Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer, with high morbidity and mortality. Racial disparity in HNSCC is observed between African Americans (AAs) and whites, effecting both overall and 5-year survival, with worse prognosis for AAs. In addition to socio-economic status and demographic factors, many epidemiological studies have also identified factors including coexisting human papillomavirus (HPV) infection, primary tumor location, and a variety of somatic mutations that contribute to the prognostic incongruities in HNSCC patients among AAs and whites. Recent research also suggests HPV-induced dysregulation of tumor metabolism and immune microenvironment as the major regulators of HNSCC patient prognosis. Outcomes of several preclinical and clinical studies on targeted therapeutics warrant the need to elucidate the inherent mechanistic and population-based disparities underlying patient responses. This review systematically reports the underlying reasons for inconsistency in disease prognosis and therapy responses among HNSCC patients from different racial populations. The focus of this review is twofold: aside from discussing the causes of racial disparity, we also seek to identify the consequences of such disparity in terms of HPV infection and its associated mutational, metabolic, and immune landscapes. Considering the clinical impact of differential patient outcomes among AA and white populations, understanding the underlying cause of this disparity may pave the way for novel precision therapy for HNSCC. REVIEW
Cancer remains a leading cause of death in the USA and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders. One such natural resource is derived from certain plants of the family Annonaceae, which are widely distributed in tropical and subtropical regions. Among the best known of these is Annona muricata, also known as soursop, graviola or guanabana. Extracts from the fruit, bark, seeds, roots and leaves of graviola, along with several other Annonaceous species, have been extensively investigated for anticancer, anti-inflammatory and antioxidant properties. Phytochemical studies have identified the acetogenins, a class of bioactive polyketide-derived constituents, from the extracts of Annonaceous species, and dozens of these compounds are present in different parts of graviola. This review summarizes current literature on the therapeutic potential and molecular mechanism of these constituents from A.muricata against cancer and many non-malignant diseases. Based on available data, there is good evidence that these long-used plants could have both chemopreventive and therapeutic potential. Appropriate attention to safety studies will be important to assess their effectiveness on various diseases caused or promoted by inflammation.
IMPORTANCE Sinonasal mucosal melanoma (SMM) is a rare malignant neoplasm characterized by a poor prognosis despite aggressive intervention including wide surgical resection. Margin status has previously been cited as an important prognostic factor for local control and overall survival (OS) in patients who undergo either an open or endoscopic surgical approach. No comparisons have been made, however, in patients who have undergone gross total resection with or without positive margins. OBJECTIVE To assess the association of margin status and surgical approach with oncologic outcomes in patients with SMM undergoing gross total resection. DESIGN, SETTING, AND PARTICIPANTS In this cohort study, patients with SMM without evidence of regional or distant disease treated with curative intent in part or full at Memorial Sloan Kettering Cancer Center from 1998 through 2016 were retrospectively assessed. Demographic data, prognostic information, and surgical pathology were reviewed. Operative reports and imaging were used to confirm gross total resection of local disease. EXPOSURES Surgical techniques including open maxillectomy, craniofacial resection, and endoscopic resection. MAIN OUTCOMES AND MEASURES Three-year local recurrence-free survival (LRFS), disease-free survival (DFS), and OS were calculated using the Kaplan-Meier method. Univariate and multivariable analyses of outcomes were carried out using the Cox proportional hazard regression method. RESULTS Seventy-two patients (39 [54%] female; mean [SD] age, 67 [12] years) met the eligibility criteria. Thirty-eight patients (53%) underwent open partial or total maxillectomy with or without ethmoidectomy or sphenoidectomy via a transfacial approach. Fourteen patients (19%) had a more extensive craniofacial approach, and 20 patients (28%) underwent endoscopic resection. The 3-year OS for all patients was 52%. The absolute 3-year difference between patients with open/craniofacial resection vs endoscopic resection for LRFS, DFS, and OS was 11% (95% CI, −21% to 43%), 16% (95% CI, −7% to 39%), and 12% (95% CI, −18% to 41%), respectively. The absolute 3-year difference between patients with a negative margin and patients with a positive margin for LRFS, DFS, and OS was 18% (95% CI, −9% to 45%), 5% (95% CI, −17% to 27%), and 15% (95% CI, −9% to 39%), respectively. Multivariable analysis revealed that none of the adjusted variables (margin status, tumor stage, or surgical approach) were significantly associated with OS. CONCLUSIONS AND RELEVANCE Outcomes for patients with SMM remain poor regardless of operative approach or postoperative margin status.
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