Immune response to anti-SARS-CoV-2 prime-vaccination in patients with cancer: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the immune response to anti-SARS-CoV-2 prime-vaccination in patients with cancer. METHODS: We performed a systematic literature search using PubMed, Embase, and Cochrane Library until 28/09/2021, and conference proceedings from ASCO and ESMO 2021 annual meetings. We screened for observational or interventional studies including subjects ≥ 16 years old with cancer diagnosis who were vaccinated against SARS-CoV-2. Prime-vaccination was defined as one dose of Ad26.COV2-S vaccine or two doses of BNT162b2, mRNA-1273, ChAdOx1-S or inactivated SARS-CoV-2 vaccine. The outcomes were humoral and adaptive immune responses (proportion of subjects with positive titers of antibody anti-SARS-CoV-2 spike protein and anti-SARS-CoV-2 cellular responses, respectively). RESULTS: We included 89 records reporting data from 30,183 subjects. The overall seropositive rate within the first month after complete anti-SARS-CoV-2 prime-vaccination was 80% [95% confidence interval (CI), 72-86%], 60% (95%CI, 53-67%) in patients with hematological malignancies (HM) versus 94% (95%CI, 88-97%) in patients with solid malignancies (SM). The diagnosis of HM was significantly associated with a lower seropositive rate on multivariate meta-regression (odds ratio 0.35, 95% CI 0.18-0.69, HM versus both, p = 0.002). The overall humoral response was 49% (95% CI, 42-56%) after incomplete prime-vaccination and 79% (95% CI, 70-86%) at 2 months after complete prime-vaccination. These responses were also lower in patients with HM at these time points. The overall cellular response rate at any time after vaccination was 61% (95% CI, 44-76%). CONCLUSION: This meta-analysis provides compelling evidence of humoral and adaptive immune responses against SARS-CoV-2 in patients with cancer, which last for at least 2 months following complete prime-vaccination.

Prognostic Significance of Lymphocyte Infiltrate Localization in Triple-Negative Breast Cancer.

High infiltration by tumor-infiltrating lymphocytes (TILs) is associated with favorable prognosis in different tumor types, but the clinical significance of their spatial localization within the tumor microenvironment is debated. To address this issue, we evaluated the accumulation of intratumoral TILs (itTILs) and stromal TILs (sTILs) in samples from 97 patients with early triple-negative breast cancer (TNBC) in the center (sTIL central) and periphery (sTIL peripheral) of tumor tissues. Moreover, the presence of primary and secondary lymphoid aggregates (LAs) and the expression levels of the cancer testis antigen (CTA), NY-ESO-1, and PD-L1 were explored. High infiltration by itTILs was observed in 12/97 samples (12.3%), unrelated to age, Ki67 expression, tumor size, histologic type and grade, and LA presence. NY-ESO-1 was expressed in tumor cells in 37 samples (38%), with a trend suggesting a correlation with itTIL infiltration (p = 0.0531). PD-L1 expression was detected in immune cells in 47 samples (49%) and was correlated with histologic grade, sTILs, and LA formation. The presence of primary LAs was significantly correlated with better disease-free survival (DFS) (p = 0.027). Moreover, no tumor progression was observed during >40 months of clinical follow up in the 12 patients with high itTILs or in the 14 patients with secondary LAs. Thus, careful evaluation of lymphoid infiltrate intratumoral localization might provide important prognostic information.

IMPACT OF BODY COMPOSITION ON THE QUALITY OF LIFE OF PREMENOPAUSAL PATIENTS WITH EARLY STAGE BREAST CANCER DURING CHEMOTHERAPY.

Body composition has been studied relatively recently as part of oncology trials in different types of tumors. There are numerous studies that define the impact of chemotherapy side effects on the quality of life (QoL) of breast cancer patients, however, there are few studies that analyze the impact of body composition on the QoL of premenopausal patients in the course of cytotoxic treatment. The study was performed on a sample of premenopausal patients treated with neoadjuvant or adjuvant AC chemotherapy for early-stage breast cancer at Day Hospital of the Department of Medical Oncology, University Hospital for Tumors in Zagreb. The study included 68 patients, median age 46.6 years. Analysis of the QoL questionnaires and their association with body composition indicated several interesting results. At the beginning of treatment, most pronounced was the connection between body composition and physical and sexual functioning and hair loss, while in subsequent treatment cycles the effect on other QoL subdomains, in particular fatigue and diarrhea, was more pronounced. In conclusion, we found body composition to have a significant impact on certain QoL subdomains during treatment.

