The efficacy of lapatinib in patients with metastatic HER2 positive breast cancer who received prior therapy with monoclonal antibodies and antibody-drug conjugate: a single institutional experience.

The choice of the anti-HER2 agent depends on country-specific availability, the specific, previously administered anti-HER2 therapy and the relapse-free interval, although there is not much published data on the use of lapatinib after progression on pertuzumab and/or T-DM1. The aim of this research is to determine efficacy of lapatinib in this setting. This research included 111 patients with metastatic HER2 positive breast cancer who received lapatinib with capecitabine at The Oncology Institute of Vojvodina. Lapatinib was given to 83 patients after trastuzumab without prior exposure to pertuzumab or T-DM1 while 28 patients received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1. In order to determine efficacy of lapatinib in both groups, we measured progression free survival (PFS) and overall survival (OS), as well as by subsets: hormonal status (ER-positive and/or PR-positive tumours versus ER-negative and PR-negative tumours), the number of positive axillary lymph nodes (four or more positive axillary lymph nodes versus less than four positive axillary lymph nodes), marker of proliferation (Ki-67 ≥ 30 versus Ki-67 < 30), disease free interval (metastatic recurrence ≤ 1 year after initial diagnosis versus metastatic recurrence > 1 year after initial diagnosis or de novo metastatic disease. Median PFS was 5.6 months (95% CI 4.6-6.6) in the group of patients who received lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM 1 and 7.4 months (95% CI 6.1-10.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.79; 95% CI 0.61-0.98; P = 0.09). The patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes, marker of proliferation Ki 67 ≥ 30 and metastatic recurrence ≤ 1 year after initial diagnosis, had a similar PFS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Median OS was 10.1 months (95% CI 8.6-NR) in the group that received lapatinib after exposure to trastuzumab, pertuzumab and/or T-DM1 and 16.3 months (95% CI 14.4-20.2) in the group of patients who received lapatinib after trastuzumab (HR, 0.76; 95% CI, 0.59-0.94; P = 0.04). Patients with negative prognostic factors such as hormone receptor negativity, more than four positive axillary lymph nodes and marker of proliferation Ki 67 ≥ 30, had no distinctly worse OS, regardless of receiving lapatinib after prior exposure to trastuzumab, pertuzumab and/or T-DM1 or without prior exposure. Lapatinib with capecitabine is an effective therapeutic option, especially in patients with negative prognostic factors, who have received prior chemotherapy, trastuzumab, pertuzumab, T-DM1 and remains an acceptable option for HER2 positive metastatic breast cancer until the novel drugs are approved in developing countries.

COVID-19 vaccines and cancer patients: acceptance, attitudes and safety.

PURPOSE: Recommendations and guidelines consider cancer patients a high-priority population for COVID-19 immunization. Vaccination process in Serbia began in January 2021 with four available vaccines. We have conducted a cross-sectional study investigating cancer patients' acceptability of anti SARS-COV2 vaccines. METHODS: The study included 767 patients with solid and hematologic malignancies treated at the Oncology Institute of Vojvodina, Serbia. During July and August 2021 patients filled in an individual paper questionnaire on anti SARS-COV2 vaccination acceptance, preferences, side effects and information origin. Data on treatment phase, diagnosis and treatment was collected from electronic health records. RESULTS: During the first six months of vaccination campaign in Serbia 41% (320/767) of the investigated oncology patients received COVID-19 vaccines. The median age of vaccinated patients was 65 years (28-84). Most of them (75%) were in active treatment of cancer. Half of the unvaccinated patients (52%) wish to get vaccinated after the end of their cancer treatment. Around 10% of the patients definitely refused vaccination. The majority of information on COVID-19 vaccines cancer patients got from their oncologist, television and newspapers. Side effects were reported by 10.93% of the patients after the first dose and 13,31% after the second dose. No serious side effects were reported. CONCLUSION: We have confirmed that patients are reluctant of receiving vaccine due to fear of side effects, especially during the active cancer treatment. However, real-world evidence and clinical trials data have gathered enough evidence to reassure any doubts of the patients and their oncologists on safety and efficacy of anti SARS-COV2 vaccines.

