The treatment paradigm for patients with advanced non–small cell lung cancer has substantially changed with the discovery of immunotherapy. The incorporation of immunotherapy into treatment algorithms has resulted in better outcomes for patients, with fewer side effects compared with classic chemotherapeutic agents. Multiple treatment options are now available for patients with advanced non–small cell lung cancer, ranging from single-agent immunotherapy to quadruple therapy, which involves dual immune checkpoint inhibitor plus chemotherapy or immune checkpoint inhibitor plus chemotherapy plus anti–vascular endothelial growth factor drugs. This article will review landmark studies that have led to U.S. Food and Drug Administration approval of immunotherapy agents alone or in combination with chemotherapy or other immunotherapy drugs to treat advanced non–small cell lung cancer.

Circulating tumor DNA (ctDNA) minimal residual disease (MRD) is a powerful biomarker with the potential to improve survival outcomes for non–small-cell lung cancer (NSCLC). Multiple groups have shown the ability to detect MRD following curative-intent NSCLC treatment using next-generation sequencing–based assays of plasma cell-free DNA. These studies have been modest in size, largely retrospective, and without thorough prospective clinical validation. Still, when restricting measurement to the first post-treatment timepoint to assess the clinical performance of ctDNA MRD detection, they have demonstrated sensitivity for predicting disease relapse ranging between 36% and 100%, and specificity ranging between 71% and 100%. When considering all post-treatment follow-up timepoints (surveillance), including those beyond the initial post-treatment measurement, these assays' performances improve with sensitivity and specificity for identifying relapse ranging from 82% to 100% and 70% to 100%, respectively. In this manuscript, we review the evidence available to date regarding ctDNA MRD detection in patients with NSCLC undergoing curative-intent treatment and the ongoing prospective studies involving ctDNA MRD detection in this patient population.

PURPOSE We hypothesized that circulating tumor DNA (ctDNA) molecular residual disease (MRD) analysis without prior mutational knowledge could be performed after neoadjuvant chemotherapy to assess oligometastatic colorectal cancer (CRC) treated surgically with curative intent. We also investigated urine as an alternative analyte for ctDNA MRD detection in this nongenitourinary setting. PATIENTS AND METHODS We applied AVENIO targeted next-generation sequencing to plasma, tumor, and urine samples acquired on the day of curative-intent surgery from 24 prospectively enrolled patients with oligometastatic CRC. Age-related clonal hematopoiesis was accounted for by removing variants also present in white blood cells. Plasma and urine ctDNA MRD were correlated with tumor cells detected in the surgical specimen, and adjuvant treatment strategies were proposed based on ctDNA-inferred tumor mutational burden (iTMB) and targetable alterations. RESULTS Seventy-one percent of patients were treated with neoadjuvant chemotherapy. Tumor-naive plasma ctDNA analysis detected MRD at a median level of 0.62% with 95% sensitivity and 100% specificity, and 94% and 77% sensitivity when only considering patients treated with neoadjuvant chemotherapy and putative driver mutations, respectively. In urine, ctDNA MRD detection specificity remained high at 100%, but sensitivity decreased to 64% with median levels being 11-fold lower than in plasma ( P < .0001). Personalized ctDNA MRD oncogenomic analysis revealed 81% of patients might have been candidates for adjuvant immunotherapy based on high iTMB or targeted therapy based on actionable PIK3CA mutations. CONCLUSION Tumor-naive plasma ctDNA analysis can sensitively and specifically detect MRD in patients with oligometastatic CRC after neoadjuvant chemotherapy. Urine-based ctDNA MRD detection is also feasible; however, it is less sensitive than plasma because of significantly lower levels. Oligometastatic patients with detectable MRD may benefit from additional personalized treatment based on ctDNA-derived oncogenomic profiling.

Development of graft‐versus‐host disease (GvHD) is a rare complication after transfusions or solid organ transplantation. Patients typically present with a skin rash, diarrhea, liver failure, and bone marrow aplasia. A diagnosis of transfusion/transplantation associated‐GvHD is made based on the clinical and histologic evidence, yet it is often delayed due to the nonspecific symptoms attributed to the patient's underlying illness. Several therapeutic approaches are being used including both increasing and withdrawing immunosuppression, and the use of cellular therapies. Unfortunately, the success rate of these approaches is low and the mortality of this complication is very high. New approaches are needed. We report on three cases of GvHD developing after solid organ transplantation treated with ruxolitinib.

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Primary splenic angiosarcoma is a very rare neoplasm with a high propensity for metastatic disease and poor prognosis. There is a paucity of literature concerning this specific sarcoma subtype and the role of systemic therapy is not well defined. A retrospective review of the prospectively maintained University of Washington/Seattle Cancer Care Alliance Sarcoma Unit database was performed to identify patients with splenic angiosarcoma treated between 2007 and 2012. In total there were 19 patients with angiosarcoma treated at the Seattle Cancer Care Alliance from 2007 to 2012. The number of patients with splenic angiosarcoma was 2 (11%). The first patient was a woman aged 57 years who was referred with metastatic splenic angiosarcoma to the liver, post-splenectomy. She was treated with 4 cycles of weekly paclitaxel prior to metastatic resection and 4 cycles of the same drug in an adjuvant scenario, achieving a pathological complete response to treatment. She is alive and on third-line systemic therapy. The second patient was a male patient aged 30 years who presented with metastatic high-grade splenic angiosarcoma and was treated with 3 lines of systemic therapy, including doxorubicin, paclitaxel and gemcitabine+docetaxel, but developed a gastrointestinal metastasis with subsequent gastrointestinal bleeding. Splenic angiosarcoma is a very rare neoplasm. Surgery remains the mainstay of management for localized disease. Paclitaxel administered weekly proved to be well-tolerated and resulted in a good radiological response in one of our patients, enabling resection of metastatic disease. Durable clinical benefit can be achieved in metastatic splenic angiosarcoma with multi modality management.

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