A meta-analysis on the risk of infection associated with intravenous iron therapy in cancer-associated anaemia: a double-edged sword?

PURPOSE OF REVIEW: The increased use of i.v. iron in the treatment of cancer-associated anemia raises concerns about its risk of infectious complications. High levels of circulating iron could increase the risk of infection by compromising natural defence mechanisms and promoting pathogen growth. Since the risk of infection is particularly high in the oncological population, we have examined whether the use of i.v. iron increases the risk of infectious complications among cancer patients. FINDINGS: Among 18 randomized trials in our systematic review, only 8 reported infectious complications, with no significant difference linked to the type of i.v. iron preparation. Two trials showed a statistically significant increase in infectious complications, one trial found a lower risk, while the remaining 5 reported no significant difference. Our meta-analysis revealed a numerical increase in infectious complications in the i.v. iron group, but the lack of statistical significance and significant heterogeneity among the trials limit definitive conclusions on the actual infection risk. SUMMARY: Our findings suggest some increased risk in infectious complications after the administration of i.v. iron for cancer associated anaemia. However, i.v. iron therapy appears generally safe and effective in cancer-associated anaemia.

A new comprehensive and stratified concept for supportive care in cancer patients.

PURPOSE OF REVIEW: Supportive care in oncology has evolved alongside effective anticancer treatments since the 1960s, beginning with the advent of chemotherapy for acute leukemia. It was initially focused on managing treatment-induced complications, and expanded to address broader aspects of patient well being; the scope of supportive care needs to be periodically re-assessed. RECENT FINDINGS: Early palliative care interventions, and more recently advance care planning emerged as vital components, improving patient outcomes and quality of life. Despite barriers, such as prognostic uncertainty, these approaches have demonstrated significant benefits for patients with advanced disease. Additionally, the management of cancer survivors requires ongoing medical surveillance and psycho-social support. In the last years, integrative medicine has also emerged as a complementary approach to address survivors' holistic needs. SUMMARY: A proposed stratified model of supportive care emphasizes interventions based on patients' prognosis, with interdisciplinary collaboration ensuring comprehensive care across all stages of the cancer journey. This model provides a framework for the development of integrated supportive care units.

A prospective, real-world, multinational study of febrile neutropenia (FN) occurrence in oncology patients receiving chemotherapy with intermediate risk of FN: a MASCC Neutropenia, Infection, and Myelosuppression Study Group initiative.

PURPOSE: Limited knowledge is available on the incidence of febrile neutropenia (FN) in intermediate-risk patients and the rationale for use of granulocyte colony-stimulating factor (G-CSF) in these patients. We aimed to estimate the rate at which patients associated with intermediate risk (10-20%) of FN would develop ≥ 1 episode of FN with a commonly used chemotherapy regimen in clinical practice. METHODS: This prospective, real-world, observational, multinational, multicenter study (December 2016-October 2019) recruited patients with solid tumors or Hodgkin's/non-Hodgkin's lymphoma. Patients receiving chemotherapy with intermediate risk of FN, but not G-CSF as primary prophylaxis were included and observed for the duration of the chemotherapy (≤ 6 cycles and ≤ 30 days after the last chemotherapy administration). RESULTS: In total, 364 patients (median age, 56 years) with 1601 cycles of chemotherapy were included in the analysis. The incidence of FN was 5% in cycle 1, 3% in cycles 2-3, and 1% in cycles 4-6. The rate of patients with ≥ 1 episode of FN was 9%, and 59% of FN events were reported during cycle 1. The rate of grade 4 neutropenia in cycle 1 was 11%, and 15% of patients experienced ≥ 1 episode of grade 4 neutropenia. CONCLUSIONS: Overall, the incidence of FN was low, with a high incidence in cycle 1 and a decrease in the subsequent cycles. These results provide the real FN risk for common chemotherapy regimens in patients generally excluded from clinical trials. Prophylactic G-CSF in intermediate-risk patients could be considered as per clinician's judgement.

The conquest of lung cancer in Central Europe.

