Tracheoesophageal puncture (TEP) is a voice restorative option adopted by many head and neck cancer patients following laryngectomy. Though generally safe, TEP may develop leakage. Lenvatinib is a ...tyrosine kinase inhibitor (TKI) with anti-tumoral activity against head and neck malignancies.TKIs, including lenvatinib, have been associated with organ perforation or fistula formation. There remains a paucity of literature on the association between lenvatinib and TEP leakage. In this report, we described a patient with adenoid cystic carcinoma of the larynx who had a TEP. After approximately two weeks of treatment with lenvatinib, the patient developed a leakage of TEP. Despite several interventions, the patient died three months afterward due to a retropharyngeal abscess secondary to Fusobacterium nucleatum. To our knowledge, this is the first report of fatal lenvatinib-associated TEP leakage. Clinicians should be cognizant of a potentially rapid development of this complication when prescribing TKI for patients with TEP.
Advanced cancers may be accompanied by paraneoplastic disseminated intravascular coagulation (DIC), resulting in thromboembolism or thrombocytopenia. Thrombocytopenia can limit the feasibility of ...myelosuppressive chemotherapy. Therefore, an alternative treatment option is needed. This report described a patient with metastatic pulmonary adenocarcinoma with
exon 20 insertion and paraneoplastic DIC. Frontline chemotherapy failed to control the disease and worsened thrombocytopenia. However, treatment with amivantamab resulted in a rapid resolution of DIC and produced a partial tumor response. Based on our experience, for patients with
exon 20 insertions with paraneoplastic DIC, amivantamab could be considered a preferred frontline treatment.
Abstract Back ground Although patients with stage IV non-small cell lung cancer (NSCLC) have a poor prognosis, a subset of patients with solitary brain or adrenal metastasis have more favorable ...outcome following surgical resection. Nevertheless, the outcome and predictive factors for survival following metastatectomy for patients with other metastatic sites are not well defined. Methods We performed a systematic review using PUBMED database for all articles which included patients with NSCLC and solitary metastasis to sites other than the adrenal gland or the brain who had undergone resection of their metastasis and definitive treatment of the primary lung cancer. Potential prognostic factors on survival including age, sex, histology, T and N stage of the primary tumor, synchronous vs. metachronous presentation, visceral vs. non-visceral metastasis and the use of perioperative chemotherapy were analyzed using multi-variable Cox proportional hazard model. Results 62 cases were eligible for the analysis. The 5-year survival rate was 50% for the entire cohort. Mediastinal lymph node involvement was independently predictive of inferior outcome; 5-year survival rate 0% vs. 64% in favor of no involvement, p < 0.001. Similarly, patients with intra-thoracic stage III disease had an inferior outcome compared to patients with stage II and stage I disease: 5-year survival rate 0% vs. 77% and 63%, respectively, p < 0.001. Other factors have no effect on outcome. Conclusion Selected patients with distant metastatic NSCLC can achieve long term survival following metastatectomy and definitive treatment of the primary tumor. Mediastinal lymph node involvement is associated with poor prognosis.
Lung cancer screening by low-dose computed tomography (LDCT) can save lives. Nevertheless, the test suffers from low accuracy. Improving its accuracy will reduce unnecessary invasive procedures and ...allow lung cancer treatment to be delivered sooner. This review describes the principles, advantages, and disadvantages of selected emerging modalities potentially useful to improve the accuracy of LDCT. A literature search was conducted using PubMed and Google scholar for relevant publications. We identified four key emerging approaches: radiomics, breath analysis, urine test, and blood test. Radiomics, which uses a computer program to extract various radiological features from radiographic images, holds the potential to improve the accuracy of LDCT. However, to date, there remains no adequately validated system. Breath analysis and urine tests represent a noninvasive and convenient means of screening by detecting substances such as volatile organic compounds associated with lung cancer. However, the results can be confounded by diets, medications, and concurrent medical conditions. Finally, a blood test to screen for protein biomarkers or methylation profiles such as Galleri® has high specificity. However, its sensitivity is low, especially for detecting early-stage lung cancer. Furthermore, the cost for mass public use can be significant. Based on our review, blood tests may have potential for future clinical utility. Its high specificity may be useful to rule in a suspicious lung nodule as malignant, so that other additional tests can be omitted. Data from a well-designed clinical trial will be needed to understand the clinical utility of this strategy.
Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown activity in melanoma, but has not been previously evaluated in metastatic non-small cell lung cancer. We conducted a ...single-arm open-label phase 1 trial ( NCT03215810 ) of TILs administered with nivolumab in 20 patients with advanced non-small cell lung cancer following initial progression on nivolumab monotherapy. The primary end point was safety and secondary end points included objective response rate, duration of response and T cell persistence. Autologous TILs were expanded ex vivo from minced tumors cultured with interleukin-2. Patients received cyclophosphamide and fludarabine lymphodepletion, TIL infusion and interleukin-2, followed by maintenance nivolumab. The end point of safety was met according to the prespecified criteria of ≤17% rate of severe toxicity (95% confidence interval, 3-29%). Of 13 evaluable patients, 3 had confirmed responses and 11 had reduction in tumor burden, with a median best change of 35%. Two patients achieved complete responses that were ongoing 1.5 years later. In exploratory analyses, we found T cells recognizing multiple types of cancer mutations were detected after TIL treatment and were enriched in responding patients. Neoantigen-reactive T cell clonotypes increased and persisted in peripheral blood after treatment. Cell therapy with autologous TILs is generally safe and clinically active and may constitute a new treatment strategy in metastatic lung cancer.
