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The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification of accurate biomarkers of clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing on tumor and matched healthy colon tissue, complemented with tumor whole-genome sequencing for further microbiome characterization. A type 1 helper T cell, cytotoxic, gene expression signature, called Immunologic Constant of Rejection, captured the presence of clonally expanded, tumor-enriched T cell clones and outperformed conventional prognostic molecular biomarkers, such as the consensus molecular subtype and the microsatellite instability classifications. Quantification of genetic immunoediting, defined as a lower number of neoantigens than expected, further refined its prognostic value. We identified a microbiome signature, driven by Ruminococcus bromii, associated with a favorable outcome. By combining microbiome signature and Immunologic Constant of Rejection, we developed and validated a composite score (mICRoScore), which identifies a group of patients with excellent survival probability. The publicly available multi-omics dataset provides a resource for better understanding colon cancer biology that could facilitate the discovery of personalized therapeutic approaches.

Background Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fluorouracil, are rare. Only seven publications report HSR to FA, mainly confirmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difficult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA. Case presentation Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The first patient described successive cycles with first back muscle pain, then chills and facial oedema and finally diffuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgE-mediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly. Conclusions These two cases of anaphylaxis to FA document the clinical manifestations associated with two different mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope to draw the practitioner’s attention to FA as a potential agent of severe hypersensitivity, especially if symptoms remain after withdrawing the most suspected chemotherapeutic agents. We want also to stress the importance of allergy testing.

Chemotherapeutic advances have enabled successful cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) expansion in treating metastatic colorectal cancer. The aims of this study were to evaluate the safety of combining liver surgery (LS) with HIPEC and CRS (which remains controversial) and its impact on overall survival (OS) rates. From 2007 to 2015, a total of 77 patients underwent CRS/HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer. Twenty-five of these patients underwent concomitant LS for suspicion of liver metastases (LM; group 2), and were compared with patients who underwent CRS/HIPEC only (group 1). Demographic and clinical data were reviewed retrospectively. Among the group 2 patients, two underwent major hepatectomies, six underwent multiple wedge resections, 16 underwent single wedge resections (one with radiofrequency ablation), and one underwent radiofrequency ablation alone. For groups 1 and 2, median peritoneal cancer index was 6 and 10 (range 0–26; p = 0.08), complication rates were 15.4 and 32.0 % (Dindo–Clavien ≥3; p = 0.15), and median follow-up was 34.2 and 25.5 months (range 0–75 and 3–97), respectively. One group 2 patient died of septic shock after 66 days. Pathology confirmed LM in 21 patients in group 2 (four with benign hepatic lesions were excluded from long-term outcome analysis). Two-year OS rates were 89.5 and 70.2 % (p = 0.04), and 2-year recurrence-free survival rates were 38.3 and 13.4 % (p = 0.01) in groups 1 and 2, respectively. Simultaneous surgery for colorectal LM and PC is both feasible and safe, with low postoperative morbidity. Further longer-term studies would help determine its impact on patient survival.

Background Anemia is usually not taken into account in internal radiotherapy. We investigated whether the hemoglobin (Hb) level could have an impact on the tumor response, as observed in external beam radiotherapy (EBRT). Methods Absorbed doses of 25 hepatic metastatic sites in eight patients who underwent a liver selective internal radiotherapy (SIRT) were computed by a 3D convolution of a dose deposition kernel with the 90Y time-of-flight positron emission tomography (TOF-PET) images acquired following therapy. Early tumor response was assessed by comparing a follow-up FDG TOF-PET scan with a baseline scan. Hb level was measured on the day of the SIRT procedure. Results All patients displayed early tumor response increasing with the tumor-absorbed dose. Significant differences between patients were noted, the response slope correlating with the Hb level. After applying a global fit on all metastases using a tumor radiosensitivity modulated by a Hb enhancement factor (HEF) linearly dependent on the Hb level, a strong correlation (R = 0.96) was observed between the early response and the absorbed dose. Hb level had a major impact on tumor response by modulating HEF by a factor 6. Conclusions These results prove the significant impact of Hb level on the tumor response and support the study of methods for correcting tumor hypoxia, such as intensively performed in EBRT. The quantitative analysis of the relationship between tumor doses and early response has the power to allow fast screening of such correction methods in limited patient series. Internal radiotherapy could be more efficient if performed earlier in the therapy line, when the disease- and treatment-related anemia remains limited.

The decay of Y has a minor branch to the 0 excited state [1], followed by an internal ee creation which happens in 32 out of one million decays [2]. Consequently, Y PET scan was proposed in order to assess the biodistribution [3] of Y-labelled therapeutic agents. A 61-year-old woman was referred for treatment of chemorefractory colorectal liver metastasis. Based on the pretreatment evaluation (including a diagnostic FDG PET/CT scan on day 1, and a prophylactic embolization of the right gastric and gastroduodenal arteries followed by a Tc-MAA SPECT/CT scan on day 8), 1.3 GBq of Y-labelled SIR-Spheres were administered by sequential catheterization of both liver lobes (day 15). Subsequently, a 30-min Y TOF PET/CT scan was performed using a Philips GEMINI TF camera. In order to prevent saturation of the detectors, a copper ring of 2.5 mm thickness was inserted into the gantry to absorb the bremsstrahlung x-rays. The TOF data were reconstructed with attenuation and scatter correction using Philips RAMLA software (eight iterations, three subsets). An additional 20 min bremsstrahlung Y-SPECT was acquired using a Trionix XLT20 triple head camera (medium energy collimator, 30% window centred on 90 keV). Data were reconstructed using OSEM (four iterations, six subsets). As illustrated, despite the differences in their respective uptake mechanism, Y-PET better reflects the tumour heterogeneity assessed by FDG PET/CT (a necrotic core surrounded by active tumour margins) than traditional bremsstrahlung Y-SPECT. This gain in resolution should therefore contribute to increasing the accuracy of the dose distribution into the tumours and their surrounding healthy tissues.