Cancer-Associated Thrombotic Microangiopathy: Literature Review and Report of Five Cases.

Thrombotic microangiopathy (TMA) is an anatomopathological lesion mediated by endothelial dysfunction and characterized by the creation of microthrombi in small vessels. In patients with cancer, it may be due to toxicity secondary to chemotherapy, tumor embolization, or hematopoietic progenitor transplantation. Cancer-associated TMA is an underestimated entity that generally appears in the final stages of the disease, although it may also be the initial manifestation of an underlying cancer. Support treatment is necessary in all cases and, depending on the cause, different targeted therapies may be used. The prognosis is very poor. In this article we present a comprehensive review of the existing literature on the physiological mechanisms of cancer-associated TMA. Afterwards, five clinical cases will be presented of patients who developed TMA and were diagnosed in our Department in 2023. We present a discussion of the different causes that triggered the condition, the possible reasons behind the underestimation of this pathology, and the measures that may be adopted.

Long-term outcomes of induction chemotherapy followed by chemoradiotherapy vs chemoradiotherapy alone as treatment of unresectable head and neck cancer: follow-up of the Spanish Head and Neck Cancer Group (TTCC) 2503 Trial.

BACKGROUND: Our previous phase-3 study (TTCC 2503) failed to show overall survival advantage of 2 induction chemotherapy (IC) regimens followed by standard concurrent chemoradiotherapy (CRT) over CRT alone in patients with unresectable locally advanced head and neck squamous-cell carcinoma (LAHNSCC). This study described the long-term survival of those patients. MATERIALS AND METHODS: Long-term follow-up study of patients with untreated LAHNSCC assigned to IC (three cycles), with either docetaxel, cisplatin and 5-fluorouracil (TPF arm) or cisplatin and 5-fluorouracil (PF arm), followed by CRT, or CRT alone, included in the previous TTCC 2503 trial. RESULTS: In the intention-to-treat population (n = 439), the median OS times were 25.4 (95% CI, 16.8-34.4), 26.2 (95% CI, 18.2-36.6) and 25.4 months (95% CI, 17.4-36.0) in the TPF-CRT, PF-CRT and CRT arms, respectively (log-rank p = 0.51). In the per-protocol population (n = 355), patients with larynx-hypopharynx primary tumors treated with IC (TPF or PF) followed by CRT had a longer median PFS than those who received CRT alone. Moreover, patients with ECOG 0 treated with IC (TPF or PF) followed by CRT had a better TTF than those with CRT alone. There were no statistically significant differences in terms of OS, PFS or TTF, according to the tumor load or affected nodes. CONCLUSION: After a long follow-up, the TTCC 2503 trial failed to show the benefit of IC-CRT in unresectable LAHNSCC regarding the primary end point. However, fit patients with ECOG 0 and primary larynx-hypopharyngeal tumors may benefit from the use of IC if administered by an experienced team. ClinicalTrials.gov identifier NCT00261703.

Epidermal growth factor receptor (EGFR) pathway polymorphisms as predictive markers of cetuximab toxicity in locally advanced head and neck squamous cell carcinoma (HNSCC) in a Spanish population.

OBJECTIVES: To examine the relationship between polymorphisms of the epidermal growth factor receptor (EGFR) pathway and toxicity in head and neck squamous cell carcinoma (HNSCC) patients treated with cetuximab. MATERIAL AND METHODS: Multicenter, retrospective, observational pilot study which included 110 patients with histologically-confirmed human papillomavirus (HPV) negative HNSCC in locally advanced stages (III-IVA-B) and who were treated with chemotherapy and radiotherapy plus cetuximab between 2003 and 2013. Genetic analyses for single nucleotide polymorphisms (SNP) in genes EGFR, CCDN1, FCGR2A, FCGR3A and KRAS-LCS6 were performed though available allelic discrimination assay and/or polymerase chain reaction-restriction fragment length polymorphism methods. RESULTS: Acneiform rash was observed in 55.5% of patients, dry skin in 45.5% and pruritus in 20.9%. A significant association with dry skin and global cetuximab-related toxicity was observed for the KRAS-LCS6 (rs61764370) variant (p<0.05); carriers of the G allele (genotypes TG+GG) in the dominant model were observed to have a decreased susceptibility of developing dry skin (OR=0.287 [95%CI=0.119-0.695]). Carriers of the A (GA+AA) allele for EGFR (rs2227983) showed a decreased risk of suffering from pruritus (OR=0.345 [0.124-0.958]). Similarly, KRAS (rs1801274) was related with lower global cetuximab-related toxicity (OR=0.266 [0.114-0.622]). CONCLUSION: This pilot study provides preliminary evidence supporting genetic variation of EGFR (rs2227983), KRAS (rs61764370) and FCGR2A (rs180127) as useful biomarkers for predicting reduced skin toxicity in HNSCC patients treated with a cetuximab-based therapy. Alternative therapeutic options should be explored for these patients.

Epidemiological characteristics of a Spanish cohort of patients diagnosed with squamous cell carcinoma of head and neck: distribution of risk factors by tumor location.

PURPOSE: Head and neck cancer is a highly heterogeneous disease comprising a large number of tumors located in the cervicofacial area. This study aimed to determine the epidemiological characteristics of squamous-cell carcinomas of the head and neck in the Spanish population, and the distribution of risk factors based on tumor locations. METHODS/PATIENTS: A cohort of 459 patients (75 oral cavity, 167 oro-/hypopharyngeal and 217 laryngeal cancers) recruited in 19 hospitals participating in the Spanish head and neck cancer cooperative group were included over 3 years (2012-2014). Epidemiological parameters and risk factors were obtained from a self-administered questionnaire, and tumor characteristics were obtained from clinical records. Multivariate multinomial logistic regression was used to assess factors associated with tumor location. RESULTS: Most patients were males (88.4 %), smokers (95 %) and drinkers (76.5 %). Relative to laryngeal cancer, pharyngeal cancer and oral cancer were more common in women than men (OR 3.58, p = 0.003 and 4.33, p = 0.001, respectively); pharyngeal cancer was more associated with rural environment (OR 1.81, p = 0.007) and weekly alcohol intake (10-140 g: OR 2.53, p = 0.012; 141-280 g: OR 2.47, p = 0.023; >280 g: OR 3.20, p = 0.001) and less associated with pack-years of smoking (21-40 packs: OR 0.46, p = 0.045; 41-70 packs: OR 0.43, p = 0.023; ≥71 packs: OR 3.20, p = 0.015). CONCLUSIONS: The distribution of these tumors differs between the sexes, with a higher proportion of oral cavity and pharyngeal tumors in women than in men. Oro-/hypopharyngeal cancers were more strongly associated with rural areas and with alcohol consumption, although less strongly associated with smoking than laryngeal tumors.