High dose chemotherapy and autologous stem cell transplantation for salvage therapy of relapsed /refractory germ cell tumors; a single center experience.

PURPOSE: The optimal management of relapsed/refractory germ cell tumors remains unsettled. In this study, we aimed to evaluate the efficacy of high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) as salvage therapy in patients who progressed after at least one line of cisplatin-based chemotherapy. METHODS: We retrospectively reported the results of 133 patients who underwent HDCT and ASCT as salvage therapy from 2016 to 2021. Patients received 3 cycles of paclitaxel, ifosfomide and cisplatin (TIP) regimen as induction and 1 cycle of carboplatin 700 mg/m2 on days 1 to 3 plus etoposide 750 mg/m2 on days 1 to 3, followed by ASCT. Demographic and clinicopathological features of patients, the International Germ Cell Cancer Collaborative Group (IGCCCG) risk group at diagnosis, serum alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (HCG) levels before HDCT, treatment related complications and survival outcomes were recorded. RESULTS: The median age of the patients was 31 (range 18-62). The median follow-up was 31.1 months (95% CI, 28.9 to 33.3 months). During the median follow-up period, 74 of the 133 patients were still alive, and 63 of these were in complete remission. The median progression-free survival (PFS) was 25.8 months (95% CI, 8.1-43.4 months). The 2-year PFS rate was 50.3% and the 2-year overall survival rate was 60.8%. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis were mediastinal primary tumor location, presence of brain metastases, and higher AFP and HCG levels at baseline. CONCLUSION: One course of HDCT and ASCT after induction with TIP is an effective and feasible treatment option for salvage treatment of relapsed/refractory germ cell tumors, with cure rates of up to 60%.

Evaluation of clinical and prognostic factors for primary gastric diffuse large B-cell lymphoma: Single-center experience.

Objective: Primary gastric lymphomas, which make up the vast majority of extranodal non-Hodgkin lymphoma, are rare and the most common subtype is primary gastric diffuse large B-cell lymphoma (PG-DLBCL). In our study, we investigated the clinical and prognostic factors of this lymphoma type as a single-center experience. Materials and Methods: Between January 2001 and February 2021, 91 patients aged ≥18 years, registered with the diagnosis of primary gastric DLBCL, diagnosed histopathologically, and whose evaluation parameters were reached, were retrospectively scanned. Results: The median age of 91 patients with a diagnosis of PG-DLBCL was 58 (20-81, minimum-maximum) years. Of the patients, 64.8% were men and 35.2% were women. While the number of patients with an International Prognostic Index (IPI) score of 0-2 (low-low-intermediate risk) was 54 (59.4%), the number of patients with an IPI score of 3 (high intermediate) was 19 (20.9%), and the number of patients with an IPI score of 4-5 (high risk) was 18 (19.8%). While 52.7% of the patients had a complete response, 20.9% had a partial response, 3.3% had stable disease, and 23.1% had progressive disease. The 10-year event-free survival (EFS) and overall survival (OS) rates for all patients, respectively, were 52.1% and 53.2%. We found factors affecting survival in univariate analysis; age groups (≤60/>60), ECOG groups (0-1/≥2), Lugano stage (I-II/III-IV), LDH level (normal/high), IPI risk groups (low/low-intermediate/high-intermediate/high) and radiotherapy (yes/no). In multivariate analysis, only; age groups (≤60/>60) and IPI risk groups (low/low-intermediate/high-intermediate/high) were found to be independent factors affecting survival. In addition, in our study, we determined that the division of the IPI intermediate risk group into low intermediate and high intermediate is one of the factors predicting prognosis. Conclusions: Few studies of PG-DLBCL have investigated the long-term survival rates of patients and primarily examined small patient groups because of the low incidence of the disease. In our study, we think that detailed evaluation of age and especially IPI risk groups play a role in predicting survival.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

The impact of transfusion burden and comorbidities on the prognosis of patients with myelodysplastic syndromes.

PURPOSE: Early comorbidity detection has been reported to be associated with treatment-related outcomes in several diseases. Two main goals of the present study were to investigate both the impact of comorbidities and transfusion frequencies on the survival and quality of life of patients with myelodysplastic syndromes (MDS). METHODS: One hundred and four MDS patients with a median International Prognostic Scoring System (IPSS) score of 0.5 (range: 0-3) were included in the study. Almost half of the patients had more than one comorbidity. RESULTS: Median short form health surveys (SF)-36 mental and physical scores were 42.1 (range: 20.6-66.1) and 38.7 (range: 18-59.7), respectively. Mean scores of the Eastern Cooperative Oncology Group (ECOG) performance scales at diagnosis and during recruitment were 1.0 (1.4 ± 1.0) and 2.0 (1.8 ± 1.1), respectively. The mean Charlson Comorbidity Index (CCI) score was 1.0 (1.4 ± 1.5). In the model that was constructed using variables with a p value < 0.100 in the univariate analysis, factors that predicted death were refractory anemia with excess blasts (RAEB) and ECOG scores at recruitment. When ECOG was removed from the model, RAEB and CCI at diagnosis moved to the forefront as mortality predictors. CONCLUSION: This study demonstrated that both CCI and ECOG performance status had an impact on survival in MDS patients who had low IPSS scores. ECOG stood out as a better and more practical predictor of survival than CCI, especially after considering its (ECOG) ease of use.

Regulation of the unfolded protein response through ATF4 and FAM129A in prostate cancer.

Cancer cells exploit many of the cellular adaptive responses to support their survival needs. One such critical pathway in eukaryotic cells is the unfolded protein response (UPR) that is important in normal physiology as well as disease states, including cancer. Since UPR can serve as a lever between survival and death, regulated control of its activity is critical for tumor formation and growth although the underlying mechanisms are poorly understood. Here we show that one of the main transcriptional effectors of UPR, activating transcription factor 4 (ATF4), is essential for prostate cancer (PCa) growth and survival. Using systemic unbiased gene expression and proteomic analyses, we identified a novel direct ATF4 target gene, family with sequence similarity 129 member A (FAM129A), which is critical in mediating ATF4 effects on prostate tumorigenesis. Interestingly, FAM129A regulated both PERK and eIF2α in a feedback loop that differentially channeled the UPR output. ATF4 and FAM129A protein expression is increased in patient PCa samples compared with benign prostate. Importantly, in vivo therapeutic silencing of ATF4-FAM129A axis profoundly inhibited tumor growth in a preclinical PCa model. These data support that one of the canonical UPR branches, through ATF4 and its target gene FAM129A, is required for PCa growth and thus may serve as a novel therapeutic target.