Erlotinib is approved for the treatment of patients with
EGFR
mutation positive, metastatic NSCLC. It is also approved as second/third line therapy for
EGFR
mutation negative patients, but in this ...setting the benefit of erlotinib is modest and there is no validated biomarker for selecting
EGFR
wild-type patients who may benefit the most from the treatment. We retrospectively assessed
EGFR
and
K-RAS
mutational status, and EGFR, c-MET and IGF1-R expression in tumor samples of 72 patients with metastatic NSCLC treated with erlotinib after at least one prior line of chemotherapy, from 2008 to 2012. We analyzed the association between biomarkers and outcome (RR, PFS, and OS).
EGFR
mutated patients achieved a better RR (56% vs 8%,
p
= .002), PFS (10 vs 3 months, HR 0.53,
p
= 0.48) and OS (20 vs 6 months, HR 0.55,
p
= .07), compared to
EGFR
wild-type patients. Among 63
EGFR
wild-type patients, those with EGFR high-expression had a better outcome in terms of RR (40% vs 2%,
p
= .002), PFS (7.5 vs 2 months, HR 0.45,
p
= .007) and OS (30 vs 5 months, HR 0.34,
p
< .001) compared to patients with EGFR intermediate or low/negative-expression. IGF1-R expression, c-MET expression and
K-RAS
mutational status did not significantly affect the outcome; however, no patients with
K-RAS
mutation or c-MET high-expression achieved an objective response. In patients with metastatic, chemo-refractory
EGFR
wild-type NSCLC, EGFR high-expression may represent a positive predictor of activity for erlotinib, whereas
K-RAS
mutation and c-MET high-expression may predict lack of activity. These findings deserve further prospective evaluation.
Cytological endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimens of mediastinal lymph node metastasis are frequently used to perform concomitant diagnosis, staging ...and genetic testing in non-small-cell lung cancer (NSCLC). The purposes of this single-center retrospective study were to evaluate EBUS-TBNA samples' adequacy for molecular testing of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and to analyze the concordance between the cell block method and liquid-based cytology (LBC) in appraising the sample cellularity and in detecting EGFR mutation.
We retrospectively examined 82 patients who underwent EBUS-TBNA from October 2012 to September 2015 and received a confirmed diagnosis of lymph node metastasis of lung adenocarcinoma. Each sample was processed using both cell block and LBC to carry out DNA analysis (adequacy criterion: tumor cell percentage > 25%) and EGFR mutation testing.
Fifty-four patients were male, 66 were current or former-smokers, and the median age was 67 years. The median size of sampled lymph nodes was 14.8 mm. Seventy-one and 66 samples were adequate to perform cell block and LBC, respectively. The κ-statistic (0.78) showed an excellent concordance. EGFR mutation was detected in eight patients using cell block and in seven using LBC, with a simple percentage agreement of 87.5%. ALK translocation was found in two patients.
This study demonstrates the feasibility of EGFR mutation analysis with both cell block and LBC, with an excellent concordance between the two methods. Considering that the majority of advanced NSCLCs are diagnosed on cytology specimens, LBC is feasible and needs to be implemented for ancillary tests (immunocytochemistry, molecular analysis).
Oesophageal gastrointestinal stromal tumors (GISTs) are rare neoplasms (about 2% of all GISTs); radical surgery is the standard treatment of all GISTs but in case of locally advanced and unresectable ...disease no clear treatment guide lines are available. Studies including neoadjuvant imatinib mesylate (IM) are relatively recent, includes small sample size of heterogeneous patients and do not report a standardized duration of neoadjuvant treatment. The main question still remains whether surgery after neoadjuvant IM gives a survival benefit in locally advanced disease. A 46-year-old man with locally advanced unresectable oesophageal GIST harboring KIT exon 11 mutation was treated in our institution for 12 months with neoadjuvant IM; a reduction of 83% of tumor volume was obtained in 9-month of neoadjuvant IM, but in the last 3 months no further response was seen. After neoadjuvant therapy, patient underwent radical surgery and adjuvant IM, which is still ongoing. Since no definitive data are available about survival benefit of surgery after neoadjuvant IM in locally advanced GISTs, a careful balance between morbidity and mortality derived from surgery should be considered and more studies are needed to better define the utility and the optimal duration of neoadjuvant treatment.
Patients with cancer have an increased risk of complications from coronavirus disease 2019 (COVID-19) infection, including death, and thus, they were considered as high-priority subjects for COVID-19 ...vaccination. We report on the compliance with the COVID-19 vaccine of patients affected by solid tumours.
Patients with cancer afferent to Medical Oncology 1 Unit of Regina Elena National Cancer Institute in Rome were considered eligible for vaccination if they were receiving systemic immunosuppressive antitumor treatment or received it in the last 6 months or having an uncontrolled advanced disease. The Pfizer BNT162b2 vaccine was proposed to all candidates via phone or during a scheduled visit. The reasons for refusal were collected by administrating a 6-item multiple-choice questionnaire.
