•Optimal treatment for refractory metastatic colorectal cancer is still questioned.•We directly compared the prognostic performance of CTr/r, REG and FTD/TPI.•Two data sets were analyzed and a ...propensity score adjustment was accomplished.•CTr/r provided superior outcomes compared to standard agents (REG and FTD/TPI).•CTr/r might be considered in the continuum of care of selected refractory mCRC.
The optimal treatment for metastatic colorectal cancer (mCRC) beyond second line is still questioned. Besides the standard of care agents (regorafenib, REG, or trifluridine/tipiracil, FTD/TPI), chemotherapy rechallenge or reintroduction (CTr/r) are commonly considered in clinical practice, despite weak supporting evidence. The prognostic performance of CTr/r, REG and FTD/TPI in this setting are herein evaluated.
PROSERpYNa is a multicenter, observational, retrospective study, in which patients with refractory mCRC, progressing after at least 2 lines of CT, treated with CTr/r, REG or FTD/TPI, are considered eligible and were enrolled in 2 independent data sets (exploratory and validation). Primary endpoint was overall survival (OS); secondary endpoints were investigator-assessed progression-free survival (PFS), objective response rate (RR) and safety. A propensity score adjustment was accomplished for survival analyses.
Data referring to patients treated between Jan-10 and Jan-19 from 3 Italian institutions were gathered (341 and 181 treatments for exploratory and validation data sets respectively). In the exploratory cohort, median OS (18.5 vs. 6.5 months), PFS (6.1 vs. 3.5 months) and RR (28.6% vs. 1.4%) were significantly longer for CTr/r compared to REG/FTD/TPI. Survival benefits were retained at the propensity score analysis, adjusted for independent prognostic factors identified at multivariate analysis. Moreover, these results were confirmed within the validation cohort analyses.
Although the retrospective fashion, CTr/r proved to be a valuable option in this setting in a real-world context, providing superior outcomes compared to standard of care agents at the price of a moderate toxicity.
Optimal treatment for refractory mCRC is questioned. We directly compared the prognostic performance of standard of care (regorafenib or trifluridine/tipiracil) and chemotherapy rechallenge or reintroduction in 2 independent data sets and performed a propensity score adjustment. Chemotherapy rechallenge or reintroduction proved superior compared to standard agents and might be considered in the continuum of care of selected refractory mCRC.
Abstract Neoadjuvant treatments (chemo or chemoradiation therapy) are used for patients with locally advanced Pancreatic Ductal Adeno-Carcinoma (PDAC). FOLFIRINOX is now considered an effective ...treatment modality for patients with metastatic pancreatic cancer and a promising option for patients with locally advanced PDAC. Complete pathologic response after neoadjuvant therapies is anecdotic and its prognostic impact is completely unclear. We report the case of a complete pathological response after treatment with FOLFIRINOX in a patient affected by a locally advanced PDAC with a review of the literature regarding the use of FOLFIRINOX for locally advanced PDAC.
In oncologic patients fever is a non-specific clinical marker of different clinical settings. Procalcitonin (PCT) seems to be the most promising infection marker. We aimed to define the potential ...role of PCT as an earlier diagnostic marker in patients with fever and solid tumor. This retrospective study enrolled 431 patients. All of them performed hemoculture (HE) and basal PCT assessment (reference laboratory cut-off: ≤0.5 or >0.5 ng/dL) before starting antibiotic therapy. Gram positive (G+), negative (G-) or Fungi infection were detected. A statistically significant difference in PCT levels between patients with positive and negative HE was observed (P < 0.0001). Moreover comparing PCT values in patients with positive and negative HE, we obtain in the positive HE subpopulation an AUC of 0.7 and a cut-off of 1.52 ng/dL reached high sensitivity (61.6%) and specificity (70.1%). Using this last cut-off, instead of the normal reference value, we achieve a risk reduction to overestimate an infection status of 23.4%. We support the clinic usefulness of serum PCT dosage in febrile advanced solid tumor patients. A PCT cut-off of 1.52 ng/dL could be helpful in the management of the antibiotic therapy preventing delays of oncologic treatments.
Purpose
Hyponatremia and bone metastasis (BMs) are known as negative prognostic factors in patients affected by metastatic non-small cell lung cancer (NSCLC). Hyponatremia is associated with higher ...risk of osteoporosis and bone fracture, but no data are available about the relationship between hyponatremia and bone metastasis. This study aims to analyze the prognostic impact of hyponatremia in NSCLC patients with bone metastases.
Methods
We retrospectively collected data about advanced NSCLC patients. Survival curves were estimated using Kaplan–Meier method, and comparisons were made using chi-square test.
