Kidney Cancer Journal 31
Combination with Stereotactic Body Radiotherapy
Offers a Promising Strategy to Overcome Resistance
to Immunotherapy in Advanced Renal Cell Cancer.
Sun X, Na A, et al. J Oncol. 2019 Nov 28;2019:1483406.
doi: 10.1155/2019/1483406. eCollection 2019.
Summary: Among various attempts at overcoming resistance
to immunotherapy, stereotactic body radiotherapy
(SBRT) has been found to potentiate the activity of
immunotherapy agents through several potential mechanisms,
including normalization of microvessels to alleviate
tumor hypoxia, improvement in efficient delivery
of drugs, abundant neoantigen exposure, and recruitment
of antitumor immune cells to alter the immunosuppressive
tumor microenvironment. Preclinical studies
and clinical case reports have predicted that the combination
of SBRT, an immunotherapy, may lead to remarkable
results.
Conclusion: This review aims to provide the biological
basis for the feasibility of combining SBRT to overcome
immunotherapy resistance and to review the currently
available clinical evidence of this combination therapy
in patients with advanced RCC.
Transcriptomic signatures related to the obesity
paradox in patients with clear cell renal cell carcinoma:
a cohort study. Sanchez A, Furberg H, Kuo F, et
al. Lancet Oncol. 2019 Dec 20. pii: S1470-2045(19)
30797-1. doi: 10.1016/S1470-2045(19)30797-1. Epub
ahead of print
Summary: Obesity is associated with an increased risk of
developing clear cell renal cell carcinoma (RCC) but, paradoxically,
obesity is also associated with improved oncological
outcomes in this cancer. Because the biological
mechanisms underlying this paradoxical association are
poorly understood, this study identified transcriptomic
differences in primary tumour and peritumoral adipose
tissue between obese patients and those at a normal
weight. This cohort study assessed data from five independent
clinical cohorts of patients with clear cell RCC
aged 18 years and older. Overweight patients were excluded
from each cohort for our analysis. The study assessed
patients from the COMPARZ phase 3 clinical trial,
a cohort from the Cancer Genome Atlas (TCGA), and a
Memorial Sloan Kettering (MSK) observational immunotherapy
cohort. We assessed overall survival in
obese patients (those with a body-mass index BMI 30
kg/m2) and in patients with a normal weight (BMI 18·5-
24·9 kg/m2, as per WHO’s BMI categories), defined as the
time from treatment initiation (in the COMPARZ and
MSK immunotherapy cohorts) or surgery (in the TCGA
cohort) to the date of any-cause death or of censoring
on the day of the last follow-up. We also evaluated and
validated transcriptomic differences in the primary tumors
of obese patients compared with those of a normal
weight. The final cohort for overall survival analysis
comprised 129 (64%) participants. Overall survival was
longer in obese patients than in those with normal
weight in the TCGA cohort, after adjustment for stage or
grade (adjusted HR 0·41, 95% CI 0·22-0·75), and in the
COMPARZ clinical trial after adjustment for International
Metastatic RCC Database (IMDC) risk score (0·68,
0·48-0·96). In the MSK immunotherapy cohort, the inverse
association of BMI with mortality (HR 0·54, 95%
CI 0·31-0·95) was not significant after adjustment for
IMDC risk score (adjusted HR 0·72, 95% CI 0·40-1·30).
Tumors of obese patients showed higher angiogenic
scores on gene-set enrichment analysis-derived hallmark
gene set angiogenesis signatures than did those of patients
at a normal weight, but the degree of immune cell
infiltration did not differ by BMI. The study found increased
peritumoral adipose tissue inflammation in
obese patients relative to those at a normal weight, especially
in peritumoral fat near the tumour.
Conclusion: The study found that aspects of the tumor
microenvironment vary by BMI in the tumor and peritumoral
adipose tissue, which might contribute to the apparent
survival advantage in obese patients with clear
cell RCC compared with patients at a normal weight.
The complex interplay between the clear cell RCC tumor
and peritumoral adipose tissue microenvironment might
have clinical relevance and warrants further investigation.
The effect of antibiotics on clinical outcomes in immune
checkpoint blockade: a systematic review and
meta-analysis of observational studies. Wilson BE,
Routy B, Nagrial A, et al. Cancer Immunol Immunother.
2019 Dec 21. doi: 10.1007/s00262-019-02453-2. Epub
ahead of print
Summary: Pre-clinical and early clinical data suggests
the microbiome plays an important role in oncogenesis
and influences response to immune checkpoint blockade
(ICB). The objective of this systematic review and
meta-analysis was to determine whether antibiotics affect
overall survival (OS) and progression free survival
(PFS) in patients with solid malignancies treated with
ICB. A systematic search of EMBASE, MEDLINE and
conference proceedings was conducted for observational
studies examining the effect of antibiotics on ICB. A random
effects study-level meta-analysis was performed
with pooling of the hazards ratio (HR) for OS and PFS.
Meta-regression was used to determine the impact of the
timing of antibiotic exposure on OS. 766 studies were
identified, and 18 studies met the inclusion criteria. Of
the 2889 patients included, 826 (28.6%) were exposed to
antibiotics. The most common malignancies were lung
(59%), renal cell carcinoma (RCC) or urothelial carcinoma
(16.3%) and melanoma (18.7%). OS was prolonged
in those without antibiotic exposure (pooled HR
1.92, 95% CI 1.37-2.68, p < 0.001). The effect of antibiotics
on OS was greater in studies defining antibiotic exposure
as 42 days prior to initiation of ICB (HR 3.43,
95% CI 2.29-5.14, p < 0.0001). PFS was also longer in patients
who did not receive antibiotics (pooled HR 1.65,
95% CI 1.3-2.1, p < 0.0001).
CONCLUSION: In patients receiving ICB, OS and PFS
are longer in patients who are not exposed to antibiotics.
Antibiotic use in the 42 days before starting ICB
appears to be most detrimental to outcome. KCJ
JOURNAL CLUB
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