Difference in Estimation of Side Effects of Chemotherapy between Physicians and Patients with Early-Stage Breast Cancer: The Use of Patient Reported Outcomes (PROs) in the Evaluation of Toxicity in Everyday Clinical Practice.

Knowledge about the patient's experience and perception of side effects and their impact on daily life is crucial for the adequate planning of interventions to provide the highest attainable levels of quality of life during oncology treatment. We conducted a study on consecutive samples of 69 early breast cancer patients treated with four cycles of neoadjuvant or adjuvant anthracycline-based chemotherapy. Patients completed the questionnaire about side effects experienced after the previous cycle of chemotherapy. The questionnaire was a modified PRO for the evaluation of treatment toxicity consisting of 18 questions related to the very common and common side effects of doxorubicin and cyclophosphamide, valued from 0 to 3 according to the subjective assessment of the patient. During the same cycles of therapy, data were also collected by the physician who completed a questionnaire consisting of the same questions as the questionnaire for patients, on the same scale. Most of the side effects reported by patients were mild to moderate in intensity, while physicians reported side effects much less frequently. The results also indicated a disproportionate reporting, in which physicians reported statistically significantly fewer side effects than patients. This study reported a level of disagreement between patients and physicians in the experience of therapy toxicity. In conclusion, use of PRO in clinical practice can help us avoid physician subjectiveness in the estimation of side effects and determine the group of patients who can benefit from additional and individualized supportive care measures, which could lead to better adherence to therapy and ultimately best outcomes.

Influence of Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in early-stage HER2 positive breast cancer.

Trastuzumab has improved the prognosis of HER2 positive breast cancer, but cardiotoxicity remains a concern. We aimed to identify risk factors for trastuzumab-induced cardiotoxicity, with an emphasis on the HER2 Ile655Val single nucleotide polymorphism. This single-center case-control study included 1056 patients with early-stage HER2 positive breast cancer that received adjuvant trastuzumab. Cardiotoxicity was defined as a decline in left ventricular ejection fraction (LVEF) > 15% in patients without previous cardiomyopathy, or > 10% in patients with baseline LVEF of < 50%. Patient characteristics and cardiac parameters were compared in 78 (7.38%) cases and 99 randomly assigned controls, and the polymorphism was genotyped using real-time polymerase chain reaction. Cardiotoxicity was independently associated with advanced age (P = 0.024), lower body mass index (P = 0.023), left breast involvement (P = 0.001), N3 status (P = 0.004), diabetes (P = 0.016), and a family history of coronary artery disease (P = 0.019). Genotype distribution was as follows: A/A (Ile/Ile) was found in 111 (62.7%) patients, A/G (Ile/Val) in 60 (33.9%) patients, and G/G (Val/Val) in 6 (3.4%) patients. The genotype was not associated with cardiotoxicity or the severity of heart failure, reversibility, and recovery time. We found no association between the HER2 Ile655Val polymorphism and trastuzumab-induced cardiotoxicity; therefore, we do not recommend routine cardiotoxicity-risk stratification using this polymorphism.

CHARACTERISTICS AND PROGNOSIS OF TRIPLE-NEGATIVE BREAST CANCER PATIENTS: A CROATIAN SINGLE INstitution RETROSPECTIVE COHORT STUDY.

Triple-negative breast cancer (TNBC) occurs in around one-sixth of all breast cancer (BC) patients, with the most aggressive behavior and worst prognosis of all BC subtypes. It is a heterogeneous disease, with specific molecular characteristics and natural dynamics of early recurrence and fast progression. Due to the lack of biomarkers or any valid treatment targets, it can only be treated with classic cytotoxic chemotherapy. We analyzed a cohort of 152 patients, median age 58 years, diagnosed with and treated for early stage TNBC at the University Hospital for Tumors, Sestre milosrdnice University Hospital Centre, Zagreb, Croatia, during the 2009-2012 period. Patients were treated with primary surgical approach, adjuvant chemotherapy and adjuvant irradiation. We observed a relatively large proportion of locally advanced TNBC at diagnosis, with large tumor size and nodal involvement, with high grade and high proliferation index Ki67. Patient age, tumor size and lymph node involvement, as expected, were significant and clinically most important prognostic factors for 5-year disease-free survival (67%; 95% CI 60%-75%) and overall absolute survival rate (74%; 95% CI 66%-81%).

