A Three-Dose mRNA COVID-19 Vaccine Regime Produces Both Suitable Immunogenicity and Satisfactory Efficacy in Patients with Solid Cancers.

BACKGROUND: The recommended booster third dose of vaccination against COVID-19 in cancer patients seems reasonable to protect them against a severe disease course. A prospective study was designed to assess the immunogenicity, efficacy, and safety of COVID-19 vaccination in this cohort. METHODS: Patients with solid malignancies on active treatment were followed up after the primary course and booster third dose of vaccination to assess their anti-SARS-CoV-2 S1 IgG levels, efficacy in the case of SARS-CoV-2 infection, and safety. RESULTS: Out of 125 patients receiving the primary course of vaccination, 66 patients received a booster third dose of mRNA vaccine, with a 20-fold increase in median anti-SARS-CoV-2 S1 IgG levels compared to Ab levels six months post-primary course of vaccination (p < 0.0001). After the booster third dose, anti-SARS-CoV-2 S1 IgG levels were comparable to healthy controls (p = 0.113). There was a decline in Ab levels 3 (p = 0.0003) and 6 months (p < 0.0001) post-third booster dose. No patients had either a severe disease course or a lethal outcome in the case of SARS-CoV-2 infection after the third booster dose. CONCLUSION: The third booster vaccination dose against COVID-19 in solid cancer patients triggers substantial immunogenicity and is safe and effective for preventing a severe COVID-19 disease course.

Solid cancer patients achieve adequate immunogenicity and low rate of severe adverse events after SARS-CoV-2 vaccination.

Background: SARS-CoV-2 vaccination in cancer patients is crucial to prevent severe COVID-19 disease course. Methods: This study assessed immunogenicity of cancer patients on active treatment receiving mRNA-based SARS-CoV-2 vaccine by detection of anti-SARS-CoV-2 S1 IgG antibodies in serum, before, after the first and second doses and 3 months after a complete primary course of vaccination. Results were compared with healthy controls. Results: Of 112 patients, the seroconversion rate was 96%. A significant reduction in antibody levels was observed 3 months after vaccination in patients receiving immune checkpoint inhibitors versus control participants (p < 0.001). Adverse events were mostly mild. Conclusion: Immunogenicity after mRNA-based vaccine in cancer patients is adequate but influenced by the type of anticancer therapy. Antibody levels decline after 3 months, and thus a third vaccination is warranted.

Because cancer patients are especially endangered by SARS-CoV-2 infection and have worse disease course and outcomes, it is crucial to protect them from this infection. This study was aimed at assessing protective antibodies after patients received mRNA-based SARS-CoV-2 vaccines. Protective antibodies (e.g., anti-SARS-CoV-2 S1 IgG antibodies) were assessed in patients' blood before vaccination, after the first and second doses and 3 months after a complete primary course vaccination. Patients' oncological treatment was unaffected by the vaccination received. The results of protective antibodies were also compared with healthy control subjects who were vaccinated in the same manner. More than 110 cancer patients participated and agreed to have their blood samples analyzed. The rate of antibody production was 96% after a complete primary course of vaccination and was similar with that of healthy control subjects. However, there were some differences noted regarding the oncological treatment that the patients were receiving, with patients who were treated with targeted therapy achieving the highest levels of protective antibodies. Adverse events after vaccination were mostly mild and did not interfere with patients' general performance. The rate of antibody production for cancer patients after SARS-CoV-2 vaccination is high and similar to that in healthy control subjects but varies with regard to the oncological treatment that patients are receiving. However, antibodies decline substantially after 3 months, and thus a third vaccination is desirable. There were no new safety concerns after vaccination, and most adverse events were mild and short-lived.

Establishing an Expert Consensus on Key Indicators of the Quality of Life among Breast Cancer Survivors: A Modified Delphi Study.

(1) Background: The needs of cancer survivors are often not reflected in practice. One of the main barriers of the use of patient-reported outcomes is associated with data collection and the interpretation of patient-reported outcomes (PROs) due to a multitude of instruments and measuring approaches. The aim of the study was to establish an expert consensus on the relevance and key indicators of quality of life in the clinical practice of breast cancer survivors. (2) Methods: Potential indicators of the quality of life of breast cancer survivors were extracted from the established quality of life models, depicting survivors' perspectives. The specific domains and subdomains of quality of life were evaluated in a two-stage online Delphi process, including an international and multidisciplinary panel of experts. (3) Results: The first round of the Delphi process was completed by 57 and the second by 37 participants. A consensus was reached for the Physical and Psychological domains, and on eleven subdomains of quality of life. The results were further supported by the additional ranking of importance of the subdomains in the second round. (4) Conclusions: The current findings can serve to optimize the use of instruments and address the challenges related to data collection and interpretation as the facilitators of the adaption in routine practice.

