Impact of the Identification of Nonhuman Genetic Signatures in the Diagnosis and Management of Carcinoma of Unknown Primary.

This report presents the case of a 62-year-old woman who was diagnosed in 1999 with stage I cervical carcinoma treated by surgical resection. In 2021, she presented to the emergency department with a complaint of predominantly right-sided lower back pain. A CT scan of the lumbosacral region revealed a bone lesion in the L5 vertebra and retroperitoneal lymphadenopathies suggestive of malignancy. Histology of the L5 vertebra biopsy showed a poorly differentiated carcinoma with an inconclusive immunophenotypic profile. Treatment for carcinoma of unknown primary was started with a combination of carboplatin and paclitaxel every 21 days. A genomic study of the biopsy specimen performed on the FoundationOne CDx platform identified a nonhuman genetic signature compatible with HPV. The presence of HPV 18 DNA in the specimen was confirmed by PCR-reverse dot blot, and the immunophenotypic profile was expanded, revealing strong and diffuse p16 expression, thus corroborating the molecular findings. In view of these findings, the case was reclassified as a recurrence of the cervical adenocarcinoma that had been diagnosed and treated 23 years earlier. Based on the new results, and according to first-line cervical carcinoma protocols, bevacizumab at 15 mg/kg every 21 days was added to her chemotherapy regimen. The identification of HPV DNA sequences by next-generation sequencing facilitated the correct diagnosis and led to a modification of the first-line therapeutic approach.

p53 and ovarian carcinoma survival: an Ovarian Tumor Tissue Analysis consortium study.

Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high-grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi-institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36-3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11-2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.

Prognostic Value and Clinical Significance of FGFR Genomic Alterations (GAs) in Metastatic Urothelial Cancer Patients.

Fibroblast growth factor receptor (FGFR) genomic alterations (GAs) represent an actionable target, key to the pathogenesis of some urothelial cancers (UCs). Though FGFR GAs are common in noninvasive UC, little is known about their role in the metastatic(m) setting and response to therapy. This study aimed to assess the impact of FGFR alterations on sensitivity to systemic treatments and survival and to validate Bajorin's and Bellmunt's prognostic scores in mUC patients according to their FGFR status. We retrospectively analyzed data from 98 patients with tumor-sequenced UC who received treatment between January 2010 and December 2020. Up to 77 developed metastatic disease and were deemed the study population. Twenty-six showed FGFR GAs. A trend toward a better response to cisplatin and checkpoint inhibitors was suggested favoring FGFR GA tumors. FGFR GA patients who received an FGFR inhibitor as first-line had poorer responses compared with other options (20% vs. 68.4%, p = 0.0065). Median PFS was 6 vs. 5 months in the FGFR GA vs. FGFR WT cohort (p = 0.71). Median OS was significantly worse in the FGFR GA vs. FGFR WT cohort (16.2 vs. 31.9 months, p = 0.045). Multivariate analyses deemed FGFR GAs as a factor independently associated with the outcome (HR 2.59 (95% CI 1.21-5.55)). Bajorin's model correctly predicted clinical outcomes in the whole study population but not in FGFR GA cases. FGFR GAs are a relevant biomarker in mUC that could condition the response to systemic therapy. New prognostic models, including this molecular determination, should be designed and validated.

The effect of medical and urologic disorders on the survival of patients with metastatic castration resistant prostate cancer treated with abiraterone or enzalutamide.

INTRODUCTION: Androgenic deprivation therapies have been linked to the development of metabolic syndrome (MS) and cardiovascular diseases, which may lead to a poorer survival in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC). We aimed to analyze whether some cardiovascular or neurological disorders, together with other medical and urological complications, may have an effect on survival outcomes, at baseline and during treatment from patients treated with androgen pathway inhibitors (API). MATERIAL AND METHODS: A retrospective study of a consecutive series of patients diagnosed with mCRPC between 2010 and 2018 treated with API in the first line setting in a single center. RESULTS: Seventy-three patients met the inclusion criteria. Baseline prognostic factors associated with worse survival were diabetes mellitus (DM) with insulin needs compared to patients without DM [hazard ratio (HR) = 0.19, p = 0.025], hypertension (HTN) (HR = 0.46, p = 0.035), and a history of stroke (HR = 0.16, p < 0.001). However, previous history of hypercholesterolemia, arrythmias, and cognitive disorders did not result in a significant worsening on survival. During treatment, patients who developed de novo HTN had the best progression free survival (PFS) (HR = 0.38, p = 0.048) and overall survival (OS) (HR 0.08, p = 0.012) compared with patients with previous HTN. Other factors related to worse outcomes included the presence of heart failure (HR = 0.31, p = 0.001), the requirement for major opioids for pain relief (HR = 0.33, p = 0.023), and the presence of bilateral ureterohydronephrosis (HR = 0.12, p = 0.008). CONCLUSIONS: Some comorbidities may be strongly involved in patient outcomes when receiving API for mCRPC. In this sense, collaborative networking between specialists and caregivers treating prostate cancer (PC) patients should be recommended, focusing on MS features, cardiovascular and neurological disorders in order to anticipate medical and surgical complications.

New oncologic emergencies: What is there to know about inmunotherapy and its potential side effects?

Over the last decade anticancer treatment has experienced encouraging changes. One of the latest developments is immunotherapy, which is increasingly becoming a mainstay for the treatment of these malignancies. Unlike conventional chemotherapy, immunotherapy enhances anti-tumor immune response by blocking inhibitory immune checkpoints, and allowing our own immune system to fight against the tumor cells, arising as a new and innovative mechanism of action. Therefore, although well tolerated, these drugs have a unique side effect profile and are known to cause immune-related adverse events (irAEs). Adverse effects of immunotherapy are most commonly observed in the skin, gastrointestinal tract, liver, lung and endocrine systems. Less common toxicities may include neurological, haematological, cardiac, ocular or rheumatologic involvement. As far as we know, cancer patients are frequently seen in the Emergency Department due to treatment related toxicities, thus there is an increasing necessity to learn about this particular side effect profile given that they entail a different and unique management than that of classic chemotherapy drugs.

Phalangeal metastasis in colon adenocarcinoma / Metástasis falángica en adenocarcinoma de colon

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