Intra and peritumoral PET radiomics analysis to predict the pathological response in breast cancer patients receiving neoadjuvant chemotherapy.

OBJECTIVE: The aim of our study was to evaluate the contribution of 18Fluorine-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) radiomic data obtained from both the tumoral and peritumoral area in predicting pathological complete response (pCR) in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). METHODS: Female patients with a diagnosis of invasive ductal carcinoma who received NAC were evaluated retrospectively. The volume of interest (VOI) of the primary tumor (VOI-T) was manually segmented, then a voxel-thick VOI was added around VOI-T to define the peritumoral area (VOI-PT). Morphological, intensity-based, histogram and texture parameters were obtained from VOIs. The patients were divided into two groups as pCR and non-complete pathological response (npCR). A "radiomic model" was created with only radiomic features, and a "patho-radiomic model" was created using radiomic features and immunohistochemical data. RESULTS: Of the 66 patients included in the study, 21 were in the pCR group. The only statistically significant feature from the primary tumor among patients with pCR and npCR was Morphological_Compacity-T (AUC: 0.666). Between response groups, a significant difference was detected in 2 morphological, 1 intensity, 4 texture features from VOI-PT; no correlation was found between Morphological_Compacity-PT and NGTDM_contrast-PT. The obtained radiomic model's sensitivity and accuracy values were calculated as 61.9% and 75.8%, respectively (AUC: 0.786). When HER2 status was added, sensitivity and accuracy values of the patho-radiomic model increased to 85.7% and 81.8%, respectively (AUC: 0.903). CONCLUSIONS: Evaluation of PET peritumoral radiomic features together with the primary tumor, rather than just the primary tumor, provides a better prediction of the pCR to NAC in patients with breast cancer.

The comparison of functional status and health-related parameters in ovarian cancer survivors with healthy controls.

PURPOSE: The primary purpose of this study was to evaluate functional status and health-related parameters in ovarian cancer (OC) survivors and to compare these parameters with healthy controls. The secondary purpose of this study was to compare these parameters in early and advanced OC survivors. METHODS: Thirty-two OC survivors (n = 15 early stage; n = 17 advanced stage) with no evidence/suspicion of cancer recurrence after completing adjuvant local and systemic treatments for at least 12 months and 32 healthy controls were recruited for functional- and health-related assessments. Participants were assessed using the following methods of measuring the following: 6-min walk test (6MWT) for functional exercise capacity, 30-s chair stand test (30 s-CST) for functional fitness and muscle endurance, a handheld dynamometer for peripheral muscle strength, and a handheld dynamometer for lower extremity strength, Medical Micro RPM for respiratory muscle strength, International Physical Activity Questionnaire-Short Form (IPAQ-SF) for physical activity level, and Eastern Cooperative Oncology Group Performance Scale (ECOG-PS) for performance status, Checklist Individual Strength (CIS) for fatigue, Treatment/Gynecological Oncology-Neurotoxicity (FACT/GOG-NTX) for neuropathy, the Hospital Anxiety and Depression Scale (HADS) for anxiety and depression level, and the World Health Organization-Five Well-Being Index (WHO-5) for generic quality of life. RESULTS: All OC survivors underwent surgery and chemotherapy, and only 9.4% received radiotherapy in addition to chemotherapy. The median recurrence-free period post-completion of adjuvant treatments was 24.00 (12.00-75.00) months. OC survivors had lower 6MWT (m) (p < 0.001, r = 1.50), peripheral muscle strength (p = 0.005, r = 0.72), knee extension (p < 0.001, r = 1.54), and respiratory muscle strength (maximal inspiratory pressure) (p < 0.001, r = 1.90) (maximal expiratory pressure) (p < 0.001, r = 1.68) compared to healthy controls. HADS-A (p = 0.005, r = 0.75) and CIS scores (p = 0.025, r = 0.59) were also higher in the OC survivors. Early-stage OC survivors had better 6MWT (m) than advanced-stage OC survivors (p = 0.005, r = 1.83). Peripheral muscle strength was lower in advanced-stage OC survivors (p = 0.013, r = 0.92). FACT/GOG-NTX scores were higher in early-stage OC survivors (p < 0.001, r = 1.42). No significant differences were observed between early- and advanced-stage OC survivors in other measures (p < 0.05). CONCLUSION: The findings suggest functional status, and health-related parameters are negatively affected in OC survivors. Additionally, higher levels of fatigue, neuropathy anxiety, and depression were reported in advanced OC survivors.