Real-World Data on Detection of Germline and Somatic Pathogenic/Likely Pathogenic Variants in BRCA1/2 and Other Susceptibility Genes in Ovarian Cancer Patients Using Next Generation Sequencing.

Detection of germline and somatic pathogenic/likely pathogenic variants (PV/LPV) in BRCA genes is at the moment a prerequisite for use of PARP inhibitors in different treatment settings of different tumors. The aim of our study was to determine the most appropriate testing workflow in epithelial ovarian cancer (EOC) patients using germline and tumor genotyping of BRCA and other hereditary breast and/or ovarian cancer (HBOC) susceptibility genes. Consecutive patients with advanced non-mucinous EOC, who responded to platinum-based chemotherapy, were included in the study. DNA extracted from blood and FFPE tumor tissue were genotyped using NGS panels TruSightCancer/Hereditary and TruSight Tumor 170. Among 170 EOC patients, 21.8% had BRCA germline or somatic PV/LPV, and additionally 6.4% had PV/LPV in other HBOC genes. Sensitivity of tumor genotyping for detection of germline PV/LPV was 96.2% for BRCA genes and 93.3% for HBOC genes. With germline genotyping-only strategy, 58.8% of HBOC PV/LPV and 68.4% of BRCA PV/LPV were detected. By tumor genotyping-only strategy, 96.1% of HBOC PV/LPV and 97.4% of BRCA PV/LPV were detected. Genotyping of tumor first, followed by germline genotyping seems to be a reasonable approach for detection of PV/LPV in breast and/or ovarian cancer susceptibility genes in non-mucinous EOC patients.

Patients-centered SurvivorShIp care plan after Cancer treatments based on Big Data and Artificial Intelligence technologies (PERSIST): a multicenter study protocol to evaluate efficacy of digital tools supporting cancer survivors.

BACKGROUND: It is encouraging to see a substantial increase in individuals surviving cancer. Even more so since most of them will have a positive effect on society by returning to work. However, many cancer survivors have unmet needs, especially when it comes to improving their quality of life (QoL). Only few survivors are able to meet all of the recommendations regarding well-being and there is a body of evidence that cancer survivors' needs often remain neglected from health policy and national cancer control plans. This increases the impact of inequalities in cancer care and adds a dangerous component to it. The inequalities affect the individual survivor, their career, along with their relatives and society as a whole. The current study will evaluate the impact of the use of big data analytics and artificial intelligence on the self-efficacy of participants following intervention supported by digital tools. The secondary endpoints include evaluation of the impact of patient trajectories (from retrospective data) and patient gathered health data on prediction and improved intervention against possible secondary disease or negative outcomes (e.g. late toxicities, fatal events). METHODS/DESIGN: The study is designed as a single-case experimental prospective study where each individual serves as its own control group with basal measurements obtained at the recruitment and subsequent measurements performed every 6 months during follow ups. The measurement will involve CASE-cancer, Patient Activation Measure and System Usability Scale. The study will involve 160 survivors (80 survivors of Breast Cancer and 80 survivors of Colorectal Cancer) from four countries, Belgium, Latvia, Slovenia, and Spain. The intervention will be implemented via a digital tool (mHealthApplication), collecting objective biomarkers (vital signs) and subjective biomarkers (PROs) with the support of a (embodied) conversational agent. Additionally, the Clinical Decision Support system (CDSS), including visualization of cohorts and trajectories will enable oncologists to personalize treatment for an efficient care plan and follow-up management. DISCUSSION: We expect that cancer survivors will significantly increase their self-efficacy following the personalized intervention supported by the m-HealthApplication compared to control measurements at recruitment. We expect to observe improvement in healthy habits, disease self-management and self-perceived QoL. Trial registration ISRCTN97617326. https://doi.org/10.1186/ISRCTN97617326 . Original Registration Date: 26/03/2021.

Trastuzumab Emtansine Plus Non-Pegylated Liposomal Doxorubicin in HER2-Positive Metastatic Breast Cancer (Thelma): A Single-Arm, Multicenter, Phase Ib Trial.