PURPOSE OF REVIEW: Discussed the main approaches for lung control and point out differences among Central Europe and other countries. RECENT FINDINGS: Three main approaches exist: smoking ban, early computed tomography screening and access to novel therapies; major differences exist between Central Europe and some other countries. SUMMARY: A major effort will be needed from Central Europe countries in all three approaches; it will require strong involvement from the political authorities.

Supportive care for cancer patients: a survey of available settings and current practices in Belgium.

INTRODUCTION: The increasing number of cancer diagnoses and deaths underlines the importance of supportive and palliative care. It is defined as "all the care and the support necessary for patients throughout their illness." AIM: To evaluate the current status of the supportive and palliative care organization in Belgium. METHODS: The Belgian Society of Medical Oncology (BSMO) supportive care task force conducted an observational study by sending a 31-point questionnaire to medical doctors responsible for the supportive care units of university, public, or private hospitals in Belgium. RESULTS: Thirty centers completed the questionnaire, of which 12 were university hospitals. Inpatient supportive care units are available in more than 50% of the centers, whereas outpatient supportive care is less available in Brussels than in Flanders and Wallonia. Multidisciplinary teams or specific units dedicated exclusively to supportive care are represented less frequently in all 3 areas of Belgium. Intensive care units for cancer patients are even scarcer. In terms of research and teaching, active research is present in 10 (33%) centers. Of complementary and alternative medicine modalities available to cancer patients, mindfulness and massage are offered most frequently. Reference guidelines for various symptoms are widely used in Flanders and Brussels but less so in Wallonia. CONCLUSION: This is the first in-depth survey in Belgium that shows the limited availability of dedicated supportive care services throughout the country. This represents an unmet need for Belgian cancer patients. Within the BSMO supportive care task force, there is a great opportunity to expand services and develop active research in the area of supportive and palliative care.

Use of granulocyte-colony stimulating factors in older patients: a review of recently published data.

PURPOSE OF REVIEW: This review presents the analysis of recently published studies about the benefit from granulocyte-colony stimulating factors (G-CSF) in older cancer patients receiving chemotherapy. RECENT FINDINGS: During the last years, no major study aiming to confirm the clinical benefit of G-CSF prophylaxis in older patients treated with chemotherapy has been published. Nonetheless, all the data made recently available confirm that age, especially if other comorbid conditions are present as well, is a major risk factor for febrile neutropenia occurrence and that G-CSF prophylaxis can reduce significantly that risk. SUMMARY: New modalities of administering G-CSF prophylaxis might be considered in older people in the future. Among these approaches, the 'same day' administration of prophylaxis and chemotherapy and the development of less-expensive approaches for G-CSF prophylaxis, such as the use of biosimilars are studied.

The close interrelation between colorectal cancer, infection and microbiota.

PURPOSE OF REVIEW: Evaluate the recent literature about the relation of clinical infection and colorectal cancer in terms of diagnosis of an occult infection and possible impact on oncological outcome and review the possible role of the gut microbiota in the role of colorectal cancer oncogenesis. RECENT FINDINGS: Data published within the 2 last years have been reviewed and the conclusions, mostly supporting previously published information, have been critically discussed. SUMMARY: Infection (bacteremia, cellulitis) might be a surrogate of occult colorectal cancer and postoperative infection complications might jeopardize long-term survival after potentially curative surgery. The role of the gut microbiota in the genesis of colorectal cancer remains an exciting though unresolved question.

Supportive care in the era of immunotherapies for advanced non-small-cell lung cancer.

