Colorectal cancer (CRC) remains a leading cause of cancer-related deaths in the United States. Although immunotherapy has dramatically changed the landscape of treatment for many advanced cancers, the benefit in CRC has thus far been limited to patients with microsatellite instability high (MSI-H):DNA mismatch repair–deficient (dMMR) tumors. Recent studies in the refractory CRC setting have led to US Food and Drug Administration approvals for pembrolizumab as well as nivolumab (with or without ipilimumab) for tumors harboring an MSI-H:dMMR molecular profile. Several randomized controlled trials are underway to move immunotherapy into the frontline for metastatic cancer (with or without chemotherapy) and the adjuvant setting. Awareness of these studies is critical given the relatively low incidence (approximately 3%–5%) of MSI-H:dMMR in advanced or metastatic CRC to support study completion, because the results could be potentially practice changing. The real challenge in this disease is related to demonstrating the benefit of immunotherapy for the vast majority of patients with CRC not harboring MSI-H:dMMR. Given the rapid pace of scientific changes, this article provides a narrative review regarding the current landscape of immunotherapy for CRC. Particular attention is paid to the currently available data that inform today’s clinical practice along with upcoming randomized controlled trials that may soon dramatically change the treatment landscape for CRC.
For many patients with GI malignancies, the seeding of the abdominal cavity with tumor cells, called peritoneal carcinomatosis, is a common mode of metastases and disease progression. Prognosis for patients with this aspect of their disease remains poor, with high disease-related morbidity and complications. Uniform and proven practices that provide optimal palliative care and quality of life for these patients are needed. The objective of this review is to critically assess the current literature regarding palliative strategies in the management of peritoneal carcinomatosis and associated symptoms in patients with advanced GI cancers. Despite encouraging results in the select population where cytoreductive surgery and intraperitoneal chemotherapy are indicated, the majority of patients who develop peritoneal carcinomatosis in the setting of GI cancers have poor prognosis, with malignant bowel obstruction representing a common terminal phase of their disease process. For all patients with peritoneal carcinomatosis, aggressive symptom control and early multimodality palliative care as further outlined should be sought.
BackgroundPost-transplant lymphoproliferative disorder is a well-recognized but rare complication of hematopoietic stem cell and solid organ transplant. Due to rarity of this disease, retrospective studies from major transplant centers has been the main source to provide treatment guidelines, which are still in evolution. The sample size of this study is among one of the largest study on PTLD till date reported throughout the world.MethodsThis study was performed at University of Florida which is one of the largest transplant center in South East United States. We performed treatment and survival analysis along with univariate and multivariate analysis to identify prognostic factors.ResultsWe reviewed 141 patients diagnosed with PTLD over last 22 years with median follow-up of 2.4 years. The estimated median overall survival of the entire group was 15.0 years. Sub group analysis showed that 5-year overall survival rates of pediatric population were 88% (median not reached). For adults, median OS was 5.35 years while for elderly patients it was 1.32 years. The estimated median OS of patients with monomorphic PTLD was 9.0 years while in polymorphic PTLD was 19.3 years. Univariate analysis identified gender, age at transplant and PTLD diagnosis, performance status, IPI score, allograft type, recipient EBV status, multiple acute rejections prior to PTLD diagnosis, PTLD sub-type, extra-nodal site involvement, immunosuppressive drug regimen at diagnosis, initial treatment best response were statistically significant prognostic factors (p < 0.05). On multivariate analysis, age at PTLD diagnosis, recipient EBV status, bone marrow involvement, and initial best response were statistically significant prognostic factors (p < 0.05). Surprisingly, use of Rituximab alone as upfront therapy had poor hazard ratio in the cumulative group as well less aggressive PTLD subgroup comprising of early lesions and polymorphic PTLD.ConclusionsOur experience with treatment and analysis of outcomes does challenge current role of Rituximab use in treatment of PTLD. Currently as we define role of immunotherapy in cancer treatment, the role of acute rejections and immunosuppressant in PTLD becomes more relevant as noticed in our study. This study was also able to find new prognostic factors and also verified other known prognostic factors.
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