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Introduction: Germline pathogenic mutations in TP53 gene are associated with a cancer predisposition syndrome known as Li Fraumeni syndrome. Albeit infrequently, non-small cell lung cancer, especially as oncogene-addicted disease, may be diagnosed in young patients with Li Fraumeni syndrome., Case Description: We report three cases of patients affected by Li Fraumeni syndrome who developed non-small cell lung cancer with EGFR or HER2 exon 20 insertions. The first patient suffered from liposarcoma and, then, brain metastases from HER2 -mutated non-small cell lung cancer: after stereotactic radiotherapy, he benefited from enrollment in a clinical trial with a HER2 -targeted therapy. The second young patient was a female with personal history of rhabdomyosarcoma, diagnosed with brain metastases from EGFR -mutated non-small cell lung cancer: enrollment in a clinical trial led to a temporary clinical benefit. The last case was a female diagnosed with breast carcinoma, ovarian granulosa cell tumor and advanced EGFR -mutated non-small cell lung cancer at a young age., Conclusions: Young patients affected by oncogene-addicted non-small cell lung cancer and with a positive familial cancer history should be referred for an accurate genetic counselling to look for Li Fraumeni syndrome. The underlying molecular connection between TP53 and HER family receptor tyrosine kinases remains unclear, but an extensive molecular characterization of tumors from patients with Li Fraumeni syndrome should always be performed, to offer patients a personalized therapeutic approach., Competing Interests: Declaration of conflicting interestThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.T. received speakers’ and consultants’ fee from Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis, Roche, MSD, Boehringer Ingelheim, Otsuka, Takeda, Pierre Fabre, Amgen, Merck, Sanofi. M.T. received institutional research grants from Astra-Zeneca, Boehringer Ingelheim.F. G. received honoraria or personal fees for the advisory role or consulting from Eli Lilly, Novartis, AstraZeneca, and Bristol-Myers Squibb outside the submitted work.The other authors declare that there is no conflict of interest.

Aim: To apply extended ctDNA-based RAS genotyping to clinical criteria for improving the selection of patients eligible for anti-EGFR-based rechallenge in a real-world setting., Methods: ctDNA testing was prospectively applied to RASwt mCRC progressed after a first-line anti-EGFR-containing regimen and at least one other line. The primary endpoint was the objective response rate., Results: Among ten enrolled patients, the anti-EGFR rechallenge resulted in an objective response rate and disease control rate of 70% and 90%. The median progression-free survival was 11.3 months and overall survival was not reached. Compared with a historical cohort retreated with anti-EGFR agents based on clinical criteria, the ctDNA-driven approach resulted in a higher chance of achieving an objective response and longer survival., Conclusions: Blood-based RASwt status may enrich metastatic colorectal cancer more likely to benefit from anti-EGFR-based rechallenge. RAS genotyping in ctDNA represents a feasible, fast, and cost-effective tool to be implemented in the clinic for advancing precision medicine.

Background: Despite ongoing developments, pancreatic cancer remains one of the most difficult tumors to treat. Even the most effective chemotherapy regimens, only marginally improve the outcome of Pancreatic cancer patients, which rarely exceeds one year. A small subset of Pancreatic cancer patients, carriers of germline variants of BRCA1/2, are clinically relevant as therapeutic targets in pancreatic cancer, both for the first-line and maintenance therapy, as they are more responsive to platinum-based chemotherapy agents and PARP inhibitors. Though, a little is known about the efficacy of olaparib monotherapy in later lines, or in poor responders to platinum-based regimens., Methods: We describe a case of a patient with pancreatic cancer harboring BRCA2 mutation, treated with radical surgery, adjuvant treatment and three different palliative chemotherapy regimens at disease recurrence (FOLFOX in first line with progression-free survival of five months, gemcitabine and nab-paclitaxel in the second line with progression-free survival of six months and FOLFIRI in the third line with progression-free survival of three months) before olaparib off-label treatment., Results: Interestingly, the patient remained 10 months on olaparib treatment, without disease progression, and without any side effects from the treatment., Conclusion: In conclusion, this case highlights the clinically relevant progression-free survival with olaparib treatment in later line and the potential of better health-related quality of life in this small subset of Pancreatic cancer patients.

Objective: To investigate the role of CTLA-4, PD-1 (programmed death-1), and PD-L1 (programmed death-ligand 1) single nucleotide polymorphisms (SNPs) in predicting clinical outcome of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs)., Methods: A total of 166 consecutive patients were included. We correlated SNPs with clinical benefit, progression-free survival, time to treatment failure, and overall survival and evaluated the incidence of SNPs in nonresponder and long clinical benefit groups., Results: Considering the entire cohort, no correlation was found between SNPs and clinical outcome; however, PD-L1 rs4143815 SNP and the long clinical benefit group showed a statistically significant association ( p = 0.02). The nonresponder cohort displayed distinctive PD-L1 haplotype ( p = 0.05)., Conclusion: PD-L1 SNPs seem to be marginally involved in predicting clinical outcome of NSCLC treated with ICI, but further investigations are required.

