Update on the management of elderly patients with colorectal cancer

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans (AU)

Validation of the CoVID-TE model as a tool to predict thrombosis, bleeding, and mortality in the oncology patient with Sars-Cov-2 infection: a study by the SEOM cancer and thrombosis group.

PURPOSE: The CoVID-TE model was developed with the aim of predicting venous thrombotic events (VTE) in cancer patients with Sars-Cov-2 infection. Moreover, it was capable of predicting hemorrhage and mortality 30 days following infection diagnosis. The model is pending validation. METHODS/PATIENTS: Multicenter retrospective study (10 centers). Adult patients with active oncologic disease/ antineoplastic therapy with Sars-Cov-2 infection hospitalized between March 1, 2020 and March 1. 2022 were recruited. The primary endpoint was to study the association between the risk categories of the CoVID-TE model and the occurrence of thrombosis using the Chi-Square test. Secondary endpoints were to demonstrate the association between these categories and the occurrence of post-diagnostic Sars-Cov-2 bleeding/ death events. The Kaplan-Meier method was also used to compare mortality by stratification. RESULTS: 263 patients were enrolled. 59.3% were men with a median age of 67 years. 73.8% had stage IV disease and lung cancer was the most prevalent tumor (24%). A total of 86.7% had an ECOG 0-2 and 77.9% were receiving active antineoplastic therapy. After a median follow-up of 6.83 months, the incidence of VTE, bleeding, and death 90 days after Sars-Cov-2 diagnosis in the low-risk group was 3.9% (95% CI 1.9-7.9), 4.5% (95% CI 2.3-8.6), and 52.5% (95% CI 45.2-59.7), respectively. For the high-risk group it was 6% (95% CI 2.6-13.2), 9.6% (95% CI 5.0-17.9), and 58.0% (95% CI 45.3-66.1). The Chi-square test for trends detected no statistically significant association between these variables (p > 0.05). Median survival in the low-risk group was 10.15 months (95% CI 3.84-16.46), while in the high-risk group it was 3.68 months (95% CI 0.0-7.79). The differences detected were not statistically significant (p = 0.375). CONCLUSIONS: The data from our series does not validate of the CoVID-TE as a model to predict thrombosis, hemorrhage, or mortality in cancer patients with Sars-Cov-2 infection.

Update on the management of elderly patients with colorectal cancer.

Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans.

Prediction of serious complications in patients with pulmonary thromboembolism and solid cancer: Validation of the EPIPHANY Index in a prospective cohort of patients from the PERSEO study.

INTRODUCTION: There is currently no validated score capable of classifying cancer-associated pulmonary embolism (PE) in its full spectrum of severity. This study has validated the EPIPHANY Index, a new tool to predict serious complications in cancer patients with suspected or unsuspected PE. METHOD: The PERSEO Study prospectively recruited individuals with PE and active cancer or receiving antineoplastic therapy from 22 Spanish hospitals. The estimation of the relative frequency θ of complications based on the EPIPHANY Index categories was made using the Bayesian alternative for the binomial test. RESULTS: A total of 900 patients, who were diagnosed with PE between October 2017 and January 2020, were enrolled. The rate of serious complications at 15 days was 11.8%, 95% highest density interval [HDI], 9.8-14.1%. Of the EPIPHANY low-risk patients, 2.4% (95% HDI, 0.8-4.6%) had serious complications, as did 5.5% (95% HDI, 2.9-8.7%) of the moderate-risk participants and 21.0% (95% HDI, 17.0-24.0%) of those with high-risk episodes. The EPIPHANY Index was associated with overall survival (OS) in patients with different risk levels: median OS was 16.5, 14.4, and 4.4 months for those at low, intermediate, and high risk, respectively. Both the EPIPHANY Index and the Hestia criteria exhibited greater negative predictive value and a lower negative likelihood ratio than the remaining models. The incidence of bleeding at 6 months was 6.2% (95% HDI, 2.9-9.5%) in low/moderate-risk vs 12.7% (95% HDI, 10.1-15.4%) in high-risk (p-value = 0.037) episodes. Of the outpatients, serious complications at 15 days were recorded in 2.1% (95% HDI, 0.7-4.0%) of the cases with EPIPHANY low/intermediate-risk vs 5.3% (95% HDI, 1.7-11.8%) in high-risk cases. CONCLUSION: We have validated the EPIPHANY Index in patients with incidental or symptomatic cancer-related PE. This model can contribute to standardize decision-making in a scenario lacking quality evidence.

Immune checkpoint inhibitor-associated thrombosis in patients with bladder and kidney cancer: a study of the Spanish Society of Medical Oncology (SEOM) thrombosis and cancer group.

