A randomized, open-label, phase 3 trial of pembrolizumab plus epacadostat versus sunitinib or pazopanib as first-line treatment for metastatic renal cell carcinoma (KEYNOTE-679/ECHO-302).

BACKGROUND: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC. METHODS: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1. RESULTS: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2-14.3) and 10.3 months (2.7-13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2-44.1] and sunitinib/pazopanib (29.2% [18.6-41.8]). Grade 3-5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects. CONCLUSIONS: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; NCT03260894 .

Real-World Efficacy and Safety of First-Line Nivolumab Plus Chemotherapy in Patients with Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: A Nationwide Observational Turkish Oncology Group (TOG) Study.

Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and identified subgroups that may experience superior outcomes. Conducted across 16 oncology centers in Turkey, this study retrospectively reviewed the clinical charts of adult patients diagnosed with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma from 2016 to 2023. This study included 111 patients (54 women, 57 men) with a median age of 58 years. The median progression-free survival (PFS) and overall survival (OS) were 11.7 months and 18.2 months, respectively, whereas the objective response rate (ORR) was 70.3%. Multivariable analyses revealed that previous curative surgery was a favorable independent prognostic factor for both PFS and OS. Conversely, an Eastern Cooperative Oncology Group performance status of 2 emerged as an adverse independent prognostic factor for OS. The safety profile of nivolumab plus chemotherapy was found to be manageable. Our findings support the use of nivolumab plus chemotherapy for the first-line treatment of Turkish patients with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma. Patient selection based on clinical characteristics is crucial for optimizing treatment outcomes.

The prognostic factors in patients with advanced hepatocellular carcinoma: impact of treatment sequencing.

The prognosis of patients with advanced HCC can vary widely depending on factors such as the stage of the cancer, the patient's overall health, and treatment regimens. This study aimed to investigate survival outcomes and associated factors in patients with hepatocellular carcinoma (HCC). In this retrospective study, data from 23 medical oncology clinics were analyzed. Progression-free survival (PFS) and overall survival (OS) values were estimated using the Kaplan-Meier method. Prognostic factors associated with survival which were identified in univariate analysis were subsequently evaluated in a multivariate Cox-regression survival analysis was conducted using the backward stepwise (Conditional LR) method to determine the independent predictors of PFS and OS. Of 280 patients, 131 received chemotherapy and 142 received sorafenib, 6 received atezolizumab plus bevacizumab and 1 received nivolumab for first-line setting. The median follow-up time was 30.4 (95%CI 27.1-33.6) months. For-first line, median PFS was 3.1 (95%CI2.7-3.5) months, and it was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab (PFS 5.8 (95%CI 4.2-7.5) than in those received chemotherapy (PFS 2.1 (95%CI 1.9-2.3) in the first-line setting (p < 0.001). Multivariate analysis revealed that male gender (HR: 2.75, 95% CI: 1.53-4.94, p = 0.01), poor ECOG performance score (HR: 1.88, 95% CI: 1.10-3.21, p = 0.02), higher baseline AFP level (HR: 2.38, 95% CI: 1.54-3.67, p < 0.001) and upfront sorafenib treatment (HR,0.38; 95% CI: 0.23-0.62, p < 0.001) were significantly associated with shorter PFS. The median OS was 13.2 (95%CI 11.1-15.2) months. It was significantly longer in patients who received sorafenib or atezolizumab-bevacizumab or nivolumab in the first-line setting followed by TKIs (sorafenib or regorafenib, OS 18.6 (95%CI 13.8-23.5)) compared to those who received chemotherapy (OS 10.3 (95%CI 6.6-14.1)) in the first-line setting. The multivariate analysis revealed that upfront chemotherapy treatment approach, male gender (HR: 1.77, 95% CI: 1.07-2.94, p = 0.02), poor ECOG performance score (HR: 1.96, 95% CI: 1.24-3.09, p = 0.004) and Child-Pugh score, presence of extrahepatic disease (HR: 1.54, 95% CI: 1.09-2.18, p = 0.01), and higher baseline AFP value (HR: 1.50, 95% CI: 1.03-2.19, p = 0.03) were significantly associated with poor prognosis. Additionally, regarding of treatment sequence, upfront sorafenib followed by regorafenib showed a significantly lower risk of mortality (HR: 0.40, 95% CI: 0.25-0.66, p < 0.001). Sorafenib followed by regorafenib treatment was associated with a significantly lower risk of mortality rather than upfront sorafenib followed by BSC group or upfront chemotherapy followed by TKIs. These findings underscore the importance of the optimal treatment sequences to improve survival in patients with advanced HCC.

Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study.

PURPOSE: Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC). METHODS: This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR). RESULTS: A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E). CONCLUSION: TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC.

Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer.

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.

The Relationship Between Plexin C1 Overexpression and Survival in Hepatocellular Carcinoma: a Turkish Oncology Group (TOG) Study.

PURPOSE: Plexin C1 is a transmembrane receptor and plexin C1 overexpression might have role in carcinogenesis. Hepatocellular carcinoma (HCC) has poor prognosis because of its aggressive behavior and limited treatment options, especially in advanced stage. We recently documented that Plexin C1 was overexpressed in HCC. We aimed to evaluate the prognostic significance of Plexin C1 overexpression in HCC in the present study. METHODS: Plexin C1 overexpression was evaluated immunohistochemically on paraffin-embedded blocks of the HCC patients. Plexin C1 immunohistochemical staining was scored. Plexin C1 overexpression staining intensity and prevalence were used for plexin scale staining evaluation and plexin scores were estimated according this staining scale. Plexin C1 score and its association with survival and clinicopathological features was assessed. RESULTS: Sixty-seven HCC patients with adequate tissue for pathological evaluation were included. Median age was 63 years with male predominance (male to female ratio was 4.75 (n 57/12). Well-differentiated HCC (53.7%) patients had higher plexin C1 overexpression (p < 0.05). Median OS was 22.1 months. Patients with lower plexin C1 score (< 12) had shorter OS (17.5 vs 30.1 months, p = 0.036). Neutrophil count, GGT, and PNR (platelet/neutrophil ratio) had prognostic significance (p = 0.047, p = 0.018, and p = 0.045). CONCLUSION: Plexin C1 overexpression is inversely correlated with grade in HCC. The patients with lower rate of Plexin C1 overexpression have worse survival outcome. It might be a prognostic factor in HCC.

Survival outcome of pulmonary metastasectomy among the patients with colorectal cancers.

OBJECTIVE: Pulmonary metastasectomy for the treatment of metastatic colorectal cancer is essential, but high ranked evidence of survival benefit is lacking. Here, we aimed to examine the prognostic factors after pulmonary metastasectomy in patients with colorectal cancer. METHODS: This is a single-center, retrospective hospital-based observational case series study. We reviewed data for 607 patients with metastatic colorectal cancer (mCRC) who were treated and observed from 2012 to 2019. Of the 607 patients with mCRC, 87 were with solitary lung metastases. Of the 87 patients, 39 were not appropriate for metastasectomy, while 15 patients recognized as suitable candidates by the multidisciplinary thoracic tumor board rejected metastasectomy. Consequently, only 33 patients were included in the final analysis. RESULTS: Rectum was detected as the primary site in 16 (48.5%) patients. Over 80% of patients had metachronous lung metastases, with a median of 29.0 months from initial diagnosis. Video-assisted thoracic surgery with wedge resection was performed in 20 (60.6%) patients. Over 90% of patients had solitary metastasis resected, with 97% of R0 resection. Median tumor size was 23.0 mm (min: 10; max: 90). Adjuvant treatment was given to 31 (93.9%) patients, while neoadjuvant treatment was given only to 8 (25%) patients. Of the 33 patients, there were 25 (75.7%) relapses. The most frequent site of relapse was lung in 15 (45.5%) patients. Interestingly, there were only 4 (12.2%) patients who had a relapse in the liver after lung metastasectomy. We found that median disease-free survival (DFS) and overall survival (OS) were 43.0 (13.0-73.0) and 55.0 (31.6-78.4) months, respectively. CONCLUSIONS: Pulmonary metastasectomy was associated with significantly long-time survival rates in mCRC (43 months of DFS and 55 months of OS). The second relapse occurred in 25 (75.7%) patients, with isolated lung metastases in nearly half of the patients (45.5%). Therefore, lung metastases in mCRC were unique and a multidisciplinary team including a thoracic surgeon should manage these patients.