The Relationship between Exercise Capacity and Muscle Strength, Physical Activity, Fatigue and Quality of Life in Patients with Cancer Cachexia.

BACKGROUND: Exercise capacity is a significant determinant of mortality for cancer patients, so knowing the possible determinants of exercise capacity will produce physical and psychological benefits for individuals with cancer cachexia. PURPOSE: To investigate the relationship between exercise capacity on peripheric and respiratory muscle strength, physical activity, fatigue and quality of life in subjects with cancer cachexia. METHODS: The study included 31 patients diagnosed with cancer cachexia. Functional capacity was assessed by 6-Minute Walk Test, hand grip strength and proximal muscle mass by hand dynamometer, respiratory muscle strength by the Maximum Expiratory Pressure and Maximum Inspiratory Pressure measurements, physical activity by International Physical Activity Questionnaire Short Form, fatigue by Brief Fatigue Inventory, and quality of life by EORT-QLQ-C30. The relationship between functional capacity and continuous independent variables was determined using Spearman's or Pearson's tests. RESULTS: A strong positive correlation was observed between exercise capacity and expiratory muscle strength (r = 0.75, p < 0.001), activity level (r = 0.68, p < 0.001), and quality of life global health status (r = 0.74, p < 0.001). Conversely, a strong negative correlation was found between exercise capacity and fatigue severity (r = -0.64, p < 0.001). CONCLUSION: Higher exercise capacity in cancer cachexia patients is linked to reduced fatigue, improved respiratory muscle strength, increased physical activity levels, and enhanced quality of life. When designing rehabilitation programs or exercise interventions for individuals with cancer cachexia, it is crucial to assess their exercise capacity and tailor the programs accordingly.

Real-world outcomes of pazopanib in metastatic soft tissue sarcoma: a retrospective Turkish oncology group (TOG) study.

AIM: Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). PATIENTS AND METHODS: This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. RESULTS: Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively. CONCLUSION: Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.

Oncological efficiency of wide local excision in dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a slow-growing, low- to intermediate-grade malignant sarcoma. Its optimal treatment is resection with wide margins; the likelihood of local control associated with this procedure exceeds 90%. The probability of regional or distant metastases is <5%. OBJECTIVE: We examined the clinical, epidemiological, and pathological features, the treatment types, and outcomes of patients to investigate the width of safe surgical margins (SM) and how the width of SMs affected recurrence in DFSP. METHODS: We retrospectively examined the records of 60 patients who were initially operated on with wide local excision for DFSP in the period 2008-2019. Optimal cutoff points for SMs were calculated with the receiver operating characteristic curve analysis and found as 1.925 cm histopathologically and 2.26 cm macroscopically. RESULTS: During the mean 89.6-month follow-up, local recurrence was seen in 36.7% and distant metastasis in 20% of the patients. Recurrences were significantly related to peripheral resection margins. Analysis by histopathologic cutoff points showed that the local recurrence rate was 84% when SM was ≤1.925 cm, but only 2.85% when >1.925 cm (p = 0.002). Recurrence-free survival was 40.92 months when SM was ≤1.925 cm and 225.75 months when s >1.925 cm (p<0.001). Analysis by macroscopic cutoff points showed that the local recurrence rate was 95.5% when SM was ≤2.26 cm, but only 4% when >2.26 cm (p = 0.001). Recurrence-free survival was 43 months when SM was ≤2.26 cm and 222 months when >2.26 cm (p<0.001). In metastatic patients, progression-free survival was 9 months with cytotoxic chemotherapy, whereas 38.4 months with tyrosine kinase inhibitor (imatinib) (p = 0.002). CONCLUSION: This study showed SMs >2.5 cm to be sufficiently safe for WLE and optimized the balance among safe margin width, reconstruction need, and surgical morbidity. In metastatic DFSP patients, tyrosine kinase inhibitor imatinib is more effective than cytotoxic chemotherapy for progression-free survival.

Genetic, Surgical and Oncological Approach to Breast Cancer, with BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53 Variants.