The paper assesses the dose-limiting toxicities and the maximum tolerated dose (MTD) of trastuzumab emtansine (T-DM1) combined with non-pegylated liposomal doxorubicin (NPLD) in HER2-positive (HER2+) metastatic breast cancer (MBC). This single-arm, open-label, phase Ib trial (NCT02562378) enrolled anthracycline-naïve HER2+ MBC patients who had progressed on trastuzumab and taxanes. Patients received a maximum of 6 cycles of NPLD intravenously (IV) at various dose levels (45, 50, and 60 mg/m2) in the "3 plus 3" dose-escalation part. During expansion, they received 60 mg/m2 of NPLD every 3 weeks (Q3W) plus standard doses of T-DM1. The MTD was T-DM1 3.6 mg/kg plus NPLD 60 mg/m2 administered IV Q3W. No clinically relevant worsening of cardiac function was observed. Among all evaluable patients, the overall response rate was 40.0% (95%CI, 16.3-67.7) with a median duration of response of 6.9 months (95%CI, 4.8-9.1). Clinical benefit rate was 66.7% (95%CI, 38.4-88.2) and median progression-free survival was 7.2 months (95%CI, 4.5-9.6). No significant influence of NPLD on T-DM1 pharmacokinetics was observed. The addition of NPLD to T-DM1 is feasible but does not seem to improve the antitumor efficacy of T-DM1 in HER2+ MBC patients.

Hypophyseal metastases: A report of three cases and literature review.

Metastatic tumours to the pituitary gland are rare. The most frequent are metastases from breast and lung. We describe three patients with metastatic tumours: (I) a 54-year-old patient with metastatic renal clear-cell carcinoma and consequent disturbances in visual acuity, cranial nerve paresis and panhypopituitarism, (II) a 60-year-old patient with a diffuse large B-cell lymphoma with panhypopituitarism and diabetes insipidus and (III) a 57-year-old patient with metastasis of breast cancer and panhypopituitarism, visual impairment and cranial nerve paresis. A transnasal endoscopic biopsy and resection of the tumour was performed in all patients, followed by the oncological treatment. Despite the rarity of the disease, it is important to suspect a metastatic pituitary tumour especially in the case of diabetes insipidus, ophthalmoplegia, rapid course of the disease and headaches. In 20-30% of patients, a metastasis to the pituitary is the first manifestation of a tumour of unknown origin. Surgical and adjuvant therapy may improve the quality of life. The survival is not affected, however, and the prognosis of the disease is usually poor.

Prognostic Role of HER2 Status and Adjuvant Trastuzumab Treatment in Lymph Node-Negative Breast Cancer Patients - a Retrospective Single Center Analysis.

BACKGROUND: The natural course of traditionally prognostically unfavorable human epidermal growth factor receptor 2 (HER2)-positive breast cancer has been changed by anti-HER2 therapy. It is not clear whether the prognosis for HER2-positive patients treated with adjuvant trastuzumab differs from that of HER2-negative patients. METHODS: We performed a retrospective study including patients with lymph node-negative invasive breast cancer treated at our institution in the period 2000-2009. Disease-free (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The Cox proportional hazards model was applied to control for other clinically important variables. RESULTS: Median follow-up was 90-109 months. The 5-year DFS rates for HER2-negative patients, HER2-positive patients without adjuvant trastuzumab and trastuzumab-treated HER2-positive patients were 88.1% (95% confidence interval (CI) 85.6-90.6%), 73.1% (95% CI 64.3-81.9%) and 90.7% (95% CI 83.1-98.3%), respectively. No significant difference in DFS was observed between trastuzumab-treated HER2-positive patients and HER2-negative patients in multivariate analysis (hazard ratio 1.15; 95% CI 0.53-2.46; p = 0.728). There were no differences in OS among the 3 groups. CONCLUSION: Based on our results, the negative prognostic effect of HER2 positivity seen before targeted anti-HER2 treatment has completely disappeared in the era of routine trastuzumab administration in the adjuvant setting.

Metastasis of an occult pulmonary carcinoma into meningioma: a case report.

Tumour-to-tumour metastasis is an infrequent pathological phenomenon. Meningioma is the most common intracranial tumour where metastatic deposits may be found, the majority of which arise from breast and lung cancers. We describe an unusual case of occult pulmonary carcinoma metastasis into the intracranial meningioma. A 77-year old lady presented with acutely deteriorating hemiparesis. Her previous medical history was unremarkable. Radiological imaging revealed an expansive lesion, classified as meningioma, which was located parasagittally in the right premotor area. A well-capsulated tumour attached to the dura was removed surgically. The pathological examination demonstrated a mixture of angiomatous meningioma and pulmonary adenocarcinoma. Possible explanations for the development of a composite tumour and pathophysiology are described.