Survival outcome of pulmonary metastasectomy among the patients with colorectal cancers

SUMMARY OBJECTIVE: Pulmonary metastasectomy for the treatment of metastatic colorectal cancer is essential, but high ranked evidence of survival benefit is lacking. Here, we aimed to examine the prognostic factors after pulmonary metastasectomy in patients with colorectal cancer. METHODS: This is a single-center, retrospective hospital-based observational case series study. We reviewed data for 607 patients with metastatic colorectal cancer (mCRC) who were treated and observed from 2012 to 2019. Of the 607 patients with mCRC, 87 were with solitary lung metastases. Of the 87 patients, 39 were not appropriate for metastasectomy, while 15 patients recognized as suitable candidates by the multidisciplinary thoracic tumor board rejected metastasectomy. Consequently, only 33 patients were included in the final analysis. RESULTS: Rectum was detected as the primary site in 16 (48.5%) patients. Over 80% of patients had metachronous lung metastases, with a median of 29.0 months from initial diagnosis. Video-assisted thoracic surgery with wedge resection was performed in 20 (60.6%) patients. Over 90% of patients had solitary metastasis resected, with 97% of R0 resection. Median tumor size was 23.0 mm (min: 10; max: 90). Adjuvant treatment was given to 31 (93.9%) patients, while neoadjuvant treatment was given only to 8 (25%) patients. Of the 33 patients, there were 25 (75.7%) relapses. The most frequent site of relapse was lung in 15 (45.5%) patients. Interestingly, there were only 4 (12.2%) patients who had a relapse in the liver after lung metastasectomy. We found that median disease-free survival (DFS) and overall survival (OS) were 43.0 (13.0-73.0) and 55.0 (31.6-78.4) months, respectively. CONCLUSIONS: Pulmonary metastasectomy was associated with significantly long-time survival rates in mCRC (43 months of DFS and 55 months of OS). The second relapse occurred in 25 (75.7%) patients, with isolated lung metastases in nearly half of the patients (45.5%). Therefore, lung metastases in mCRC were unique and a multidisciplinary team including a thoracic surgeon should manage these patients.

Stereotactic body radiotherapy for oligoprogressive lesions in metastatic castration-resistant prostate cancer patients during abiraterone/enzalutamide treatment.

BACKGROUND: Metastasis-directed therapy (MDT) utilizing stereotactic body radiotherapy (SBRT) for oligoprogressive lesions could provide a delay in next-line systemic treatment (NEST) change while undergoing androgen receptor-targeted agents (ARTA) treatment. We evaluated prognostic factors for prostate cancer-specific survival (PCSS) and progression-free survival (PFS) to characterize patients receiving treatment with ARTA who may benefit from MDT for oligoprogressive lesions. The impact of MDT on delaying NEST and the predictive factors for NEST-free survival (NEST-FS) were also assessed. MATERIALS AND METHODS: The clinical data of 54 metastatic castration-resistant prostate cancer patients with 126 oligoprogressive lesions receiving abiraterone (1 g/day) or enzalutamide (160 mg/day) before or after systemic chemotherapy were analyzed. A median of three lesions (range: 1-5) were treated with MDT. The primary endpoints were PCSS and PFS. The secondary endpoints were time to switch to NEST and NEST-FS. RESULTS: The median follow-up time was 19.1 months. Univariate analysis showed that the number of oligoprogressive lesions treated with SBRT and the time between the start of ARTA treatment and oligoprogression were significant prognostic factors for PCSS, and the timing of ARTA treatment (before or after chemotherapy) and the prostate-specific antigen (PSA) response after MDT were significant prognostic factors for PFS. Multivariate analysis showed that early MDT for oligoprogressive lesions delivered less than 6 months after the beginning of ARTA and higher PSA levels after MDT were significant predictors of worse PCSS and PFS. The median total duration of ARTA treatment was 13.8 months. The median time between the start of ARTA treatment and the start of MDT for oligoprogressive lesions was 5.2 months, and MDT extended the ARTA treatment by 8.6 months on average. Thirty-two (59.3%) patients continued ARTA treatment after MDT. ARTA treatment after chemotherapy, early oligoprogression requiring MDT, and lower radiation doses for MDT were independent predictors of NEST-FS in multivariate analysis. CONCLUSIONS: MDT for oligoprogressive lesions is effective and may provide several benefits compared to switching from ARTA treatment to NEST. Patients with early progression while on ARTAs and inadequate PSA responses after MDT have a greater risk of rapid disease progression and poor survival, which necessitates intensified treatment.