Results
Six hundred forty-seven patients were enrolled into the study. BMs were present in 264 patients (41%) at diagnosis, while hyponatremia appeared in 237 (37%) patients during the first-line treatment. Patients without BMs had a median overall survival (mOS) of 15.9 months (95% CI 14.1–17.9) versus 11.4 months (95% CI 9.4–13.4) for patients with BMs (
p
= 0.001). Eunatremic patients had a better outcome (mOS 16.3 months, 95% CI 14.6–18.0 vs 10.3 months, 95% I 7.6–12.8,
p
= 0.003). Considering the two variables, patients with BMs and hyponatremia had a mOS of 10.1 months (95% CI 4.3–15.9), patients with hyponatremia without BMs 11.9 months (95% CI 11.4–12.4), while mOS was 13.1 months (95% CI 12.0–14.2) for eunatremic patients with BMs versus 17.1 months (95% CI 15.2–19.1) in eunatremic patients without BMs (
p
= 0.0020). Hyponatremic patients developed metachronous BMs significantly earlier (3.73 vs 5.76 months,
p
= 0.0187).
Conclusions
Our study showed that hyponatremia is an important prognostic factor and it should be necessarily considered to enhance the management of NSCLC patients with BMs.
KRAS wild-type mutational status is necessary but not sufficient to get benefit from epidermal growth factor receptor inhibition. Predictive markers are currently being evaluated. In this study, we ...investigated early hypomagnesemia as a predictor of efficacy and outcome in terms of time to progression (TtP) and overall survival (OS) in a cohort of patients affected by advanced colorectal adenocarcinoma KRAS wild-type cetuximab-treated.
One hundred and forty-three patients affected by stage IV colorectal adenocarcinoma KRAS wild type receiving cetuximab + irinotecan (CTX+IRI) as third-line anticancer treatment and resistant to oxaliplatin- and irinotecan-based chemotherapy were retrospectively included. Magnesium plasma levels were measured before the first day and 7, 14, 21 and 28 days after CTX+IRI infusion.
The median magnesium basal value showed a statistically significant decrease after the start of CTX+IRI treatment (at 28 days, P < 0.0001). Patients with an early decrease of magnesium levels >50% compared with the basal level had a higher tumor response rate (55.8% versus 16.7%, P < 0.0001), a longer TtP (6.3 versus 3.6, P < 0.0001) and a longer median OS (11.0 versus 8.1, P = 0.002).
We have shown that early hypomagnesemia could be a predictor of efficacy and outcome in those patients. Magnesium circulating level is an easy and inexpensive biomarker to routinely be detected in patients treated with cetuximab.
Recent literature highlights the importance of pro-inflammatory cytokines in the biology of breast cancer stem cells (CSCs), unraveling differences with respect to their normal counterparts. ...Expansion of mammospheres (MS) is a valuable tool for the in vitro study of normal and cancer mammary gland stem cells. Here, we expanded MSs from human breast cancer and normal mammary gland tissues, as well from tumorigenic (MCF7) and non-tumorigenic (MCF10) breast cell lines. We observed that agonists for the retinoid X receptor (6-OH-11-O-hydroxyphenanthrene), retinoic acid receptor (all-trans retinoic acid (RA)) and peroxisome proliferator-activated receptor (PPAR)-γ (pioglitazone (PGZ)), reduce the survival of MS generated from breast cancer tissues and MCF7 cells, but not from normal mammary gland or MCF10 cells. This phenomenon is paralleled by the hampering of pro-inflammatory Nuclear Factor-κB (NF-κB)/Interleukin-6 (IL6) axis that is hyperactive in breast cancer-derived MS. The hindrance of such pathway associates with the downregulation of MS regulatory genes (SLUG, Notch3, Jagged1) and with the upregulation of the differentiation markers estrogen receptor-α and keratin18. At variance, the PPARα agonist Wy14643 promotes MS formation, upregulating NF-κB/IL6 axis and MS regulatory genes. These data reveal that nuclear receptors agonists (6-OH-11-O-hydroxyphenanthrene, RA, PGZ) reduce the inflammation dependent survival of breast CSCs and that PPARα agonist Wy14643 exerts opposite effects on this phenotype.
hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking.
hERG1 ...expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb.
(i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo.
hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.
Background: Triple-negative breast cancer (TNBC) is an aggressive disease, nevertheless exhibiting a high response rate to chemotherapy. Since the retinoblastoma protein (pRb) loss confers a high ...sensitivity to chemotherapy regimens, we evaluated the prevalence of pRb loss in TNBCs and its relevance on the clinical outcome of patients treated with adjuvant chemotherapy. Patients and methods: pRb status was prospectively evaluated by immunocytochemistry in 518 consecutive patients with complete receptor information. The predictive value of pRb status in TNBCs was determined according to the adjuvant therapeutic treatments. Results: Fifty-three tumors were identified as TNBCs. The prevalence of pRb loss was significantly higher in TNBCs than in the other cancer subtypes. All patients with TNBCs lacking pRb and treated with systemic chemotherapy (cyclophosphamide, methotrexate and 5-fluorouracil) were disease free at a medium follow-up time of 109 months, whereas the clinical outcome of those expressing pRb was significantly poorer (P = 0.008). Analysis of disease-free survival including the established anatomo-clinical prognostic parameters indicated pRb loss as the only significant predictive factor. Conclusions: pRb loss is much more frequent in TNBCs than in the other breast cancer subtypes. Patients with TNBCs lacking pRb had a very favorable clinical outcome if treated with conventional adjuvant chemotherapy.
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