Immune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-P is more often observed in patients with nonsmall cell lung cancer (NSCLC) than in those ...with other cancers. Likewise, it is more common in those receiving programmed cell death (PD)-1/PD-1 ligand inhibitors rather than cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors alone. The frequency of ICI-P is higher when anti-PD-1 and anti-CTLA-4 are administered concomitantly. Despite the low fatality rate (≈13%), ICI-P is the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy. Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines.
Background
New mutational detection techniques like next-generation sequencing have resulted in an increased number of cases with uncommon mutation and compound mutations 3%–14% of all epidermal ...growth factor receptor (EGFR) mutations. In rare exon 18 mutations (3%–6%), G719X and E709X represent the majority, but CMut associating these exon 18 points mutations are even rarer, making the understanding of the impact of epidermal growth factor receptor tyrosine kinase inhibitors still limited. Three generations of EGFR tyrosine kinase inhibitors (TKIs) are available to target EGFR mutations, but according to the types of mutations, the sensitivity to TKI is different. Afatinib, osimertinib, and neratinib have showed some effectiveness in single exon 18, but no report has precisely described their efficiency and acquired mechanism of resistance in a CMut of exon 18–18 (G719A and E709A).
Case presentation
We report a case of a 26-year-old woman with bilateral advanced adenocarcinoma of the lung harboring a compound mutation associating G719A and E709A in exon 18, who developed an EGFR amplification as resistance mechanism to osimertinib. She presented a significant clinical and morphological response under sequential TKIs treatment (afatinib, osimertinib, and then neratinib).
Conclusion
A non-small cell lung cancer (NSCLC) with rare compound mutation exon 18–exon 18 (G719A and E709A) and EGFR amplification can be overcome with adapted sequential second- and third-generation TKIs. This report has potential implications in guiding decisions for the treatment of these rare EGFR mutations.
: We aimed to evaluate the prognostic value of imaging biomarkers on 18F-FDG PET/CT in extensive-stage small-cell lung cancer (ES-SCLC) patients undergoing first-line chemo-immunotherapy.
In this ...multicenter and retrospective study, we considered two cohorts, depending on the type of first-line therapy: chemo-immunotherapy (CIT) versus chemotherapy alone (CT). All patients underwent baseline 18-FDG PET/CT before therapy between June 2016 and September 2021. We evaluated clinical, biological, and PET parameters, and used cutoffs from previously published studies or predictiveness curves to assess the association with progression-free survival (PFS) or overall survival (OS) with Cox prediction models.
Sixty-eight patients were included (CIT: CT) (36: 32 patients). The median PFS was 5.9:6.5 months, while the median OS was 12.1:9.8 months. dNLR (the derived neutrophils/(leucocytes-neutrophils) ratio) was an independent predictor of short PFS and OS in the two cohorts (
< 0.05). High total metabolic tumor volume (TMTV
if > 241 cm
) correlated with outcomes, but only in the CIT cohort (PFS for TMTV
in multivariable analysis: HR 2.5; 95%CI 1.1-5.9).
Baseline 18F-FDG PET/CT using TMTV could help to predict worse outcomes for ES-SCLC patients undergoing first-line CIT. This suggests that baseline TMTV may be used to identify patients that are unlikely to benefit from CIT.
What is already known about this subject?•Rearranged during transfection (RET) gene fusion are unfrequent (1%-2%) but validated as target mutations in non-small cell lung cancer ...(NSCLC).•Selpercatinib and, pralsetinib have been authorized by the US-FDA in second line or more in NSCLC RET+.•The predominant independent mechanism of resistance to RET tyrosine kinase inhibitors (TKI) is the MET amplification but data to overcome MET resistance concern only selpercatinib resistance.What are the new findings and how might they impact on clinical practice in the foreseeable future?•We report here the first case of a patient who developed a MET amplification as an initial mechanism of acquired resistance to pralsetinib for an advanced KIF5B-RET driven lung adenocarcinoma, successfully treated with a combination of pralsetinib and crizotinib then capmatinib due to an isolated cerebral progression.•An isolated progression under crizotinib should raise suspicion of poor penetration through the blood-brain barrier and motivate the switch by an anti-MET with better cerebral penetration like capmatinib.•Early evaluation by 18FDG/CT might be a compelling method to justifying the pursuit or not of combination TKI without being predictive of the duration of response.