Multi-institutional validation of the ESMO-ESGO-ESTRO consensus conference risk grouping in Turkish endometrial cancer patients treated with comprehensive surgical staging.

In this study, 683 patients with endometrial cancer (EC) after comprehensive surgical staging were classified into four risk groups as low (LR), intermediate (IR), high-intermediate (HIR) and high-risk (HR), according to the recent consensus risk grouping. Patients with disease confined to the uterus, ≥50% myometrial invasion (MI) and/or grade 3 histology were treated with vaginal brachytherapy (VBT). Patients with stage II disease, positive/close surgical margins or extra-uterine extension were treated with external beam radiotherapy (EBRT)±VBT. The median follow-up was 56 months. The overall survival (OS) was significantly different between LR and HR groups, and there was a trend between LR and HIR groups. Relapse-free survival (RFS) was significantly different between LR and HIR, LR and HR and IR and HR groups. There was no significant difference in OS and RFS rates between the HIR and HR groups. In HR patients, the OS and RFS rates were significantly higher in stage IB - grade 3 and stage II compared to stage III and non-endometrioid histology without any difference between the two uterine-confined stages and between stage III and non-endometrioid histology. The current risk grouping does not clearly discriminate the HIR and IR groups. In patients with comprehensive surgical staging, a further risk grouping is needed to distinguish the real HR group.Impact statementWhat is already known on this subject? The standard treatment for endometrial cancer (EC) is surgery and adjuvant radiotherapy (RT) and/or chemotherapy is recommended according to risk factors. The recent European Society for Medical Oncology (ESMO), European Society of Gynaecological Oncology (ESGO) and European Society for Radiotherapy and Oncology (ESTRO) guideline have introduced a new risk group. However, the risk grouping is still quite heterogeneous.What do the results of this study add? This study demonstrated that the current risk grouping recommended by ESMO-ESGO-ESTRO does not clearly discriminate the intermediate risk (IR) and high-intermediate risk (HIR) groups.What are the implications of these findings for clinical practice and/or further research? Based on the results of this study, a new risk grouping can be made to discriminate HIR and IR groups clearly in patients with comprehensive surgical staging.

Prediction of Peritoneal Recurrence in Patients with Gastric Cancer: a Multicenter Study.

PURPOSE: The peritoneum is the common recurrence site of gastric cancer (GC) presenting with worse survival. Although some predictive clinicopathological factors have been identified, there is no comprehensive assessment of peritoneal recurrence risk prediction for patients treated with adjuvant chemotherapy (CR) or chemoradiotherapy (CRT) after surgery. We aimed to predict peritoneal recurrence and develop a new scoring model in GC. METHODS: This retrospective study included 274 GC patients who presented with recurrence after curative gastrectomy followed by adjuvant chemotherapy (CT) or chemoradiotherapy (CRT). Risk factors for peritoneal recurrence were analyzed using the following parameters: age, gender, tumor location and characteristics, and differences between treatment modalities. All parameters were assessed by binary logistic regression analysis to compare the patients with and without peritoneal recurrence. Then, a new risk scoring model was developed. RESULTS: Peritoneal recurrence was observed in 115 (44.1%) patients. Peritoneal recurrence was higher in female gender (odds ratio (OR), 1.93; 1.07-3.49, P = 0.030, 1 point), T4a-b stage (OR, 2.47; 1.14-5.36, P = 0.022, 1 point), poor/undifferentiated (OR, 2.04; 1.31-4.06, P = 0.004, 1 point), and signet cell carcinoma (OR, 2.04; 1.04-4.02, P = 0.038, 1 point) after adjusted for resection and dissection types. The risk scoring model was developed using the related parameters: Peritoneal recurrence rates were 24.6%, 42.6%, and 71.4% for group 1 (0 point), group 2 (1-2 points), and group 3 (3-4 points), respectively. CONCLUSION: Female gender, T4 tumor stage, undifferentiated histopathology, and signet cell type had a tendency to peritoneal recurrence after adjusted for treatment modalities. Patients with 3 or 4 risk factors had an 8.8-fold increased risk for the development of peritoneal recurrence.

