Oncology

Cancer and Coronary Artery Disease: Common Associations, Diagnosis and Management Challenges Opinion statement Coronary artery disease (CAD) and cancer often occur in the same patients via common biological pathways and shared risk factors. A variety of chemotherapeutic agents and radiotherapy can influence the development and progression of CAD. The diagnosis of ischaemic heart disease may be challenging in certain cases such as premature CAD secondary to radiotherapy. The management of CAD in cancer patients in the stable, acute and chronic settings can often be complicated by issues related to ongoing or previous cancer treatment or the cancer itself. A multidisciplinary approach in the setting of a cardio-oncology service is often best-served to optimally treat such patients.

Pain in Cancer Survivors: How to Manage Opinion statement Managing pain in cancer survivors requires that oncologists understand the common painful syndromes that can occur from treatment or disease. Assessment no longer singularly focuses on pain characteristics (e.g., intensity, quality, location), now incorporating a strong focus on functional impairment and potential improvement that might occur with adequate treatment. Improvement in function is now the goal used to measure success. In addition, assessment must incorporate risk factors that might predispose patients to substance use disorder so that interventions can be implemented to mitigate this risk. Universal precautions are measures that help assess and ensure adherence to the treatment plan and may include the use of agreements, urine toxicology, and review of dispensing information derived from state prescription drug monitoring program (PDMP). These are generally obtained annually for all individuals, although some states have instituted mandatory review of the PDMP whenever prescribing an opioid. For patients at moderate to high risk for misuse of opioids, where opioids are warranted for the treatment of their pain syndrome, universal precautions are instituted more frequently. Other measures may include prescribing a 1- to 2-week supply of medications if compulsive use leads the patient to running out of drug early, and in some cases, family members may be employed to dispense daily allotments of the medication. When opioids are no longer indicated, gradual tapering of the drug by approximately 10% per month is generally sufficient to prevent withdrawal symptoms and ensure patient acceptance.

Malignant Melanoma: Autoimmunity and Supracellular Messaging as New Therapeutic Approaches Opinion statement Melanoma is one of the most aggressive forms of cancer, with a high mortality rate in the absence of a safe and curable therapy. As a consequence, several procedures have been tested over time, with the most recent (immunological and targeted) therapies proving to be effective in some patients. Unfortunately, these new treatment options continue to generate debate related to the therapeutic strategy (intended to maximize the long-term results of patients with melanoma), not only about the monotherapy configuration but also regarding association/succession between distinct therapeutic procedures. As an example, targeted therapy with BRAF inhibitors proved to be effective in advanced BRAF-mutant melanoma. However, such treatments with BRAF inhibitors lead to therapy resistance in half of patients after approximately 6 months. Even if most benign nevi incorporate oncogenic BRAF mutations, they rarely become melanoma; therefore, targeted therapy with BRAF inhibitors should be viewed as an incomplete or perfectible therapy. Another example is related to the administration of immune checkpoint inhibitors/ICIs (anti-CTLA-4 antibodies, anti-PD-1/PD-L1 antibodies), which are successfully used in metastatic melanoma. It is currently believed that CTLA-4 and PD-1 blockade would favor a strong immune response against cancer cells. The main side effects of ICIs are represented by the development of immune-related adverse events, which in some cases can be lethal. These ICI side effects would thus be not only therapeutically counterproductive but also potentially dangerous. Surprisingly, a subset of immune-related adverse events (especially autoimmune toxicity) seems to be clearly correlated with better therapeutic results, perhaps due to an additional therapeutic effect (currently insufficiently studied/exploited). Contrary to the classical approach of cancer (considered until now an uncontrolled division of cells), a very recent and comprehensive theory describes malignancy as a supracellular disease. Cancerous disease would therefore be a disturbed supracellular process (embryogenesis, growth, development, regeneration, etc.), which imposes/coordinates an increased rhythm of cell division, angiogenesis, immunosuppression, etc. Melanoma is presented from such a supracellular perspective to be able to explain the beneficial role of autoimmunity in cancer (autoimmune abortion/rejection of the melanoma-embryo phenotype) and to create premises to better optimize the newly emerging therapeutic options. Finally, it is suggested that the supracellular evolution of malignancy implies complex supracellular messaging (between the cells and host organism), which would be interfaced especially by the extracellular matrix and noncoding RNA. Therefore, understanding and manipulating supracellular messaging in cancer could open new treatment perspectives in the form of digitized (supracellular) therapy.

