Background
An elevated pre-treatment neutrophil to lymphocytes ratio (NLR) is associated with poor prognosis in various malignancies. Optimal cut-off is highly variable across studies and could not ...be determined individually for a patient to inform his prognosis. We hypothesize that NLR variations could be more useful than baseline NLR to predict progression-free survival (PFS) and overall survival (OS) in patients (pts) receiving anti-PD1 treatment.
Patients and methods
All pts with metastatic renal cell carcinoma (mRCC) and metastatic non-small cell lung cancer (mNSCLC) who received anti-PD1 nivolumab monotherapy in second-line setting or later were included in this French multicentric retrospective study. NLR values were prospectively collected prior to each nivolumab administration. Clinical characteristics were recorded. Associations between baseline NLR, NLR variations and survival outcomes were determined using Kaplan–Meier’s method and multivariable Cox regression models.
Results
161 pts (86 mRCC and 75 mNSCLC) were included with a median follow-up of 18 months. On the whole cohort, any NLR increase at week 6 was significantly associated with worse outcomes compared to NLR decrease, with a median PFS of 11 months vs 3.7 months (
p
< 0.0001), and a median OS of 28.5 months vs. 18 months (
p
= 0.013), respectively. In multivariate analysis, NLR increase was significantly associated with worse PFS (HR 2.2;
p
= 6.10
−5
) and OS (HR 2.1;
p
= 0.005). Consistent results were observed in each cohort when analyzed separately.
Conclusion
Any NLR increase at week 6 was associated with worse PFS and OS outcomes. NLR variation is an inexpensive and dynamic marker easily obtained to monitor anti-PD1 efficacy.
Microphthalmia Transcription Factor (MITF)family translocation renal cell carcinoma (tRCC) is a rare RCC subtype harboring TFE3/TFEB translocations. The prognosis in the metastatic (m) setting is ...poor. Programmed death ligand-1 expression was reported in 90% of cases, prompting us to analyze the benefit of immune checkpoint inhibitors (ICI) in this population.
This multicenter retrospective study identified patients with MITF family mtRCC who had received an ICI in any of 12 referral centers in France or the USA. Response rate according to RECIST criteria, progression-free survival (PFS), and overall survival (OS) were analyzed. Genomic alterations associated with response were determined for 8 patients.
Overall, 24 patients with metastatic disease who received an ICI as second or later line of treatment were identified. Nineteen (82.6%) of these patients had received a VEGFR inhibitor as first-line treatment, with a median PFS of 3 months (range, 1-22 months). The median PFS for patients during first ICI treatment was 2.5 months (range, 1-40 months); 4 patients experienced partial response (16,7%) and 3 (12,5%) had stable disease. Of the patients whose genomic alterations were analyzed, two patients with mutations in bromodomain-containing genes (PBRM1 and BRD8) had a clinical benefit. Resistant clones in a patient with exceptional response to ipilimumab showed loss of BRD8 mutations and increased mutational load driven by parallel evolution affecting 17 genes (median mutations per gene, 3), which were enriched mainly for O-glycan processing (29.4%, FDR = 9.7 × 10
).
MITF family tRCC is an aggressive disease with similar responses to ICIs as clear-cell RCC. Mutations in bromodomain-containing genes might be associated with clinical benefit. The unexpected observation about parallel evolution of genes involved in O-glycosylation as a mechanism of resistance to ICI warrants exploration.
Urachal cancer (UrC) is a rare, non-urothelial malignancy. Its natural history and management are poorly understood. Although localized to the bladder dome, the most common histological subtype of ...UrC is adenocarcinoma. UrC develops from an embryonic remnant, and is frequently diagnosed in advanced stage with poor prognosis. The treatment is not standardized, and based only on case reports and small series. This large retrospective multicentric study was conducted by the French Genito-Urinary Tumor Group to gain a better understanding of UrC.
data has been collected retrospectively on 97 patients treated at 22 French Cancer Centers between 1996 and 2020.
The median follow-up was 59 months (range 44-96). The median age at diagnosis was 53 years (range 20-86), 45% were females and 23% had tobacco exposure. For patients with localized disease (Mayo I-II, n=46) and with lymph-node invasion (Mayo III, n=13) median progression-free-survival (mPFS) was 31 months (95% CI: 20-67) and 7 months (95% CI: 6-not reached (NR)), and median overall survival (mOS) was 73 months (95% CI: 57-NR) and 22 months (95% CI: 21-NR) respectively. For 45 patients with Mayo I-III had secondary metastatic progression, and 20 patients were metastatic at diagnosis. Metastatic localization was peritoneal for 54% of patients. Most patients with localized tumor were treated with partial cystectomy, with mPFS of 20 months (95% CI: 14-49), and only 12 patients received adjuvant therapy. Metastatic patients (Mayo IV) had a mOS of 23 months (95% CI: 19-33) and 69% received a platin-fluorouracil combination treatment.
