A prospective cohort study of TIMP1 as prognostic biomarker in gastric and colon cancer.

BACKGROUND: Tissue inhibitor metalloproteinase 1 (TIMP1) inhibits proteins which has proteolytic activity, but in cancer it contributes for tumoral invasion and metastization. The authors investigated the expression of TIMP1 in different digestive cancer types. The aim of this study was to test TIMP1 as a serum marker since in clinical practice there is a lack of biomarkers to monitor the response to treatments or to detect early relapses. METHODS: It was performed a prospective study with recently diagnosed patients with gastrointestinal cancers. Patients with esophageal, gastric, colon, rectal, hepatocarcinoma, and cholangiocarcinoma at any stage, that did not perform any type of treatment, were included. Enzyme-linked immunosorbent assays and chemiluminescence were used to quantify levels of TIMP1. The differences of the Kaplan-Meier survival curves were tested for statistical significance with the log rank test, and the 95% confidence intervals were calculated. Multivariate analysis was done using the COX proportional hazard model and a forward stepwise method. Statistical analyses were done using the IBM SPSS Statistics version 26.0. P value inferior to 0.05 was considered significant. RESULTS: A total of 190 patients were recruited: 54.7% males, median age of 68 years old, 57.9% with colorectal cancer followed by esophagogastric disease with 22.6%. TIMP1 level were increased in 29.5%. In colon cancer, patients with higher levels of TIMP1 are associated with worse progression free survival (PFS) (P=0.007) and overall survival (OS) (P=0.036). No relationship was seen with Rat sarcoma virus (RAS), B-raf (BRAF) and Microsatellite instability status (MSI). In gastric cancer, patients with higher levels of TIMP1 are associated with worse OS (P=0.020), with no difference in PFS. CONCLUSIONS: Higher TIMP1 levels in gastric and colon cancer patients are associated with worse prognosis. Further studies are needed: higher number of patients and sequential measurements of TIMP1 during patient treatments.

Giant Metastatic Breast Phyllodes Tumour with an Elusive Diagnosis: A Case Report and Literature Review.

BACKGROUND: The term phyllodes tumours, which account for less than 1% of breast neoplasms, describes a spectrum of heterogenous tumours with different clinical behaviours. Less than 30% present as metastatic disease. Complete surgical resection is the standard of care so that recurrence rates are reduced. The role of adjuvant chemotherapy or radiation therapy is controversial. Patients with metastatic disease have a median overall survival of around 30 months. CASE DESCRIPTION: The authors present the case of a 57-year-old woman with an exuberant left malignant phyllodes tumour with bilateral involvement, as well as lung and axillar metastasis. The patient underwent haemostatic radiation therapy and started palliative chemotherapy with doxorubicin, achieving partial response with significant improvement in quality of life. A posterior simple mastectomy revealed a small residual tumour. DISCUSSION: Metastatic malignant phyllodes tumours are rare, so therapeutic strategies rely on small retrospective studies and guidelines for soft tissue sarcoma. Palliative chemotherapy protocols include anthracycline-based regimens, either as monotherapy with doxorubicin or doxorubicin together with ifosfamide. With few treatment options, management of these patients must rely on a continuum of care. LEARNING POINTS: Phyllodes tumours are a rare type of breast neoplasm.The differential diagnosis of breast cancer should include phyllodes tumours.Accurate and rapid diagnosis is required.

Prognostic factors for early relapse in non-metastatic triple negative breast cancer - real world data.

BACKGROUND: Triple negative breast cancer (TNBC) has the worst prognosis amongst all subtypes. Studies have shown that the achievement of pathologic complete response in the breast and axilla correlates with improved survival. The aim of this study was to identify clinical or pathological features of real-life TNBC patients with a higher risk of early relapse. MATERIALS AND METHODS: Single-centre retrospective analysis of 127 women with TNBC, stage II-III, submitted to neoadjuvant treatment and surgery between January 2016 and 2020. Multivariate Cox regression analysis for disease free survival (DFS) at 2 years was performed and statistically significant variables were computed into a prognostic model for early relapse. RESULTS: After 29 months of median follow-up, 105 patients (82.7%) were alive and, in total, 38 patients (29.9%) experienced recurrence. The 2-year DFS was 73% (95% CI: 21.3-22.7). In multivariate analysis, being submitted to neoadjuvant radiotherapy [HR 2.8 (95% CI: 1.2-6.4), p = 0.017] and not achieving pathologic complete response [HR 0.3 (95% CI: 0.1-1.7), p = 0.011] were associated with higher risk of recurrence. In our prognostic model, the presence of at least one of these variables defined a subgroup of patients with a worse 2-year DFS than those without these features (59% vs. 90%, p < 0.001, respectively). CONCLUSIONS: In this real-life non-metastatic TNBC cohort, neoadjuvant radiotherapy (performed due to insufficient clinical response to neoadjuvant chemotherapy or significant toxicity) impacted as an independent prognostic factor for relapse along with the absence of pathologic complete response identifying a subgroup of higher risk patients for early relapse that might merit a closer follow-up.

Immunotherapy and predictive immunologic profile: the tip of the iceberg.