What is the predictive value of preoperative CA 125 level on the survival rate of type 1 endometrial cancer?

Background/aim: To investigate the utility of preoperative serum cancer antigen 125 (CA 125) levels in type 1 endometrial carcinoma (EC) as a marker for determining poor prognostic factors and survival. Material and methods: All patients with endometrial cancer, who had been treated between 2012 and 2020, were retrospectively reviewed, and finally, 256 patients with type 1 endometrium carcinoma were included in the study. The relationship between the clinicopathological characteristics, CA 125 level, and survival rates were analyzed. The cut-off value for the preoperative serum CA 125 level was defined as 16 IU/L. Results: The median serum CA 125 levels were significantly higher in patients with deep myometrial invasion, lymph node metastasis, lymphovascular space invasion, cervical stromal and adnexal involvement, advanced stage, positive peritoneal cytology, recurrence, and adjuvant therapy requirement. Serum CA 125 cut-off values determined according to clinicopathologic factors ranged from 15.3 to 22.9 IU/L (sensitivity 61%­77%, specificity 52%­73%). The disease-specific survival rate was significantly higher in patients with CA 125 levels < 16 IU/L (P = 0.047). Conclusion: The data showed that choosing a lower threshold value for the CA 125 level (16 IU/L) instead of 35 IU/L, could be more useful in type 1 EC patients with negative prognostic factors.

Efficacy of regorafenib in the second-and third-line setting for patients with advanced hepatocellular carcinoma: A real life data of multicenter study from Turkey.

PURPOSE: After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the second- or third-line setting. METHODS: In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a second- or third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included. RESULTS: In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (pPFS=0.22 and pOS=0.85). CONCLUSION: Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.

Half-dose bevacizumab experience in relapsed ovarian cancer patients in Turkey due to formal regulations: similar effectiveness with lower rate of hypertension.

PURPOSE: Ovarian cancer is the fifth leading cause of cancer related death in women. Platin-based doublet regimens plus bevacizumab is standard treatment in relapse. Due to formal regulation of Turkish Ministry of Health, adjuvant bevacizumab has not been reimbursed and clinicians can use bevacizumab at a dose of 7.5 mg/kg/3wk in platin-resistant and sensitive relapse settings. The primary aim of this study was to evaluate 7.5 mg/kg/3wk bevacizumab dosing in platin-resistant and sensitive relapse ovarian cancer and compare these findings with the current literature. METHODS: A total of 106 patients with relapsed ovarian cancer and treated with bevacizumab (bevacizumab is not reimbursed as a part of adjuvant treatment in Turkey) on their first relapse were included. RESULTS: At a median follow-up of 32.1 months (5.3-110.8), 56 (52.8%) patients died. Progression-free survival (PFS) and overall survival (OS) were estimated at 18.8 months (14.4-23.3) vs 29.7 months (24.3-35.1) of the whole group overall survival. We observed that 78.4% of patients treated with primary surgery without neoadjuvant treatment and 59 (57.8%) out of the 102 patients with debulking surgery relapsed. A significant number of patients (81%) treated with primary surgery without neoadjuvant treatment and 59 (76.6 %) had secondary debulking surgery at relapse. In relapse, 38 patients were treated with single agent liposomal doxorubicin (LPD) plus bevacizumab. On the other hand, 68 patients were treated with carboplatin and LPD plus bevacizumab. Multivariate analysis failed to show any clinicopathological characteristics with significant effect on PFS. However, cytoreductive surgery at relapse showed significant effect on OS. Bevacizumab-related toxicities were detected in 23 (21.7%) patients; hypertension, pulmonary embolism, perforation, and other toxicities (nephrotic syndrome in 2, osteonecrosis in 2, cerebrovascular and cardiac ischemia in 3 patients) were seen in 12 (11.3%), 3 (2.8%), 1 (0.9%) and 7 (6.6%) patients, respectively. CONCLUSIONS: In conclusion, our findings showed that 7.5 mg/kg/3week dosing of bevacizumab in relapsed ovarian cancer could have similar effectiveness compared to standard 15 mg/kg/3week dosing. Increase of OS and PFS in patients treated with primary and secondary debulking surgery with no-visible disease was more pronounced. No new safety information was observed but lower rate of grade 3 or above hypertension with similar rate of severe vascular and intestinal complications were detected.

