Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

HIPEC in Ovarian Cancer: When and to Whom?

OBJECTIVE: To evaluate the optimal candidates for hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Health Sciences University, Dr. Abdurrahman Yurtasian Ankara Oncology Training and Research Hospital, Ankara, Turkey, between 2013 and 2021. METHODOLOGY: Ovarian cancer patients who underwent HIPEC and CRS for peritoneal involvement were included in this study. Thermosolutions were prepared as a closed system by using HT 2000 hyperthermic perfusion device. Then, cisplatin was applied at 100 mg/m2 at 42-42.5 °C for 60 minutes after CRS. RESULTS: A total of 47 patients were enrolled. The median age was 54 years (27-80) at the time of diagnosis. Forty (85.1%) patients had high grade serous carcinoma and 22 (46.7%) patients had clinical stage 3C disease. The median peritoneal cancer index (PCI) was 13 (3-24) in the whole population. HIPEC was applied as first-line treatment in 25 (51%) patients. Eleven (23.4%) patients had HIPEC in the post-neoadjuvant interval whereas 10 (21.3%) patients had it in platinum sensitive relapse. Median progression free survival (PFS) was 31(95% CI:11-50), 33 (95% CI:1-67), and 18 (95% CI:8-27) months in the primary, post-neoadjuvant interval, and platinum-sensitive relapse HIPEC groups, respectively. The patients with lower PCI (PCI<13) had significantly better OS than others with higher PCI (PCI>13, 145 months versus 42 months, p=0.034). CONCLUSION: HIPEC with CRS should be considered in selected serous carcinoma patients with peritoneal involvement, especially for the patients with primary ovarian cancer with lower PCI (PCI<13). KEY WORDS: Ovarian cancer, HIPEC, Peritoneal cancer index.

Adjuvant Capecitabine after Neoadjuvant Chemotherapy in Triple Negative Breast Cancer with Lymph Node Metastasis.

OBJECTIVE: To evaluate the effect of complete pathological response (pCR) on prognosis in patients with axillary lymph node-positive triple-negative breast cancer (TNBC) and the efficiency of adjuvant capecitabine. STUDY DESIGN: Analytical study. Place and Duration of the Study: University of Health Sciences, Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, between March 2015 and December 2021. METHODOLOGY: The study included 92 patients with TNBC with enlarged axillary lymph nodes and treated with neoadjuvant chemotherapy. The patients were classified as those with and without postoperative pCR and compared in terms of survival. Subsequently, the patients who did not achieve pCR were classified as receiving and not receiving adjuvant capecitabine and were compared for DFS (disease-free survival) and OS (overall survival). Parameters that showed statistical significance were re-evaluated with Cox regression analysis. RESULTS: The 5-year DFS rate was 84.3% in those who achieved pCR, while it was 55.1% in those who did not (p=0.026). The 5-year OS rate was 82.8% in the pCR arm, while it was 51.0% in the non-pCR arm (p=0.070). The 5-year DFS rate was 66.3% in adjuvant capecitabine-receiving patients, while it was 40.8% in the non-capecitabine arm (HR=0.40, p=0.031). The 5-year OS rate was 68.9% in adjuvant capecitabine-receiving patients, while it was 29.6% in the non-capecitabine arm (HR= 0.40, p=0.062).  Conclusion: Obtaining pCR following NAC in a locally advanced TNBC is an independent prognostic marker for DFS and OS. In the presence of residual disease, improvement in DFS and OS with adjuvant capecitabine was demonstrated by the real-life data. KEY WORDS: Triple-negative breast cancer, Neoadjuvant chemotherapy, Capecitabine, Survival.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Vitiligo-like lesions associated with ribociclib in a woman with metastatic breast cancer.

