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.

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.

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.

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.

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.

Prophylaxis of febrile neutropenia in adults receiving chemotherapy needs to be adapted to the risk.

A major advance in the management of febrile neutropenia (FN) has been the stratification of the population of adult patients with FN for the risk of complications and death. Using validated reliable predictive instruments, such as the Multinational Association for Supportive Care in Cancer score, it is possible to identify a population of 'low-risk' patients, who can benefit from simplified and less expensive therapeutic approaches (e.g., orally administered antimicrobial therapy and early home return). Prevention of FN by the use of granulopoietic colony-stimulating factor (G-CSF) has been successfully applied to patients at 'high risk' of developing FN. In addition to the aggressiveness of chemotherapy, which usually defines the 'high-risk' status, the role of a series of factors that increase both the risk of FN and the complications rate has been recognized and should probably be taken into consideration when selecting patients for G-CSF prophylaxis. The cost of the G-CSF is the major limiting factor for their broad use; further efforts should be made to match the cost issue with the need of protecting from the development of FN most patients treated with chemotherapy for cancer.

Adverse events of targeted therapies.

PURPOSE OF REVIEW: There is currently an explosion in the number of so-called targeted therapies. As new indications for these agents multiply, there is also an increase of new and less new side-effects. RECENT FINDINGS: Given this rapidly evolving field, any literature on that topic is rapidly obsolete and needs re-evaluation. SUMMARY: Targeted therapies are associated with a wide spectrum of adverse events, which cannot always be easily separated from the complications linked to cancer, its therapy, and comorbidities. A high awareness of these events might improve the patient's quality of life and contribute to the recognition of new syndromes.