The prognostic value of haematologic parameter changes during treatment in cervical cancer patients treated with definitive chemoradiotherapy.

We retrospectively analysed the prognostic significance of changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) during treatment with definitive chemoradiotherapy (CRT) in 104 cervical cancer patients. The absolute white blood cell, ANC and ALC decrease during treatment, NLR increased throughout treatment and reached to a plateau at fifth week. The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in low-haematological risk (LHR) group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. In multivariate analysis, high-haematological risk (HHR) group and lymph node metastasis were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. IMPACT STATEMENT What is already known on this subject? The ANC and NLR after 3rd week of definitive CRT were significantly higher and ALC after 3rd week of treatment was significantly lower in patients with progressive disease compared patients with no evidence of disease. Patients in LHR group had significantly higher number of patients with smaller tumour size, early stage disease and without lymph node metastasis. Lymph node metastasis and HHR and were negative prognosticators of overall and disease-free survival (DFS). The presence of lymph node metastasis and HHR could serve as a predicative factor of poor prognosis for cervical cancer patients. What the results of this study add? Weekly changes in ANC, ALC, and NLR, especially after 3rd week of treatment are predictive factors of disease progression, not the high-risk features of disease. Furthermore, in HHR group more patients with extensive stage disease, larger tumour and lymph node metastasis were observed compared to LHR group. What the implications are of these findings for clinical practice and/or further research? The patients may be stratified according to risk factors. The treatment intensification maybe required for HHR patients compared to LHR patients. Since our findings are preliminary, further studies are required to support these findings.

The hematologic parameters in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

Currently, there are no predictive markers of response to abiraterone. We calculated neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) at baseline and at 4 and 12 weeks after initiation of abiraterone, and we evaluated prostate-specific antigen (PSA) response every 4 weeks in 102 metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone either pre- or postchemotherapy. With a median follow-up was 24.0 months (range: 0.3-54.9), median overall survival (OS) was 20.8 months. High-NLR patients who remained high or who returned to low NLR after 4 and 12 weeks showed significantly worse OS than patients with low baseline NLR. NLR and prostate-specific antigen response to abiraterone was a significant predictor of OS and progression-free survival (PFS) in metastatic castration-resistant prostate cancer patients treated with abiraterone delivered either pre- or postchemotherapy.

Outcome of loco-regional radiotherapy in metastatic castration-resistant prostate cancer patients treated with abiraterone acetate.

PURPOSE: To evaluate the potential benefit of curative radiotherapy (RT) to the primary tumor in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone. MATERIALS AND METHODS: The clinical parameters of 106 mCRPC patients treated with abiraterone were retrospectively evaluated. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after the systemic treatment was analyzed. Local RT to the primary tumor and pelvic lymphatics was delivered in 44 patients (41%), and 62 patients (59%) did not have RT to the primary tumor. After propensity match analysis, a total of 92 patients were analyzed. RESULTSN: Median follow-up time was 14.2 months (range: 2.3-54.9 months). Median overall survival (OS) was higher in patients treated with local RT to the primary tumor than in those treated without local RT with borderline significance (24.1 vs. 21.4 months; p = 0.08). Local RT to the prostate and pelvic lymphatics significantly diminished the local recurrence rate (16 patients, 31% vs. 2 patients, 5%; p = 0.003). In multivariate analysis, the prostate specific antigen (PSA) response ≥50% of the baseline obtained 3 weeks after abiraterone therapy was the only significant prognostic factor for better OS and progression-free survival (PFS). Patients treated with primary RT to the prostate had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT. CONCLUSIONS: Local prostate RT significantly improved OS and local control in mCRPC patients treated with abiraterone. The patients treated with primary RT had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.

