Updates of Peripheral T Cell Lymphomas Based on the 2017 WHO Classification

Purpose of Review

This review will describe and update the readers on the recent changes of the 2017 WHO classification in regard to peripheral T cell lymphomas.

Recent Findings

Significant advances in molecular studies have resulted in revisions of the classification as well as introduction of provisional entities (such as breast implant-associated ALCL, nodal PTCL with TFH phenotype).

Summary

Major advances in molecular and gene expression profiling have expanded our knowledge of T cell lymphomas, including updates in the diagnostic criteria and sub-classification which will facilitate in improving patient care and research.

     

Treatment Decisions and Adherence to Adjuvant Endocrine Therapy in Breast Cancer

Purpose of Review

Treatment decisions regarding adjuvant endocrine therapy in breast cancer has become increasingly complex, with non-adherence to treatment one of the most crucial issues. We aimed to review the literature on both aspects focusing on new finding regarding assessment, determinants, and interventions of decision-making and adherence to adjuvant endocrine therapy.

Recent Findings

A shared decision-making process is wanted by the patients and can improve patient-related outcomes. Information needs, preferences, and values regarding adjuvant endocrine therapy vary widely. Nearly two-thirds of patients do not take the adjuvant endocrine therapy exactly as prescribed either by not initiating, missing doses, or stopping the treatment early.

Summary

Implementation of tools for a shared decision can be useful in clinical practice, but further development is needed in the field of adjuvant endocrine therapy. Targeted interventions are desirable to improve patients’ adherence to adjuvant endocrine therapy, thereby improving the quality of care and outcomes in breast cancer.

     

Novel Therapies in Acute Lymphoblastic Leukemia

Purpose of Review

Treatment options for patients with acute lymphoblastic leukemia (ALL) beyond standard chemotherapy have grown significantly in recent years. In this review, we highlight new targeted therapies in ALL, with an emphasis on immunotherapy.

Recent Findings

Major advances include antibody-based therapies, such as naked monoclonal antibodies, antibody-drug conjugates and bispecific T cell engaging (BiTE) antibodies, as well as adoptive cellular therapies such as chimeric antigen receptor (CAR) T cells. Apart from the above immunotherapeutic approaches, other targeted therapies are being employed in Philadelphia chromosome-positive (Ph+) ALL, Philadelphia-like (Ph-like) ALL, and T cell ALL.

Summary

These new treatment strategies are changing the treatment landscape of ALL and challenging the current standard of care. Clinical trials will hopefully help determine how to best incorporate these novel therapies into existing treatment algorithms.

     

Preplanned safety analysis of the JFMC37-0801 trial: a randomized phase III study of six months versus twelve months of capecitabine as adjuvant chemotherapy for stage III colon cancer

Background

Six months of adjuvant chemotherapy is regarded as the standard of care for patients with stage III colon cancer. However, whether longer treatment can improve prognosis has not been fully investigated. We conducted a phase III study comparing 6 and 12 months of adjuvant capecitabine chemotherapy for stage III colon cancer, and report here the results of our preplanned safety analysis.

Methods

Patients aged 20–79 years with curatively resected stage III colon cancer were randomly assigned to receive 8 cycles (6 months) or 16 cycles (12 months) of capecitabine (2500 mg/m²/day on days 1–14 of each 21-day cycle). Treatment exposure and adverse events (AEs) were evaluated.

Results

A total of 1304 patients (642 and 636 in the 6-month and 12-month groups, respectively) were analyzed. The most common AE was hand-foot syndrome (HFS). HFS, leukocytopenia, neutropenia, and hyperbilirubinemia (any grade) occurred more frequently in the 12-month group than in the 6-month group. HFS was the only grade ≥3 AE to have a significantly higher incidence in the 12-month group (23 vs 17%, p = 0.011). The completion rate for 8 cycles was 72% in both groups, while that for 16 cycles was 46% in the 12-month group. HFS was the most common AE requiring dose reduction and treatment discontinuation.

Conclusions

Twelve months of adjuvant capecitabine demonstrated a higher cumulative incidence of HFS compared to the standard 6-month treatment period, while toxicities after 12 months of capecitabine were clinically acceptable.

Trial registration

UMIN-CTR, UMIN000001367.

     

Predictive factors for survival in neoadjuvant radiochemotherapy for advanced rectal cancer

Introduction

Neoadjuvant radiochemotherapy followed by radical surgery is the standard approach in advanced rectal carcinoma. Tumor response is determined in histological specimen.

Objective

To assess predictive factors for survival in 115 patients.

Patients and Method

115 patients treated with neoadjuvant radiochemotherapy followed by radical surgery with total mesorectal excision, in our hospital from January 2007 to December 2014. All patients received pelvic radiotherapy with concomitant chemotherapy, followed by radical surgery and in some adjuvant chemotherapy.

