To determine long-term survival and prognostic factors, 208 patients with primary tracheal tumors were evaluated in a retrospective multicenter study including 26 centers. Ninety-four patients had squamous cell carcinoma, four had adenocarcinoma, 65 had adenoid cystic carcinoma, and 45 patients had miscellaneous tumors. The following resections were performed: tracheal resection with primary anastomosis, 165; carinal resection, 24; and laryngotracheal resection, 19. Postoperative mortality rate was 10.5% and correlated with the length of the resection, the need for a laryngeal release, the type of resection, and the histologic type of the cancer. Fifty-nine percent of patients with tracheal cancer and 43% of patients with adenoid cystic carcinomas had postoperative radiotherapy. The 5- and 10-year survivals, respectively, were 73% and 57% for adenoid cystic carcinomas and 47% and 36% for tracheal cancers (p < 0.05). Among patients with tracheal cancers, survival was significantly longer for those with complete resections than for those with incomplete resections. On the other hand, the presence of positive lymph nodes did not seem to decrease survival. Postoperative radiotherapy increased survival only in the case of incompletely resected tracheal cancers. Long-term prognosis was worsened by the occurrence of second primary malignancies in patients with tracheal cancers and by the occurrence of late pulmonary metastases in patients with adenoid cystic carcinomas.
Resection of renal lung metastases is a safe and effective treatment. No factor influenced the 5-year survival in this series except the complete resection. Extra-pulmonary metastases does not contra-indicate pulmonary resection. In selected patients, repeat resection for recurrent disease is warranted.
Purpose: The recent success of anti-PD1 antibody in metastatic colorectal cancer (CRC) patients with microsatellite instability (MSI), known to be associated with an upregulated Th1/Tc1 gene signature, provides new promising therapeutic strategies. However, the partial objective response highlights a crucial need for relevant, easily evaluable, predictive biomarkers. Here we explore whether in situ assessment of Tbet+ tumor infiltrating lymphocytes (TILs) reflects a pre-existing functional antitumor Th1/Tc1/IFNγ response, in relation with clinicopathological features, microsatellite status and expression of immunoregulatory molecules (PD1, PDL1, IDO-1). Methodology: In two independent cohorts of CRC (retrospective n = 80; prospective n = 27) we assessed TILs density (CD3, Tbet, PD1) and expression profile of PDL1 and IDO-1 by immunohistochemistry/image analysis. Furthermore, the prospective cohort allowed to perform ex vivo CRC explant cultures and measure by Elisa the IFNγ response, at baseline and upon anti-PD1 treatment. Results: The density of Tbet+ TILs was significantly higher in MSI CRC, especially in the medullary subtype but also in a subgroup of MSS (microsatellite stable), and positively correlated with PD1 and PDL1 expression, but not with IDO-1. Finally, a high number of Tbet+ TILs was associated with a favorable overall survival. These Tbet+ TILs were functional as their density positively correlated with basal IFNγ levels. In addition, the combined score of Tbet+ PD1+ TILs coupled with IDO-1 expression predicted the magnitude of the IFNγ response upon anti-PD1. Conclusion: Altogether, immunohistochemical quantification of Tbet+ TILs is a reliable and accurate tool to recapitulate a preexisting Th1/Tc1/IFNγ antitumor response that can be reinvigorated by anti-PD1 treatment.
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