Efficacy of Capecitabine and Temozolomide Regimen in Neuroendocrine Tumors: Data From the Turkish Oncology Group.

INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.

Relationship between pathological response and molecular subtypes in locally advanced breast cancer patients receiving neoadjuvant chemotherapy.

Majority of patients with breast cancer were diagnosed with locally advanced stages of the disease (54%). This study aimed to explain the pathological response received to neoadjuvant chemotherapy (NACT) according to the molecular classification of breast cancer in patients with locally advanced tumors. One hundred and one patients with locally advanced breast cancer treated with neoadjuvant chemotherapy were analyzed. Patients were classified into five molecular subtypes based on the profile of the estrogen receptor, progesterone receptor, HER2, and Ki-67. We determined associations between complete pathological response (no invasive tumor after neoadjuvant chemotherapy) and molecular subgroups. Most patients had luminal A tumors (n: 28, 27.7%). The overall rate of complete pathological response (pCR) was 34.7% (n:35). Tumors that presented with the highest rate of pCR were pure HER2-positive, at 60% (n:6; OR, 3.2; 95% CI, 0.8-12.2). According to logistic regression analysis, the factors affecting pCR were HER2 positivity and clinically positive axilla before NACT. Luminal A tumors had a significantly lower pCR rate. (7.1%,p: 0.001). Despite the low pCR rate, Luminal A tumor had the best survival rate in the subgroups (p < 0.001). However, there was no difference between EFS and OS according to pCR in any molecular subgroups. Pathological complete response is directly related to the subtypes of breast cancer. A high complete pathological response rate is observed in the pure HER2-positive group. However, EFS and OS were not statistically significant in patients with and without pCR.

A case report of Wernicke Korsakoff syndrome in a patient with cholangiocellular carcinoma: An underestimated cause of encephalopathy in cancer patients.

INTRODUCTION: Wernicke's encephalopathy, a disorder caused by thiamin deficiency, is characterized by a classical triad of encephalopathy, ataxia, and ophthalmoplegia. Although alcoholism is the most common predisposing factor, it can also be associated with nonalcoholic states (hyperemesis gravidarum, intestinal obstruction, bariatric surgery, and others). This work presents a case of nonalcoholic Wernicke-Korsakoff syndrome diagnosed in a cholangiocellular carcinoma patient and literature review. CASE REPORT: A 65-year-old male patient with a history of cholangiocellular carcinoma (Klatskin tumor) was treated with radiotherapy at the operation site after Roux-en-Y hepaticojejunostomy. During follow-up, the patient developed gastric outlet obstruction and was diagnosed with peritoneal carcinomatosis after a palliative gastrojejunostomy. As the patient could not tolerate oral nutrition during hospitalization, total parenteral nutrition was administered. After 10 days of admission, the patient showed decreased response to verbal stimuli as well as bilateral horizontal nystagmus, lethargy, and disorientation. Furthermore, the patient displayed confabulation. Clinical and imaging findings were consistent with Wernicke's encephalopathy. Therefore, treatment with intravenous thiamin replacement was initiated. The patient's encephalopathy regressed on the second day after treatment, and he recovered the place-person-time orientation. In the following month, the abnormal imaging findings were almost entirely resolved. CONCLUSION: In order to prevent irreversible brain damage induced by chronic thiamin deficiency, thiamin replacement therapy with parenteral nutrition solutions should be included as a treatment for hospitalized cancer patients unable to receive enteral nutrition for a long time.

A single center's experience of the extrapulmonary neuroendocrine carcinomas.

Objective: Extrapulmonary neuroendocrine carcinoma (EP-NEC) is a rare tumor type, and a standard therapy for EP-NEC has not yet been established. The purpose of this research was to explore the overall survival (OS) and therapeutic effects of platinum-etoposide combination therapy in EP-NEC. Methods: This retrospective study was conducted based on the medical records from January 2010 to March 2020. Eligible patients had been pathologically diagnosed with EP-NEC. Results: Forty-seven patients were included in the study. About 72.3% (n=34) of the patients were diagnosed with metastatic disease at the first diagnosis. The most common primary tumor site was the stomach. The median progression-free survival (PFS) of the patient group, who received the combination of platinum/etoposide, was 5.83 months (95% CI 4.46-7.20), whereas the median OS of the patients, who were found to have metastatic disease at the first diagnosis, was 13.6 months (95% CI 9.01-18.18). There was no difference in PFS and OS between patients with and without liver metastasis. Conclusion: The outcome of advanced EP-NECs with platinum/etoposide chemotherapy remains poor. Obviously, there is a need for new, more effective treatment options.

Bevacizumab-induced isolated oculomotor nerve palsy in glioblastoma multiforme.