Patients with resectable stage IIIA - N2 lung cancer represent a very heterogeneous population with variable risks of postoperative recurrence depending on the type of N2 involvement (unisite N2, ...multisite N2, bulky N2, extra-capsular rupture, incomplete resection…). This heterogeneity associated with the difficulty of carrying out prospective randomized studies with sufficient power in stages IIIA - 2, results in the absence of clear and consensual recommendations (except for stages IIIA - N2 resectable R0, since LungART and PORT-C studies). The objective of this article is to make an update on the place of postoperative radiotherapy in the management of stages IIIA - N2 following the publication of two recent randomized trials (PORT-C and LungART) but also compare them fort a better understanding of the current issues raised by these first published results. Indeed, these two trials do not find any benefit in terms of progression free survival and overall survival of postoperative radiotherapy but exploratory analyzes from these two studies seem to show a potential benefit of postoperative in some pN2 populations at high risk of locoregional recurrence (N2 multisite, N2 bulky…). In addition, the advent of immunotherapy (atezolizumab or pembrolizumab) and targeted therapies (osimertinib) in the adjuvant situation are redebating the place of a possible indication for postoperative radiotherapy in stage IIIA - 2.
•Lung sarcomatoid carcinoma is a rare tumor with high mutations rates.•We should pay attention to IHC positive results for ALK in case of unusual phenotype.•Our case suggests alectinib resistance to ...ALK-amplified tumors.•Our case reports the first case of efficacy of immunotherapy in ALK-amplified tumors.
Immunohistochemistry (IHC) is considered as a screening method for ALK rearrangement thanks to its excellent sensitivity. Strong marking on immunohistochemistry give the go-ahead to start ALK tyrosine kinase inhibitors (ALK TKI). Lack of therapeutic response may then lead to the suspicion of molecular alterations other than ALK rearrangements.
We present a patient with strong ALK and PD-L1 positive IHC expression lung sarcomatoid carcinoma with initial life-threatening disease progression after beginning ALK TKI. We also review the literature to summarize ALK amplification clinical features and therapeutic management in lung cancers.
Fluorescence in situ Hybridization (FISH) revealed ALK amplification on the initial anatomopathological samples. Lack of ALK rearrangement and strong PD-L1 positive IHC expression led to the initiation of immune checkpoint inhibitor (ICI) as a second line of treatment, with an excellent response.
We demonstrated that IHC positive test, in these cases, must be interpreted with caution. FISH analysis has to be recommended to confirm IHC results in case of unusual phenotype, such as smoker or lung cancer other than adenocarcinoma. Although lung carcinoma with ALK rearrangement seems to be not sensitive to ICI, further investigations should be conducted on other types of ALK molecular alterations. ALK amplifications, as observed in the present case, should not be an impediment to taking into account the PD-L1 marking for the initiation of treatment by immunotherapy.
Two patients underwent percutaneous image-guided electrochemotherapy on blastic spine metastases involving posterior walls of the lumbar vertebral bodies with epidural extension. These treatments ...were performed safely under cone beam computed tomography. Local tumor control was obtained on the subsequent follow-up as well as pain relief and disability improvement. Electrochemotherapy might be considered for patients with thus far no other alternative in order to obtain tumor control and improvement in patients’ quality of life.
Oligometastatic (OM) disease is defined by a low metastatic tumor spread. OM non-small cell lung cancer (NSCLC) treatment aims to improve the patient’s prognosis and quality of life, in an ...attempt-to-cure objective. Oncogenic-driven metastatic NSCLC accounts for about 20–25% of NSCLCs, with an ever-increasing number of potentially druggable molecular alterations. Due to specific targeted therapy, the care and prognosis of mutated NSCLC is quite different from non-oncogenic-driven NSCLC. However, OM-NSCLC treatment guidelines do not specifically discuss oncogenic-driven OM-NSCLC patients. We conducted a narrative review regarding retrospective and prospective studies published from inception to May 2020 dealing with oncogenic-driven OM-NSCLC in order to: (I) describe the specific patterns of metastatic spread of oncogenic-driven NSCLC (i.e., bone and pleural tropism in EGFR mutated NSCLC and serous and brain metastases in ALK NSCLC); (II) review the low level of current evidence for local ablative therapy (LAT) strategies in patients with oncogenic-driven OM-NSCLC, focusing on the benefit/risk of tyrosine kinase inhibitors (TKI) and LATs combination and (III) present strategies to help to select the best candidate for an attempt-to-cure approach. Finally, the optimal strategy may be to introduce a targeted therapy, then treat all tumor sites with LAT, and finally continue TKI for unknown prolonged duration in an attempt to prolong progression free survival in most patients, improve overall survival for some patients, and potentially lead to a cancer cure for a few patients.
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