Benefit and outcome of using temozolomide-based chemoradiotherapy followed by temozolomide alone for glioblastoma in clinical practice.

PURPOSE: Temozolomide (TEM), an oral alkylating agent, has shown promising activity in the last 10 years in the treatment of glioblastoma multiforme (GBM). Our goal was to show the benefit of concomitant therapy involving 3D conformal radiotherapy and temozolomide in clinical practice. METHODS: This was a retrospective/prospective study and included a total of 113 patients with GBM diagnosis. Forty- seven patients received postoperative radiotherapy and 66 received concomitant temozolomide plus 3D conformal radiotherapy. RESULTS: The mean overall survival of patients who received postoperative radiotherapy alone was 9.93±6.475 months, compared to statistically longer overall survival in the group of patients who received radiotherapy plus temozolomide (13.89±8.049 months) (p=0.006). The latter group was divided into two subgroups, one consisting of patients who received 6 complete cycles of temozolomide, and a second with patients who received incomplete treatment. Statistically significant longer overall survival was registered in the first subgroup compared to the second (p=0.006). CONCLUSION: The concomitant usage of temozolomide and radiotherapy was beneficial, and statistically significant difference among groups and subgroups was observed regarding overall survival.

Modulatory effect of neoadjuvant chemotherapy on the prognosis of patients with breast cancer.

PURPOSE: To evaluate the changes in biological markers ER, PR, HER2 and Ki67 in residual tumor after surgery for locally advanced breast cancer (LABC), and also to evaluate the outcome of breast cancer patients treated with neoadjuvant chemotherapy (NAC). METHODS: 144 breast cancer patients treated with NAC at the Oncology Institute of Vojvodina, Serbia from 2011 to 2015 were included in this study. Changes in biologic markers ER,PR, HER2/neu and Ki-67 were evaluated at diagnostic core biopsy and at the final surgery tissue specimens. RESULTS: Of 144 patients pathological complete response was achieved in 17 (12%) and these were excluded from the study. Evaluated were 127 patients with residual tumor after the final surgery. A change in hormone receptor status (ER,PR) occurred in 9.4% of the patients (ER in 5%, PR in 14.5%) and HER2 status in 4.7% of the patients. ER and PR status change from negative to positive was associated with better overall survival (OS), but without statistical significance (p=0.16). Patients with conversion of HER2 status from negative to positive lived longer (65 vs 42 months). Furthermore, it was determined that HER2 change from negative to positive was associated with better OS (p=0.03). Ki-67 changed in 17 (11.8%) patients. The decrease of Ki-67 expression after NAC was associated with better outcome. Median follow up was 37.5 months (range 16.2-76.8). CONCLUSION: Changes in hormone receptor status, HER2 status and Ki-67 occurred after NAC in patients with LABC. A change from negative to positive hormone receptor status and HER2 status offers new treatment options, like endocrine therapy, and/or trastuzumab therapy for breast cancer patients. The decrease of Ki-67 expression after NAC was associated with better outcome.

Unusual metastasis of esophageal cancer.

INTRODUCTION: Carcinoma of the esophagus is in the eighth place by the frequency of malignant diseases and the sixth cause of death from cancer worldwide. It usually metastasizes to regional lymph nodes, liver, lungs, central nervous system, and bones, but metastases can appear to unusual locations such as facial skin and lips. CASE REPORT: We presented a 56- year-old man who reported to his physician because of upper lip swelling. A physical checkup of the patients also showed a lesion on the skin of the left temporal region and both lesions were biopsied. Based on the results of histopathological and immunohistochemical analyses of the samples a diagnosis of metastatic adenocarcinoma to the skin was established. Additional diagnostic procedures, including esophagogastroduodenoscopy, detected the infiltration into the distal part of esophagus, which was histopathologically confirmed as adenocarcinoma of esophagus. The results of positron emission tomography/computed tomography (PET/CT) examination showed the invasion of the disease. Because of the disease expansion, a multidisciplinary oncology team suggested chemo- and radiotherapy treatment. The patient has received 4 cycles of platinum-based chemotherapy so far. CONCLUSION: The physicians should always consider unusual skin lesions as the first sign of cancer spreading.