INTRODUCTION: Bevacizumab, a monoclonal antibody against the vascular endothelial growth factor receptor, is the standard treatment of recurrent glioblastoma multiforme. In addition to common systemic side effects of bevacizumab, there are rare cases of cranial nerve palsy. CASE REPORT: We report a case of transient oculomotor nerve palsy after systemic administration of bevacizumab. Twenty-four hours after the systemic infusion of bevacizumab, transient oculomotor nerve palsy developed in a 49-year-old male patient. In the cranial MRI, there was no malignancy-related progression. MANAGEMENT AND OUTCOME: Bevacizumab treatment was discontinued. Methylprednisolone was started considering that bevacizumab increased the inflammatory response. Oculomotor nerve palsy resolved in 14 days. DISCUSSION: There are many side effects of bevacizumab whose mechanisms of action have not been fully explained. Cranial nerve involvement is rarely reported. Our case is the first reported case of bevacizumab-induced oculomotor nerve palsy.

The demographic characteristics, prognosis, and relationship with cancer subtypes of hospitalized COVID-19 patients with malignancy: A single-center experience.

Undoubtedly, cancer patients have suffered the most from the COVID-19 pandemic process. However, cancer is a heterogeneous disease, and each patient has responded differently to COVID-19. We aimed to describe the clinical characteristics and outcomes of patients with cancer and COVID-19. We retrospectively reviewed 45 cancer patients hospitalized in the Cerrahpasa Medical Faculty COVID-19 department from March 23 to October 23, 2020. We analyzed the demographic characteristics, symptoms, laboratory findings, treatment, prognosis, and cancer subtypes of patients and mortality who were hospitalized for COVID-19. Between March 23 and October 23, 2020, 45 hospitalized cancer patients who had laboratory-confirmed COVID-19 infection were included, with a median age of 60 years (range: 23-92). Patients were divided into two groups a survivor and a non-survivor. Symptoms, demographic information, comorbidities, treatments for COVID-19, and laboratory findings of the two groups were evaluated separately. Two parameters were found, which showed a significant difference between non-survivors and survivors displaying a disadvantage for COPD and low platelet count (p = 0.044-0.038). The mortality rate of all patients was 66%. The presence of comorbidities such as COPD and low platelet count in cancer patients with COVID-19 infection may draw the attention of physicians.

Classical versus non-classical EGFR mutations: Erlotinib response and impact of renal insufficiency.

INTRODUCTION: Erlotinib is an effective treatment option for EGFR-mutant non-small cell lung cancer. It is important to predict patients who will respond better to erlotinib. We designed this study to investigate the effect of renal insufficiency (RI) on erlotinib treatment outcomes. METHODS: All patients receiving erlotinib were stratified into 3 groups. Group 1 consisted of non-RI subjects with classical epidermal growth factor receptor (EGFR) mutations, Group 2 consisted of those with RI (Estimated glomerular filtration rate <60 mL/min) and classical EGFR mutations, and Group 3 consisted of those with non-classical EGFR mutations. RESULTS: 82 patients were included in the study. Median progression-free survival (PFS) in patients with classical mutation was approximately 6 months shorter in those with RI, although not statistically significant. Median overall survival (OS) in Group 1, 2 and 3 was 34.1 months, 35.2 months, and 15 months, respectively and although not statistically significant, median OS was 20 months shorter in Group 3. Univariate and multivariate cox-regression analysis revealed shorter PFS and OS in males and those with ECOG ≥2 while PFS and OS were longer in those with recurrent lung tumors and generating rash during erlotinib treatment. There was no difference between RI and non-RI patients in terms of adverse events except for fatigue and appetite loss. CONCLUSIONS: This research showed OS in patients with and without RI was comparable. Although not statistically significant, PFS in patients with classical mutation was approximately 6 months shorter in those with RI patients.

Immune-related adverse events associated with immune checkpoint inhibitors in patients with cancer.

INTRODUCTION: With the widespread use of immune checkpoint inhibitors (ICIs), we are facing challenges in the management of immune-related adverse events (irAEs). We aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs. METHODS: Patients who were treated with at least one ICI in clinical trials, expanded access programs, or routine clinical practice were included. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, methods of management, and treatment outcomes. RESULTS: A total of 255 patients were screened retrospectively. Of these, 71 (27.8%) patients developed irAEs. More than 2 different types of irAEs were detected in 16 (6.2%) out of 255 patients. A total of 3177 doses were given to 255 patients. In 93 (2.9%) of the 3177 doses, 1 episode of irAEs was experienced. A total of 22 out of 93 (23.7%) episodes were reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most frequently seen irAEs were pneumonitis, hepatitis, and hypothyroidism. With regard to treatment, 39 out of 93 episodes (42%) of any grade irAEs occurred after anti-programmed cell death-1 therapy, 47 (50.5%) occurred following administration of anti-programmed death-ligand 1, and 7 (7.5%) occurred after combination treatments. CONCLUSION: With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology.

Loss of skeletal muscle area and fat-free mass during dabrafenib/trametinib and vemurafenib/cobimetinib treatments in patients with BRAF-mutant metastatic malignant melanoma.

