Be-TeaM: An Italian real-world observational study on second-line therapy for EGFR-mutated NSCLC patients.

OBJECTIVES: Molecular diagnostics and care of non-small cell lung cancer (NSCLC) are continuously evolving. Few data document the current strategies to manage advanced NSCLC patients beyond progression in clinical practice. PATIENTS AND METHODS: Be-TeaM is an Italian multi-center observational study conducted on consecutive EGFR-mutated stage IV NSCLC patients, progressed during/after a first-line EGFR-TKI. It consists of a retrospective phase, from first-line EGFR-TKI therapy start until study entry (i.e. beginning of the diagnostic process), and a prospective phase, until treatment choice or for 3 months if no therapy was prescribed. Primary objective was to describe the diagnostic and therapeutic approaches adopted after progression in a real-world setting. RESULTS: Of 308 patients enrolled in 63 centers from July 2017 to June 2018, 289 were included in the analysis. In first line, 53.3 % received gefitinib, 32.5 % afatinib and 14.2 % erlotinib. The testing rate (i.e. rate of all patients undergone any biopsy -liquid and/or tissue- for the T790 M detection) was 90.7 %, with liquid biopsy being the most frequently executed. Of 262 biopsied patients, 64.5 % underwent only 1 liquid biopsy, 10.7 % only 1 tissue biopsy and 18.3 % >1 biopsy, both liquid and solid in 85.4 %. The T790M positivity rate was 45.3 %; of 166 patients undergone only a liquid biopsy and tested for the mutation, 39.8 % were T790M+ and 60.2 % T790M-/undetermined. By the observation end, 87.9 % patients had a post-progression treatment chosen, osimertinib being the most frequent among the T790M+. CONCLUSION: Be-TeaM provides the first snapshot of current practices for the management of NSCLC patients beyond progression in Italy; in clinical practice, assessing the T790M status is not always feasible.

Outcome of EGFR-mutated adenocarcinoma NSCLC patients with changed phenotype to squamous cell carcinoma after tyrosine kinase inhibitors: A pooled analysis with an additional case.

The onset of a new histology is a resistant mechanism to tyrosine kinase inhibitors (TKI) in lung adenocarcinoma (ADK), but this phenomenon has not yet been fully clarified. We present a pooled analysis of the outcomes of EGFR-mutated ADK patients with changed phenotype to squamous cell carcinoma (SqCC) following TKI, along with the description of an additional case. A 67-year-old woman with EGFR-mutated NSCLC received gefitinib and subsequently osimertinib, due to the presence of T790 M at progression. The re-biopsy after third-generation TKI revealed SqCC histology along with the basal EGFR mutation, while T790 M disappeared. The patient rapidly progressed and died despite two chemotherapy cycles. Since this first description of SqCC transformation appearing after treatment with the third-generation TKI osimertinib, other 16 patients, with EGFR-mutated ADK developing a transformation to SqCC histology after treatment with TKIs, were up to now published. From our pooled analysis emerged that most patients were female (82%), 41% were former smokers and no current smokers were identified. Median time to SqCC onset was 11.5 months. In all cases, basal EGFR mutation was maintained, and 11 patients (65%) developed an acquired mutation on exon 20. Interestingly also 790 M mutation appeared in 8 patients (47%). The median survival after SqCC diagnosis was 3.5 months regardless the treatments received. Therefore, EGFR-mutated lung ADK destined to develop a squamous phenotype were often smokers and maintained the baseline genomic alterations. The prognosis after SqCC diagnosis was extremely poor and current treatments largely inefficacious.

Idiopathic intracranial hypertension: a possible complication in the natural history of advanced prostate cancer.

Idiopathic intracranial hypertension is a variety of intracranial hypertension that is extremely rare in men. Obesity and hypogonadism are the most important predictive factors. Etiological hypotheses include increased central venous pressure, and various hormonal and metabolic changes commonly found in obese patients. We described the case of an obese man with prostate cancer who showed a consistent bodyweight increase during treatment with taxanes and prednisone. He was hospitalized because of a severe loss of vision as a consequence of idiopathic intracranial hypertension. A complete symptom remission was obtained after 3 weeks of anti-edema therapies (steroids, acetazolamide). Castration-resistant prostate cancer is a risk factor for idiopathic intracranial hypertension. Long-term androgen deprivation therapy, bodyweight increase, and fluid retention during chronic steroid administration and taxane chemotherapy might favor the disease onset. This severe complication has a good outcome, and should be suspected in the presence of symptoms and signs of intracranial hypertension.

Allergy and tumour outcome after primary cancer therapy.

BACKGROUND: Over the last decade several papers have dealt with the possible interference of allergies in both the infectious disease incidence and tumour development. In the light of all these observations we analysed several tumour patients for a possible interaction between a state of allergy and tumour development and progression after primary cancer therapy. METHODS: This study included 1,055 patients with different types of solid tumours admitted consecutively between 1994 and 2002 to the Cagliari University Polyclinic. After primary surgery or medical therapy (or both), 92 allergic subjects and 182 non-allergic patients were studied over a follow-up period of 6-96 months (median 23). RESULTS: Among 1,055 tumour-bearing patients, the prevalence of allergy was found to be about 8% versus 16-37% in a population of non-tumour-bearing subjects. After primary cancer therapy, allergic patients turned out to have a 20% higher probability of being cured and about a 50% lower risk of tumour progression as compared to non-allergic ones. The observed differences were statistically significant (p=0.013). CONCLUSIONS: On the basis of our findings, we suggest that allergic subjects seem to have a better prognosis than non-allergic ones for disease outcome after cancer therapy.