Precision Medical Approaches to the Diagnoses and Management of Brain Metastases Opinion statement Brain metastases represent a common and devastating complication of cancer with survival on the order of a few months in most patients. Melanoma, breast cancer, and lung cancer remain the primary disease histologies with the highest rates of metastatic spread to the brain. The incidence of brain metastases has continued to rise, likely explained by multiple factors. Improvement in progression-free survival in systemic cancer is likely attributable to advances in medical therapy, earlier supportive and symptomatic care, and improved precision around diagnosis and detection. In this context, longer survival and improved extracranial control disease has likely contributed to the increased development of metastatic spread intracranially. The foundation of management remains systemic therapy, as well as a combination of surgery and radiation therapy. In the era of targeted therapies, specific agents have demonstrated improved CNS penetration, however with varying degrees of durable responses. Most patients develop resistance to targeted agents, limiting their duration of use for patients. In this era of personalized medicine, the role of genomic characterization in cancer has been critical in the field of brain metastases, as alterations unique to both the brain metastases and its systemic predecessor have been identified, potentially offering new avenues for therapy.

Applications of Cardiac Computed Tomography in the Cardio-Oncology Population Opinion statement The increased risk for cardiovascular events in aging cancer survivors and those undergoing certain chemotherapeutic treatments has raised concern for more rigorous screening and surveillance methods above that of the general population. At this time, there are limited guidelines for how to best manage this vulnerable cohort. Questions regarding timing of screening, choice of imaging modality and risk reduction strategies—especially in those patients with known atherosclerotic disease—remain to be elucidated. Over a decade of case series, retrospective studies and clinical trials have shed light on the evolving role of cardiac computed tomography (CT) in this population, of which there is a relative paucity of data regarding its potential utility in the specific cardio-oncology population. Focusing on ability of cardiac CT to evaluate multiple cardiac and vascular structures, provide diagnostic and prognostic information, as well as assist interventional and surgical colleagues in surgical/percutaneous valve replacement and revascularization strategies is the premise for this review.

Adjuvant Therapy Options in Renal Cell Carcinoma: Where Do We Stand? Opinion statement Adjuvant therapy for non-metastatic renal cell carcinoma (RCC) remains controversial. Of the four reported randomized controlled trials evaluating adjuvant vascular endothelial growth factor (VEGF) inhibition, only one met its primary endpoint. The S-TRAC study demonstrated a statistically significant improvement in disease-free survival (DFS) of greater than 1 year with adjuvant sunitinib compared to placebo in patients with high-risk localized RCC and earned it FDA approval. However, the larger ASSURE study which reported first did not find a difference in DFS or overall survival between 1 year of adjuvant sunitinib or sorafenib compared to placebo. Given the discordant results of the two sunitinib studies, two other negative studies of adjuvant targeted therapy with pazopanib and axitinib, the lack of definite overall survival benefit in any study, and the high incidence of treatment-related adverse events with sunitinib, we do not recommend the routine use of adjuvant sunitinib. The decision to offer adjuvant sunitinib should be considered on an individual basis after an informed discussion of the potential toxicities and the risk/benefit ratio. Despite numerous efforts and recently published works, there is a paucity of prognostic and predictive molecular biomarkers in RCC. Further investigation is needed to discover new tools that can enhance the identification of patients who are most likely to benefit from adjuvant treatment beyond pathologic stage. Immune checkpoint inhibitors have great potential to significantly improve outcomes in high-risk localized RCC. Building on their established efficacy in the metastatic setting, several ongoing clinical trials are evaluating their value as single agents or in combination in the neoadjuvant and adjuvant settings. At this time, we recommend participation in clinical trials as the preferred therapeutic option for patients with high-risk, non-metastatic RCC planned for nephrectomy.

