The role of spleen volume change in predicting immunotherapy response in metastatic renal cell carcinoma.

INTRODUCTION: Resistance to immune checkpoint inhibitors (ICI) is a significant issue in metastatic renal cell carcinoma (mRCC), as it is in the majority of cancer types. An important deficiency in immunooncology today is the lack of a predictive factor to identify this patient group. Myeloid-derived suppressor cells (MDSC) are a type of cell that contributes to immunotherapy resistance by inhibiting T cell activity. While it accumulates in the tumor microenvironment and blood, it can also accumulate in lymphoid organs such as the spleen and cause splenomegaly. Therefore we aimed to evaluate the effect of increase in splenic volume, which can be considered as an indirect indicator of increased MDSC cells, on survival outcomes in mRCC patients. METHODS: We analyzed 45 patients with mRCC who received nivolumab as a second-line or subsequent therapy. Splenic volume was analyzed from baseline imaging before starting nivolumab and from control imaging performed within the first 6 months of treatment initiation. Additionally, we analyzed how patients' body mass index (BMI), IMDC risk score, ECOG performance status, nephrectomy status, neutrophil-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR) and sites of metastasis. RESULTS: Median splenic volume change was 10% (ranging from - 22% to + 117%) during follow-up. Change in splenic volume was found to be associated with overall survival (OS) and progression-free survival (PFS) (p = 0.025, 0.04). The median PFS in patients with increased splenic volume was 5 months, while it was 17 months in patients without increased splenic volume. (HR 2.1, 95% CI (1-4), p = 0.04). The median OS in patients with increased splenic volume was 9 months, while it was 35 months in patients without increased splenic volume (HR 2.7, 95% CI (1.1-6.2), p = 0.025). In four patients with decreased splenic volume, neither PFS nor OS could reach the median value. Log-rank p value in respectively (0.015, 0.035), The group in which an increase in volume was accompanied by a high NLR had the shortest survival rate. Basal splenic volume was analyzed separately. However, neither PFS nor OS differed significantly. CONCLUSION: Our findings suggest that the change in splenic volume throughout immunotherapy regimens may be utilized to predict PFS and OS in mRCC patients undergoing treatment.

Retrospective Evaluation of the Efficacy of Gemcitabine-Based Therapies After FOLFIRINOX Failure in Advanced Pancreatic Cancer, Multi-Center Real-Life Data.

OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.

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.

Clinicopathological Features and First-Line Treatment Outcomes of Geriatric Patients With Extensive-Stage Small Cell Lung Cancer: A Multicenter Study.

Introduction The geriatric patient population diagnosed with extensive stage small cell lung cancer (SCLC) is underrepresented in clinical studies. We aimed to evaluate the clinicopathological characteristics, first-line treatment patterns and treatment outcomes of patients aged 65 years or older with extensive stage SCLC. Material and methods In this multicenter, retrospective cohort study, patients aged 65 years or older, diagnosed with extensive-stage SCLC, between January 2009 and December 2021 were included. Patients who were under 65 years of age at the time of diagnosis and did not develop progression after curative treatment and patients with a second malignancy were excluded from the study. The clinicopathological characteristics, first-line treatment patterns and treatment outcomes were analyzed. Results A total of 132 patients were included in the study. The median age was 70 years (range:65-91), and 118 (89.4%) patients were male. There were 77 (58.3%) patients with eastern cooperative oncology group (ECOG) performance status (PS) of 0-1. There were 26 (19.7%) patients in the limited stage disease and 106 (80.3%) patients in the extensive stage disease at the time of diagnosis. First-line chemotherapy was given to 86 (65.2%) patients. Of the patients who could not receive treatment, 18 patients (13.6%) due to patient refusal, and 28 patients (21.2%) due to comorbid diseases and poor performance status with organ dysfunctions. The most common treatment regimen used as first-line treatment was cisplatin+etoposide (n=47, 54.7%), and followed by carboplatin+etoposide (n=39, 45.3%). First-line chemotherapy responses were complete response in 4 (4.7%) patients, partial response in 35 (40.7%) patients, stable disease in 13 (15.1%) patients, and progressive disease in 34 (39.5%) patients. The most common grade 3-4 adverse events was neutropenia in 33 (38.4%) patients. Forty nine patients (57.0%) completed the planned first-line treatment. The mPFS was 6.1 months and the mOS was 8.2 months with first-line treatment. We found that ECOG PS status was the most important negative prognostic factor for both PFS and OS. There was no difference between carboplatin+etoposide and cisplatin+etoposide regimens in terms of PFS, OS, adverse events and treatment compliance. Conclusion Thus, it may be an appropriate approach not to give up chemotherapy treatment easily in elderly patients with a diagnosis of extensive stage SCLC. It should be kept in mind that finding factors that might affect the prognosis and tailoring the tretment precisely on case-by-case basis in geriatric cancer patients have an impact on survival.