Introduction: Pazopanib, a tyrosine kinase inhibitor (TKI), is a standard treatment for various tumours, including metastatic non-adipocytic soft-tissue sarcomas. In literature, erythrocytosis has been described as a TKI-related condition., Case Report: A 59-year-old man underwent surgical removal of a sub-scapular mass consistent with myxofibrosarcoma. After distant relapse, he first started chemotherapy, and then Pazopanib. He was found to have increased levels of hemoglobin (Hb) and hematocrit (Hct). He was asymphtomatic, with no history of pulmonary disease nor smoking habit. Erythropoietin (EPO) level was higher than normal. A polycythemia vera was ruled out. Management & outcome: The patient started a prophylactic therapy with lysine acetylsalicylate, and we observed a reduction of Hb, but not Hct. Due to disease progression, we interrupted Pazopanib. After a week from drug discontinuation, Hb levels got back to the normal range, Hct was lowering. We decided not to perform phlebotomy, considering the declining trend in Hb and Hct values and the absence of symptoms., Discussion: We postulated a Pazopanib-related secondary erythrocytosis, since Hb and Hct levels increased from baseline during treatment, then normalized when Pazopanib was discontinued. We used the Naranjo Nomogram to assess the correlation between the adverse effect and Pazopanib, the correlation was "Probable", a score of 5. To the best of our knowledge, this is the first case report of Pazopanib-related secondary polycythemia in a patient with sarcoma. It is important to pay attention to blood count and to any symptoms potentially related to erythrocytosis in patients treated with TKIs.

Introduction: Non-small cell lung cancer presents at an advanced stage at diagnosis in two-thirds of cases. The most frequent metastatic sites are the central nervous system, adrenal glands and bones. By contrast, the thyroid gland is an extremely rare site of dissemination., Case Description: A 64-year-old Caucasian man previously treated with radiosurgery and brain metastasectomy followed by right middle lobectomy for a squamous cell lung carcinoma had a metachronous solitary metastasis to the thyroid gland, as confirmed by fine-needle aspiration cytology and open biopsy. He underwent curative radiotherapy, with an initial response. At 9 months' follow-up the tumor relapsed both in the thyroid and the lung., Discussion and Conclusions: Review of the literature confirmed that thyroid metastasis from lung cancer is very uncommon in clinical practice. No data on the role of surgery or curative radiotherapy in thyroid metastasis are available because of the lack of prospective studies addressing the impact on survival of these treatment strategies either alone or in combination. In the case described here, radical treatment with radiotherapy allowed to obtain a modest benefit in terms of relapse-free survival. A diagnosis of metastasis to the thyroid gland should be suspected in patients who present a thyroid nodule or suggestive imaging findings when there is a history of malignancy, including lung cancer. Indeed, an early diagnosis allows to pursue radical treatment that, in selected patients, could lead to long-term survival.

Immune checkpoint inhibitors (ICPIs) are considered one of the most important breakthroughs in cancer treatment of the past decade; notably, different studies of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have reported impressive clinical activity and durable responses in patients with advanced non-small cell lung cancer (NSCLC). These findings have led to the changing of the current therapeutic algorithm of advanced NSCLC, adding a new standard first-line treatment option for patients with PD-L1-positive tumors. Pembrolizumab, a highly selective anti-PD-1 humanized monoclonal antibody, was approved by the United States Food and Drug Administration (US FDA) in October 2016 for previously untreated metastatic NSCLC patients whose tumors have high PD-L1 expression, tumor proportion score (TPS) ⩾ 50%, as well as for metastatic NSCLC patients whose tumors express PD-L1 with TPS ⩾ 1% progressing on or after platinum-based chemotherapy. However, many issues remain outstanding, mainly regarding the identification of an optimal biomarker which can help selecting patients more likely to respond to ICPIs. In this review, we discuss the clinical results obtained so far with the anti-PD-1 pembrolizumab in advanced NSCLC, commenting on the role of PD-L1 as a predictive factor and providing an update of the future perspectives.

Aims and background. The incidence of asymptomatic pulmonary embolism in cancer patients is unknown and strictly related to the imaging used for tumor assessment. Recent findings suggest a similar clinical outcome of asymptomatic pulmonary embolism events compared to symptomatic events with a significant impact on survival. The aim of the present study was to determine the prevalence of asymptomatic pulmonary embolism in a population of lung cancer outpatients and to investigate its clinical features. Methods. Outpatients with a diagnosis of lung carcinoma undergoing chemotherapy were selected from October 2006 to June 2009. Disease and patient characteristics, risk factors and treatment modalities were collected. All the computed tomography images performed for each patient during the study period were retrospectively reviewed to identify pulmonary embolism. Results. A total of 141 consecutive patients were included and 657 computed tomography scans were completely reviewed (from two to six consecutive scans for each patient). Asymptomatic pulmonary embolism in the study population had a prevalence of 14.9% (21 patients). Most of the events occurred in patients with adenocarcinoma, advanced stage and poor performance status, during the early phases of first-line chemotherapy or at the same time of the cancer diagnosis. Compared with the symptomatic pulmonary embolism events (5 patients), asymptomatic events occurred earlier (time from cancer diagnosis to pulmonary embolism of 3.5 [95% CI, 2.0-4.9] versus 12.1 months [95% CI, 6.3-17.9; P = 0.02]) and had a better prognosis (survival from PE of 7.5 [95% CI, 3.4-11.6] versus 1.9 months [95% CI, 0-3.9; P = 0.04]). Conclusions. Our findings indicate an underestimation of embolic events among lung cancer outpatients due to their frequent asymptomatic natur. Such a high prevalence suggests the importance to pay more attention to pulmonary embolism prevention in this population.

The female genital tract is an infrequent site of metastasis, in particular from extragenital primary tumors such as non-small cell lung cancer. Ovarian metastases have been described as disseminations of lung adenocarcinoma; rare cases of secondary localizations in adnexa, cervix and vagina were also observed in the literature, but none of these had endometrial involvement. We report the first case, to our knowledge, of non-small cell lung cancer with metastatic spread to the endometrium.