Radiation-induced esophagitis is a common toxicity of radiation therapy of the chest, characterized by disruption of the epithelium due to damage to the underlying basal cells. The frequency of radiation-induced esophagitis correlates with the dose of radiation the esophagus receives and the volume that is treated with that dose. Modern radiation techniques are decreasing the size of the treatment field, potentially reducing the incidence and severity of esophagitis; however, it remains an important concern in patients with lung cancer treated with chemoradiotherapy. The pathogenesis of esophagitis is similar to that of head and neck mucositis, but there have been very few trials of treatments for the prevention of radiation-induced esophagitis. Current research is limited to several natural products which have shown activity in small randomized trials. However, several agents are currently being tested in clinical trials for the treatment of radiation-induced esophagitis. A successful agent to reduce/prevent esophagitis may allow higher doses of radiation to be delivered to the cancer and increase the curability of localized lung cancer. This review highlights the current understanding and limitations of data in radiation-induced esophagitis and current and potential future approaches to treatment.
Novel drugs and continuous therapy have improved outcomes in patients with multiple myeloma (MM); however, current therapies are largely non-curative with diminishing durations of response with subsequent therapies. Cellular therapies including chimeric antigen receptor T (CAR-T) cells have started to illustrate deeper and longer durations of relapse in the relapsed/refractory population. Current research seeks to expand on the durability of response, novel combinations, and targets, as well as the timing of CAR-T cells in the treatment schema. This review summarizes the updates in cellular therapy for MM.
Abnormal activation of mesenchymal epithelial transition (MET) receptor tyrosine kinase is associated with oncogenesis. Various underlying mechanisms, including alteration, amplification, gene rearrangement, and exon skipping in the transcript account for abnormal MET signaling. One of the critical alterations in MET leading to non-small cell lung carcinoma (NSCLC) is MET exon 14 (METex14) skipping, a driver mutation, which accounts for approximately 3–4% of lung adenocarcinoma. METex14 skipping results in the formation of a functionally active and stable truncated receptor lacking the juxtamembrane regulatory domain responsible for MET ubiquitination. Several MET kinase inhibitors have been developed targeting MET receptors, and many are in clinical trials. The US Food and Drug Administration has recently approved capmatinib (Tabrecta; Novartis, Basel, Switzerland) for the treatment of NSCLC with METex14 skipping alteration. We review the current understanding of the implications of aberrant MET activation in NSCLC harboring METex14 skipping alteration, available diagnostic options, potential therapies in the pipeline, and the future clinical landscape for such alterations.
Esophageal cancer is the seventh most common malignancy, for which there are few effective treatment options, especially for patients with advanced disease. Therefore, the therapeutic development of immune checkpoint inhibitors has been the focus for patients with advanced esophageal cancer. Nivolumab, a human monoclonal immunoglobulin G4 antibody that inhibits programmed cell death protein 1, has been developed for this patient population. The phase II ATTRACTION-1 trial showed promising efficacy for nivolumab in patients with advanced esophageal cancer who were refractory or intolerant to fluoropyrimidine-, platinum-, and taxane-based chemotherapies. The phase III ATTRACTION-3 trial showed the superiority of nivolumab over taxane in patients with advanced esophageal squamous cell carcinoma (ESCC) who were refractory or intolerant to previous fluoropyrimidineand platinum-based chemotherapy. Based on these results, the FDA approved nivolumab as a treatment for patients with advanced ESCC after prior fluoropyrimidineand platinum-based chemotherapy. Additionally, the CheckMate 577 trial has shown that nivolumab improves disease-free survival when used as an adjuvant treatment in patients with resectable tumors who received neoadjuvant chemoradiation followed by surgery, and in whom a pathological complete response was not achieved. Clinical trials to evaluate the efficacy of nivolumab in combination with cytotoxic drugs as first-line chemotherapy, in combination with chemoradiotherapy, or for the treatment of perioperative patients with esophageal cancer are ongoing and might contribute to the establishment of new standard treatments.
BRAF V600E-mutated metastatic colorectal cancer is notoriously difficult to treat due to an aggressive tumor biology and resistance to chemotherapy. Single-agent BRAF inhibition has proven ineffective in this patient population. Approaches combining BRAF with epidermal growth factor receptor and mitogen-activated extracellular signal-regulated kinase inhibition are effective in overcoming resistance to BRAF monotherapy, and this treatment combination provides a superior overall survival benefit compared with irinotecan-based chemotherapy. Encorafenib plus cetuximab is now a US Food and Drug Administration-approved treatment option for patients with BRAF V600E-mutated metastatic colorectal cancer after prior therapy. Ongoing clinical trials using immunotherapy and other targeted agents aim to further improve on these outcomes. We highlight the epidemiology and mutational landscape of BRAF-mutated colorectal cancer, as well as novel treatment options for patients with this subtype of metastatic colorectal cancer.