Cachexia index in predicting outcomes among patients receiving immune checkpoint inhibitor treatment for metastatic renal cell carcinoma.

INTRODUCTION: Immune checkpoint inhibitors (ICI) have transformed treatments for patients with metastatic renal cell carcinoma (mRCC). Although some patients benefit greatly from ICI treatments, an effective marker to determine which patients will benefit from these treatments is lacking. Moreover, chronic inflammation and sarcopenia have been associated with poor survival rates among cancer patients. Accordingly, in this study, we investigated how the cachexia index (CXI), used as a combined score for sarcopenia and chronic inflammation, affects the survival outcomes of patients with mRCC receiving ICI. METHODS: We retrospectively screened data from 52 mRCC patients who had followed up between October 2010 and October 2021 after receiving ICI as a second-line or later treatment. Patients' respective basal CXI score were calculated according to the following formula, based on their L3 vertebral skeletal musculoskeletal area (SMI), neutrophil-lymphocyte ratio (NLR), and albumin (Alb) levels: CXI = (SMI x Alb) / NLR. Additionally, we analyzed how patients' subcutaneous adipose tissue (SAT), body mass index (BMI), ECOG performance status, The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score, nephrectomy status, sites of metastasis, and histological subtypes affected survival outcomes. RESULTS: Our univariate analysis significantly associated CXI score, NLR, nephrectomy status, and patient age with overall survival (OS). However, only CXI scores' significance was confirmed through multivariate analysis. The median OS (mOS) was 7 months for patients whose CXI score < the median value and 48 months for patients with a CXI score ≥ the median value. (HR 4.5, 95% CI [1.9-11], p = 0.001). Only CXI was significantly associated with progression-free survival (PFS) outcomes. The median progression-free survival (mPFS) was 4 months for patients whose CXI score < the median value and 17 months for patients with a CXI score ≥ the median value. (HR 2.6, 95% CI [1.3, 5.3], p = 0.007). Sarcopenia, sarcopenic obesity, and sarcopenia combined with NLR were not found to significantly affect OS. CONCLUSION: Our findings suggest that CXI score, a combined indicator of sarcopenia and chronic inflammation parameters, may serve as a useful marker in predicting the outcomes of ICI-based treatments for mRCC patients.

The Relationship Between Caregiver Burden and Posttraumatic Growth in Caregivers of Patients With Metastatic Cancer.

Objective In this study, we aimed to examine the effect of post-traumatic growth and depressive symptoms on caregiver burden in caregivers of cancer patients. Methods This was a single-center cross-sectional observational descriptive study conducted at a medical oncology clinic. The study included 214 caregivers of cancer patients. Participants were assessed with a sociodemographic information form, the Turkish versions of the Zarit Caregiver Burden Scale (ZCBS), the Posttraumatic Growth Inventory (PTGI), and the Beck Depression Inventory (BDI). Results The mean ZCBS, PTGI, and BDI scores were 42.7 ±13.8, 67.8 ±22.3, and 13.5 ±9.8, respectively. There was a negative correlation (r=-0.407, p<0.001) between the ZCBS and the PTGI total scores, a positive correlation (r=0.636, p<0.001) between the ZCBS total and BDI scores, and a negative correlation (r=-0.426, p<0.001) between the PTGI total and BDI scores. Age, gender, income level, and history of psychiatric treatment were not independent predictive factors for the ZCBS total scores. PTGI total score (B=-0.107, 95% CI: -0.178 to -0.037, p=0.003) and BDI score (B=0.776, 95% CI: 0.602-0.950, p<0.001) were independent predictive factors for ZCBS total scores. Conclusions Our study revealed a significant negative relationship between caregiver burden and PTGI in caregivers of metastatic cancer patients, and it was found that depression negatively affects burden in caregivers. Posttraumatic growth can be a protective buffer against the burden of care and depression among caregivers.

Thirty-day mortality rates after immunotherapy initiation.

Background: The aim of this study was to determine the cause of death in patients who died within 30 days after the first dose of immunotherapy. Methods: The data of 1432 patients treated with immunotherapy in six tertiary referral hospitals were retrospectively analyzed. Results: It was determined that 34 (2%) of the patients died within 30 days after the first dose of immunotherapy. Death occurred in all patients who received palliative therapy, and most patients (88%) received immunotherapy as second- or subsequent-line of therapy. The most common cause of death was disease progression and thromboembolic events. Conclusion: Preliminary results of the current study might give some clues to define the patient population in whom the fatal side effects of immunotherapy might be encountered.