Results

In univariate analysis, distance to anal verge, radial margin, perineural invasion, and good grade regression are predictive factors for both, specific and disease free survival; and in multivariant, only radial margin and perineural invasion were predictive factors for survival. We found distance to anal verge (<5 cm) as the only clinical factor to predict a positive margin in the histologic specimen.

Conclusions

Perineural invasion and positive radial margin are predictive factors for both specific and disease free survival.

     

Palliative Care in Lung Cancer: When to Start

Purpose of Review

Despite recent advances in the care of patients with advanced non-small cell lung cancer (NSCLC), significant morbidity and mortality remains. Symptoms caused by the cancer and its treatments can be profoundly debilitating. Palliative care aims to reduce this burden. In this review, we discuss the definition, purpose, benefits, and optimal timing of palliative care in advanced NSCLC.

Recent Findings

Several studies evaluating the value of early palliative care for patients with advanced NSCLC and other advanced malignancies have identified benefits for patients, caregivers, and health systems.

Summary

For patients with advanced NSCLC, introduction of palliative care early in the disease course improves quality of life and even overall survival. Early institution of palliative care should become standard of care for patients with advanced NSCLC.

     

Wo ist die molekulare Pathologie sinnvoll?

Background

The increasing importance of molecular pathology in routine oncological diagnostics.

Objective

Current recommendations, developments and future applications of molecular pathology in the clinical course of malignant melanoma, colorectal cancer and non-small cell lung cancer (NSCLC).

Material and methods

The article is based on a literature review investigating clinically relevant aspects of molecular diagnostics in various databases, e.g. PubMed, the European Society of Medical Oncology (ESMO) and the World Health Organization (WHO).

Results and conclusion

The translation of preclinical research and the application in clinical practice are characterized by an increasing speed. The advanced classification of malignant diseases is of high relevance in current therapeutic approaches.

     

Recent Advances in the Biology and Treatment of T Cell Acute Lymphoblastic Leukemia

Purpose of Review

This article provides an overview of the current knowledge regarding the biology and treatment of T cell acute lymphoblastic leukemia (T-ALL) and highlights the most recent findings in this field over the past 5 years.

Recent Findings

Remarkable progress has been made in the genomic landscape of T-ALL over the past few years. The discovery of activating mutations of NOTCH1 and FBXW7 in a majority of patients has been a seminal observation, with several early phase clinical trials currently exploring these as potential therapeutic targets. Characterization of early T cell precursor ALL, incorporation of minimal residual disease assessment into therapeutic protocols, and use of pediatric-intensive regimens along with judicious use of allogeneic HCT have significantly improved risk stratification and treatment outcomes.

Summary

Improved risk stratification and the use of novel targeted therapies based on recent genomic discoveries are expected to change the therapeutic landscape of T-ALL and hopefully improve the outcomes of this historically poor prognosis disease.

     

Prognostic significance of immune cells in the tumor microenvironment and peripheral blood of gallbladder carcinoma patients

Background

The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC.

Methods

98 patients with GBC were recruited in this retrospective study. Using immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+ cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral venous blood samples were also collected, and absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were measured. The relationships between these variables and patient outcome were evaluated.

Results

Survival analysis revealed that the density of CD3+ cell infiltrates in the tumor microenvironment was positively correlated with overall survival (OS) and the density of CD15+ cell infiltrates was negatively correlated with the OS. The combined analysis showed that a high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates was an independent prognostic factor for GBC. In peripheral blood, survival analysis suggested that ANC and NLR were negatively correlated, while ALC was positively correlated with OS. Multivariate survival analysis showed that NLR was an independent prognostic factor for gallbladder cancer prognosis.

Conclusions

The results indicate that the combination of high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates in tumor samples and pretreatment peripheral blood NLR were independent prognostic factors in patients with GBC.

     

Two years survival of primary cardiac leiomyosarcoma managed by surgical and adjuvant therapy

Background

Cardiac tumors are a very rare entity. Leiomyosarcoma represents less than 1% of cases.

Case presentation

a 51-year-old woman diagnosed with primary left atrium leiomyosarcoma. She was treated by optimal surgery and adjuvant chemotherapy. She is still alive after a follow-up of 24 months without evidence of local or distant recurrence.

Conclusions

Cardiac leiomyosarcoma is a rare tumor with a dismal prognosis. Surgery is the mainstay of treatment. Adjuvant treatment is still controversial.

     

Prolymphocytic Leukemia: New Insights in Diagnosis and in Treatment

Purpose of Review

We aimed to produce a comprehensive update on clinical and biological data regarding two rare lymphoid neoplasms, B and T prolymphocytic leukemias, and assess therapeutic management in the light of new molecular insights and the advent of targeted therapies.