The interplay between cancer and the immune system has been under investigation for more than a century. Immune checkpoint inhibitors have changed the outcome of several tumors; however, there is a significant percentage of patients presenting resistance to immunotherapy. Besides the action mechanism, it is essential to unravel this complex interplay between host immune system and tumorigenesis to determine an immune profile as a predictive factor to immune checkpoint blockade agents. Tumor expression of programmed death-ligand 1 (PD-L1), tumor mutational burden, or mismatch repair deficiency are recognized predictive biomarkers to immunotherapy but are insufficient to explain the response rates and heterogeneity across tumor sites. Therefore, it is crucial to explore the role of the tumor microenvironment in the diversity and clonality of tumor-infiltrating immune cells since different checkpoint molecules play an influential role in cytotoxic T cell activation. Moreover, cytokines, chemokines, and growth factors regulated by epigenetic factors play a complex part. Peripheral immune cells expressing PD-1/PD-L1 and the biologic roles of soluble immune checkpoint molecules are the subject of new lines of investigation. This article addresses some of the new molecules and mechanisms studied as possible predictive biomarkers to immunotherapy, linked with the concept of immune dynamics monitoring.

Acute toxicity and tolerability of anthracycline-based chemotherapy regimens in older versus younger patients with breast cancer: real-world data.

OBJECTIVES: To compare the non-cardiac acute toxicity and tolerability profile of anthracycline-based regimens between older versus younger women diagnosed with breast cancer in a real-world setting. METHODS: Retrospective cohort of female patients diagnosed with breast cancer and treated with neoadjuvant or adjuvant anthracycline-based regimens between 2017 and 2019. Patients were grouped in young versus older, using an age of 65 as cut-off. Differences in non-cardiac acute toxicity and change in treatment plan were examined. RESULTS: Among the 559 patients, 19.5% were aged ≥ 65 years. Regimens used were fluorouracil, epirubicin, and cyclophosphamide in 56.2% of patients, doxorubicin and cyclophosphamide in 33.3%, and epirubicin and cyclophosphamide in 10.5%; there were no differences in incidence of grade 3 or 4 toxicities between regimens (p = 0.184). Acute grade 3 or 4 toxicities occurred more frequently in the older group (33.9% versus 10.7%, p < 0.0001, OR 4.304, 95%-CI [2.619-7.073]). Delay of at least one chemotherapy cycle due to toxicity occurred more frequently in the older group (24.8% versus 9.3%, p < 0.0001, OR 3.199, 95%-CI [1.867-5.481]). Early termination of treatment also occurred more frequently in the older group (11.9% versus 1.6%, p < 0.0001, OR 8.571, 95%-CI [3.331-22.048]). CONCLUSION: Although acute grade 3 or 4 toxicities were more frequent in older patients, which resulted in increased cycle delay and/or premature termination of treatment, overall treatment was still reasonably well-tolerated, with 88.1% of older patients completing the planed anthracycline regimen.

ACE-27 as a prognostic tool of severe acute toxicities in patients with head and neck cancer treated with chemoradiotherapy: a real-world, prospective, observational study.

PURPOSE: To evaluate the association between comorbidities as assessed by the "Adult Comorbidity Evaluation 27" (ACE-27) and the development of severe acute toxicities in patients with head and neck cancer treated with chemoradiotherapy. METHODS: Prospective, single-center cohort of patients with head and neck cancer treated with chemoradiotherapy (cisplatin 100 mg/m2 on days 1, 22, and 43; intensity-modulated radiotherapy 60 to 69.96 gray, in 30 to 33 fractions,) between June 2018 and December 2019. ACE-27 was assessed before the start of treatment. Patients were divided in two groups based on ACE-27 grading (none to mild versus moderate to severe comorbidities). Differences in incidence of severe acute toxicity and change in treatment plan between groups were examined. RESULTS: A total of 101 patients were included: 90.1% were male, and median age was 57 years. ACE-27 grading was none in 6.9% of patients, mild in 52.5%, moderate in 29.7%, and severe in 10.9%. Severe acute toxicities occurred more frequently in patients with moderate to severe comorbidities (75.6% versus 48.3%), with a statically significant difference (p = 0.006, OR 3.314, 95%-CI (1.382-7.944)). In the group with moderate to severe comorbidities, omission of at least one cisplatin cycle (75.6% versus 60.0%) and premature ending of radiotherapy (12.2% versus 5.0%) also occurred more frequently (p ≥ 0.05). CONCLUSION: In patients with head and neck cancer treated with chemoradiotherapy, the presence of moderate to severe comorbidities seems to correlate with higher incidences of severe acute toxicities. ACE-27 may identify patients at higher risk of major toxicities and assist decisions regarding treatment.

Streptococcal sex syndrome: a curious association between sex and cellulitis.

Women undergoing pelvic lymphadenectomy and radiation therapy for gynaecological cancer are prone to acute and often recurrent cellulitis as a consequence of compromised lymphatic circulation. Vaginal intercourse can trigger the infection, a condition named streptococcal sex syndrome (SSS). We report a 63-year old female patient with a history of pelvic lymphadenectomy and radiation therapy for gynaecological cancer. She presented to the obstetrics/gynaecology department for vaginal haemorrhage during sexual intercourse the day before. Gynaecological examination was unremarkable but she was febrile and presented inflammatory signs on the abdomen and lower left limb. The diagnostic workup suggested cellulitis and intravenous antibiotics were initiated, with complete recovery. Blood cultures were positive for Streptococcus mitis/oralis. One month later, the infection recurred at the same location, promptly after sexual intercourse.