Rare cancers and therapy最新文献

Lentigo maligna (LM) and lentigo-maligna melanoma (LMM) are pigmented skin lesions that may exist on a continuous clinical and pathological spectrum of melanocytic skin cancer. LM is often described as a "benign" lesion and is accepted as a melanoma in situ; LM can undergo malignant transformation to particularly aggressive melanoma. LMM is an invasive melanoma that shares properties of LM, as well as exhibiting the metastatic potential of malignant melanoma. Unfortunately, LM/LMM diagnosis based on dermoscopy is rather ambiguous, and these lesions are often mistaken for junctional dysplastic nevi over sun-damaged skin, pigmented actinic keratosis, solar lentigo, or seborrheic keratosis. Diagnosis must be made on biopsy using distinct dermatopathologic features. These include a pagetoid appearance of melanocytes, melanocyte atypia, non-uniform pigmentation/distribution of melanocytes, and increased melanocyte density in a background of extensive photodamage. Advancements in immunohistochemical staining techniques, including soluble adenylyl cyclase (antibody R21), makes diagnosis easier and allows the definition of borders down to a single cell. After a pathologic diagnosis, there are a variety of treatment options, both surgical and non-surgical. Although surgical removal with a wide excision border is the preferred treatment due to decreased recurrence rates, experimental combination therapies are gaining popularity. However, no matter the treatment, LM/LMM carries a high recurrence rate, and patients must be monitored rigorously for recurrence as well as the appearance of additional skin lesions/cancers.

Multiple myeloma (MM) is a clonal plasma cell disorder defined by bone marrow infiltration and osteolytic bone lesions and is the second most common hematologic malignancy after non-Hodgkin lymphoma. The landscape of MM treatment was transformed at the dawn of the twenty-first century by the introduction of novel agents including proteasome inhibitors (bortezomib) and immunomodulatory drugs (thalidomide, lenalidomide), which have prolonged the survival of MM patients. The recently revised International Myeloma Working Group diagnostic criteria for MM added validated biomarkers (clonal bone marrow plasma cell ≥60%, involved:uninvolved serum free light chain ratio ≥100, or >1 focal lesion on magnetic resonance imaging) to identify near inevitable progression to symptomatic MM requiring therapy. In addition, the definition of myeloma-defining CRAB features (hypercalcemia, renal failure, anemia, and bone lesions) has been refined based on advances in imaging and laboratory techniques since the 2003 IMWG consensus. Despite expanded treatment options, MM remains an incurable disease. Drug resistance and clonal evolution remain problematic, and novel therapeutic agents are needed. New approaches to myeloma treatment include anti-CD38 antibodies, next generation proteasome inhibitors, epigenetic modulation with histone deacetylase inhibitors, and targeting the tumor microenvironment. In this article, the diagnosis, staging, and prognostic stratification of newly diagnosed MM will be reviewed. Clinical data pertaining to the emerging targeted agents will be discussed, and a suggested framework for integration of these new therapeutic options will be provided.

Acute promyelocytic leukemia (APL) is a molecularly well-defined disease, characterized by a specific chromosomal translocation; the improvement in biologic and clinical knowledge and subsequent introduction of molecularly targeted therapies have transformed the management of APL, with survival rates now exceeding 80%. Minimal residual disease (MRD) assessment in APL is the most important tool for its treatment; the prognostic role of the molecular detection of promyelocytic leukemia retinoic acid receptor α (PML-RARα) transcript after consolidation therapy in the early identification of the following hematologic relapse is now well established and guides preemptive therapy. First experiences performed with a qualitative polymerase chain reaction (PCR) approach were replaced with more accurate real-time quantitative PCR (RQ-PCR), which guarantees a numeric quantification of MRD. The identification of arsenic trioxide (ATO) as a valid therapy not only in relapsed patients but also as an alternative to standard therapy alone or in association with all-trans-retinoic acid enlarges the setting of validation of MRD evaluation in APL patients, considering a possible different clearance of PML-RARα with innovative therapy different from the standard ones. MRD monitoring demonstrated its validity also in the setting of relapsed patients with interesting results in the autologous and allogeneic stem cell transplantation setting or with the use of other biological agents. The aim of this review is to report and discuss the actual state of the art of MRD in APL.