The Need for Effective Adjuvant Therapy in Uterine Leiomyosarcoma: A Single-centre Experience.

OBJECTIVE: To evaluate the efficacy of adjuvant chemotherapy (ACTx) in completely resected uterine leiomyosarcoma (ULMS) in terms of survival outcomes. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital, Ankara, Turkey from February 2009 to November 2019. METHODOLOGY: Patients older than 18 years, who underwent complete surgical resection with a diagnosis of non-metastatic ULMS were evaluated retrospectively. The patients were divided into two groups: patients who received ACTx (group I) and patients who received only surgical treatment (group II). Both groups were compared in terms of main patient and tumour characteristics, relapse rates, relapse-free survival (RFS) and overall survival (OS). RESULTS: Forty-five patients with a median age of 52.1 years (IQR, 45.8-58.2) were included in the study. Group I consisted of 26 (57.8%) patients and group II consisted of 19 (42.2%) patients. Median RFS was 43.8 months (95% CI, 7.4-80.2) and the median OS was 81.3 months (95% CI, 39.4-123.1) for all patients (N = 45). Median RFS was 27.1 months (95% CI, 6.8-47.4) in group I (n = 26) and 43.8 months (95% CI, 11.8-75.8) in group II (n = 19) (p = 0.985). Median OS was 85.6 months (95% CI, 38.3-132.9) in group I (n = 26) and 81.2 months (95% CI, 62.1-100.4) in group II (n = 19) (p = 0.699).  Conclusion: There was no survival benefit of ACTx in completely resected ULMSs, in accordance with the literature data. There is a need for prospective randomised clinical trials evaluating the role of ACTx in ULMSs. Key Words: Uterine leiomyosarcoma, Complete resection, Adjuvant chemotherapy, Relapse, RFS, OS.

Systemic Immune-inflammation Index (SII) Predicts Pathological Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

OBJECTIVE: To determine the relationship between inflammatory markers and pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC), who received neoadjuvant chemoradiotherapy (NACRT). STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Dr. Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey from January 2014 to June 2020. METHODOLOGY: Patients older than 18 years of age, who underwent NACRT with a diagnosis of LARC, and who had no disease or drug-use that could affect inflammatory parameters, were included in the study. Inflammatory indices (neutrophil-to-lymphocyte ratio-NLR, platelet-to-lymphocyte ratio-PLR, lymphocyte monocyte ratio-LMR, systemic immune-inflammation index-SII, prognostic nutritional index-PNI) and changes in these indices, were calculated from blood samples taken before NACRT and before surgery. The relationship between pCR and calculated inflammatory indices was evaluated by comparing patients with and without pCR. RESULTS: Out of the 932 patients, who received NACRT with a diagnosis of LARC, 188 were eligible for the study. Median values of baseline SII for pCR and non-pCR groups were 729.3 (595.4-894.8) and 869.9(567.2-1145.2, p=0.049). Baseline NLR and PLR levels were lower in the pCR group than the non-pCR group in univariate analysis with a tendency to statistical significance. In the logistic regression analysis, which included NLR, PLR, and SII, only SII <748 was found to be an independent predictive factor of pCR (OR: 0.471, 95% CI; 0.224-0.991, p=0.047). CONCLUSION: Baseline SII might be an independent predictive factor for pCR in patients receiving NACRT with a diagnosis of LARC. Key Words: Locally advanced rectal cancer, Neoadjuvant chemoradiotherapy, Pathological complete response, Inflammatory index, Systemic immune-inflammation index, SII, NLR, PLR, LMR, PNI.

Outcomes of Autologous Stem Cell Transplantation (ASCT) in Relapsed/Refractory Germ Cell Tumors: Single Center Experience from Turkey.

PURPOSE: Germ cell tumors (GCTs) are rare and highly curable malignancies. However, salvage treatments for relapsed or refractory disease are needed in approximately 20-60% of the patients. As salvage therapy, autologous stem cell transplantation (ASCT) administered after high-dose chemotherapy (HDCT) may be a feasible option as well as standard dose chemotherapy (SDCT). This study aimed to evaluate the efficacy and toxicity of ASCT in salvage therapy of GCTs retrospectively.  Materials and Methods: Male patients older than 18 years of age who underwent ASCT due to a relapsed/refractory GCT were included in the study. RESULTS: The median age of 18 patients included in the study was 28 (19-46). The majority of patients (n:16, 88.8%) had non-seminomatous GCT histology. All of the patients had relapsed or refractory GCTs and received bleomycin, etoposide, cisplatin (BEP) combination therapy previously. Half of the patients were in the poor risk group. ASCT was administered as a second-line therapy in 14 (77.7%) patients and third-line therapy in four (22.2%) patients. There is no ASCT-related exitus. Febrile neutropenia (FN) developed in almost all patients. Complete response (CR) was obtained in 7 (38.8%) patients, partial response (PR) in four (22.2%) patients after ASCT. The 2-year PFS was 44.4% and the median PFS was 8.7 (2.7-12.6) months. Median OS was 22.7 (3.9-41.7) months and 3 years OS was 50.0%. CONCLUSION: In conclusion, ASCT was found to be an effective and safe treatment option in salvage therapy of GCT patients in our study.

