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.

Low total pathologic complete response rate to preoperative chemotherapy in patients with invasive lobular carcinomaof the breast.

INTRODUCTION: Total pathologic complete response (tpCR; ypT0/is ypN0) after preoperative chemotherapy (PCT) is associated with better outcome in locally advanced breast cancers. However, the tpCR rate according to histology is not usually considered in trials. MATERIAL AND METHODS: Patients with invasive lobular breast carcinoma (ILC), who were included in three phase II trials (AT, ATX, and TXH), were eligible. Expression of markers and clinical phenotypes (CPh) were determined by immunohistochemistry. The primary endpoint was tpCR rate in patients with ILC. Secondary endpoints were breast-conserving surgery rate (BCSR), event-free survival (EFS), and overall survival (OS). RESULTS: In the subgroup of patients with ILC (n = 16) the median age was 50 years, 56.25% were premenopausal, median tumour size was 5 cm, and 68.75% had clinically node involvement. Six patients (37.5%) had clinical stage II, and 10 (62.5%) had clinical stage III. Hormone receptor-positive disease was present in 93.75% of the patients, and median Ki-67 was 25%. CPh were Luminal A-like in 37.5%, Luminal B-like in 50%, HER2-positive in 6.25%, and triple negative in 6.25% of tumours. Only one patient (6.25%) had a tpCR, and another patient had a pathologic complete response (pCR) only in the breast. With a median follow-up of 146 months, median EFS was 120 months (95% CI: 68-139), and median OS was not reached. Ten-year EFS and OS probability were 47% and 60%, respectively. BCSR was only 12.5%. CONCLUSIONS: PCT in patients with ILC is associated with low tpCR rate because the majority of these patients have Luminal tumours with low chemo-sensitivity.

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.

Chemotherapy Plus Bevacizumab as Neoadjuvant or Conversion Treatment in Patients with Colorectal Liver Metastases.

AIM: To evaluate the efficacy of chemotherapy plus bevacizumab as neoadjuvant or conversion treatment for colorectal liver metastases (CLM). PATIENTS AND METHODS: A retrospective chart review was carried out of 74 patients with CLM treated with neoadjuvant or conversion chemotherapy plus bevacizumab. RESULTS: The overall response rate was 63.4%. An optimal morphological response by computed tomography was reported in 35% of patients. The rate of complete resection was 71.6%. Complete or major pathological response (pR) was attained in 58.2%. The median overall survival (OS) was not reached. Median progression-free (PFS) and relapse-free (RFS) survival were 14.6 and 8.7 months. Among patients reaching an optimal pR, median OS was not reached (p=0.08), and a trend towards longer RFS and PFS was seen. CONCLUSION: Neoadjuvant or conversion chemotherapy with bevacizumab is an active and tolerable option for CLM with minimal post-surgery complications. Optimal pR is associated with a longer OS and a trend for prolonged PFS and RFS.

Metastatic triple negative breast cancer: Optimizing treatment options, new and emerging targeted therapies.

Triple negative breast cancer (TNBC) is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. It also has a distinct epidemiology. TNBCs are frequently of high histologic grade, typically more aggressive and difficult to treat than hormone receptor-positive tumors, and they are associated with a higher risk of early relapse with visceral metastasis after surgery, chemotherapy and/or radiotherapy. The lack of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression precludes the use of targeted therapies in advanced stages, and the only approved systemic treatment option is chemotherapy with or without bevacizumab. In patients with advanced TNBC, responses to chemotherapy occur, but are often of short duration and it is associated with poor prognosis. The median overall survival for patients with metastatic TNBC is about 9-12 months with conventional cytotoxic agents. Given the suboptimal outcomes with chemotherapy, new targeted therapies for TNBC are urgently needed. This review summarizes the clinical efficacy, perspectives and future challenges of using new treatment options for metastatic TNBC, such as poly-ADP-ribose-polymerase inhibitors, antiandrogen therapies and immune checkpoint inhibitors (antiprogrammed death receptor-1/PD-L1 monoclonal antibodies).