PURPOSE OF REVIEW: The therapeutic armamentarium for advanced non-small-cell lung cancer has evolved considerably over the past years. Immune checkpoint inhibitors targeting programmed cell death-1 such as pembrolizumab and nivolumab or programmed cell death ligand 1 such as atezolizumab, durvalumab and avelumab have shown favorable efficacy results in this patient population in the first-line and second-line setting. These immunotherapies are associated with a distinct toxicity profile based on autoimmune organ toxicity which is a new challenge for supportive care during treatment with these drugs. RECENT FINDINGS: The differential diagnosis of events occurring during immune checkpoint inhibitor treatment is broad: they can be due to immune-related or nonimmune-related adverse events, atypical tumor responses (pseudoprogression or hyperprogression) or events related to comorbidities or other treatments. SUMMARY: The management of these patients includes a thorough baseline clinical, biological and radiologic evaluation, patient education, correct follow-up and management by a multidisciplinary team with a central role for the medical oncologist. Immune-related toxicities should be managed according to available guidelines.

The concept of oligometastases in colorectal cancer: from the clinical evidences to new therapeutic strategies.

PURPOSE OF REVIEW: The concept of oligometastases, defining cancers with limited metastatic capacity and attaining a limited number of secondary sites, is now widely accepted, particularly in colorectal cancer. Currently, however, accurate predictive markers for oligometastatic tumors are still lacking. For this reason, it remains challenging to translate this concept into clinical recommendations. In the present work, we review recent publications on oligometastases in colorectal cancer, showing the evidences for such presentation and underlying the need for the identification of biomarkers, necessary to further develop new therapeutic strategies. RECENT FINDINGS: This review of recently published series confirms that long-term survival and cure could be obtained in patients undergoing surgical resection for colorectal metastases, particularly in the cases of liver metastases. Similar results are observed in other secondary sites such as in pulmonary metastases. Furthermore, in patients with unresectable metastases, significant survival benefit could be still obtained using nonresectional targeted approaches, as thermal ablation or stereotactic radiotherapy. Although these clinical evidences could now serve as proof-of-concept for the existence of an oligometastatic phenotype in colorectal cancer, neither clinical characteristics nor biological biomarkers have been established to be able to prospectively define the patients that will benefit from such therapeutic approaches targeting the metastatic sites. This emphasizes the need for further studies aiming at better defining early clinical and biological characteristics of these patients. As, currently, the reliable identification of the oligometastatic patients could only rely on the demonstration of favorable long-term outcomes after metastases-directed therapies, we propose that retrospective studies will be pivotal to analyze this question. SUMMARY: Extensive research is undergoing to define biologically the oligometastatic phenotype in colorectal cancer. Currently, the selection of the patients for potentially curative metastasectomy remains mostly empirical.

Febrile neutropenia (FN) occurrence outside of clinical trials: occurrence and predictive factors in adult patients treated with chemotherapy and an expected moderate FN risk. Rationale and design of a real-world prospective, observational, multinational study.

BACKGROUND: Febrile neutropenia (FN) is a common occurrence during chemotherapy. Granulocyte colony-stimulating factors (G-CSFs) can significantly reduce the risk of FN. International guidelines recommend G-CSF for patients receiving chemotherapy with FN risk of ≥20% or 10% to 20% with defined risk factors. Prophylaxis is not typically recommended for FN risk of < 10%; however, few studies have investigated FN incidence in lower-risk patients in real-world settings and tried to identify higher-risk subgroups. METHODS: This real-world prospective, observational, multinational study aims to estimate the rate of development of FN with a chemotherapy line expected to be associated with a 10% to 20% risk of FN. Eligible patients (> 18 years of age) will have a solid tumour or Hodgkin/non-Hodgkin lymphoma and a planned chemotherapy regimen with expected risk of FN of 10% to 20% (according to published guidelines). Patients will be observed for the duration of the chemotherapy line (first cycle administered without FN prophylaxis). Primary endpoint is incidence of FN after the first chemotherapy cycle. Secondary outcomes include: FN-associated morbidity and mortality; time to first FN occurrence; other FN risk factors and impact of FN on quality of life. A risk model using occurrence of FN as a binary outcome will be developed. Data will be stratified by age, comorbidities and other risk factors. DISCUSSION: This study will provide insight into the real FN risk for common chemotherapy regimens and predictive factors for FN, including patients generally excluded from randomised clinical trials, from which reported FN rates have been variable. This study builds on knowledge of predictive factors from other research and will provide information on patients with 10% to 20% FN risk.