Immunotherapy with a checkpoint inhibitor has revolutionized the treatment of advanced non-small cell lung cancer. Replacing cytotoxic chemotherapy in some settings, immunotherapy with checkpoint ...inhibitors enables many patients to live longer with much fewer side effects. Nonetheless, immunotherapy alone only works for about one-fifth of unselected patients and despite the durability of response, treatment will eventually fail. There are several important cofactors within the tumor microenvironment which can contribute to the efficacy of immunotherapy. These include T-cells, chemokines, and antigen presentations. Preliminary research has shown that these cofactors can be altered by epigenetic modulation. Specifically, hypomethylating agents or histone deacetylase inhibitors can lead to changes in the compositions and characteristics within the tumor microenvironment in a way that enhances the efficacy of checkpoint inhibitor. In recent clinical trials of combined immuno-epigenetic therapy, tumor responses were observed among patients who were previously resistant or refractory to immunotherapy. Furthermore, biological correlative studies also confirmed the mechanism of action of these agents, especially among patients who derived benefit. Nonetheless, at present, the efficacy in terms of tumor response seems modest and side effects, though mostly not serious, can result in treatment interruption or interfere with the quality of life.
Immunotherapy with checkpoint inhibitors (ICI) is widely used to treat a variety of neoplasms. ICI can induce an immune response against cancer; however, ICI can also induce autoimmunity, an ...undesirable side effect. Autoimmune colitis is one of the most well-known and troubling side effects of ICI. In this report, we described a series of 5 patients who developed ICI-induced colitis. During the course of this complication, all developed Clostridium difficile infection (CDI). This report described the course of the 2 medical conditions in these patients. On the basis of our experiences, CDI may occur as a superimposed infection during ICI-induced colitis. Although ICI-induced colitis may be a risk factor for CDI, the observed association may be fortuitous. Future study will be needed to characterize the association between CDI and ICI-induced colitis. Clinicians should be mindful of possible co-occurrence of both conditions to promptly and adequately institute effective interventions.
Ultra-late recurrence, defined as recurrence occurring 10 years or longer after curative treatment, is uncommon for non-small cell lung cancer (NSCLC). To date, factors associated with ultra-late ...recurrence remain unknown. We report a case with ultra-late recurrence and reviewed the literature published during 2010-2023. This is a case of a 66-year-old woman, with a significant smoking history and a previous history of lung adenocarcinoma, who underwent surgery for a brain metastasis detected on imaging. The pathology confirmed lung adenocarcinoma with an epidermal growth factor receptor (EGFR) exon 20 insertion, a finding consistent with the initial lung surgery a decade ago. With receiving intrathecal topotecan, the patient has maintained stable disease 10 months post-surgery. Given the rarity of ultra-late recurrence of NSCLC, we also conducted a pooled analysis with the outcome of interest being a time to recurrence. Data from this case report was analyzed along with previously published 26 cases of ultra-late recurrence. Multivariable analysis indicated that the only factor significantly predicting time to recurrence was anaplastic lymphoma kinase (ALK) rearrangement.
Histone deacetylase inhibitors (HDACi) enhance tumor immunogenicity through several mechanisms and may improve response to immune checkpoint inhibitors (ICIs). In a phase I/Ib trial, we tested the ...oral HDACi vorinostat combined with the programmed cell death protein 1 inhibitor pembrolizumab in advanced/metastatic non-small cell lung cancer.
Patients received intravenous pembrolizumab (200 mg every 3 weeks) plus oral vorinostat (200 or 400 mg/day). Primary endpoint was safety/tolerability. Secondary endpoints included response rate, progression-free survival, disease control rate (DCR), and overall survival. Tumor gene expression changes, T-cell density, and myeloid cell levels were studied in serial tissue specimens.
Thirty-three patients were treated (13 in phase I, 20 in phase Ib). In phase I, both ICI-naïve and ICI-pretreated patients were enrolled to determine dose-limiting toxicities (DLT). No DLTs were observed, and the recommended phase I dose was pembrolizumab 200 mg and vorinostat 400 mg. Any-grade adverse events were mainly fatigue (33%) and nausea/vomiting (27%). Of six ICI-naïve and 24 ICI-pretreated patients evaluable for response, four (13%) had partial response two confirmed, one unconfirmed with subsequent prolonged stable disease (SD), one unconfirmed with subsequent progressive disease (PD), 16 (53%) had SD, and 10 (33%) had PD for a DCR of 67%. In the ICI-pretreated cohort, three patients (one confirmed, two unconfirmed) had partial response and 10 had SD. Pretreatment CD8
T-cell presence in tumor stromal regions was associated with treatment benefit.
Pembrolizumab plus vorinostat was well tolerated and demonstrated preliminary antitumor activity despite progression on prior ICI treatment.
Breast implants are prevalent in the United States. Patients with breast implants may be susceptible to iatrogenic implant rupture during cardiothoracic surgery. To our knowledge, however, this ...complication has never been described following robot-assisted thoracic surgery (RATS). We described a patient who developed a rupture of a saline breast implant after undergoing a robot-assisted left lower lobectomy. We hypothesized that a tear to the breast implant may have occurred either during the extraction of one of the surgical ports or during the forceful extraction of the resected specimen. This case highlights another potential complication of minimally invasive thoracic surgery. For patients with breast implants undergoing thoracic RATS, extra care should be made to the site of port placement and the avoidance of excessive force during surgery.
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