Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

Trastuzumab ± Capecitabine Maintenance After the First-Line Treatment of HER2-Positive Advanced Gastric Cancer: Retrospective Observational Real-Life Data of Turkish Oncology Group.

PURPOSE: In the ToGA trial for HER2-positive advanced gastric cancer, cisplatin plus fluoropyrimidine was given for 6 cycles; trastuzumab was given until disease progression. However, there is a lack of real-life data about trastuzumab maintenance after 6 cycle chemotherapy. This study aims to present real-life data of trastuzumab ± capecitabine maintenance after 6 cycles of platinum, fluoropyrimidine, and trastuzumab in non-progressive patients. METHODS: This is a retrospective multicenter study of the Turkish Oncology Group. A total of 35 HER2-positive, inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma patients being non-progressive at the end of 6 cycle chemotherapy and being given trastuzumab ± capecitabine as maintenance treatment were included from sixteen oncology centers. Baseline characteristics, objective tumor responses, progression free and overall survival data, and toxicities were determined. RESULTS: About 68% of the patients were given CF, and 32% were given FOLFOX with trastuzumab as the first-line treatment. The best response in 6 cycle chemotherapy was complete 8 (22%), partial 24 (68%), and stable disease 3 (8%). All patients had trastuzumab maintenance (median cycle 13; range 7-51), and 49% of the patients had capecitabine with trastuzumab (median capecitabine cycle 6; range 2-30). The median PFS of the patients was 12.0 months (95% CI 10.3-13.7), and median OS was 17.4 months (95% CI 15.2-19.5). There were 2 patients with grade 1 cardiotoxicity. CONCLUSION: Trastuzumab maintenance ± capecitabine after 6 cycles of trastuzumab plus combined chemotherapy treatment revealed efficacy and safety in non-progressive HER2-positive advanced gastric cancer.

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study.

PURPOSE: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. METHODS: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. RESULTS: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). CONCLUSION: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

Identifying Knowledge and Practices regarding Cancer Patient Malnutrition: A Survey Study among Oncologists.

Malnutrition is one of the most common complications of cancer and its treatments with a prevalence of up to 80% among cancer patients. Thus, standardized and target-oriented attitudes of oncologists toward nutritional management are particularly important. This study aims to report the questionnaire-based evaluation of different views toward medical nutrition among medical and radiation oncologists with the purpose to underline the problems and requirements of cancer nutrition. A national web-based survey composed of 26 multiple choice questions about participant demographics, level of knowledge about cancer nutrition, and approaches to malnutrition were completed by 247 oncologists. The survey was answered by a total of 247 (34%) radiation and medical oncologists. The majority of the oncologists (77%) were working at the University Hospitals and Education & Research Hospitals. Most of them were specialists with 5-10 years of experience. Nutritional status was routinely assessed in oncology units of 84% of (206) oncologists. However, only 50% reported nutritional evaluation follow-ups without waiting for a patient's declaration and 5 (2%) oncologists reported the absence of nutritional evaluation in their unit. Additionally, more than 79% of participants reported that their knowledge was not enough about enteral and parenteral nutrition while 8% were skeptical about the benefits of medical nutrition. Although the role of nutrition as an essential part of cancer care is widely recognized, the availability of limited high-quality evidence, problems of accessibility, lack of routine nutritional evaluation, and varying indicators for malnutrition are some of the problems preventing standardized nutritional management. Therefore, there are a variety of approaches and barriers to the implementation of guidelines. Further studies are needed to identify areas of improvement, as well as strategies to implement nutritional therapy in cancer care.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Real-life comparison of the afatinib and first-generation tyrosine kinase inhibitors in nonsmall cell lung cancer harboring EGFR exon 19 deletion: a Turk Oncology Group (TOG) study.

BACKGROUND: The new second-generation tyrosine kinase inhibitors (TKIs) have superior survival outcome and worse toxicity profile when compared with first-generation TKIs according to the results of clinical trials. However, there are limited studies that investigate the efficacy and safety of the new generation TKIs in real-world patients. Thus, we aimed to compare the efficacy and safety of the afatinib, an irreversible inhibitor of ErbB family receptor, and first-generation TKIs in real-world patients. MATERIALS AND METHODS: We included advanced nonsmall cell lung cancer (NSCLC) patients who had EGFR exon 19del mutation and treated with afatinib or first-generation TKIs as upfront treatment between 2016 and 2020. All patient's information was collected retrospectively. The study cohort was divided as afatinib arm and erlotinib/gefitinib arm. RESULTS: A total of 283 patients at the 24 oncology centers were included. The 89 and 193 of whom were treated with afatinib and erlotinib/gefitinib, respectively. After 12.9 months (mo) of follow-up, the median PFS was statistically longer in the afatinib arm than erlotinib/gefitinib arm (19.3 mo vs. 11.9 mo, p: 0.046) and the survival advantage was more profound in younger patients (< 65 years). The 24-mo overall survival rate was 76.1% and 49.5% in the afatinib arm and erlotinib/gefitinib arm, respectively. Although all-grade adverse event (AE) rates were similar between the two arms, grade 3-4 AE rates were higher in the afatinib arm (30.7% vs. 15.2%; p: 0.004). DISCUSSION: In our real-world study, afatinib has superior survival outcomes despite worse toxicity profile as inconsistent with clinical study results and it is the good upfront treatment option for younger patients and elderly patients who have good performance status.