Objective: The aim of this study was to determine the frequency of germline variants in BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53 in patients admitted to a medical genetics clinic with breast cancer and to assess these identified variants according to published genetic, surgical and oncological perspectives. Materials and Methods: Medical history, and cancer diagnosis information for 195 independent probands with operated breast cancer were collected from requisition forms and medical records. The exonic regions and exon-intron junctions in BRCA1, BRCA2, CDH1, PALB2, PTEN and TP53 genes were sequenced. Analysis of fastq files was performed on the Qiagen Clinical Insight-Analyse Universal with panel-specific pipeline and vcf files were interpreted clinically using Qiagen Clinical Insight-Interpret. Results: Gene variants (pathogenic, likely pathogenic and variants of unknown significance) were detected in 53 (27.2%). Detailed information about the patients (age of diagnosis, family history, gender), cancer stage, tumour characteristics (ER, PR, human epidermal growth factor receptor 2 status) and all information related to the detected variants (gene, location, nucleotide and amino acid change, exon number, impact, mutation classification, dbSNP number and HGMD variant class) were assessed. In total, 58 mutations were identified including 14 novel, previously unreported variants. Conclusion: Molecular characterization and identification of mutations have important implications for predictive, preventive, and personalized medicine, including genetic counseling and development of specific treatment protocols. We emphasize variants of unknown significance (VUS) as the clinical significance of VUS changes over time and variant classification is important for clinical molecular genetic testing and clinical guidance. This study may provide new insights into risk assessment for variants in CDH1, PALB2, PTEN and TP53, in addition to BRCA1 and BRCA2, which may prove useful for clinical management of breast cancer patients. Further studies are needed to identify the common gene variants in the Turkish population and evaluate the pathogenity of VUS.

HALP score and GNRI: Simple and easily accessible indexes for predicting prognosis in advanced stage NSCLC patients. The Izmir oncology group (IZOG) study.

Objective: The Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score and the Geriatric Nutrition Risk Index (GNRI) are used as prognostic factors in different types of cancers. In this study we analyzed the prognostic value of the HALP Score and the GNRI calculated prior to first-line treatment in patients diagnosed with de novo metastatic non-small cell lung cancer (mNSCLC). Materials and methods: De novo mNSCLC patients were retrospectively evaluated from January 2016 to December 2019. Patients with Driver's mutation, severe comorbidities, active infection, or insufficient organ function, and those receiving anti-inflammatory treatment were excluded from the study. Optimal cut-off points for the HALP score and the GNRI were calculated with the receiver operating characteristic (ROC) curve analysis. Predictive factors for overall survival (OS) were assessed with univariate and multivariate Cox proportional hazard analyses, and OS was studied with the Kaplan-Meier analysis. Results: The study included 401 patients in total. In the ROC curve analysis, the cut-off points were found 23.24 (AUC = 0.928; 95% CI: 0.901-0.955, p < 0.001) for HALP, and 53.60 (AUC = 0.932; 95% CI: 0.908-0.955, p < 0.001) for GNRI. Groups with lower HALP scores and lower GNRI had significantly shorter OS compared to those with higher HALP scores and GNRIs. Univariate analysis showed that male gender, smoking, high ECOG score, low HALP score and low GNRI were associated with worse survival rates. Multivariate analysis showed that low HALP score (HR = 2.988, 95% CI: 2.065-4.324, p < 0.001); low GNRI score (HR = 2.901, 95% CI: 2.045-4.114, p < 0.001) and smoking history (HR = 1.447, 95% CI: 1.046-2.001, p = 0.025) were independent factors associated with worse OS rates. Conclusion: Our study showed the HALP score and the GNRI to be of prognostic value as simple, cost-effective, and useful markers that predict OS in de novo mNSCLC patients.

GNRI And Conut Scores: Simple Predictors of Sarcopenia in Metastatic Colorectal Cancer Patients.