This study aimed to assess whether dabrafenib/trametinib and vemurafenib/cobimetinib treatments are associated with a change in skeletal muscle area (SMA) and total fat-free mass (FFM) assessed by computed tomography (CT), and to compare the efficacy and safety profile of these treatments in patients with metastatic melanoma. Thirty-one patients treated with B-Raf proto-oncogene, serine/threonine kinase/MAPK extracellular receptor kinase inhibitors were included between 2016 and 2019. Eighteen patients received dabrafenib/trametinib and remaining patients received vemurafenib/cobimetinib. CT scans were performed at baseline and at 4-6 months of follow-up to measure cross-sectional areas of SMA. FFM and skeletal muscle index (SMI) values were calculated. Of the patients, including 18 treated with dabrafenib/trametinib (58.1%) and 13 with vemurafenib/cobimetinib (41.9%); 58.1% were male, 41.9% were female and median age was 52 years. A significant decrease in SMA was observed after dabrafenib/trametinib and vemurafenib/cobimetinib treatments (P = 0.003 and P = 0.002, respectively). A significant decrease in FFM values was observed after dabrafenib/trametinib and vemurafenib/cobimetinib treatments (P = 0.003 and P = 0.002, respectively). Dose-limiting toxicity (DLT) was observed in 35.9% of the patients with sarcopenia. No significant difference was seen between the dabrafenib/trametinib and vemurafenib/cobimetinib groups in median progression-free survival (PFS) (11.9 vs. 7.3 months, respectively, P = 0.28) and in median overall survival (OS) (25.46 vs. 13.7 months, respectively, P = 0.41). Baseline sarcopenia was not significantly associated with PFS or OS (P = 0.172 and P = 0.326, respectively). We found a significant decrease in SMI values determined at 4-6 months compared to the values before treatment both in dabrafenib/trametinib and vemurafenib/cobimetinib groups. DLT was similar with both treatments. Baseline sarcopenia was not significantly associated with PFS or OS.

Impact of neutrophil-lymphocyte and platelet-lymphocyte ratio on antiEGFR and bevacizumab efficacy in metastatic colorectal cancer.

PURPOSE: The purpose of this study was to determine the influence of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) on antiEGFR and bevacizumab efficacy in metastatic colorectal cancer patients. METHODS: All metastatic colorectal cancer patients who had received chemotherapy and biological agents as first-line treatment at Erciyes University Hospital were retrospectively reviewed. NLR and PLR were each divided into two groups, as high and low. The NLR high group was compared with the low group and the PLR high group was compared with the low group in patients in terms of progression-free survival (PFS) and overall survival (OS), separately. Cox regression and the Kaplan Meier method were used. RESULTS: One hundred and thirty (58%) of the patients had received bevacizumab and 94 (42%) had received antiEGFR therapy (cetuximab or panitumumab). In the bevacizumab group, PFS was 9 months in the NLR high group and 11 months in the NLR low group (p=0.013). OS was 23 months in the NLR high group and 27 months in the NLR low group (p=0.734). There was no statistically significant OS difference in patients who had received antiEGFR therapy according to NLR. There was no statistically significant PFS difference in patients who received bevacizumab according to PLR. In the antiEGFR group, PFS was 9 months (95% CI, 8.07-13.55) in the PLR high group and 18 months (95% CI, 12.02-18.68) in the PLR low group, with statistically significant difference (p=0.040). There was no statistically significant OS difference in patients who had received antiEGFR therapy according to PLR. CONCLUSIONS: NLR and PLR are important inflammatory markers. In patients who had received bevacizumab, PFS was longer in the NLR low group than in the high group. In patients who had received antiEGFR, PFS was longer in the PLR low group than in the high group.

Biweekly cisplatin and gemcitabine with two different doses in non small cell lung cancer patients: A retrospective singlecenter experience.

PURPOSE: Non-small-cell lung cancer (NSCLC) constitutes 80-85% of all lung cancers. Patients with advanced-stage NSCLC may benefit from chemotherapy. Gemcitabine and cisplatin is a well-established therapy for this malignancy. Recently, biweekly administration is becoming more acceptable, but the most effective and tolerable dose remains unclear. The purpose of this study was to compare the toxicity and efficacy of 1000 mg/m2 gemcitabine (GEM 1000) and 1500 mg/m2 gemcitabine (GEM 1500) in combination with 50 mg/m2 cisplatin. METHODS: Gemcitabine was administered at a dose of 1000 or 1500 mg/m2 with cisplatin administered at a dose of 50 mg/m2 on day 1. The treatment was repeated every 2 weeks for a total of 4 courses. Response rates, progression-free survival (PFS), overall survival (OS) and toxicities were assessed. RESULTS: 114 patients with IIIB and IV stages of NSCLC were included. Seventy two patients (63%) received GEM 1000 and 42 (37%) received GEM 1500. The overall reponse rate (ORR), PFS and OS were 24%, 6 months and 13 months respectively in the GEM 1000 group and 36%, 6 months and 15 months in the GEM 1500 group, respectively. Grade 3-4 neutropenia and thrombocytopenia were observed in 4% of the GEM 1000 group and 9% of the GEM 1500 group (p=0.41). CONCLUSION: Biweekly administration of GEM 1000 and 1500 is a well tolerated regimen. Although the GEM 1000 group showed a lower response rate than the GEM 1500 group, PFS and OS were similar.