Recent Findings

B cell prolymphocytic leukemia (B-PLL) diagnosis remains challenging in the absence of clear immunophenotypic or cytogenetic signature and overlap with mantle cell lymphoma. New molecular defects have been identified in T cell prolymphocytic leukemia (T-PLL), especially in the JAK STAT pathway. Like in chronic lymphocytic leukemia (CLL), B-PLL treatment depends on the presence of TP53 dysfunction. In T-PLL, alemtuzumab still remains the standard of care. Allogeneic transplantation is the only curable option. Thanks to reduced intensity conditioning regimens, it has become accessible to a larger number of patients.

Summary

PLL prognosis remains poor with conventional therapies. However, great advances in the understanding of both T- and B-PLL pathogenesis lead to promising new therapeutic agents.

     

Current Concepts in the Treatment of Resectable Pancreatic Cancer

Purpose of Review

The diagnosis of pancreatic cancer carries with it a high mortality rate. Despite advances in the field, this has remained relatively unchanged over the last few decades. Current options for the treatment of resectable pancreatic ductal adenocarcinoma will be reviewed here in conjunction with the historical data that support them. We will focus on updates in treatment guidelines and ongoing clinical trials of interest.

Recent Findings

For localized disease, standard of care includes resection followed by adjuvant chemotherapy ± chemoradiation. Recently, a report was published supporting the use of doublet therapy with gemcitabine and capecitabine (as opposed to gemcitabine monotherapy), which prompted a practice-changing update to major treatment guidelines. Multiple trials using neoadjuvant treatment, novel therapies, and different forms of radiation are ongoing.

Summary

Although pancreatic cancer is an active area of research, outcomes remain dismal. Clinical trials will need to be more robust and innovative to drastically improve survival statistics.

     

A risk prediction model to allow personalized screening for cervical cancer

Importance

Cervical cancer screening guidelines are in evolution. Current guidelines do not differentiate recommendations based on individual patient risk.

Objective

To derive and validate a tool for predicting individualized probability of cervical intraepithelial neoplasia grade 2 or higher (CIN2+) at a single time point, based on demographic factors and medical history.

Design

The study design consisted of an observational cohort with hierarchical generalized linear regression modeling.

Setting

The study was conducted in a setting of 33 primary care practices from 2004 to 2010.

Participants

The participants of the study were women aged ≥?30 years.

Main outcome and measures

CIN2+ was the main outcome on biopsy, and the following predictors were included: age, race, marital status, insurance type, smoking history, median income based on zip code, prior human papilloma virus (HPV) results.

Results

The final dataset included 99,319 women. Of these, 745 (0.75%) had CIN2+. The multivariable model had a C-statistic of 0.81. All factors but race were independently associated with CIN2+. The model categorized women as having below-average CIN2+ risk (0.15% predicted vs. 0.12% observed risk), average CIN2+ risk (0.42% predicted vs. 0.36% observed), and above-average CIN2+ risk (1.76% predicted vs. 1.85% observed). Before screening, women at below-average risk had a risk of CIN2+ well below that of women with ASCUS and HPV negative (0.12 vs. 0.20%).

Conclusions and relevance

A multivariable model using data from the electronic health record was able to stratify women across a 50-fold gradient of risk for CIN2+. After further validation, use of a similar model could enable more targeted cervical cancer screening.

     

Cancers et environnement : explorer les comportements de recherche et les sources d’information des personnes atteintes et non atteintes d’un cancer

Aim

To explore information-seeking behaviors on links between cancers and environment.

Method

Focus groups and individual semi-structured interviews realized, respectively, with individuals without and with personal cancer experience.

Results

The majority of respondents reported informationscanning behaviors. Only half cancer patients searched for information regarding the links between cancers and environment.

Conclusion

Little information is sought on links between cancers and environment.

     

Standards in der psychosozialen Versorgung von Krebspatienten

Background

There are many scientific studies demonstrating the relevance of psychosocial distress for cancer patients and their psychosocial needs, which has contributed to developing psychosocial care as an integrated component of modern cancer treatment.

Aim

The aim of this review article is an analysis of the psychosocial care of cancer patients in the German health care system and the factors influencing patient care needs. In addition, the requirements for standards and quality assurance in psychosocial care of cancer patients are discussed.

Material and methods

This review is based on a systematic search of the literature within the national evidence-based guidelines for psycho-oncology and a selective search of recently published papers on this topic in Medline.

Results and discussion

Although psychosocial care of cancer patients in Germany has been improved within the last decades, there are still gaps in psychosocial care especially in the area of outpatient care. In terms of the restricted financial resources in the healthcare system there is a need for systematically developed standards and guidelines as a basis for the implementation of inpatient and outpatient psycho-oncological services.