OXALIPLATIN INDUCED PULMONARY FIBROSIS: A CASE REPORT.

Oxaliplatin is part of the standard chemotherapy regimens for treating colorectal carcinoma. Pulmonary fibrosis is a serious but rare side effect of oxaliplatin treatment, which resulted in patient death in more than half of the reported cases. The precise pathophysiological mechanism of this phenomenon has not been clarified yet. Analysis of the reported cases strongly suggests that early diagnosis and immediate corticosteroid treatment are crucial for better prognosis. Here we report a case of pulmonary fibrosis related to the FOLFOX regimen in a patient with early colorectal carcinoma.

Association of Breast Cancer Symptoms with Patients' Quality of Life and Depression; A Croatian Cross-Sectional Study.

AIM: To find out which symptoms are the most associated with a breast cancer patients' quality of life (QoL) and depression. SUBJECTS AND METHODS: We performed this cross-sectional study from February to April 2015 at the Department of Medical Oncology, University Hospital for Tumors, Zagreb University Hospital Center "Sestre milosrdnice", Zagreb, Croatia on the sample of 147 breast cancer patients. Primary outcomes were EORTC QLQ-C30 version 3.0 Global QoL scale and Beck Depression Inventory II. RESULTS: After the adjustment for other symptoms, sociodemographic and clinical variables, fatigue (ß=-0.47, P<0.001), pain (ß=-0.24, P=0.023), and appetite loss (ß=-0.18, P=0.037) were statistically significantly correlated with QoL. Fatigue was the only symptom significantly associated with depression (ß=0.39, P=0.006). CONCLUSION: Fatigue, pain, appetite loss contributes the most to the overall breast cancer patients QoL. Although correlated, fatigue and pain contribution to lower QoL is independent from each other. Future studies should investigate whether there is an interaction between fatigue and pain changes over course of treatment. Fatigue and number of children are positively, while age and treatment in daily hospital are negatively associated with depression measured by BDI-II.

Rapid hair depigmentation in patient treated with pazopanib.

Pazopanib is multitargeted tyrosine kinase inhibitor used for the treatment of metastatic renal cell carcinoma. Hair colour change is a common side effect of pazopanib therapy which usually develops gradually during few months of therapy. We report a case of the patient who developed multiple pazopanib side effects followed by rapid overnight hair and eyebrow depigmentation after only few weeks of therapy. In our research, we found no literature data of rapid loss of hair pigment due to therapy with any of listed multitargeted tyrosine kinase inhibitors. To the best of our knowledge, this is the first such case being reported. We presume that summation of different mechanisms probably led to rapid hair depigmentation. Considering the fact that pazopanib treatment was very effective in our patient, this side effect could be a good predictor of therapy success, although it presents very stressful event for patient and his family.

UNCOMMON SIDE EFFECTS OF SUNITINIB THERAPY IN A PATIENT WITH METASTATIC RENAL CELL CANCER: CASE REPORT.

- Sunitinib is an orally administered multikinase inhibitor. This therapy can provoke uncommon side effects such as pancytopenia, tumor lysis syndrome, cardiac disorders, thromboembolic incidents, intestinal perforation, pancreatitis, acute renal failure, etc. We report a case of a 63-year-old female admitted to the hospital due to abdominal pain, nausea, vomiting and elevated blood pressure. One month earlier, sunitinib therapy for metastatic renal cell carcinoma was initiated. During the first cycle of therapy, after three weeks of sunitinib 50 mg daily, symptoms started and she stopped taking the drug. At admission, laboratory tests revealed elevated serum and urine amylase, C-reactive protein, urea and creatinine, and lowered platelet and leukocyte counts and hemoglobin value. Urine test showed proteinuria, erythrocyturia, leukocyturia and granulated cylinder. The patient was diagnosed with acute pancreatitis grade III, acute renal failure grade II, pancytopenia and urinary infection, and was hospitalized for five days. She was treated symptomatically and with antibiotic therapy because of persistently elevated C-reactive protein and pathologic urinary sediment, which led to subjective and clinical improvement. Acute pancreatitis, renal insufficiency and pancytopenia are rarely described side effects of sunitinib therapy, and clear connection between these conditions and drug activity is not yet determined. Medical specialists who prescribe and treat patients with sunitinib should be aware of the possible occurrence of these conditions and perform regular checkups of sunitinib treated patients.