Natural history and management of Fanconi anemia patients with head and neck cancer: A 10‐year follow‐up

Abstract

Objective To describe the management and outcomes of Fanconi anemia (FA) patients with head and neck squamous cell carcinoma. Study Design Cohort study. Methods Demographic information, prognostic factors, therapeutic management, and survival outcomes for FA patients enrolled in the International Fanconi Anemia Registry (IFAR) who developed head and neck squamous cell carcinoma (HNSCC) were analyzed. Results 35 FA patients were diagnosed with HNSCC at a mean age of 32 years. The most common site of primary cancer was the oral cavity (26/35, 74%). Thirty patients underwent surgical resection of the cancer. Sixteen patients received radiation therapy with an average radiation dose of 5050 cGy. The most common toxicities were high-grade mucositis (9/16, 56%), hematologic abnormalities (8/16, 50%), and dysphagia (8/16, 50%). Three patients received conventional chemotherapy and had significant complications while three patients who received targeted chemotherapy with cetuximab had fewer toxicities. The 5-year overall survival rate was 39% with a cause-specific survival rate of 47%. Conclusions Fanconi anemia patients have a high risk of developing aggressive HNSCC at an early age. FA patients can tolerate complex ablative and reconstructive surgeries, but careful post-operative care is required to reduce morbidity. The treatment of FA-associated HNSCC is difficult secondary to the poor tolerance of radiation and chemotherapy. However, radiation should be used for high-risk cancers because of the poor survival in these patients.

Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia

“…While variability occurs, recurrent features include developmental anomalies and malformations, most commonly growth retardation, cutaneous pigment displacement, and radial ray defects. Other frequent aspects of FA comprise early-onset bone marrow failure and cancer predisposition, specifically for acute myelogenous leukemia and head and neck squamous cell carcinoma (1)(2)(3)(4). FA results from faults in the FA/BRCA pathway for DNA interstrand cross-link (ICL) repair, in which proteins encoded by 21 FA genes reported thus far -designated as or aliased with the prefix FANC-and serial letters of the alphabet, FANCA to FANCV -and associated proteins interact (5)(6)(7)(8)(9).…”

Mutational and Functional Analysis of FANCB as a Candidate Gene for Sporadic Head and Neck Squamous Cell Carcinomas

“…Defects in FANCB are associated with genetic instability and hypersensitivity to DNA crosslinking agents such as platinumderivatives (33), both of which are also hallmarks of HNSCC cells. Remarkably, all FA patients including FANCB patients have an extremely high incidence of spontaneous HNSCCs (21)(22)(23). Importantly, other groups demonstrated that FANCB can be significantly down-regulated in sporadic HNSCC (40) and that up to 31% of sporadic HNSCC tumors demonstrate hypermethylation of the FANCB promoter locus (41).…”

“…Importantly, SCCs of the head, neck, and esophagus and in women also vulvar and cervical cancers occur at astonishingly high rates in FA patients, up to 14% of patients by 40 years of age (21)(22)(23). This strongly suggests that defects in the FA pathway might increase the risk of developing HNSCCs.…”

Screening for mutations in two exons of FANCG gene in Pakistani population

“…Moreover, solid tumors tend to develop later in the course of disease. Median age of onset of solid tumors is around 30 years in literature 43 . But in our part of world patients hardly cross the age of 20 years, mainly because of limited availability of bone marrow transplant and other health facilities.…”