Faculty Bibliography

Cancer care has been greatly impacted during the COVID-19 pandemic. The number of cases and deaths caused by the COVID-19 pandemic continues to escalate throughout the United States and the world. Worldwide, over 150 million people have been diagnosed with the coronavirus and more than 3 million have died. Now that we have gained additional experience with COVID-19, we are starting to learn its full impact on oncology care and its effects on the practice of medicine and clinical research.

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.

PURPOSE:Given the evidence that coordinate inhibition of AKT induces autophagy, we studied the combination of the AKT inhibitor, MK-2206 with hydroxychloroquine (HCQ) in patients with advanced solid tumors. METHODS:Patients were treated with weekly MK-2206 (135 mg or 200 mg) plus HCQ (200 mg, 400 mg or 600 mg BID). RESULTS:Thirty-five patients were enrolled across 5 dose levels. Two DLTs of grade 3 maculo-papular rash were observed at dose level 2 (MK-2206 200 mg weekly plus HCQ at 400 mg BID) and 1 DLT of grade 3 fatigue at dose level 2B (MK-2206 135 mg weekly plus HCQ 600 mg BID). The maximum tolerated dose (MTD) was declared as dose level 2B. The most common adverse events attributed to MK-2206 were hyperglycemia (N = 18; 51%), fatigue (N = 17; 49%), maculo-papular rash (N = 16; 46%), diarrhea (N = 12; 34%), anorexia (N = 11; 31%), and nausea (N = 11; 31%). Patients experiencing adverse events attributed to HCQ were small in number (N = 13) and primarily included fatigue (N = 5; 14%) and maculo-papular rashes (N = 3; 9%). Statistically significant effects on the pharmacokinetic properties of MK-2206 were observed in combination with HCQ. In addition, the plasma concentrations of HCQ in the combination with MK-2206 were significantly higher than the plasma levels of HCQ as monotherapy in prior studies. The best overall response of stable disease was observed in 5/34 (15%) patients. CONCLUSION:The combination of MK-2206 and hydroxychloroquine was tolerable, but with substantial number of drug-related AEs and minimal evidence of antitumor activity.

OBJECTIVES:The survival of patients with metastatic colorectal cancer (CRC) has been increasing over recent decades due to improvements in chemotherapy and surgery. There is a need to refine prognostic information to more accurately predict survival as patients survive for any given length of time to assist multidisciplinary cancer management teams in treatment decisions. MATERIALS AND METHODS:We performed a single center retrospective analysis of patients treated with metastatic CRC (unresectable and resectable) who survived >24 months between 2005 and 2015 (N=155). Patient tumor and treatment related variables were collected. Overall survival (OS) estimates conditional on surviving >24 months were compared with actuarial survival estimates of a cohort of patients (33,104 resected, 39,382 unresected) from the National Cancer Database (NCDB). RESULTS:With a median follow-up of 44.2 months, the median OS of resected patients (n=86) was not reached. The median OS of unresected patients was 75.9 months. The conditional survival probabilities of living 1, 2, or 3 years longer after 24 months of survival are 92%, 72%, and 52%, respectively, in unresectable patients and 98%, 92%, and 89% in patients who were resected. The corresponding NCDB 1, 2, and 3 year actuarial survival was 38%, 20%, and 11% for unresected patients and 68%, 46%, and 32% for resected. CONCLUSIONS:These results indicate that CRC patients who survive 24 months with metastatic colorectal cancer have an excellent prognosis and surgery may be appropriate in a subset of patients initially deemed unresectable.

Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide, with a majority of HCC patients not suitable for curative therapies. Approximately 70% of initially diagnosed patients cannot undergo surgical resection or transplantation due to locally advanced disease, poor liver function/underlying cirrhosis, or additional comorbidities. Local therapeutic options for patients with unresectable HCC, who are not suitable for thermal ablation, include transarterial embolization (bland, chemoembolization, radioembolization) and/or external beam radiation therapy (EBRT). Regarding EBRT specifically, technological advancements provide a means for safe and effective radiotherapy delivery in a wide spectrum of HCC patients. In multiple prospective studies, EBRT delivery in a variety of different fractionation schemes or in combination with transcatheter arterial chemoembolization (TACE) demonstrate improved outcomes, particularly with combination therapy. The Barcelona Clinic Liver Cancer classification provides a framework for treatment selection; however, given the growing complexity of treatment strategies, this classification system tends to simplify decision-making. In this review, we discuss the current literature regarding unresectable HCC and propose a modified treatment algorithm that emphasizes the role of radiation therapy for Child-Pugh score A or B patients with ≤3 nodules measuring >3 cm, multinodular disease or portal venous thrombosis.

Prior studies examining the risk of second primary malignancy (SPM) after a first primary cancer generally have used large datasets such as the Surveillance, Epidemiology, and End Results (SEER) registry and excluded survivors of previous primaries and developers of synchronous primaries. The goal of this study was to provide a more complete representation of multiple cancer risk in squamous cell carcinoma of the anus (SCCA) patients. A single-institution retrospective study of 46 patients treated definitively for SCCA between January 2006 and July 2017 was conducted. Of the 46 patients, 18 (39%) had either a primary malignancy before SCCA (n=9) or SPM after an index SCCA (n=9). Six patients had ≥3 total malignancies. In our cohort, patients without SPMs tended to die from SCCA recurrence, while patients with SPMs were more likely to die from their SPM than from SCCA. Our study suggests that patients with SCCA are often either survivors of previous cancers or develop later malignancies. Several risk factors may play a role including HPV infection, HPV-related or treatment-related immunosuppression, somatic mutations due to chemotherapy, and genetic factors. Patients with SCCA require lifelong surveillance given their elevated risk of malignancy. Future work should focus on identifying genomic or immunologic factors that may predispose SCCA patients to develop multiple primary malignancies.