Prognostic value of germline mutations in metastatic hormone-sensitive prostate cancer (mHSPC).

BACKGROUND: About 8% to 12% of patients presenting with mHSPC exhibit germline pathogenic variants (PV) in cancer predisposition genes. The aim of this study is to assess the presence of germline PV as a prognostic factor in the setting of mHSPC and to determine whether mutational status can predict rapid progression to castration resistance. METHODS: Genetic analysis using a multigene next-generation sequencing (NGS) panel was performed on 34 patients diagnosed with mHSPC undergoing treatment. We assessed the prevalence of germline PV and examined differences based on clinical-pathological characteristics, family history (FH), prostate-specific antigen (PSA) response, impact on time to castration-resistant prostate cancer (TTCRPC), and overall survival (OS). RESULTS: Germline PV were identified in 6 patients (17,6%). When comparing the clinical-pathological characteristics of PV carriers (n = 6) to noncarriers (n = 28), no significant associations were observed except for the presence of FH of hereditary breast and ovarian cancer (HBOC) syndrome and/or Lynch syndrome (P = 0.024). At a median follow-up of 33 months, significant differences in OS were observed based on the presence of PV (26 months in carriers vs. 74 months in noncarriers; P < 0.01). Patients who harbored a BRCA2 mutation (n = 3) showed a worse clinical outcome, presenting a shorter TTCRPC (7 months vs. 23 months; P = 0.005) and lower OS (7 months vs. 74 months; P < 0.001) compared to noncarriers (n = 31). CONCLUSION: mHSPC germline PV carriers had a worse survival outcome. Furthermore, BRCA2 germline mutation was an independent poor prognostic factor for mHSPC disease, associated with earlier progression to castration-resistant prostate cancer, and shorter OS. These results highlight the importance of evaluating germline mutational status in patients with hormone-sensitive prostate cancer.

Update on thymic epithelial tumors: a narrative review.

Background and Objective: Thymoma, thymic carcinoma and thymic neuroendocrine tumors originate from the epithelial cells of the thymus and account for the thymic epithelial tumors (TETs). Although TETs are uncommon, they are the most frequent tumor type in the anterior mediastinum. Multidisciplinary approach is essential for their correct management. The aim of the present review is to summarize the update management for TETs. Methods: For this review, we searched in Excerpta Medica database (EMBASE) and MEDLINE until 6 September 2023. The terms used in the search included thymoma, thymic carcinoma, thymic epithelial tumors, management, immunotherapy, multiple tyrosine kinases inhibitors. Key Content and Findings: The therapeutic approach is based on histology and tumor stage and may involve surgery with or without neoadjuvant or adjuvant treatment. In the metastatic setting, platinum-based chemotherapy is the standard of care and patients who do not respond to first-line treatment have limited treatment options mainly because of the poor efficacy shown in subsequent lines of therapy. Conclusions: Future research should focus on identifying predictive biomarkers for patients with TETs, and should implement multicenter collaborations and appropriate clinical trials tailored for rare tumor types. Immune check point inhibitors, mammalian target of rapamycin (mTOR) and antiangiogenic multikinase inhibitors have also been studied in this clinical setting.

Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial.