OBJECTIVE: To evaluate the correlation between sarcopenia and inflammation- and nutrition-based markers in metastatic colorectal cancer (mCRC) patients. MATERIALS AND METHODS: Age, body mass index (BMI), neutrophil/lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), prognostic nutrition index (PNI), cachexia index (CIn), skeletal muscle index (SMI), controlling nutritional status (CONUT) score, and geriatric nutritional risk index (GNRI) were evaluated in 185 patients. Ideal cut-off values for the GNRI score were determined with the ROC curve analysis, and the patients were divided into two groups as low and high GNRI. Sarcopenia was diagnosed using CT scanning, the gold standard method. Univariate and multivariate Cox proportional hazard analyses were done based on the above-listed parameters to assess the correlation between sarcopenia and changes in immuno-nutrition and inflammatory response. Kaplan-Meier analysis was also done to evaluate survival. RESULTS: Univariate analysis of the 185 patients based on the EGWSOP 2018 threshold values showed correlation between the presence of sarcopenia and male gender, diagnosed colon cancer, history of metastasectomy, BMI < 24, high mGPS score, PNI score ≥ 45, high CONUT score, and low GNRI score (p < 0.05). In multivariate analysis, low GNRI (HR: 2.40; 95% CI: 1.03-5.544; p = 0.040), and high-CONUT scores (HR: 2.01; 95% CI: 1.06-3.73; p = 0.029) were identified as independent prognostic factors for the presence of sarcopenia. CONCLUSION: GNRI and CONUT scores are elementary and practical predictors for sarcopenia, a condition which is associated with poor outcomes in mCRC patients.

The relationship between sarcopenia detected in newly diagnosed colorectal cancer patients and FGF21, irisin and CRP levels.

AIM: Sarcopenia is a progressive and generalized syndrome that can be linked to many causes such as cancers, and is caused by a quantitative and qualitative disorder (loss of muscle strength and/or physical performance) of skeletal muscle mass. Although sarcopenia has some hypothetical explanation in clinical practice, the mechanisms underlying this condition have not been clearly differentiated in patients with cancer. We aimed to investigate the relationship between irisin, FGF21 and CRP in detecting sarcopenia in colorectal cancer patients. MATERIAL AND METHODS: Current prospectively study included non-metastatic newly diagnosed colorectal cancer patients. Patients were divided into 2 groups of 25 people, those with and without sarcopenia. Body composition measurements by examined by BIA. To measure the level of iris and FGF21 from patients, blood samples were taken into the biochemistry tube and their levels were measured. RESULTS: The median age of the patients included in the study was 60 years (range: 21-81), 68% were men. It was found that there was a significant relationship between sarcopenia and gender and BMI measurement. When Spearman correlation analysis was performed between skeletal muscle mass index and FGF21, irisin and CRP, there was a positive correlation between skeletal muscle mass index and irisin and FGF21, while there was a negative correlation between skeletal muscle mass index and CRP. [respectively: (r: 0.282, p: 0.048), (r: 0.564, p: < 0.001) and (r: - 0.360, p: 0.010)]. Similar results were found between hand-grip strength and FGF21, irisin and CRP. [respectively: (r: 0.342, p: 0.015), (r: 0.290, p: 0.041) and (r: - 0.476, p < 0.001)]. When sarcopenia was treated as the dependent variable in the logistic regression analysis, and FGF21, irisin, CRP, gender and BMI were treated as the independent variables, irisin and CRP levels were determined as independent predictors. CONCLUSION: This study was revealed that there is a negative relationship between sarcopenia and irisin and FGF-21 in operated non-metastatic colorectal cancer patients and there may be a relationship between sarcopenia and inflammation. It suggests that these biomarkers may play a role in the pathophysiology of sarcopenia. However, our results need to be validated in different types of cancer and with more patients.

Predicting pathological response and overall survival in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy: the role of PET/computed tomography.

BACKGROUND: Gastric cancer is the second leading cause of cancer-related deaths, with a 5-year survival rate of about 20-25%. The ability to predict pathological response (PR) to neoadjuvant chemotherapy (NACT); hence, overall survival (OS) probability of patients can allow the clinician to individualize treatment strategies. We investigated the role of F-18 fluorodeoxyglucose PET-computed tomography (F-18 FDG PET/CT) in predicting histopathologic response and prognosis in locally advanced gastric cancer (LAGC) patients undergoing NACT. METHODS: F-18FDG PET/CT images taken before and after NACT, adenocarcinoma histopathology and operation pyesis reports of 43 LAGC patients were analyzed. Maximum (SUVmax) and mean (SUVmean) standardized uptake values, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of lesions were measured before and after NACT. Changes in percentage were calculated for ΔSUVmax%, ΔSUVmean%, ΔMTV%, ΔTLG%, and cutoff values were determined by receiver operating characteristic curve analysis. NACT response in pathology pyesis was determined according to the College of American Pathologists classification. PR and OS were analyzed with Kaplan-Meier and Cox proportional hazards regression models based on cutoffs found with PET measurements. RESULTS: Cutoffs were ΔSUVmax = 33.31%, ΔSUVmean = 42.96%, ΔMTV = 30.38%, and ΔTLG = 28.14%, and all patients showed significance in PR and OS based on these cutoffs (all P < 0.01). PET/CT findings before and after NACT (ΔMTV > 30.38%, ΔTLG > 28.14%) predicted PR with 100% sensitivity and specificity. Multivariate analysis showed ΔSUVmean as an independent risk factor predicting OS (hazard ratio 0.348, 95% confidence interval 2.91-22.3, P = 0.03). CONCLUSIONS: Metabolic parameters obtained with F-18 FDG PET/CT scanning before and after NACT in LAGC patients can accurately predict PR and OS.