Epidemiology of Head and Neck Squamous Cell Carcinomas: Impact on Staging and Prevention Strategies Opinion statement The epidemiology of head and neck squamous cell carcinoma (HNSCC) has shifted dramatically over the last 50 years, as smoking-related HNSCCs decrease in incidence while human papillomavirus (HPV)-related cancers rise. The shift in HNSCC risk factors has changed patient demographics, the distribution of affected anatomical subsites, and prognosis of this illness. As such, the medical community has responded by devising novel staging systems and prevention strategies. The medical community will require continued vigilance in reducing HNSCC traditional risks factors for HNSCC, such as cigarette use, and emerging risk like HPV infection.

Treatment of Radiation-Induced Cognitive Decline in Adult Brain Tumor Patients Opinion statement Patients with either primary or metastatic brain tumors quite often have cognitive impairment. Maintaining cognitive function is important to brain tumor patients and a decline in cognitive function is generally accompanied by a decline in functional independence and performance status. Cognitive decline can be a result of tumor progression, depression/anxiety, fatigue/sleep dysfunction, or the treatments they have received. It is our opinion that providers treating brain tumor patients should obtain pre-treatment and serial cognitive testing in their patients and offer mitigating and therapeutic interventions when appropriate. They should also support cognition-focused clinical trials.

Surgical Options for Locally Advanced Oropharyngeal Cancer Opinion statement Oropharyngeal squamous cell carcinoma (OPSCC) incidence rates have been steadily increasing over the past several decades, and this has been largely attributed to human papillomavirus (HPV)-related OPSCC. The rise of HPV-related OPSCC and the observed distinct survival advantage it offers compared to HPV-unrelated OPSCC have resulted in the development of a new staging system specifically for OPSCC in the eighth edition of the AJCC Staging Manual for head and neck cancer. The observations on HPV-related OPSCC and its prognostic implications have coincided with increasing utilization of transoral surgical approaches to oropharyngeal tumors, such as transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). These approaches were once thought to only be applicable to patients with low T-stage OPSCC tumors; however, they are being increasingly utilized in locally advanced OPSCC cases as several studies have shown that both of these transoral approaches are oncologically sound alternatives to concurrent chemoradiation therapy (CCRT), which was previously the standard-of-choice treatment in patients with locally advanced disease. Moreover, these transoral approaches have displayed better long-term swallowing outcomes compared to CCRT, as severe dysphagia is often the most bothersome functional impairment to OPSCC survivors who have undergone CCRT. While open surgical approaches were previously not utilized in the locally advanced OPSCC setting due to the risk of severe surgical complications compared to the potential benefits of organ preservation with CCRT and comparable survival rates after either treatment regimen, these approaches are still reasonable options for select patients in the salvage surgery setting, as they allow for maximum exposure to the deep oropharyngeal anatomy. Data from multiple clinical trials evaluating the potential for TORS to de-escalate radiation dose or CCRT regimen in certain settings will inform clinical decision-making for OPSCC patients for the next decade and allow for more personalized treatments tailored to an individual patient's disease burden.

Optimal Management of Upper Tract Urothelial Carcinoma: an Unmet Need Opinion statement Upper tract urothelial carcinoma (UTUC) is a rare genitourinary entity of the renal pelvis and the ureter characterized by a more aggressive disease phenotype when compared with urothelial carcinoma of the bladder (UCB) with more than half of UTUC cases presenting with invasive disease at diagnosis compared to 20% for bladder tumors. There is growing evidence suggesting that its distinct natural history from that of bladder cancer can be related to several genetic and epigenetic differences. Treatment of low-risk disease consists of kidney-sparing surgeries such as ureteroscopic and percutaneous treatments, segmental ureterectomy, and adjuvant topical and intracavitary chemo-immunotherapies. The standard of care for high-risk non-metastatic disease remains radical nephroureterectomy and bladder cuff excision with increasing utilization rates of minimally invasive approaches leading to reduced morbidity without compromising outcomes while the role of lymphadenectomy is still being investigated. The prognosis of UTUC has been stagnant over the past decade highlighting the need for further studies on the role of multimodal therapy (neoadjuvant/adjuvant chemotherapy, immunotherapy, targeted therapy) to optimize management and improve outcomes.