Summary
Post‐transplant lymphoproliferative disorder (PTLD) is rare and heterogeneous lymphoid proliferations that occur as a result of immunosuppression following solid organ transplant (SOT) and ...haematopoietic stem cell transplant (HSCT) with the majority being driven by EBV. Although some histologies are similar to lymphoid neoplasms seen in immunocompetent patients, treatment of PTLD may be different due to difference in pathobiology and higher risk of treatment complications. The most common treatment approach in SOT PTLD after failing immunosuppression reduction (RIS) takes into consideration a risk‐stratified sequential algorithm with rituximab +/− chemotherapy based on phase 2 studies. In HSCT PTLD, RIS alone and chemotherapy are usually ineffective making rituximab +/− RIS as the gold standard of frontline treatment. In this review, we give an update on the treatment of PTLD beyond RIS. We highlight the most recent studies that attempted to incorporate more aggressive chemotherapy regimens and novel treatments into the traditional risk‐stratified sequential approach. We also discuss the role of EBV‐cytotoxic T lymphocytes in treatment of EBV‐driven PTLD. Other novel agents with potential role in PTLD will be discussed in addition to the challenges that could arise with chimeric antigen receptor T‐cell therapy and immune checkpoint inhibitors in this population.
Cytokines regulate both the innate and adaptive immune responses to cancer. Although antitumor activity has been seen for several cytokines in preclinical models, they have had limited success as ...single therapeutic agents in clinical trials of cancer immunotherapy. However, the possible combinations of cytokines with other immune therapeutics and the advancement in genetic engineering, synthetic biology and cellular and immune therapy has led to the revival of interest in cytokines as anticancer agents. This article will review several immunostimulatory cytokines with anticancer activity, focusing on the those that have been studied in treatment of lymphoma and highlighting recent advances of potential clinical relevance.
Prognosis for patients with refractory/relapsed (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Immune-based therapeutic treatments such as CD19 Chimeric Antigen Receptor (CAR) T cell therapies ...have dramatically changed the treatment landscape for R/R DLBCL leading to durable remissions in ~ 50% of patients. However, there remains an unmet need for developing novel therapies to improve clinical outcomes of patients not responding or relapsing after CAR T cell therapies. Lack of suitable immunotherapeutic targets and disease heterogeneity represent the foremost challenges in this emerging field. In this review, we discuss the recently approved and emerging novel immunotherapies for patients with R/R DLBCL in the post-CAR T era and the cell surface targets currently used.
The economic burden of metastatic pancreatic cancer Malangone-Monaco, Elisabetta; Doleh, Yunes; Cole, Ashley ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
October 2020, 2020-10-00, 20201001, Letnik:
20, Številka:
7
Journal Article
Recenzirano
Objectives: Pancreatic cancer (PC) is a costly disease with a limited life-expectancy as it generally presents as an advanced, metastatic disease. Though current literature suggests cost varies by ...first line treatment, there is limited real-world knowledge about the economic burden of pancreatic cancer. This study describes the economic burden of pancreatic cancer patients overall and by observed first line treatments.
The IBM MarketScan databases were used to identify adult metastatic PC patients from January 1, 2010 through 3/31/2017. Those without other primary cancers, pregnancy, or prior PC treatment, and with 6 months of continuous enrollment prior to PC were included. Treatment patterns and healthcare utilization and expenditures were measured during the variable-length follow-up period. Continuous measures were presented as per patient per month (PPPM).
A total of 6,360 patients met all inclusion criteria. Almost half (46.8%) of patients were untreated. Gemcitabine alone (15.6%) and FOLFIRINOX (11.4%) were the most commonly observed first line regimens. Treated patients incurred $17,513 PPPM (Gemcitabine alone) to $27,889 PPPM (FOLFIRINOX) during follow-up. Untreated patients incurred the highest unadjusted ($30,777 PPPM) and adjusted ($20,392 PPPM) cost.
Metastatic PC patients incur a high economic burden driven by high utilization of healthcare resources, which varies by first line treatment. Also, the high proportion of untreated patients is alarming as these patients may be the most expensive of all patients. There is an unmet need in these patients for effective treatments that also reduce their economic burden.
The improvement in outcomes seen with the introduction of rituximab, a CD20 monoclonal antibody in combination with chemotherapy or as a single agent in the treatment of indolent non-Hodgkin ...lymphomas has paved the way for development of various forms of monoclonal antibodies that act in different ways against non-Hodgkin lymphoma tumor cells. These could directly target a single surface antigen resulting in various ways of tumor cells toxicity and killing. Other forms of monoclonal antibodies include antibody-drug conjugates and bispecific antibodies. The role of therapeutic monoclonal antibodies in the treatment of lymphoma will be reviewed, highlighting their mode of action, clinical efficacy, and side effects.
Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in ...patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4-8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
In the follow-up of Hodgkin's lymphoma patients, the focus in the first 5 years is to detect recurrence, while after 5 years, the focus is on limiting and detecting late effects of treatment. In the ...first 5 years post-treatment, routine history and physical and computed tomography (CT) imaging (more frequent in the first 2 years) are generally appropriate. However, there are limited data to support the role of positron emission tomography scanning as routine follow-up. Beyond 5 years post-treatment, annual history and physical is appropriate, although there is no longer a role for routine imaging for recurrences. Women irradiated to the chest area at a young age (<35) would benefit from annual mammogram screening given the increased breast cancer risk. Magnetic resonance imaging can be considered, although there is a lack of data supporting its role in this population. Low-dose chest CT for lung cancer screening in patients with history of mediastinal irradiation and/or alkylating chemotherapy exposures and a smoking history can be considered, although data on its utility is lacking. Cardiac screening with echocardiogram and exercise tolerance tests in patients with history of mediastinal irradiation and/or adriamycin exposure may be appropriate, although the optimal screening interval would depend on mediastinal dose, adriamycin dose, presence of other cardiac risk factors and findings at the baseline screening. Patients at risk for cardiac disease due to treatment exposure would also benefit from lipid screening every 1-3 years.
Combined-modality therapy, consisting of chemotherapy followed by radiation therapy (RT), represents the standard of care for most patients with unfavorable-prognosis early-stage Hodgkin's lymphoma. ...The most widely accepted chemotherapy regimen is ABVD (Adriamycin, bleomycin, vinblastine, and dacarbazine); however, recent trials have evaluated other regimens such as BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) and Stanford V. After chemotherapy, the standard radiation field is involved-field RT, although there is increasing interest now in involved-node RT. The authors review recent trials on chemotherapy and RT for unfavorable-prognosis early-stage Hodgkin's lymphoma. This article presents illustrative clinical cases, with treatment recommendations from an expert panel of radiation oncologists and medical oncologists.
The loss of expression of NES1, a novel putative tumor suppressor gene, is an early marker of breast tumorigenesis. NES1 is expressed in normal breast tissue and ductal hyperplasia but is absent or ...markedly diminished in invasive cancer. In cases of ductal carcinoma
in situ (DCIS), NES1 expression has been shown previously to be present in approximately 50% of specimens. This study examined the expression level of NES1 in diagnostic biopsy samples found to contain pure DCIS. These data were then correlated with the pathologic findings found at definitive local surgery.
Twenty-nine cases with initial biopsy showing DCIS without invasive carcinoma followed by subsequent reexcision were discovered and archived. Formalin-fixed tissue specimens were obtained for analysis. Each biopsy specimen was subjected to hematoxylin-eosin staining and reviewed by two pathologists to confirm the diagnosis of pure DCIS. NES1 cDNA (1069 bp), including 238 bp of 5′ and 3′ untranslated region and the entire protein-coding region, was cloned into a vector. To generate the antisense and sense RNA probes, the plasmid was linearized and the transcription reaction was carried out with polymerases T7 and T3, respectively. The detection of
in situ hybridization probes was performed using an mRNA
locator-Biotin Kit. Staining was characterized as negative (0/1+) or positive (2+/3+). Subsequent to an initial biopsy diagnosis of DCIS, all cases had a definitive surgical procedure. Detailed sectioning of the resultant tissue was performed and subjected to hematoxylin-eosin staining to determine the presence or absence of invasive carcinoma.
The initial diagnostic biopsy specimens showed that 17 of 17 high-grade, 3 of 7 intermediate-grade, and 3 of 5 low-grade DCIS specimens were negative for NES1 expression. Of the 6 cases of DCIS found to be positive for NES1 expression, none (0%) were subsequently found to have invasive carcinoma at definitive surgery. In contrast, the loss of NES1 expression in the initial diagnostic biopsy was associated with a 40% incidence of invasive carcinoma at definitive surgery. Additional stratification by nuclear grade showed invasive carcinoma in 5 (83%) of 6 NES1-negative, low- to intermediate-grade DCIS (
p ≤0.01) and 4 (24%) of 17 NES1-negative, high-grade DCIS (
p ≤0.05).
These results show that a lack of NES1 expression in DCIS identified at the diagnostic biopsy predicts for a high risk of invasive cancer in the definitive surgical specimen. The predictive value of NES1 expression appears to be particularly relevant for low- and intermediate-grade DCIS.
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