UrC is a rare tumor of the bladder where patients are younger with a higher number of females, and a lower tobacco exposure than in standard urothelial carcinoma. For localized tumor, partial cystectomy is recommended. The mOS and mPFS were low, notably for patients with lymph node invasion. For metastatic patients the prognosis is poor and standard therapy is not well-defined. Further clinical and biological knowledge are needed.
Purpose
This prospective study aimed (1) to assess the non-small cell lung cancer (NSCLC) evolutive patterns to immunotherapy using FDG-PET and (2) to describe their association with clinical ...outcome.
Design
Fifty patients with metastatic NSCLC were included before pembrolizumab or nivolumab initiation. FDG-PET scan was performed at baseline and after 7 weeks of treatment (PET
interim
1) and different criteria/parameters of tumor response were assessed, including PET response criteria in solid tumors (PERCIST). If a first PERCIST progressive disease (PD) without clinical worsening was observed, treatment was continued and a subsequent FDG-PET (PET
interim
2) was performed at 3 months of treatment. Pseudo-progression (PsPD) was defined as a PERCIST response/stability on PET
interim
2 after an initial PD. If a second PERCIST PD was assessed on PET
interim
2, a homogeneous progression of lesions (termed immune homogeneous progressive-disease: iPD
homogeneous
) was distinguished from a heterogeneous evolution (termed immune dissociated-response: iDR). A durable clinical benefit (DCB) of immunotherapy was defined as treatment continuation over a 6-month period. The association between PET evolutive profiles and DCB was assessed.
Results
Using PERCIST on PET
interim
1, 42% (21/50) of patients showed a response or stable disease, most of them (18/21) reached a DCB. In contrast, 58% (29/50) showed a PD, but more than one-third (11/29) were misclassified as they finally reached a DCB. No standard PET
interim
1 criteria could accurately distinguished responding from non-responding patients. Treatment was continued in 19/29 of patients with a first PERCIST PD; the subsequent PET
interim
2 demonstrated iPD
homogeneous
, iDR and PsPD in 42% (8/19), 26% (5/19), and 32% (6/19), respectively. Whereas no patients with iPD
homogeneous
experienced a DCB, all patients with iDR and PsPD reached a clinical benefit to immunotherapy.
Conclusion
In patients with a first PD on PERCIST and treatment continuation, a subsequent PET identifies more than half of them with iDR and PsPD, both patterns being strongly associated with a clinical benefit of immunotherapy.
Purpose
Anemia is common in oncology and negatively impacts quality of life. However, there is lack of knowledge about iron deficiency (ID) epidemiology. The aim of this study was to prospectively ...assess iron status in patients with locally advanced or metastatic cancer beginning chemotherapy.
Methods
In this prospective, multicenter cohort study, anemia and ID were evaluated in patients with locally advanced or metastatic solid tumors and lymphoma before starting chemotherapy. Blood samples were collected at inclusion (W0), 6 weeks (W6), and 12 weeks (W12). Prevalence was evaluated in the general population, according to tumor location and was correlated with tumor response.
Results
One hundred twenty-nine patients were enrolled between 2013 and 2015; 119 had solid tumors and 10 lymphomas. At W0, there were no significant difference between locations with a prevalence around 50–60% (range 47.2–70.4%) and only a trend for colorectal cancer (70.4%,
P
= 0.069) due to a higher prevalence of absolute ID (18.5%). Prevalence of ID+ decreased between W0 and W6 and remained stable until W12 due to the proportion of patients with ID and without anemia. However, anemia prevalence increased during W0 and W6 and remained stable to W6 from W12 due to patients with anemia but without ID. A significant correlation between tumor response and ID prevalence was found (
P
= 0.036).
Conclusions
We confirm the high prevalence of ID and anemia in cancer patients. ID status is correlated to tumor response providing a strong rationale for iron monitoring during cancer management.
Highlights • The candidate-gene approach in HNSCC is relevant as few studies have investigated the topic. • Radiation-induced toxicity is a crucial point in terms of efficacy and clinical sequelae. • ...The association between SNPs and toxicity is discussed as regards the known functional significance of each SNP.
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