BACKGROUND: The prognostic value of the Systemic Inflammation Response Index (SIRI) in advanced pancreatic cancer is recognized, but its correlation with patients´ nutritional status and outcomes remains unexplored. AIM: To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer. METHODS: The PANTHEIA-Spanish Society of Medical Oncology (SEOM) study is a multicentric (16 Spanish hospitals), observational, longitudinal, non-interventional initiative, promoted by the SEOM Real World-Evidence work group. This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI. The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers. Patients with pathologically confirmed metastatic pancreatic adenocarcinoma, treated from January 2020 to January 2023, were included. The index was calculated using the product of neutrophil and monocyte counts, divided by lymphocyte counts, obtained within 15 days before initiation chemotherapy. This study evaluated associations between overall survival (OS), SIRI and weight loss. RESULTS: A total of 50 patients were included. 66% of these patients were male and the median age was 66 years. Metastasis sites: 36% liver, 12% peritoneal carcinomatosis, 10% lung, and 42% multiple locations. Regarding the first line palliative chemotherapy treatments: 50% received gemcitabine plus nab-paclitaxel; 28%, modified fluorouracil, leucovorin, irinotecan and oxaliplatin, and 16% were administered gemcitabine. 42% had a weight loss > 5% in the three months (mo) preceding diagnosis. 21 patients with a SIRI ≥ 2.3 × 103/L exhibited a trend towards a lower median OS compared to those with a SIRI < 2.3 × 103/L (4 vs 18 mo; P < 0.000). Among 21 patients with > 5% weight loss before diagnosis, the median OS was 6 mo, in contrast to 19 mo for those who did not experience such weight loss (P = 0.003). Patients with a weight loss > 5% showed higher SIRI levels. This difference was statistically significant (P < 0.000). For patients with a SIRI < 2.3 × 103/L, those who did not lose > 5% of their weight had an OS of 20 mo, compared to 11 mo for those who did (P < 0.001). No association was found between carbohydrate antigen 19-9 levels ≥ 1000 U/mL and weight loss. CONCLUSION: A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss. An elevated SIRI is suggested as a predictor of survival, emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.

Complete response to third-line treatment with trifluridine/tipiracil (TAS-102) in stage IV colon adenocarcinoma.

A clinical case of a 61-year-old female diagnosed with stage IV right colon adenocarcinoma (unresectable liver and multiple lymph node metastases at the time of diagnosis), Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma rat sarcoma viral oncogene homolog (NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type, proficient mismatch repair (pMMR), in whom a complete response to the third-line of systemic treatment with trifluridine/tipiracil (TAS-102) was obtained. The complete response has been maintained for more than 2 years after its suspension.

Neoadjuvant immunotherapy for dMMR/MSI-H locally advanced rectal cancer: The future new standard approach?

INTRODUCTION: This is a review of the evidence from studies of the efficacy and tolerability of neoadjuvant immunotherapy for mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) Locally Advanced Rectal Cancer (LARC). METHODS: For this review, we searched EMBASE and MEDLINE until 22 September 2022. The terms used in the search included mismatch repair-deficient, microsatellite instability, rectal cancer, neoadjuvant and immunotherapy. RESULTS: A total of 92 studies were obtained but only 9 were selected for the final analysis (one prospective and eight retrospective studies), including less than 20 patients per study. Neoadjuvant immunotherapy provides overall response rates of 100% (with and completed clinical response between 40 and 100%). CONCLUSION: Our review discusses completed prospective and retrospective studies, ongoing clinical trials, and the clinical practice of using neoadjuvant immunotherapy for MSI-H/dMMR LARC. The promising results obtained, would open the door to exploring other alternatives for these patients, offering the possibility of avoiding chemoradiation therapy and surgery in the future.

Biomarkers of Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer: Beyond PD-L1.

Immunotherapy has markedly improved the survival rate of patients with non-small cell lung cancer (NSCLC) and has introduced a new era in lung cancer treatment. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Thus, it is crucial to identify potential biomarkers suitable for screening the population that may benefit from immunotherapy. Based on the current clinical trials, the aim of the present study was to review the biomarkers for immune checkpoint inhibition that may have the potential to predict the response to immunotherapy in patients with lung cancer. A non-systematic literature review was done. We searched for eligible randomized controlled trials (RCTs) from PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2015 to January 2021. The keywords included biomarkers, immunotherapy, immune checkpoint inhibition, programmed death ligand 1 (PD-L1), and non-small cell lung cancer. Additional biomarkers beyond PD-L1 that have been shown to have predictive capacity include tumor mutational burden, microsatellite instability, lung immune prognostic index, gut microbiome, and certain alterations in genes (eg, STK11 deletion, LKB1 kinase mutation, MDM2/4 amplification) that confer immunoresistance. The biomarkers reviewed in this article could help us better select the appropriate immunotherapy treatment for patients with NSCLC.