PURPOSE: Both venous and arterial thrombotic events (VTE/AT) can be associated with immune checkpoint inhibitors (ICI). However, there is a paucity of information apropos patients in routine clinical practice. METHODS/PATIENTS: Retrospective, multicenter study promoted by the Thrombosis and Cancer Section of the Spanish Society of Medical Oncology (SEOM). Individuals with kidney or bladder cancer who initiated ICI between 01/01/2015 and 12/31/2020 were recruited. Minimum follow-up was 6 months (except in cases of demise). The primary objective was to calculate the incidence of ICI-associated VTE/AT and secondary objectives included to analyze their impact on survival and identify variables predictive of VTE/AT. RESULTS: 210 patients with kidney cancer were enrolled. The incidence of VTE/AT during follow-up (median 13 months) was 5.7%. Median overall survival (OS) was relatively lower among subjects with VTE/AT (16 months, 95% CI 0.01-34.2 vs. 27 months, 95% CI 22.6-31.4; p = 0.43). Multivariate analysis failed to reveal predictive variables for developing VTE/ AT. 197 patients with bladder were enrolled. There was a 9.1% incidence rate of VTE/AT during follow-up (median 8 months). Median OS was somewhat higher in patients with VTE/AT (28 months, 95% CI 18.4-37.6 vs 25 months, 95% CI 20.7-29.3; p = 0.821). Serum albumin levels < 3.5 g/dl were predictive of VTE/ AT (p < 0.05). CONCLUSIONS: There appears to be no association between developing VTE/AT and ICI use in patients with renal or bladder cancer. Serum albumin levels are a predictive factor in individuals with bladder cancer.

Case-Control Analysis of the Impact of Anemia on Quality of Life in Patients with Cancer: A Qca Study Analysis.

Anemia is a common condition in cancer patients and is associated with a wide variety of symptoms that impair quality of life (QoL). However, exactly how anemia affects QoL in cancer patients is unclear because of the inconsistencies in its definition in previous reports. We aimed to examine the clinical impact of anemia on the QoL of cancer patients using specific questionnaires. We performed a post-hoc analysis of a multicenter, prospective, case-control study. We included patients with cancer with (cases) or without (controls) anemia. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life questionnaire version 3.0 (EORTC QLQ-C30) and Euro QoL 5-dimension 3-level (EQ-5D-3L) questionnaire. Statistically significant and clinically relevant differences in the global health status were examined. From 2015 to 2018, 365 patients were included (90 cases and 275 controls). We found minimally important differences in global health status according to the EORTC QLQ-C30 questionnaire (case vs. controls: 45.6 vs. 58%, respectively; mean difference: -12.4, p < 0.001). Regarding symptoms, cancer patients with anemia had more pronounced symptoms in six out of nine scales in comparison with those without anemia. In conclusion, cancer patients with anemia had a worse QoL both clinically and statistically.

A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry.

BACKGROUND: The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry. METHOD: TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain. RESULTS: Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p<0.0001). The 12-month cumulative incidence of venous rethrombosis was 7.1% (95% CI, 4.7-10.2) in stage IV vs 3.0% (95% CI, 0.9-7.1) in stages I-III. The 12-month cumulative incidence of major/clinically relevant bleeding was 9.6% (95% CI, 6.1-14.0) in the presence of risk factors. CONCLUSION: CAT continues to be a relevant problem in the era of immunotherapy and targeted therapies. The initial TESEO data highlight the evolution of CAT, with new agents and thrombotic risk factors.

A Case-Control Analysis of the Impact of Venous Thromboembolic Disease on Quality of Life of Patients with Cancer: Quality of Life in Cancer (Qca) Study.

Although there is published research on the impact of venous thromboembolism (VTE) on quality of life (QoL), this issue has not been thoroughly investigated in patients with cancer-particularly using specific questionnaires. We aimed to examine the impact of acute symptomatic VTE on QoL of patients with malignancies. This was a multicenter, prospective, case-control study conducted in patients with cancer either with (cases) or without (controls) acute symptomatic VTE. Participants completed the EORTC QLQ-C30, EQ-5D-3L, PEmb-QoL, and VEINES-QOL/Sym questionnaires. Statistically significant and clinically relevant differences in terms of global health status were examined. Between 2015 and 2018, we enrolled 425 patients (128 cases and 297 controls; mean age: 60.2 ± 18.4 years). The most common malignancies were gastrointestinal (23.5%) and lung (19.8%) tumors. We found minimally important differences in global health status on the EQ-5D-3L (cases versus controls: 0.55 versus 0.77; mean difference: -0.22) and EORTC QLQ-C30 (47.7 versus 58.4; mean difference: -10.3) questionnaires. There were minimally important differences on the PEmb-QoL questionnaire (44.4 versus 23; mean difference: -21.4) and a significantly worse QoL on the VEINES-QOL/Sym questionnaire (42.7 versus 51.7; mean difference: -9). In conclusion, we showed that acute symptomatic VTE adversely affects the QoL of patients with malignancies.

Clinical experience with plerixafor as a mobilization regimen for autologous peripheral blood stem cell transplantation in patients with refractory germ cell tumors.

