UNASSIGNED: The therapeutic landscape for non-small cell lung cancer (NSCLC) has evolved considerably in the last few years. The targeted drugs and molecular diagnostics have been developed together at a fast pace. This narrative review explores the evolution of anaplastic lymphoma kinase (ALK) targeting therapies from discovering the ALK protein, molecular tests, present clinical trial data and future perspectives. Since the body of evidence on lung cancer is growing daily, most oncologists need time to implement data in their daily practice.
UNASSIGNED: We developed a narrative review to provide up-to-date help in the clinical decision-making of ALK-altered NSCLC patients. In 2022, the authors reviewed PubMed\'s published pivotal randomized Phase 3 trial results.
UNASSIGNED: The development of ALK inhibitors was a revolution that is still ongoing; second and third-generation ALK inhibitors provided more than 30 months of progression-free survival (PFS) and impressive \"brain-control\". Brigatinib provided a survival benefit for patients with baseline brain metastases (HR 0.43, 95% CI: 0.21-0.89), and Lorlatinib demonstrated intracranial response rates of 82%, with 71% of complete intracranial responses. Personalized medicine is the new paradigm, from performing broad genetic panels for diagnosis to individual targeted therapy or combinations of different targeted agents.
UNASSIGNED: In the future, performing broad molecular panels should be the standard of care in the front line and after each progression to detect arising resistance mechanisms. Longer PFS will substantially convert a deadly condition into an almost chronic disease in the following decades. Treatment sequencing will be the cornerstone for patient survival, and liquid biopsies may replace tissue biopsies.

Metastases from lung cancer to the oral cavity and to the head and neck generally are very infrequent and usually manifest in advanced stages of the disease. Even more rarely, they are the first sign of an unknown metastatic disease. Nevertheless, their occurrence always represents a challenging situation both for clinicians, in the management of very unusual lesions, and for pathologists, in the recognition of the primary site. We retrospectively studied 21 cases of metastases to the head and neck from lung cancer (sixteen males and five females, age range 43-80 years; eight cases localized to the gingiva [two of these to the peri-implant gingiva], seven to the sub-mandibular lymph nodes, two to the mandible, three to the tongue, one case to the parotid gland; in eight patients, metastasis was the first clinical manifestation of an occult lung cancer) and proposed a wide immunohistochemical panel for a proper identification of the primary tumor histotype, including CK5/6, CK8/18, CK7, CK20, p40, p63, TTF-1, CDX2, Chromogranin A, Synaptophysin, GATA-3, Estrogen Receptors, PAX8, PSA. Furthermore, we collected data from previously published studies and narratively reviewed the relevant literature.

Spinal cord compression secondary to metastatic epidural lung cancer generally has a worse prognosis when compared with other metastatic tumors. The purpose of this study was to determine the impact of open surgery on the survival time, ambulation status, and associated prognostic variables of these patients over the past 2 decades.
We searched the PubMed, MEDLINE, and CENTRAL databases to identify patients with spinal cord compression secondary to metastatic lung cancer. We assessed the role of the following factors on survival outcome and ambulation recovery: Karnofsky Performance Scale, number of extraspinal bone metastases, number of metastases in the vertebrae, major internal organs involvement, vertebral location of spinal metastases, and neurologic status.
Our initial search yielded 367 articles, from which 11 studies met the eligibility criteria for a total of 395 patients. Significant correlations with the survival period and the recovery in ambulation were found in the prognostic score for the number of metastases in vertebrae (R = 0.74 and 0.88, respectively), and in the prognostic score for metastases to major internal organs (R = 0.82 and 0.81, respectively). A significant correlation with survival period was found in the numbers of extraspinal bone metastases (R = -0.82). The rates of major complications were comparable with those for open surgery for metastatic tumors of other origin.
Fewer vertebral metastases and less major internal organ involvement were associated with longer survival periods and greater ambulation recovery in patients undergoing open surgery for spinal cord compression secondary to metastatic lung cancer.

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The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as immunotherapy has raised some issues on their safety profile. Regarding infectious complications, it has emerged that these compounds do not intrinsically increase susceptibility to opportunistic infections, which mainly correlate with the co-administration of systemic immunosuppressive therapy (high-dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune-related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well-known complications of these targeted drugs. These observations lead experts\' opinion to suggest primary anti-Pneumocystis prophylaxis in patients undergoing CTLA-4 and PD-1/PDL1 agents who will receive prednisone 20 mg daily for ≥ 4 weeks. Few data on invasive fungal infections in this context are available. We report here a case of probable invasive pulmonary aspergillosis (p-IPA) complicating first-line immunotherapy with pembrolizumab for metastatic lung cancer that was further aggravated by multidrug-resistant Pseudomonas aeruginosa superinfection of fungal cavities; the patient received concurrent systemic corticosteroid therapy as anti-edema treatment for cerebral metastases. Reviewing literature about Aspergillus diseases in subjects receiving CTLA-4 and PD-1 and PDL1-targeted agents, we found three cases of invasive aspergillosis and one case of exacerbation of chronic progressive pulmonary aspergillosis after nivolumab treatment; to the best of our knowledge, this is the first report of p-IPA complicating pembrolizumab immunotherapy. Briefly, in this new setting of biological/targeted drugs, waiting for growing clinical experience, we recommend a high level of alertness in diagnosing any infectious complications.

Endobronchial aspergilloma is a rare and unusual presentation of lung aspergilloma; the natural history for such rare diseases is poorly understood. This report presents two cases of endobronchial aspergilloma complicated by primary and metastatic lung cancer, and summarizes previous reports that suggest that an endobronchial lung cancer lesion may promote the colonialization and growth of Aspergillus species in the bronchus. Therefore, if endobronchial aspergilloma is found, the complication of primary or metastatic endobronchial lung cancer should be carefully considered.

The present study reports the case of a 67-year-old female patient who was initially diagnosed with pulmonary aspergilloma. This diagnosis was based on a chest computed tomography (CT) scan showing a cavitary lesion of 3.5 cm in diameter, with fungus ball-like shadows inside, and an air crescent sign in the right upper lung. At 63 years old, the patient was treated for transitional cell cancer of the urothelium (non-invasive, pT1N0M0) by total cystectomy, ileal conduit diversion and urostomy. For 4 years post-operatively, the patient was healthy and had no clinical symptoms, and the air crescent sign was not identified by chest CT until the patient had reached 67 years of age. However, a final diagnosis of lung metastasis of transitional cell cancer of the urothelium was histopathologically identified subsequent to video-assisted thoracic surgery. Although it is rare that transitional cell cancer moves to the lung and makes a cavitary lesion, a differential diagnosis of cancer is necessary, even when examining infected patients with air crescent signs that are characteristic of aspergilloma. The physician must be mindful of metastatic pulmonary tumors that closely resemble aspergillomas, not only in infectious diseases, but also in oncological practice. Primary surgical removal should be considered.