Anti-EGFR Antibody Plus Chemotherapy Treatment in a Patient with Synchronous Merkel Cell Carcinoma and Colorectal Cancer.

Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous malignancy. During early stages, surgery is the primary treatment followed by radiotherapy in patients at high risk of recurrence. Definitive radiation therapy is an alternative for patients who are not surgical candidates, reserving chemotherapy for metastatic disease. We present a case of a male patient diagnosed with MCC and stage IV colorectal cancer and we focus on the skin tumor shrinkage after specific colorectal cancer treatment.

Review of risk of COVID-19 in cancer patients and their cohabitants.

BACKGROUND: Patients with a history of active malignancy are at increased risk of infection and COVID-19-related complications. Sanitary protection measures are not specifically recommended within households. This study examined the risk of seroconversion in cancer patients according to their household exposure. PATIENTS AND METHODS: This seroprevalence study was a prevalence study conducted in Torrejon de Ardoz (Spain). It analysed the seroprevalence of IgM and IgG antibodies in 104,299 volunteers (participation rate of 74.8% of population) from 29 May to 05 June 2020. Personal authorisation was requested to collect by questionnaire the test results from cancer patients, who attended the Outpatient Department of the University Hospital of Torrejón, and their cohabitants between 01-19 June 2020. RESULTS: A total of 229 cancer patients were included in the study. Sixty-four of the 229 individuals tested positive for SARS-CoV-2 IgG antibodies (27.9%) and 22 were positive for SARS-CoV-2 IgM antibodies (9.6%). The overall seroprevalence (IgG or IgM positive) was 31.4% (general population seroprevalence was 10% in Spain). Of 72 seropositive patients, 54.2% had intrafamilial exposure vs 45.8% who did not. Among seronegative patients, 30.6% had seropositive cohabitants. The probability of seropositivity for a cancer patient was significantly related to intrafamilial exposure (OR 2.684, 95% CI 1.51-4.76, p = 0.001). CONCLUSIONS: Cancer patients are a high-risk group for SARS-CoV-2 infection. Recommendations against virus transmission need to be implemented even in a household scenario, as it was the main factor significantly related to seroconversion.

Seroprevalence of SARS-CoV-2-specific antibodies in cancer outpatients in Madrid (Spain): A single center, prospective, cohort study and a review of available data.

BACKGROUND: Coronavirus disease in 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has emerged as a global pandemic. Published data suggests that patients with a history of or active malignancy are at increased risk of infection and developing COVID-19 related complications. To date, the published data has analyzed the seroprevalence of COVID-19 infection in the general population, but not in cancer patients. Here we present the results of prevalence of IgG and IgM antibodies against SARS-CoV-2 in cancer patients from the University Hospital of Torrejón (Torrejón de Ardoz, Madrid, Spain). METHODS: SARS-CoV-2 IgG and IgM antibodies was assessed using a commercially available rapid test (Testsealabs® IgG/IgM Rapid Test Cassette) and collect the result from cancer outpatients who attended the medical oncology consult at University Hospital of Torrejón between June 1st and June 19th, 2020. FINDINGS: We analyzed the serological test results of 229 cancer patients. We estimated an overall seroprevalence (IgG or IgM positive) of 31.4%. The probability of SARS-CoV-2 seropositivity was similar between men and women, type of treatment and cancer stage. The probability of seropositivity was significantly higher in cancer patients with pneumonia compared with cancer patients without pneumonia (Odds Ratio (OR) 7.65 [95% confidence interval (CI) 1,85-31,58]). INTERPRETATION: Our results show a higher rate of SARS-CoV-2 antibodies in cancer patients than in the general population. The role of those antibodies in the immune response against the virus infection is unclear.

Chemotherapy in a Breast Cancer Patient Heterozygous Carrier of Ornithine Transcarbamylase Deficiency.