Although selected older adults with acute myeloid leukemia can benefit from intensive therapies, recent evidences support the use of lower-intensity therapies (hypomethylating agents or low-dose cytarabine) in most of these patients and emphasize the importance of tolerability and quality of life. Individualized approaches to treatment decision-making beyond consideration of chronologic age alone should therefore be considered. One promising strategy is to combine low-intensity treatments with novel agents.

Sarcomas are uncommon malignancies accounting for about 1% of all adult malignancies. Sarcomas are a heterogeneous group of tumors which includes more than 100 different subtypes. Surgery is the mainstay therapy for localized disease. In selected patients the combination of surgery with radiotherapy achieves better local control and offers the best chance of cure. Systemic treatment including cytotoxic chemotherapy or targeted therapies remains the mainstay therapy for most patients with advanced disease. There are a wide variety of clinical situations, such that an individualized treatment plan must be defined by a multidisciplinary tumor board. Treatment decisions should take into consideration the histology, site of disease, stage, performance status, treatment goals, and the patient's wishes. The management of patients should be carried out in a center with expertise in the treatment of sarcomas for optimal outcome. This review will cover the different treatment modalities of adult soft tissue sarcomas.

Oropharyngeal cancers caused by human papillomaviruses (HPV) have a different epidemiology, prognosis, genetic mutational landscape, response to treatment, and outcome when compared to HPV-negative cancers. In this review, a summary of our current understanding of HPV in head and neck cancer and the important advances that have shown HPV to be an etiological agent are discussed. HPV-positive and HPV-negative tumors are compared discussing clinicopathological factors, prognosis, outcome following treatment, and the molecular and genetic differences. Currently, the standard of care for oropharyngeal cancer is both surgery and post-operative radiotherapy with or without cisplatin or concurrent chemo-radiotherapy. The latter is used more often, especially in cancers of tonsil and base of tongue. However, there is increased interest in trying to de-intensify treatment and in the development of new treatments to target the underlying different molecular pathways of HPV-positive cancers. The current clinical trials involving surgery, chemotherapy, and radiation therapy are discussed. The new targeted treatments are also summarized. Although there is currently is no evidence from prospective studies to support a change in the treatment algorithm, the treatment options for patients with HPV-positive disease are likely to change in the future.

Patients suffering from pancreatic neuroendocrine tumors (pNETs) are now candidates to receive novel approved drugs that have demonstrated benefit in disease control rate and delay the time taken for tumor progression in Phase III clinical trials; for example, sunitinib, everolimus and lanreotide. Though pNETs represent a rare and heterogeneous disease, recent approaches are being taken to better understand the molecular pathways involved in carcinogenesis. Consequently, new treatment strategies are now available and others still under investigation show promising results. However, some questions around how to approach patients with pNETs are still unresolved, such as what the best sequence of treatments we can offer to each of our patients in the clinic at any time of their disease would be. Therapeutic decisions are, at the moment, guided by clinical judgment, based on different parameters coming from retrospective analysis and non-randomized clinical trials. However, advances in genomic research would lead to a more precise approach using therapeutic targets that would also allow the development of new agents, prognostic or predictive biomarkers and a better understanding of resistance mechanisms. The following article is a comprehensive review of the approved and investigational drugs in pNET, and highlights the current concerns about treatment sequencing, but also provides an update of some of the present and future efforts for an improvement in the therapeutic algorithm of the disease.

In recent years the availability of several tyrosine kinase inhibitors (TKI) in the therapeutic armamentarium for chronic myeloid leukemia has dramatically changed the objectives and expectations of healthcare providers and patients. For many, but not all, patients the forerunner of TKI, imatinib, is still an excellent treatment option. Unfortunately, nearly 30-40% of imatinib-treated patients discontinue therapy in the long-term, because of failure and/or intolerance. Second-generation tyrosine kinase inhibitors are more potent drugs which are suitable for treatment of approximately 50% of patents for whom imatinib is unsuitable, and with high success and rapid responses. Bosutinib, an orally bioavailable Src/Abl tyrosine kinase inhibitor, has proved to be effective in vitro against resistant chronic myeloid leukemia cells that do not harbor the T315I or V299L ABL kinase domain mutations. During clinical development the manageable safety profile of bosutinib have become evident for both simple and more advanced treatment. In this review we summarize preclinical and clinical data for bosutinib and discuss its ideal field of action in comparison with other TKI.