INTRODUCTION: Cyclin-dependent kinase 4/6 inhibitors are new generation drugs that have recently been used in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negativenegative metastatic breast cancer. Recent studies have shown that the use of cyclin-dependent kinase 4/6 inhibitors significantly improves the outcomes of these patients. The most common side effects of cyclin-dependent kinase 4/6 inhibitors are hematological toxicity, gastrointestinal side effects, and fatigue. We aimed to present a case of metastatic breast cancer who was treated with ribociclib and developed vitiligo-like lesions after treatment. CASE REPORT: A 56-year-old female patient was diagnosed with locally advanced hormone receptor (+)/human epidermal growth factor receptor 2 (-) breast cancer in May 2000. She was followed up with hormonal therapy after adjuvant chemotherapy and radiotherapy. The patient progressed with lung metastases in 2012. Ribociclib, anastrozole, and leuprolide acetate were started in November 2021 after multiple-line chemotherapy. After six cycles of ribociclib, vitiligo-like lesions that developed in the last 1 month were detected on the upper extremities, both hands, neck, chest, and upper back. MANAGEMENT AND OUTCOME: The patient was referred to dermatology. Topical immunosuppressive therapy and oral corticosteroids were recommended. At the first and third-month follow-up examinations, vitiligo-like lesions were observed to persist. DISCUSSION: Vitiligo-like lesions are not a life-threatening side effect. However, it significantly affects the quality of life and disrupts the patient's compliance with treatment. Cyclin-dependent kinase  4/6 inhibitors can inhibit cell division or cause premature cell death by acting on the melanocyte cell cycle.

The impact of COVID-19 pandemic on anxiety levels among patients who have to go to the hospital due to chronic illnesses: A prospective study.

INTRODUCTION: Cancer and hemodialysis (HD) patients are at high risk for COVID-19. In our study, we aimed to evaluate the effect of pandemic on anxiety in these patients. METHODS: One hundred and six oncology and 97 HD patients participated in the study. Anxiety levels were assessed by using the Beck Anxiety Inventory (BAI) and State-Trait Anxiety Inventory (STAI). At the end of 8-month follow-up, these questionnaires were re-administered. RESULTS: During this period, 38 patients (38/203; 18.7%) had COVID-19 infection. Twenty-three patients (23/203; 11.3%) died due to COVID-19 and/or other causes. One hundred and thirteen of the remaining patients were participated in the second questionnaire. Having COVID-19 was not the independent factor for changes in STAI, and BAI scores in any regression models. CONCLUSION: Having COVID-19 does not affect the increased anxiety levels in HD and oncology patients. The effect of the pandemic may have remained in the background, as these patients have more concerns about their own diseases.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice.  Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Evaluation of the Preoperative Haematological Parameters Predicting the High T-Stage and Fuhrman Grade in Renal Cell Carcinoma.

OBJECTIVE: To investigate the role of cost-effective and widely used hemogram parameters in predicting stage and histological grade. STUDY DESIGN: An analytical study. PLACE AND DURATION OF STUDY: Konya Research and Training Hospital, Turkey from January to June 2020. METHODOLOGY: Pre-nephrectomy hemogram parameters and post-nephrectomy pathology reports of 180 renal cell carcinoma patients, among 553 patients, who had undergone nephrectomy between 2009-2019 were evaluated. The patients were grouped as low risk and high risk in terms of TNM stage and Fuhrman grade; and clinicopathological variables were compared between the groups. Multivariate logistic regression analysis was used to determine the parameters predicting independently the high T stage (T3-T4) and the high Fuhrman grade (G3-G4). RESULTS: While 31 (17.2%) of 180 patients were in the high T stage; 69 (38.3%) were in the high Fuhrman grade. In the logistic regression analysis, NLR, LMR, and hematocrit predicted independently high T stage, while hematocrit and LMR predicted independently the high Fuhrman grade. CONCLUSION: LMR, NLR, and hematocrit were found to be more significant than other parameters, which are among the hemogram parameters that can guide clinicians during staging, which is important for prognosis and treatment decisions. KEY WORDS: Renal cell carcinoma, Tumor staging, Tumor grading.

Cancer among syrian refugees living in Konya Province, Turkey.

