most frequent type. However, around a quarter of cases consist of non-serous epithelial ovarian cancer (EOC), which is a heterogeneous group of malignancies that includes endometroid, mucinous, clear cell carcinoma (CCC), and carcinosarcoma. Another relevant group of nonepithelial tumors are those arising from germ cells or sex-cord stromal cells, which account for about 10% of all ovarian cancers. Although there are similarities in the presentation, evaluation, and management of these tumors, they have unique characteristics in terms of epidemiology, tumor biology, tumor marker expression, and response to treatment, warranting a different approach to each one of them. Collectively, the treatment of most of EOC include surgical cytoreduction followed by adjuvant systemic platinum-based chemotherapy. The most common chemotherapy and route of administration for systemic treatment is paclitaxel plus carboplatin given intravenously. However, the treatment of EOC has been rapidly evolving and emerging targeted therapies such as poly (adenosine diphosphate-ribose) polymerase inhibitors, immune checkpoint inhibitors, and antiangiogenic agents are also available. On the other hand, non-EOC responds well to combination chemotherapy used to treat testicular cancer (bleomycin, etoposide, cisplatin) and has a good prognosis. Frontline chemotherapeutic regimen selection differs according to histological subtype, molecular alterations, and patient characteristics. Here, we review specific characteristics of non-serous and non-EOC emphasizing the peculiarities of systemic therapy for each subtype.

Autoantibodies in prediction of the development of rheumatoid arthritis among healthy relatives of patients with the disease.

OBJECTIVE: Although blood bank-based studies have shown that rheumatoid arthritis (RA)-related autoantibodies are present before the onset of RA, information on their positive predictive value (PPV) for development of RA in healthy individuals is scarce. This study was undertaken to assess the 5-year PPV of serum IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) for the development of RA among healthy relatives of patients with RA. METHODS: Healthy relatives of RA patients were invited to participate in a cohort study. At baseline, information on participants' medical history was obtained, and serum levels of IgM-RF and anti-CCP antibodies were determined (by nephelometry and second-generation anti-CCP enzyme-linked immunosorbent assay, respectively). The subjects were followed up every 4 months via a structured interview (Community Oriented Program for Control of Rheumatic Diseases [COPCORD] questionnaire). When the COPCORD questionnaire indicated possible arthritis, subjects underwent an in-office rheumatology assessment including joint count. The study end point was defined as fulfillment of the American College of Rheumatology criteria for RA. RESULTS: Eight hundred nineteen initially healthy relatives of 252 patients with RA were included (69% female, 41% offspring, mean ± SD age 35 ± 12 years). Eleven (1.3%) were positive for both anti-CCP-2 and RF, 12 (1.5%) only for anti-CCP-2, and 16 (2%) only for RF. RA developed in 17 (2.1%) of the relatives during the 5-year followup (3,313 person-years for the seronegative group and 60.8 person-years for the anti-CCP-2-positive group). The PPV was 64% when both anti-CCP-2 and RF were positive and 58% when only anti-CCP-2 was positive. Offspring of patients with RA had an independent 3-fold increased risk of developing RA. CONCLUSION: Results of the present study indicate that the magnitude of risk for developing RA in healthy relatives of patients with RA can be estimated using simple routine laboratory tests.

The number needed to offend: a cross-sectional study of potential offensiveness of rheumatic diagnostic labels.

This study aims to explore the different connotations and potential offensiveness of ten mechanistic labels in newly referred Mexican patients with rheumatic symptoms as well as in Mexican and Canadian rheumatologists. Patients with musculoskeletal complaints newly referred for a rheumatology assessment were interviewed consecutively before they saw the rheumatologist. Patients were asked to choose one of nine feelings provoked by ten different illness mechanism labels. Rheumatologists gave a medical diagnosis after seeing the patients. Mexican and Canadian rheumatologists were invited to answer a structured questionnaire about their feelings at the moment they identified each of the ten different provided scenarios. Patients' and rheumatologists' feelings were classified as "offended" or "nonoffended." The "offensive score" was used to calculate a "number needed to offend" (NNO). One hundred and fifty patients were included. Inherited, immunological, and inflammatory labels had the fewest negative connotations (NNOs 17, 12, and 14, respectively), and psychological, functional, idiopathic, and sleep disturbance labels had the most (NNO 2 and 3, respectively). Functional labels were almost four times more offensive than organic labels. Stratified by rheumatologist diagnosis, patients with functional disorders were more accepting of organic-based mechanistic labels. A higher potential to offend was observed when patients with functional somatic conditions were given functional mechanistic labels (NNOs 1 to 4). The survey was completed by 186 Mexican rheumatologists and 71 Canadian rheumatologists. Primarily functional disorders such as somatization and anxiety had a high potential to evoke offensive feelings (NNOs 3 to 7). No significant differences in the NNO were found between Mexican and Canadian rheumatologists. Getting or giving mechanistic/explanatory labels is emotional. Both patients and rheumatologists experienced offended feelings with functional or idiopathic labels.