[Palliative chemotherapy in metastatic adrenal carcinoma beyond the first line: a case report and literature review]. / Quimioterapia paliativa tras progresión a la primera línea en el carcinoma suprarrenal metastásico: caso clínico y revisión de la literatura.

There are no approved therapeutic regimes for adrenal carcinoma following progression to a first line of chemotherapy/mitotane although a high percentage of patients are candidates to receive them. In the present article we review the possible therapeutic alternatives after the progression to a first line of treatment in patients with adrenal carcinoma and we report a case in which a prolonged overall survival is achieved, much higher than expected, probably in relation to the multidisciplinary management of the case and the use of most of the therapeutic arsenal available.

En el carcinoma suprarrenal metastásico no existen esquemas de tratamiento aprobados tras la progresión a una primera línea de quimioterapia/mitotane, si bien un alto porcentaje de pacientes son candidatos a recibirlos. En este artículo realizamos una revisión sobre las posibles alternativas terapéuticas tras la progresión a una primera línea de tratamiento en pacientes con carcinoma suprarrenal metastásico. A propósito de la misma, se presenta un caso clínico en el que se consigue una prolongada supervivencia global, mucho mayor de la esperable, probablemente debido al manejo multidisciplinario del caso y a la utilización de la mayor parte del arsenal terapéutico disponible.

Opioids for management of episodic breathlessness or dyspnea in patients with advanced disease.

BACKGROUND: Episodic breathlessness (EB) or dyspnea is a common symptom with a very negative impact on the quality of life of patients with cancer and with non-oncological advanced diseases, mainly cardiorespiratory and neurological. OBJECTIVE: The purpose of this non-systematic review is to ascertain the role played by opioids in the management of episodic breathlessness. METHODS: 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 (August 2015), were selected. Terms used in the search included episodic breathlessness, acute breathlessness, episodic dyspnea, opioids, morphine, fentanyl, oxycodone, and breakthrough dyspnea. CONCLUSIONS: Although the pathophysiology and mechanism of action of opioids for management of breathlessness, and specifically EB, are not fully known, there is scientific evidence, and particularly great clinical evidence, of the benefit of this drug class for dyspnea management. It is important to differentiate hospitalized patients from outpatients because venous or subcutaneous access is easier in hospitalized patients, but use of transmucosal fentanyl, especially in faster formulations like intranasal application, opens up new possibilities to manage outpatients due to its fast onset of action. The main problem is the lack of data available and the multitude of unanswered questions about opioid type, administration route, safety, and dose titration.

Prevalencia y etiopatogenia del dolor oncológico neuropático en el anciano / Prevalence and aetiopathogenesis of neuropathic pain in elderly cancer patients

Es muy difícil estimar la prevalencia del dolor neuropático ya que la mayoría de los estudios que evalúan el dolor crónico no diferencian el nociceptivo del neuropático. Aún más complicado es obtener información de estudios que aborden específicamente el dolor neuropático en ancianos y más concretamente en población oncológica. En esta revisión no sistemática se analizan los artículos más relevantes acerca de la prevalencia y etiopatogenia del dolor oncológico neuropático en el anciano (AU)

The prevalence of neuropathic pain is difficult to estimate as most studies evaluating chronic pain do not differentiate neuropathic from nociceptive pain. There are only a few studies of neuropathic pain in the elderly, specifically in the oncology population. This article is a non-systematic review of the relevant evidence on the prevalence and aetiopathogenesis of neuropathic cancer pain in the elderly (AU)

[Prevalence and aetiopathogenesis of neuropathic pain in elderly cancer patients]. / Prevalencia y etiopatogenia del dolor oncológico neuropático en el anciano.

The prevalence of neuropathic pain is difficult to estimate as most studies evaluating chronic pain do not differentiate neuropathic from nociceptive pain. There are only a few studies of neuropathic pain in the elderly, specifically in the oncology population. This article is a non-systematic review of the relevant evidence on the prevalence and aetiopathogenesis of neuropathic cancer pain in the elderly.