From 1st March to 20th March 2021, of 914 eligible patients, 102 refused vaccination (11.2%, 95% confidence interval CI 9.1–13.2). The most frequent (>10%) reasons reported were concerns about vaccine-related adverse events (48.1%), negative interaction with concomitant antitumor therapy (26.7%), and the fear of allergic reaction (10.7%). The refusal rate (RR) after 15th March (date of AstraZeneca-AZD1222 suspension) was more than doubled compared with the RR observed before (19.7% versus 8.6%, odds ratio OR 2.60, 95% CI 1.69–3.99; P < 0.0001). ECOG-PS 2 was associated with higher RR compared with ECOG-PS 0-1 (OR 2.94, 95% CI 1.04–8.34; P = 0.04). No statistically significant differences in RR according to other clinical characteristics were found.
Our experience represents the first worldwide report on the adherence of patients with cancer to COVID-19 vaccination and underlines how regulatory decisions and media news spreading could influence the success of the campaign.
•High mortality rate related to coronavirus disease 2019 (COVID-19) was observed in patients with cancer.•Cancer patients have high priority for COVID-19 vaccination for their vulnerability.•A refusal rate of 11.2% was found in our large cohort of eligible cancer patients.•Adequate information and clear regulatory decisions are required to promote vaccination.
We assessed the immunogenicity and safety of the BNT162b2 vaccine in a large cohort of patients with cancer (CP).
From March 1, 2021 to March 20, 2021, this prospective cohort study included 816 CP ...afferent to our institution and eligible for the vaccination. A cohort of 274 health care workers (HCW) was used as age- and sex-matched control group. BNT162b2 was administered as a two-dose regimen given 21 days apart. Blood samples to analyze anti-Spike (S) IgG antibodies (Ab) were collected prevaccination timepoint (TP) 0, and at 3 weeks (TP1) and 7 weeks (TP2) after the first dose.
Patients characteristics: median age 62 (range, 21-97); breast/lung cancer/others (31/21/48%); active treatment/follow-up (90/10%). In the whole CP cohort, the serologic response rate (RR) and the titre of anti-S IgG significantly increased across the TPs; at TP2, the responders (IgG >15 AU/mL) were 94.2%. Active chemotherapy and chronic use of steroids were independent predictors of lower RR. Adverse events (AE) after the booster predicted higher likelihood of response (OR, 4.04; 95% confidence interval, 1.63-9.99;
= 0.003). Comparing the matched cohorts, the responders were significantly lower in CP than in HCW at TP1 (61.2% vs. 93.2%) and TP2 (93.3% vs. 100%), while the geometric mean concentration of IgG did not significantly differ at TP2 being significantly lower in CP (23.3) than in HCW (52.1) at TP1. BNT162b2 was well tolerated in CP; severe-grade AEs were 3.5% and 1.3% after the first and second doses, respectively.
BNT162b2 assures serologic immunization without clinically significant toxicity in CP. The second dose is needed to reach a satisfactory humoral response.
We previously reported on the immunogenicity and safety of BNT162b2 in a large cohort of patients with cancer after the first and second doses (Di Noia et al., 2021) 1. Herein, we present result ...after six months of follow-up.
This prospective study included patients affected by solid tumors and afferent to our institution who received two doses of BNT162b2 vaccine. A cohort of vaccinated healthcare workers (HCW) was used as control-group. Both cohorts were evaluated for the titer of anti-Spike (S) IgG at prefixed time-points (TPs). Time-point 4 was scheduled at 24–26 weeks after the second dose.
In the current analysis, 400 patients and 232 healthcare workers were evaluated. Responders (IgG > 15 AU/mL) in patients group were 86.5% compared with 94.4% among healthcare workers. Also the IgG titer at TP4 was significantly inferior in patients than in healthcare workers (70.81 vs 134.64 AU/ml, p < 0.001). There was a more rapid decline of the antibody level from TP3 to TP4 in patients than in healthcare workers (1.78 vs 1.3 fold). The estimated IgG half-life was significantly shorter for patients (73 days) than in healthcare workers (118 days) as well as the time to reach negative serological status (340 vs 532 days).
The decline of humoral response to the vaccine observed in patients with solid cancer after six months from the first dose support the urgent need of an early additional dose.
•In the sixth month after the first dose, patients with a positive serological status were 86.3%.•IgG titer was inferior in patients than in healthcare workers due to a more rapid decline.•The estimated time to reach negative serological status was 11.3 months for patients.
Display omitted
•Respiratory microbiome is a promising and unexplored topic for cancer research.•Lung cancer is enriched in peculiar microbial communities.•Differences in microbiome ...composition/diversity are reported in lung cancer patients.•Lung microbiome detection and modulation in lung cancer deserves dedicated studies.
Giving the potential contribute in cancer initiation and progression, lung microbiota represents a promising topic in cancer research, although still unexplored. We performed a systematic literature search to identify clinical studies evaluating lung microbiota composition, its correlation with lung cancer patients’ clinico-pathological features and prognosis. Of the identified 370 studies, 21 were eligible and included. Although studies were heterogeneous, lung cancer resulted to be enriched in peculiar microbial communities, with differences in composition and diversity according to clinico-pathological parameters. Few studies explored how lung microbiota influences cancer outcome. In light of these findings and borrowing the suggestions coming from gut microbiota, we speculate that respiratory microbiome may influence pathogenesis, progression and outcome of lung cancer. Taking advantage of the experience of chronical lung diseases, prospective studies should be designed to evaluate lung microbiota changes throughout any phase of lung cancer course, particularly with the advent of immunotherapy as pivotal treatment.
PDF