Combination of trastuzumab and taxane-containing intensified chemotherapy in first-line treatment of HER2-positive advanced gastric cancer.

PURPOSE: Taxane-containing combinations are recommended for the first-line therapy of advanced gastric cancer. It is not known which chemotherapy regimen is the best with trastuzumab for HER2-positive patients. The aim of this study was to compare taxane-containing intensified chemotherapy versus standard chemotherapy in combination with trastuzumab in the first-line treatment of HER2-positive advanced gastric adenocarcinoma. METHODS: This study is a retrospective multicenter study of the Turkish Oncology Group. A total of 130 HER2-positive patients with inoperable locally advanced, recurrent, or metastatic gastric adenocarcinoma being given chemotherapy plus trastuzumab as the first-line treatment were included from 16 different oncology centers. Trastuzumab combination with intensified chemotherapy including taxane or standard chemotherapy was compared in terms of progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: There were 108 patients in the standard and 22 patients in the intensified chemotherapy group. PFS of the standard and intensified group were 5.6 months (95% confidence interval [CI] 4.8-6.4) and 5.3 months (95% CI 2.6-8), respectively (p = 0.70). OS of the standard and intensified group were 11.1 months (95% CI 8.3-13.9) and 15.2 months (95% CI 12.7-17.7), respectively (p = 0.03). Repeated analysis excluding patients given any previous therapy revealed similar results. The intensified group had more fever and febrile neutropenia. CONCLUSION: Trastuzumab combination with intensified chemotherapy provides better OS in first-line treatment of HER2-positive advanced gastric cancer. Further large-scale studies should be performed in HER2-positive patients.

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.

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

The impact of total neo-adjuvant treatment on nonoperative management in patients with locally advanced rectal cancer: The evaluation of 66 cases.

BACKGROUND: The study aimed to assess if adherence to a total-neoadjuvant-treatment (TNT) protocol followed by observation(watch-and-wait) led to the successful nonoperative-management of low-rectal-cancer. METHODS: In this study, patients with primary, resectable-T3-T4, N0-N1 distal-rectal-adenocarcinoma underwent-chemoradiotherapy + consolidation-chemotherapy (TNT). During the-TNT-period, endoscopy, MRI, and FDG-PET/CT were performed. We allocated patients with complete-clinical-tumor-regression, who underwent endoscopy every two months, MRI every-four-months, and PET/CT every-six-months-after-treatment, to the observation-group(OG). All other patients were referred for surgery. The OG was followed-up. The primary endpoint was local tumor-ecurrence after allocation to the OG. RESULTS: Between 2015 and 2018, we enrolled 66-patients. Of 60-patients who were eligible to participate, 39 had complete-clinical-response(cCR) and were allocated to the OG, six underwent local-excision (LE), and 15 underwent total-mesorectal-excision (TME). The median follow-up duration was 22 (9-42) months. The local-recurrence-rate in the OG was 15.3%, and the LE and TME rates were 16.6% and 0%, respectively. All recurrence cases were salvaged through either LE or TME. The-distant-metastasis rate was 5.1%, 16.6%, and 12.5% in the OG, LE, and TME groups, respectively. The endoscopic negative-predictive-value(NPV) was 50%, and the positive-predictive-value(PPV) was 76.9% in the surgery group (LE + TME). MRI; NPV-50%, PPV-76.9%. PET/CT; NPV-100%, PPV-93.3%. Six patients(28.57%) from surgery group achieved complete pathological response (cPR). CONCLUSION: Our results indicated a high proportion of selected-rectal-cancers with-cCR after neo-adjuvant-therapy could potentially be managed non-operatively, and major surgery may be avoided.

Tumor budding for predicting prognosis of resected rectum cancer after neoadjuvant treatment.

BACKGROUND: Rectum cancer is a type of colorectal cancer. Its etiology and etiopathogenesis are similar to other colon diseases. We aimed to evaluate the tumor budding for predicting prognosis of resected rectum cancer patients. METHODS: We retrospectively collected the data of 75 operated rectum adenocarcinoma patients who were treated neoadjuvant chemoradiotherapy between 2013 and 2018 in Umraniye Research and Training Hospital and Acibadem University Medical Oncology Outpatient Clinic. Tumor budding was investigated as a prognostic factor for disease-free survival. RESULTS: This study included 75 rectum cancer patients and 51 were male (68%). Median age was 56 (range 19 to 77 years). There were 29 (39%) and 46 (61%) patients in tumor budding low-intermediate and high groups respectively. In multivariate analysis, tumor budding was found to be an independent prognostic factor for disease-free survival (p = 0.00). CONCLUSIONS: According to our study, having high tumor budding suggests a high likelihood of relapse. Therefore, we might need additional follow-up protocol in these patients.

