The advent of precision therapy in gastrointestinal malignancies: Targeting the human epidermal growth factor receptor family in colorectal and esophagogastric cancer

Until recently, systemic therapy for gastrointestinal malignancies was restricted to relatively noncancer-specific cytotoxic chemotherapy. Over the last 15 years targeted therapies have become available, most notably bevacizumab in the case of advanced colorectal cancer. Unfortunately, there are no predictive biomarkers to guide the use of this agent. In this review article, we describe the advent of "Precision Medicine" (in part, the use of patient-specific molecular markers to inform treatment) in gastrointestinal cancers: The use of monoclonal antibodies targeting epidermal growth factor receptor in advanced colorectal cancer, and human epidermal growth factor receptor 2-neu in advanced esophagogastric cancer. In both instances, biomarkers help in selecting appropriate patients for such treatment

Real-world predictors of survival in patients with limited-stage small-cell lung cancer in Manitoba, Canada

BackgroundAlthough therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential.ObjectiveThis real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada.MethodsA retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (<6 months), medium (6−24 months), and long term (>24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models.ResultsOver the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1−2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3−4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival.ConclusionSurvival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI

Real-world predictors of survival in patients with extensive-stage small-cell lung cancer in Manitoba, Canada: a retrospective cohort study

BackgroundExtensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions.ObjectiveThis real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada.MethodsA retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: <6 months; medium: 6–24 months; long: >24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models.ResultsThis analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and five-year OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1–2, and 16%, 3%, and 3% for those with ECOG PS 3–4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors – including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels – were less common but still seen in long-term survivors.ConclusionAlthough rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ES-SCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future

The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos. With an improved understanding of the relationship between the immune system and cancer progression, immunotherapies are playing a greater role in the treatment of many cancers. Several early- and late-phase trials in malignant pleural mesothelioma, including assessments of the first-line efficacy of combination ipilimumab/nivolumab treatment, have now demonstrated promising results for both immune checkpoint inhibition and cell-based therapies. These immune therapies are likely to play a central role in the treatment of this disease going forward

Immune Checkpoint Inhibition as Primary Adjuvant Therapy for an IDH1-Mutant Anaplastic Astrocytoma in a Patient with CMMRD: A Case Report—Usage of Immune Checkpoint Inhibition in CMMRD

Constitutional mismatch repair deficiency (CMMRD) is a rare autosomal recessive hereditary cancer syndrome due to biallelic germline mutation involving one of the four DNA mismatch repair genes. Here we present a case of a young female with CMMRD, homozygous for the c.2002A>G mutation in the PMS2 gene. She developed an early stage adenocarcinoma of the colon at the age of 14. Surveillance MRI of the brain at age 18 resulted in the detection of an asymptomatic brain cancer. On resection, this was diagnosed as an anaplastic astrocytoma. Due to emerging literature suggesting benefit of immunotherapy in this patient population, she was treated with adjuvant dual immune checkpoint inhibition, avoiding radiation. The patient remains stable with no evidence of progression 20 months after resection. The patient’s clinical course, as well as the rational for considering adjuvant immunotherapy in patients with CMMRD are discussed in this report