Meta-analysis and indirect treatment comparison of lipegfilgrastim with pegfilgrastim and filgrastim for the reduction of chemotherapy-induced neutropenia-related events.

Background Granulocyte colony-stimulating factors are effective at reducing the risk and duration of neutropenia. The current meta-analysis compared the neutropenia-related efficacy and safety of lipegfilgrastim to those of pegfilgrastim and filgrastim. Methods Embase was searched for trials examining the efficacy/safety of lipegfilgrastim, pegfilgrastim, or filgrastim. Outcomes included febrile neutropenia, severe neutropenia, duration of severe neutropenia, time to recovery of absolute neutrophil count, and incidence of bone pain. Direct comparisons were made using random-effects models. No trials directly compared lipegfilgrastim and filgrastim. Indirect comparisons were made between lipegfilgrastim and filgrastim with pegfilgrastim as the common comparator. Results This meta-analysis included a total of 5769 patients from 24 studies. Over all cycles, lipegfilgrastim showed a lower, nonsignificant risk of febrile neutropenia compared with pegfilgrastim. Lipegfilgrastim has a lower risk of febrile neutropenia versus filgrastim but was also not statistically significant. The risk ratio for severe neutropenia in cycle 1 was 0.80, a 20% reduction in favor of lipegfilgrastim. For cycles 2-4, the risk ratio was 0.53 (0.35, 0.79) for lipegfilgrastim versus pegfilgrastim. The risk of severe neutropenia in cycles 2-4 was also significantly lower for lipegfilgrastim (risk ratio 0.45, 0.27, 0.75, respectively). No significant differences were found for febrile neutropenia and severe neutropenia in cycle 1. However, in cycles 2-4, lipegfilgrastim was associated with significant and clinically meaningful reductions in risk of severe neutropenia versus either pegfilgrastim or filgrastim. Conclusions Compared with pegfilgrastim or filgrastim, lipegfilgrastim has a statistically significantly lower absolute neutrophil count recovery time; however, differences in duration of severe neutropenia and bone pain were nonsignificant.

Concurrent driver mutations/rearrangements in non-small-cell lung cancer.

PURPOSE OF REVIEW: The concept of mutually exclusive oncogenic driver alterations has prevailed over the past decade, but recent reports have stressed the possible occurrence of dual-positive non-small-cell lung cancer (NSCLC) and even triple-positive disease for these oncogenes. This entity presents novel prognostic and therapeutic challenges. The present review highlights the available data in an effort to clarify the clinical and pathological significance of coexisting mutations as well as the subsequent therapeutic consequences. RECENT FINDINGS: Patients with a known driver oncogene can be successfully treated with the appropriate tyrosine kinase inhibitor, which will provide them with significant responses and lesser toxicities compared with cytotoxic therapy. Unfortunately, most patients will eventually progress. Although some resistance mechanisms have been identified, others remain to be determined but the emergence of secondary oncogenes could be part of the answer. SUMMARY: Approximately 20-25% of NSCLC harbor treatable driver mutations/rearrangements; epidermal growth factor receptor mutation, anaplastic lymphoma kinase and ROS-1 gene rearrangements are the main alterations for which a Food and Drug Administration-approved tyrosine kinase inhibitor can be used.Because of recent technological advances, high sensitivity assays with a broad range of genomic targets have become more easily accessible in clinical practice, which has led to an increased detection of coexisting driver alterations in patients with advanced NSCLC. The prognostic/predictive and therapeutic implications of this novel entity are still unsettled for the time being. Randomized trials specifically designed to address this subset of patients will soon be necessary to help determine the optimal therapeutic agent to administer.

Physical long-term side-effects in young adult cancer survivors: germ cell tumors model.