Urea cycle disorders (UCDs) are an unusual genetic condition that may lead to hyperammonemia in catabolic situations such as surgery, infections or chemotherapy administration. Without specific treatment, it causes life-threatening encephalopathy. We present the case of a young woman, heterozygous carrier of ornithine transcarbamylase deficiency (OTCD) with breast cancer, who was treated with surgery, chemotherapy, radiotherapy and hormone therapy while following a protocol to minimize the risk of metabolic decompensation due to her condition.

High-Dose 8% Capsaicin Patch in Treatment of Chemotherapy-Induced Peripheral Neuropathy. A Systematic Review.

INTRODUCTION: This is a review of the evidence from studies of the efficacy and tolerability of topically applied and high-concentration (8%) capsaicin in chemotherapy-induced peripheral neuropathy. METHODS: For this review, we searched EMBASE and MEDLINE to June 20, 2020. The terms used in the search included capsaicin, capsaicin 8% patch, chemotherapy-induced peripheral neuropathy, and cancer. RESULTS: A total of 98 studies were obtained, but only five were selected for the final analysis, with a total of 95 patients included. Three of the studies are prospective and two retrospective, including less than 30 patients per study. Capsaicin 8% patch provides significant pain relief in chemotherapy-induced peripheral neuropathy in all of them. However, the small number of studies (and patients) evaluated require caution with these results. CONCLUSION: Additional clinical trials are required to establish the definitive role of the capsaicin patch in the future.

Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia: Review of the Literature and a Single-center Experience.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder that is commonly underdiagnosed. In 2015, it was recognized by the World Health Organization (WHO) classification of lung tumors as a premalignant lesion. DIPNECH syndrome is characterized by cough, exertional dyspnea, wheezing, and, less frequently, hemoptysis. We report the clinical and histological features and imaging findings in four cases of DIPNECH from our institution (Torrejon University Hospital, Madrid, Spain) between the years 2012 and 2019. DIPNECH represents a rare and poorly understood pulmonary disorder. Our limited single-center experience shows the slow and stable evolution of the disease. However, some exceptional cases may progress poorly if distant metastases occur.

[Microbiota, cancer and immune therapy]. / Microbiota, cáncer e inmunoterapia.

The relationship between cancer and microbes is complex and not entirely known. The objective of this manuscript is to review the scientific evidence on the relationship between the microbiome, cancer and immunotherapy. A non-systematic literature review was done in the databases MEDLINE, COCHRANE, and DATABASE, and articles of greater scientific rigor, mainly reviews or prospective studies/randomized clinical trials published to date (May 2018), were selected. Terms used in the search included: microbiome, microbiota, cancer, immune checkpoint inhibitors, PD-L1, PD-1 and CTLA-4.

La relación entre el cáncer y la microbiota es compleja y no del todo conocida. El objetivo de esta publicación es revisar la evidencia científica sobre la relación existente entre el microbioma, el cáncer y la inmunoterapia. Para ello se ha realizado una revisión no sistematizada de la literatura por medio de la consulta de la base de datos de MEDLINE, COCHRANE y DATABASE y se han seleccionado los artículos de mayor rigor científico, principalmente revisiones y estudios prospectivos/ensayos clínicos randomizados publicados hasta mayo de 2018. Los términos utilizados en la investigación fueron microbioma, cáncer, inmunoterapia, inhibidores de immune checkpoints, PD-L1, PD-1 y CTLA-4.

Metastatic Thymic Carcinoma with Long Survival After Treatment with Sunitinib.

Thymic carcinomas are the most aggressive histological subtype of thymic tumors with limited data to guide correct management. No standard treatments are available for patients with advanced thymic carcinoma after progressing while on platinum-based chemotherapy. We present a case of a patient with metastatic thymic carcinoma with an unusual response and favorable evolution after receiving treatment with sunitinib, obtaining a progression-free survival of 23 months, much higher than reported to date. We review the literature on the efficacy of sunitinib in metastatic thymic carcinoma after progression to first-line treatment with platinum combinations.