BACKGROUND: With more than 3.6 million Syrian refugees Turkey hosts the world's largest number of Syrians. Considering the morbidity, mortality, and healthcare spending, cancer is one of the leading health and economic burden for patients and healthcare systems. However, very limited information available in the scientific literature to understand the burden and characteristics of cancer in countries hosting Syrian refugees. The aim of the present study is to evaluate the demographic and clinical characteristics, treatment outcome of Syrian cancer patients living in Konya, Turkey. METHODS: We retrospectively reviewed medical records of Syrian cancer patients at three major institutions from 2005 to 2020. The information regarding demographic and clinical characteristics of patients were identified. The number of days between the first symptom and diagnosis was considered as the "diagnostic interval". Patients who failed to attend clinics within four weeks of appointment were assumed abandoned treatment. Survival curves were estimated using the Kaplan-Meier method. RESULTS: We identified 230 adult and 38 children refugee diagnosed with cancer during the study period. With regards to adult patients, there were 114 (49.6%) male and 116 (50.4%) female. The median age at diagnosis was 52.4, 47.3 years for male, female respectively. The five most common cancer by site among all were; breast (24.8%), colorectal (10.9%), lung (7.4%), central nervous system (CNS) (7.0%), and stomach (5.2%). 93 (40.4%) had metastatic disease at diagnosis. The overall survival probability was 37.5% at five years for the adult population. Data were extracted for 20 boys and 18 girls with childhood cancer. Their median age at diagnosis was 5.8 and 6.0 years respectively. The three most common childhood cancer were; leukemias (21.1%), lymphomas (21.1%), and CNS (13.2%). Excluding leukemia, 13 (43.3%) of childhood cancer cases had the advanced disease at diagnosis. Three year survival probality was 69.5%. The median diagnostic interval for adult and childhood cancer was 96.5 (IQR = 53-165) and 23 (IQR = 13.5-59) days respectively. Twenty-one adults and four children had treatment abandonment. CONCLUSION: This study contributes to understanding the burden of cancer among Syrian refugees living in Konya, growing health issue for refugees. Larger and prospective studies will help to measure the real burden and compare the difference in cancer risk factors, care, and outcomes among the refugee and host populations.

Adjuvant carboplatin and paclitaxel after concurrent cisplatin and radiotherapy in patients with locally advanced cervical cancer.

INTRODUCTION: Standard treatment for locally advanced cervical cancer (LACC) includes concomitant chemoradiotherapy (CRT) that typically controls localized disease. However, most patients develop distant metastasis, ultimately leading to death. OBJECTIVE: To determine the role of adjuvant carboplatin and paclitaxel for clinical outcomes in patients with LACC. METHODS: Between 2010 and 2017, 109 patients with LACC were retrospectively evaluated. All patients received cisplatin (40 mg/m2) with concurrent external-beam radiotherapy (up to 50.4 Gy), followed by intra-cavitary brachytherapy. Forty-six of 109 patients received a median of six cycles (range 3-6 cycles) of adjuvant chemotherapy consisting of paclitaxel (175 mg/m2) and carboplatin (CRT + chemotherapy group; area under the curve 5). The remaining 63 patients did not receive adjuvant chemotherapy (CRT group). RESULTS: Disease-free survival and overall survival after a median follow-up of 24.5 months (range 2.6-94.75 months) were 93.5% and 95.7% and 69.8% and 82.5 % for the CRT + chemotherapy and CRT groups, respectively (p = 0.001, p = 0.012, respectively). No acute grade 3/4 gastrointestinal or genitourinary toxicities were seen during CRT. During adjuvant chemotherapy, the most troublesome side effects were hematologic and neurologic toxicities; however, most were manageable. No chronic grade 3/4 genitourinary toxicities were seen. DISCUSSION: Adjuvant chemotherapy in patients with LACC significantly improved both disease-free survival and overall survival without increasing unmanageable toxicity. Future larger prospective trials are warranted to verify these findings.