Comparison of clinicopathological and survival features of right and left colon cancers.

PURPOSE: Right-sided colon cancers (RCCs) and left-sided colon cancers (LCCs) have different embryological, epidemiological, physiological, pathological, genetic, and clinical characteristics, which result in differences in the course, prognosis, and outcome of disease. This study aimed to compare RCCs and LCCs regarding clinicopathological and survival characteristics. METHODS: The present retrospective study included data of patients who were followed-up and treated for colon cancer from 2008 through 2017. Rectosigmoid, descending colon, and splenic flexure tumors were considered LCC, whereas hepatic flexure and ascending colon tumors were considered RCC. Tumors were staged according to the American Joint Committee on Cancer classification. RESULTS: The study included 1725 patients (female, 58.7%) having colon cancer with a mean age of 64±12 years. Of the patients, 83.2% (n=1436) had LCC and 16.8% (n=289) had RCC. The rate of patients aged ≥65 years and the rate of patients with a family history of colon cancer were higher in the RCC patients. The rate of metastatic patients was 29.1% in the RCC group and 23.2% in the LCC group (p=0.087). The median follow-up period was 18 months in the RCC group and 23 months in the LCC group (p=0.011). Although the median survival time was higher in the LCC group (62 vs. 43 months), no significant difference was determined between the RCC and LCC groups in terms of survival. CONCLUSIONS: There are numerous clinicopathological differences between RCC and LCC and these differences are reflected in prognostic and survival differences among certain subgroups.

Evaluation of prognostic factors in localized high-grade undifferentiated pleomorphic sarcoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology.

Most data on prognostic factors for patients with high-grade undifferentiated pleomorphic sarcoma (HGUPS) is obtained from analyses of soft tissue sarcomas. The purpose of this study was to evaluate the clinicopathologic features and their impact on outcomes specifically in patients diagnosed with HGUPS. In this multicenter trial, we retrospectively analyzed 112 patients who were diagnosed and treated at 12 different institutions in Turkey. We collected data concerning the patients, tumor characteristics, and treatment modalities. There were 69 males (61.6 %) and 43 females (38.4 %). Median age was 56 years (19-90). The most common anatomic site of tumor origin was the upper extremity. Pleomorphic variant was the predominant histological subtype. Median tumor size was 8.2 cm (0.6-30 cm). Tumors were mainly deeply seated (57.1 %). Fifty-seven patients (50.9 %) were stage II and the remainder were stage III at the time of diagnosis. Median follow-up was 30 months (2-160). The primary site of distant metastasis was the lung (73.5 %) and the second most common site was the liver (11.7 %). The 5-year overall survival, distant metastasis-free survival, and local recurrence-free survival rates were 56.3, 53.4, and 67.2 %, respectively. Multivariate analysis showed that Eastern Cooperative Oncology Group (ECOG) performance score of II (p = 0.033), deep tumor location (p = 0.000), and development of distant metastasis (p = 0.004) were negatively correlated with overall survival, and perioperative radiotherapy and negative microscopic margins were significant factors for local control rates (p = 0.000 for each). Deep tumor location (p = 0.003) was the only adverse factor related to distant metastasis-free survival. Deep tumor location, ECOG performance score of II, and development of distant metastasis carry a poor prognostic implication on overall survival. These will aid clinicians in predicting survival and treatment decision.

Gastric carcinoma with bone marrow metastasis: a case series.

Gastric cancer is a major cause of cancer-related mortality. At the time of diagnosis, majority of the patients usually have unresectable or metastatic disease. The most common sites of metastases are the liver and the peritoneum, but in the advanced stages, there may be metastases to any region of the body. Bone marrow is an important metastatic site for solid tumors, and the prognosis in such cases is poor. In gastric cancer cases, bone marrow metastasis is usually observed in younger patients and in those with poorly differentiated tumors. Prognosis is worsened owing to the poor histomorphology as well as the occurrence of pancytopenia. The effect of standard chemotherapy is unknown, as survival is limited to a few weeks. This report aimed to evaluate 5 gastric cancer patients with bone marrow metastases to emphasize the importance of this condition.