Nearly 270,000 new breast cancer cases are predicted to be diagnosed in the USA in 2019 with more than 70% being estrogen receptor positive and treated using endocrine therapy. The suppression of estrogen biosynthesis or action via the use of ovarian suppression, aromatase inhibitors and selective estrogen receptor modulators/degraders, respectively, is effective in approximately 70% of women. The systemic inhibition of estrogen during breast cancer treatment is also associated with side effects due to the important endocrine functions of this steroid hormone, including its role in the maintenance of energy homeostasis and bone health. The current work will present perspectives of the impact of endocrine therapy from the point of view of breast medical oncology, endocrinology, and basic science.
Journal Publication Date: August 6, 2020 Personalized medicine is the new-generation concept of managing cancer, which primarily focuses on the development of targeted therapies blocking specific cellular pathways that potentiate the tumorigenesis and identify people that respond best. The combination of gemcitabine and a platinum agent, remains the first-line therapy in advanced cholangiocarcinoma. Thus far, there are no specific guidelines on the next step in the care of patients who progressed on, or could not tolerate, the first-line therapy. However, a better knowledge of molecular pathogenesis and advancements in the development of targeted therapy offers hope that we may improve outcomes in advanced cholangiocarcinoma. Among the newly discovered molecular alterations, targeting isocitrate dehydrogenase (IDH1/2) mutations, fibroblast growth factor receptor 2 (FGFR2) fusions, RAS-MAPK pathway activation, BRCA1/2 mutations, NTRK fusions, and human epidermal growth factor receptor 2 (HER2), hold great promise for improving the future management of cholangiocarcinoma. In tumors with high microsatellite instabilities or mismatch repair deficiencies irrespective of programmed death ligand (PD-L) 1 expression, immunotherapy, alone or in combination with targeted agents and chemotherapy, are currently being evaluated. This review article details the potential targetable molecular pathways and future directions in implementing personalized medicine in this dismal cancer.
Systemic therapy for advanced, hormone receptor-positive (HR+), human epidermal growth factor receptor 2-unamplified (HER2-) breast cancer has drastically evolved over the past several decades, from oophorectomy to combination endocrine and molecularly targeted therapy. Cyclin-dependent kinase (CDK) 4/6 inhibitors are the latest addition to this arsenal of therapies, and while they have been rapidly adopted by most oncologists, many still question whether they belong in the first-line metastatic setting. Recent reporting of overall survival data, however, has re-invigorated the debate and strongly supports first-line use of CDK 4/6 inhibitors. This article will provide an overview of the evolution of systemic therapy in HR+, HER2breast cancer, summarize the data that led to the approval of CDK 4/6 inhibitors, detail the new overall survival data reported in the PALOMA-3, MONALEESA-7, MONALEESA-3, and MONARCH-2 trials, and then discuss why our patients should receive these drugs in the first-line setting for advanced disease.
Support: No funding was received in the publication of this article. Soft tissue sarcomas represent a group of over 80 rare malignant tumors that arise from tissues of mesenchymal origin throughout the body. Advanced soft tissue sarcoma is treated with single-agent or combination systemic chemotherapy, but is associated with a poor prognosis. Pazopanib (Votrient, Novartis, Basel, Switzerland) is an oral multitarget tyrosine kinase inhibitor that has received regulatory approval as a second-line and beyond treatment for metastatic soft tissue sarcoma based on the findings of the phase III PALETTE study (ClinicalTrials.gov identifier: NCT00753688). However, there is a population of elderly and debilitated patients with soft tissue sarcoma who are not fit for standard first-line chemotherapy that is anthracycline-based. As pazopanib is well tolerated with minimal side effects, a phase II study (ClinicalTrials.gov identifier: NCT02300545) investigated the use of pazopanib as front-line therapy in patients with non-resectable or metastatic soft tissue sarcomas who are not candidates for chemotherapy.
Locally advanced rectal cancer has broadly been defined as T3, T4, or lymph node-positive disease. In the 1990s, adjuvant chemoradiation was considered the optimal management for locally advanced rectal cancer. However, the paradigm shifted when the German CAO/ARO/AIO-94 Rectal Cancer trial established neoadjuvant chemoradiation as the standard of care, based on reduced rates of toxicity and local recurrence, as well as higher rates of sphincter preservation compared with postoperative chemoradiation. Both short-course radiation and long-course chemoradiation are currently accepted methods for neoadjuvant treatment, with recent trials showing equivalence in outcomes. While surgery remains the cornerstone of treatment, there are data supporting the use of magnetic resonance imaging for risk stratification in rectal cancer and encouraging prospective data regarding nonoperative management. This review summarizes data on the evolution of treatment for locally advanced rectal cancer and discusses emerging evidence for nonoperative management.
Although outcomes for patients with multiple myeloma (MM) have improved over the past decade, the disease remains incurable and even patients who respond well to induction therapy ultimately relapse and require additional treatment. Conventional chemotherapy and high-dose therapy with stem cell transplantation (SCT) have historically been utilized in the management of relapsed MM, but in recent years the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, as well as the proteasome inhibitor bortezomib, have assumed a primary role in this setting. This review focuses on the role of thalidomide, lenalidomide and bortezomib in relapsed and refractory MM, with additional discussion dedicated to emerging drugs in relapsed MM that may prove beneficial to patients with this disease.