     

Update on the Treatment of Anaplastic Large Cell Lymphoma

Purpose of Review

Given the rarity of anaplastic large cell lymphoma (ALCL), studies evaluating new therapies have typically grouped ALCL together with other peripheral T cell lymphomas (PTCL). Thus, the treatment paradigm for ALCL largely mirrors that of PTCL in general. In this review, we discuss the current standard of care as well as emerging therapies, including antibody-based drugs, in systemic ALCL as well as primary cutaneous and breast implant-associated ALCL.

Recent Findings

High CD30 expression in ALCL has allowed the use of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in both systemic and primary cutaneous ALCL. Recent clinical trials with brentuximab have shown substantial activity in the relapsed/refractory setting. A randomized phase III study is ongoing comparing brentuximab plus CHP (cyclophosphamide, doxorubicin, prednisone) with standard CHOP in the front-line setting.

Summary

The use of targeted therapies and other novel agents have improved outcomes for ALCL patients and in the future can complement or even replace the current standard of care and front-line treatment options.

     

Palliative Care in Patients with Leukemia: When and How?

Purpose of Review

Patients with hematologic malignancies get more aggressive treatment and the end-of-life, more ICU deaths, and prolonged hospital stays. In comparison to solid tumors, their access to palliative care and hospice is less.

Recent Findings

Multiple factors seem to play a role including curative goals, different treatment options, stronger relationship between patients and oncologist, symptom burden, and limitations of hospice care.

Summary

Improving the perception of palliative care in these patients, characterizing their needs, and more education can help to increase referrals and access to palliative care. Innovative ways to improve integration between hematology-oncology and palliative care are needed.

     

A phase II trial of capecitabine plus cisplatin (XP) for patients with advanced gastric cancer with early relapse after S-1 adjuvant therapy: XParTS-I trial

Backgrounds

In Japan, standard regimens for advanced gastric cancer (AGC) include S-1 chemotherapy. The standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine alone is platinum-based chemotherapy, while the standard treatment for early relapse after adjuvant chemotherapy with fluoropyrimidine plus platinum is second-line chemotherapy. To evaluate the efficacy and safety of capecitabine plus cisplatin (XP) treatment for AGC patients who relapse within 6 months after S-1-based therapy, we conducted a multicenter phase II trial (NCT01412294).

Methods

HER2-negative gastric cancer patients treated with adjuvant chemotherapy including S-1 for more than 12 weeks and relapsed within 6 months were treated with capecitabine 1000 mg/m² bid for 14 days plus cisplatin 80 mg/m² on day 1 of a 3-week cycle. The primary endpoint was PFS; secondary endpoints were OS, time to treatment failure, overall response rate (ORR) and safety.

Results

Forty patients (median age 64) were enrolled; of those, 37 (92.5%) received adjuvant S-1 monotherapy. Median PFS was 4.4 months (95% CI 3.6–5.1), which was longer than the 2-month protocol-specified threshold (p < 0.001). Median OS was 13.7 months (95% CI 9.0–17.7) and ORR was 8/30 (26.7%) (95% CI 14.2–44.4). Most common grade ≥ 3 adverse events were neutropenia (23%), anemia (18%), elevated serum creatinine (18%), fatigue (13%), diarrhea (7.5%), and anorexia (7.5%).

Conclusions

XP was safe and effective in patients with early relapse after S-1 adjuvant chemotherapy for curatively resected gastric cancers. XP may be a good option for the treatment of patients after early failure after adjuvant S-1.

Trial registration

NCT01412294.

     

Metabolic iodine and tumours

Purpose

Purpose of the work is to highlight a possible connection between metabolic iodine and natural tumour control.

Method

Method adopted is to use information available in the literature.

Result

Result indicated a means of the purpose being attained.

Conclusion

Conclusion drawn is that a tumour control method derives from the relationship studied.

     

Where Are We Going with Sentinel Lymph Node Mapping in Gynecologic Cancers?

Purpose of Review

Sentinel lymph node (SLN) mapping is a standard of care for lymphatic assessment of many early-stage gynecologic malignancies. We review the current data, emphasizing the utility of SLN mapping in the management of gynecologic cancers.

Recent Findings

Endometrial cancer: recent studies have focused on confirming the safety and efficacy of SLN mapping for high-risk patients. Cervical cancer: the LACC Trial demonstrated reduced survival with minimally invasive surgery, calling into question the validity of prior studies evaluating SLN mapping with a minimally invasive approach. Vulvar cancer: the ongoing GROINS-V-II trial is investigating whether patients with SLN metastasis <?2 mm in diameter can safely undergo adjuvant radiation ± chemotherapy without completion inguinal lymphadenectomy.

Summary

NCCN guidelines have incorporated SLN mapping as a lymphatic assessment strategy for endometrial, cervical, and vulvar malignancies. SLN mapping appears to reduce morbidity while still maintaining an appropriate detection rate of lymphatic metastasis. Additional clinical trials will further our knowledge of these procedures.