Immunohistochemical HER2 Status Evaluation in Breast Cancer Pathology Samples: A Multicenter, Parallel-Design Concordance Study.

OBJECTIVE: As patients with increased human epidermal growth factor receptor (HER2) overexpression are more likely to benefit from trastuzumab treatment, the accuracy of HER2 receptor status in breast cancer patients is significant for appropriate disease management. However, this assessment is not harmonized and results may be highly variable between centers. The aim of this study was to investigate the degree of interlaboratory variability in the results of HER2 expression reported by 5 participating centers and to assess the concordance between these centers and a reference laboratory.Materials and Methods: A total of 30 breast cancer samples were tested and scored for HER2 expression using immunohistochemical method in 5 centers from Turkey and in a reference laboratory from Netherlands (Academic Medical Center, Amsterdam). All the participating centers had an experience of more than 10 years regarding the HER2 testing. The results were compared both among the centers and with the reference laboratory. RESULTS: When the concordance of participating centers and the reference laboratory was evaluated regarding negative (0-1+), equivocal 2(+) and positive 3(+) classification of HER2 immunostaining, the highest concordance was found in Center-A, and the lowest in Center-C (Kendall's tau-b concordance coefficient 0.911 and 0.724, respectively). The concordance of the centers with reference laboratory was 80.0% both in equivocal and positive samples, while it increased up to 91.8% in negative samples. CONCLUSIONS: This study showed that in general there is sufficiently good agreement between the reference laboratory and the participating centers for immunohistochemical HER2 assessment.

BRCA mutations in women with inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer (IBC) often affects women at a relatively young age. To the authors' knowledge, the rate of BRCA variants among patients with IBC is not known. To determine the association between BRCA status and IBC, the authors evaluated its rate and compared the clinicopathologic characteristics of patients with IBC with those of patients with other breast cancers (non-IBC). METHODS: Patients who presented at the study institution's cancer genetics program and who underwent BRCA genetic testing were included in the current study. The authors compared clinicopathologic data between patients with IBC and those with non-IBC using propensity score matching to identify predictors. RESULTS: A total of 1789 patients who underwent BRCA genetic testing (1684 with non-IBC and 105 with IBC) were included. BRCA pathogenic variants were found in 27.3% of patients with non-IBC and 18.1% of patients with IBC (P = .0384). After propensity score matching, there were no significant differences noted between patients with IBC and those with non-IBC, including the rate of BRCA pathogenic variants (P = .5485). However, a subgroup analysis of the 479 patients with BRCA pathogenic variants demonstrated that patients with IBC (19 patients) were diagnosed at significantly younger ages compared with patients with non-IBC (P = .0244). CONCLUSIONS: There was no clear association observed between BRCA pathogenic variants and IBC. However, among patients who tested positive for BRCA pathogenic variants, those with IBC were younger at the time of diagnosis compared with those with non-IBC breast cancers. These results confirm that genetic testing is important for patients with IBC who meet the current clinical criteria for genetic testing in breast cancer. Cancer 2018;124:466-74. © 2017 American Cancer Society.

Attitudes of cancer patients after diagnosis: How cancer affects social life? A Turkish Oncology Group study.

PURPOSE: Each year, 12.7 million people learn that they have cancer and 8.2 million people die of cancer worldwide. Cancer is a major public health issue which causes fundamental changes in the lives of patients and their families. The purpose of this study was to evaluate the lives of patients after diagnosis and determine the changes in their lifestyles. METHODS: Between September 2013 to December 2013, a questionnaire consisting of 22 questions was administered during a face to face interview to patients at 13 different Oncology Units in Turkey. Each patient was queried during the administration of his/her chemotherapy. Eight of the questions featured independent choices, and 14 had dependent (multiple) choices. RESULTS: A total of 1300 patients were included in the study. Of patients 9.5% were 71 years of age and older which was the oldest age group. The mean patient age was 54.6±13.8 years. Of the whole group of patients 58.5% were female and 41.5% male. After diagnosis, 64% of the patients reported that they were complying with guidelines for a healthy lifestyle and 80% said that they were eating healthier food. At the time they filled in the questionnaire, more than half of the patients (57.3%) felt optimistic about their disease. CONCLUSIONS: Diagnosis of cancer may change the patients' dietary and reading habits, social relationships, activities and more importantly, their point of life view.