Partial skull base tumour resection in combination with radiosurgery: an escape procedure or a reasonable solution of treatment?

Despite advancement in microsurgical techniques for skull base tumour surgery, approaches of this kind still represent a significant challenge for neurosurgeons due to the size of the tumour and its interference and proximity to important neural and vascular structures. After incomplete resection, gamma knife radiosurgery is becoming an alternative or adjunctive treatment option. In this article, some examples of our experience in combined treatment of the skull base tumours with surgical procedure and gamma knife therapy for the remaining tumour tissue are presented.

Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer - correlation with traditional prognostic factors.

BACKGROUND: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. PATIENTS AND METHODS: 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman's rank correlation, Mann Whitney U test and χ(2) test for statistical analysis. RESULTS: Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). CONCLUSIONS: Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated.

Preoperative total serum cholesterol as a prognostic factor for survival in patients with resectable non-small-cell lung cancer.

BACKGROUND: Coexisting hypocholesterolemia in cancer has been known for a very long time but its relationship to cancer is still controversial. Hypocholesterolemia has been reported in patients with lung cancer, although its association with survival has not been explored. OBJECTIVES: The purpose of the study was to determine whether preoperative total serum cholesterol is a prognostic factor for survival after lung cancer resection. METHODS: The retrospective study comprised 198 patients (162 men, 36 women) operated upon for resectable non-small-cell lung cancer (clinical stages I-IIIB) between January 1992 and April 1994. Total serum cholesterol concentration was determined preoperatively in each patient. The effects of sex, age, stage, histological type and preoperative total serum cholesterol concentration on survival were tested in univariate and multivariate analysis. RESULTS: Preoperative total serum cholesterol was a significant prognostic factor in both univariate and multivariate analysis. The median value for total serum cholesterol was 5.3 mmol/l and patients below that cut-off had significantly shorter overall survival times than patients in the high cholesterol group (5-year survival 41% vs. 56%, P < 0.05). In a multivariate Cox proportional-hazard regression model, only stage and preoperative total serum cholesterol were found to be of significance for survival (relative risk 0.84 for each mmol/l increase in concentration, CI 0.71-1.00, P < 0.05). CONCLUSIONS: Our results suggest that preoperative total serum cholesterol may be an important prognostic factor for overall survival after lung cancer resection. It may prove to be a valuable tool in the follow-up of patients with lung cancer and in detection of high-risk cases.

Variable presentations of Currarino syndrome in three members of the same family.

The article presents an autosomal dominant Currarino syndrome with incomplete penetrance in three out of four members of the same family. The mother had only a bony sacral defect and no other signs. In the older daughter, the syndrome was completely developed with presacral cystic teratoma, a sacral defect and abdominal discomfort. The younger daughter had no clinical or imaging features of the disease. The only son harboured presacral meningocele, urinary stenosis and a sacral defect. The daughter and son with developed variants of the syndrome were successfully operated on and are now symptom free.

Dumbbell synovial sarcoma of the thoracolumbar spine: a case report.

STUDY DESIGN: A case report is of a giant dumbbell-shaped synovial sarcoma of the thoracolumbar spine is presented. OBJECTIVE: To report a case of a rare dumbbell-shaped tumor treated by multimodal approach. Surgical procedures, adjuvant treatment, and outcome were discussed. SUMMARY OF BACKGROUND DATA: Synovial sarcomas of the spine are very rare tumors. Radical surgical resection is the goal, but is often not feasible. Dumbbell-shaped spinal synovial sarcoma with a giant extraspinal extension has not yet been reported. The rationale for 2-step surgical procedure and adjuvant therapy is discussed in light of the clinical picture, preoperative imaging and extension of the disease. METHODS: A 32-year-old male patient presented with signs of quickly progressive paraparesis. A dumbbell-shaped tumor at the level Th12-L1 was found with a giant retroperitoneal extension. Tumor was nonradically excised in a 2-step operation: first through a dorsal approach with laminectomy and removal of the intraspinal extradural part, and later through a laparotomy with removal of the retroperitoneal part. Histologic examination revealed highly malignant synovial sarcoma. Patient was treated with chemotherapy and radiotherapy after surgery. RESULTS: Patient was in remission and symptom free for 1 year after surgery; he then developed a local recurrence and died soon afterwards. CONCLUSION: A good treatment result was achieved initially. A combined approach in cases like this is warranted, with as radical surgery as possible in order to avoid local recurrence, a common cause of treatment failure in sarcomas.