The purpose of this study was to report our experience with administration of plerixafor for the mobilization of hematopoietic stem cells (HSCs) in patients with refractory or recurrent germ cell tumors who were candidates for salvage therapy with high-dose chemotherapy and HSC transplantation and for whom mobilization of HSCs had not been achieved by standard therapies. This retrospective and observational study selected patients who were eligible for autologous HSC transplantation (AHSCT) and received plerixafor after failure of HSC mobilization by granulocyte colony-stimulating factor (G-CSF). A total of 5 patients (4 male and 1 female), aged 19-41 years (mean age, 29.6 years) were initially selected. Four patients (80%) achieved an adequate HSC mobilization with plerixafor and subsequently received high-dose chemotherapy followed by HSC transplantation. In these patients, the number of CD34+ cells collected following plerixafor mobilization was 1.8×106-10.3×106 cells/kg, with a peak CD34+ cell count of 7.0-32.0 cells/µl. Following HSC infusion, these 4 patients achieved a neutrophil count of >0.5×103/mm3 and a platelet count of >20,000/µl between days 10 and 14. Therefore, patients with high-risk germ cell tumors eligible for AHSCT who are refractory to mobilization by G-CSF, may benefit from the use of plerixafor, possibly to the same extent as patients with lymphoma and multiple myeloma.

Effectiveness of oxaliplatin desensitization protocols.

INTRODUCTION: Hypersensitivity reaction (HSR) to antineoplastic drugs can force doctors to stop treatment and seek other alternatives. These alternatives may be less effective, not as well tolerated and/or more expensive. Another option is to use desensitization protocols that induce a temporary state of tolerance by gradually administering small quantities of the antineoplastic drug until the therapeutic dosage is reached. The aim of this study is to assess the effectiveness of oxaliplatin desensitization protocols. MATERIALS AND METHODS: A retrospective observational study was carried out between January 2006 and May 2011. The inclusion criteria were patients undergoing chemotherapy treatment with oxaliplatin who had developed an HSR to the drug and who were candidates for continuing the treatment using a desensitization protocol. The patients' clinical records were reviewed and variables were gathered relating to the patient, the treatment, the HSR, and the desensitization protocol administered. The data were analysed using version 18.0 of the statistics program SPSS. RESULTS: A total of 53 desensitization protocols were administered to 21 patients. In 89 % of these cases, no new reactions occurred while the drug was being administered. New reactions of mild severity only occurred in 11 % of cases, and none of these reactions were severe enough for treatment to be stopped. All patients were able to complete the desensitization protocol. CONCLUSION: This study confirms that oxaliplatin desensitization protocols are safe and effective and allow patients to continue with the treatment that initially caused an HSR.

The role of RANK-ligand inhibition in cancer: the story of denosumab.

The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-bone destruction was kept at bay a little longer. The next generation of bone metastasis treatments is well on its way in clinical development, and among them, the most advanced drug is denosumab. Denosumab is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption. In this review, we give an overview of relevant preclinical and clinical data regarding the use of denosumab in patients with solid tumors in general and prostate cancer in particular.

Adjuvant chemotherapy for stages II, III and IV of colon cancer.

Colorectal cancer is the third most frequent malignant neoplasm in Western countries. After complete resection, 5-year overall survival varies according to the initial stage. Adjuvant chemotherapy (CT) is indicated in patients with colon cancer at high-risk stage II, stage III and after complete resection of metastases. 5-Fluorouracil (5FU), alone or modulated with levamisol or leucovorin (LV), oral fluoropyrimidines, raltitrexed, irinotecan and oxaliplatin have been studied as adjuvant therapy for colon cancer. Nowadays, oxaliplatin-based regimens, FOLFOX or FLOX, are considered as the standard adjuvant CT. If there are contraindications for oxaliplatin, the best alternatives are capecitabine or continuous infusion of 5FU/LV. The role of monoclonal antibodies, cetuximab and bevacizumab, combined with oxaliplatin/fluoropyrimidine-based CT is under investigation in clinical trials. This article reviews the state of the art and the future perspectives of adjuvant therapy in colon cancer. Prognostic and predictive factors are also commented on.

Surgical resection of a solitary pancreatic metastasis from colorectal cancer: a new step to a cure?

Isolated metastases to the pancreas from colorectal cancer (CRC) are very rare. We report a case of a 37-year-old man with a hereditary nonpolyposis CRC with a solitary metastasis to the pancreas who was treated with right hemicolectomy, neoadjuvant chemotherapy, complete surgical resection of the pancreatic metastasis, and adjuvant chemotherapy. After 12 months of follow-up, the patient remains free of disease. Differential diagnosis of isolated metastasis to the pancreas should be performed with pancreatic primary adenocarcinomas and neuroendocrine tumors. Symptoms and signs might be similar in these diseases: pain, weight loss, obstructive jaundice, and duodenal obstruction. Nevertheless, both primary and secondary tumors might be totally asymptomatic. Imaging techniques such as computed tomography, ultrasonography, magnetic resonance imaging, positron emission tomography, or endoscopic retrograde colangiopancreatography can provide relevant information about pancreatic lesions. However, it remains difficult to distinguish primary from metastatic pancreatic tumors. Although there is currently very limited experience with the surgical resection of isolated pancreatic metastases from CRC, it should be considered in selected patients with low surgical risk in order to prolong progression-free survival and overall survival. Additional chemotherapy is recommended.