PURPOSE OF REVIEW: After the important advances in the treatment of germ cell tumors (GCTs) leading to high cure rates, physical long-term side-effects represent an important cause of death in these young adult survivors. Highlighting these physical long-term side-effects, their monitoring and their prevention modalities is necessary for a better management of these cancer survivors. RECENT FINDINGS: Impaired fertility, increased risk of developing a second cancer, cardiac, pulmonary, renal and neural toxicity, hearing and vision impairment are the major physical side-effects in young adult cancer survivors. Long-term cardiac toxicity, next to second malignancies, represents life-threatening conditions in testicular cancer survivors. The long-term nephrotoxity in testicular GCTs survivors is most frequently associated to the treatment either in those treated with cisplatin-based chemotherapy, mainly Bleomycine, Etoposide, Cisplatin, or those receiving infradiaphragmatic radiation therapy, whereas pulmonary toxicity is mainly attributed to bleomycin related toxicities. SUMMARY: There are no clear and comprehensive data concerning the monitoring and prevention of long-term side-effects in testicular cancer survivors. Physical activity and interventions in modifiable cardiovascular risk factors and lifestyles may reduce the incidence of long-term side-effects in these cancer survivors.

Supportive care for patients undergoing immunotherapy.

Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections. Checkpoint inhibitors have been approved for use in different malignancies including metastatic melanoma, advanced non-small cell lung cancer, metastatic renal cell carcinoma, refractory Hodgkin's lymphoma, metastatic bladder cancer, and advanced head and neck cancer, and the list continues to grow. In general, these agents seem to be better tolerated in most patients and less toxic compared to conventional chemotherapy. However, the toxicities here, termed immune-related adverse events (irAEs), are unique and different from what we have seen in the past. There is no prospective data on these toxicities, and guidelines or recommendations are currently based on symptomatic management from the ongoing clinical trials. Treating oncologists need to be aware and alert themselves to the subtleties in presentation and the big difference in the way we manage the irAEs. Although most irAEs are low-grade and manageable, they have the potential to be life-threatening and extremely severe if not promptly treated. Additionally, irAEs could even lead to death, if managed incorrectly. The MASCC workshop addressed the various irAEs, per organ system, clinical presentation, management recommendations, and individual toxicities.

Side-effects of checkpoint inhibitor-based combination therapy.

PURPOSE OF REVIEW: After the dramatic and often long-standing response rates of checkpoint inhibitors as single agents, the new era for checkpoint inhibitors is combined therapy (either with other checkpoint inhibitors, chemotherapies, targeted therapies or immunotherapies) that is aiming to do even better. Although one can speculate that these combinations will result in improved results, high cost and potential toxicity are limiting factors for their use. In this review, we plan to report on the different side-effects of the checkpoint inhibitor-based combination therapies and to discuss the future perspectives of these new modalities. RECENT FINDINGS: Many checkpoint inhibitor-based combinations are associated with high response rates (>50%) in melanomas and nonsmall cell lung cancers (NSCLCs). As a result, the combination of nivolumab and ipilimumab for metastatic melanoma was recently approved by the Food and Drug Administration; however, 30% of the patients had to discontinue this combination because of high toxicity. In NSCLC, the combination of chemotherapy and anti-programmed cell death protein 1 or anti-programmed cell death protein ligand 1 agents is leading to high response rate (exceeding 65%) but with more than 40% of the patients presenting grade 3/4 toxicities. Despite the discouraging results with the combination of ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4) with vemurafenib (anti-proto-oncogene protein B-raf-targeted therapy) due to hepatotoxicity, more recent trials are showing less frequent and severe toxicities with other combinations of checkpoint inhibitors and targeted therapies. SUMMARY: Despite the high toxicity rates observed with some checkpoint inhibitor-based combination therapies, these combinations will likely become the new paradigm for the management of various malignancies, namely, melanomas, renal cell carcinomas and NSCLC, provided that their side-effects can be effectively managed.

Supportive/palliative care in cancer patients: quo vadis?

Supportive care in cancer has become a paradigm for the treatment in oncology. Now, we have guidelines and active research in that field, making this area of clinical oncology both authoritative and rapidly progressing.The present paper focuses on the clinical experience of a group involved with supportive care in cancer patients for more than 25 years; it is hoped that our considerations might be helpful for further developments in this concept.