Being a Cancer Patient during the Time of COVID-19: Impact of the Pandemic on the Anxiety and the Sleeping Quality of Oncology Patients.

OBJECTIVE: In this study, we aimed to assess anxiety and sleep quality in cancer patients treated or followed up at our clinic at the time of the outbreak of the COVID-19 pandemic. METHODS: Seven hundred and sixty-one patients who were either treated or followed up at our oncology clinic between April 2020 and May 2020 were included. Patients were assessed with the State-Trait Anxiety Inventory (STAI) and the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Mean scores of the 761 participants were STAI, 43.45 ± 9.34 (range, 23-75), and PSQI, 5.67 ± 4.24 (range, 0-19). Quality of sleep was found bad in 447 (58.7%) (global score ≥5). Univariate analyses demonstrated statistical differences by stage of cancer, status of treatment, subgroup of treatment, monthly income, and levels of education in anxiety and sleep quality levels. Multivariate analyses showed active treatment (OR: 21.4; 95% CI: 9.08-50.4; p < 0.001) as the major independent variable that affected sleep quality; the major independent variable associated with anxiety was low income (OR: 4.43; 95% CI: 1.69-11.5; p = 0.002). CONCLUSION: Anxiety and sleep quality levels were found comparable to pre-pandemic reports, and the pandemic was not observed to have additional negative impact on cancer patients. Also, universal basal anxiety and sleep disorder that accompany cancer or active treatment were observed in our study. The accurate effects of the pandemic can be analyzed in further studies using repeated data obtained from the same patient group.

Worse patient-physician relationship is associated with more fear of cancer recurrence (Deimos Study): A study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

OBJECTIVE: Fear of cancer recurrence (FCR) is an important psychological trauma associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study was to evaluate the impact of patient-physician relationship on FCR. METHODS: The study was designed as a multicentre survey study. The cancer survivors, who were under remission, were evaluated with structured questionnaires. Patient-physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory was used. RESULTS: Between January and April 2019, 1,580 patients were evaluated. The median age was 57.0 (19-88), and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r = -.134, p < .001). In multivariate analysis, young age, female gender, history of metastasectomy and worse PPR were associated with high levels of FCR. CONCLUSION: It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practised. In addition, the cancer survivors, who are under the risk of FCR, should be evaluated and managed.

Breast cancer survivors suffer from persistent postmastectomy pain syndrome and posttraumatic stress disorder (ORTHUS study): a study of the palliative care working committee of the Turkish Oncology Group (TOG).

PURPOSE: Persistent postmastectomy pain syndrome (PMPS) is one of the most important disturbing symptoms. Posttraumatic stress disorder (PTSD) is an anxiety disorder which is characterized by reactions to reminders of the trauma that has been experienced. The purpose of this study is to evaluate the predictors of PMPS and PTSD in Turkish breast cancer survivors and the correlation between PMPS and PTSD. METHOD: The study is designed as a multicenter survey study. Breast cancer patients in remission were evaluated. Patients were evaluated with structured questionnaires to assess the PMPS and clinical parameters associated with it. The Turkish version of the posttraumatic stress disorder checklist-civilian version (PCL-C) was used. RESULTS: Between February 2015 and October 2015, 614 breast cancer survivors in outpatient clinics were evaluated. The incidence of PMPS documented is 45.1 %. In the multivariate analysis low income, presence of PTSD and <46 months after surgery were associated with increased risk of PMPS. PTSD was documented in 75 %, and the mean PCL-C score was 32.4 ± 11.1. PMPS and being married at the time of the evaluation were linked with PTSD. CONCLUSIONS: It is the first data about the association between PMPS and PTSD. The clinicians should be aware of PMPS and PTSD in breast cancer survivors.