Adding taxane to platin-5-fluorouracil combination does not improve survival rate in patients ≥ 65 years of age with advanced gastric cancer: A retrospective-multicenter study.

PURPOSE: Advanced gastric cancer (AGC) has a dismal prognosis. Platin-5-fluorouracil (CF) combination chemotherapy is the most widely used protocol and addition of a taxane (TCF) seems to increase survival and toxicity rates. We aimed to evaluate efficacy and toxicity of TCF as compared to CF in patients older than 65 years and compare them with the patients younger than 65 years. METHODS: A total of 341 patients with AGC have been treated at six different oncology centers in Turkey between 2010 and 2014 and evaluated retrospectively. The characteristics of the patients whose tumors were histologically confirmed and whose survival data were available were registered and analyzed. The study group consisted of 234 patients younger than 65 years (group 1) and 107 patients older than 65 years (group 2). All of the data obtained from the patients were statistically analyzed. RESULTS: The median age of the patients was 58.2 years and the mean follow-up time 14.4 months. For the entire group, progression-free survival (PFS) and overall survival (OS) were 9 and 13 months, respectively. Using TCF over CF regimen increased the OS by 4.2 months (i.e., group 1 and 2 together). For group 2, patients with liver metastases and without surgery of the primary tumor were treated with significantly more TCF as compared to CF, respectively. Although TCF yielded significantly higher PFS and OS in group 1 (p=0.0001 and p=0.017), there was no significant difference in group 2 as compared to CF. Also, grade 3-4 toxicity was statistically defined as one of the possible reasons of worsened OS in patients older than 65 years and receiving TCF. CONCLUSIONS: The addition of taxanes to CF backbone leads to a significant increase in both PFS and OS in patients younger than 65 years of age but the triplet regimen with taxanes does not provide superior survival in patients older than 65 years of age.

A study on basic demographic and disease characteristics of cancer-diagnosed Syrian refugees treated in the border city of Turkey, Sanliurfa; a hospital-based retrospective case series study.

PURPOSE: Turkey hosts around 3 million Syrian refugees which is more than any other country in the world. Along with some other adaptation issues like cultural, language, and economic difficulties, significant problems in managing medical problems, chronic diseases like cancer in particular, have to be fixed. However, there are few studies which explore main patient and clinicopathological characteristics in Syrian refugees with cancer. The purpose of this study was to highlight the aforementioned characteristics along with management issues after cancer diagnosis of these patients. METHODS: This study was designed as a hospital-based retrospective observational case-series study of 134 Syrian refugees cancer patients between 2015 and 2017. RESULTS: The patient median age was 47.5 years (range 18- 80). Out of the 134, 102 (76.1%) were female. The most common cancer types were breast (n=57, 42.5%) and gynecological cancers (n=14, 10.4%). The majority of patients were diagnosed at advanced stage (n=60, 44.8%). There were 91 (67.9%) and 43 (32.1%) patients admitted to our center from refugee camps and staying in a house, respectively. The median follow-up was 14 months (range 1-111) and 11 (8.2%) patients died. One and two-year survival rate of the whole group were 93% and 86%, respectively. There were 12 (9%) patients with grade 3-4 hematological and non-hematological toxicities. Neutropenia was the most common grade 3-4 toxicity (n=8, 6%). The patients staying in refugee camp (n-91) or in a house (n=43) finished all planned cycles of chemotherapy with a rate of 71% (n=65) and 79% (n=34), respectively. Statistical analysis failed to show significant relationship between the staying site (either camp or house), chemotherapy compliance rate, grade 3-4 toxicities with p=0.347 and p=0.09, respectively. CONCLUSION: Our results revealed that breast cancer and gynecological cancers were the most common cancer types which are good candidates for cancer screening. Unfortunately, the majority of patients had cancer diagnosed at advanced stage. However, after diagnosis they could reach all health facilities including surgical operation, radiotherapy, and systemic chemotherapy similar to Turkish cancer patients. Therefore, our results suggested that major problem for the Syrian refugees adapting them into national screening program which may resulted that cancer diagnosis at earlier stage with high cure rate.

Prognostic value of procalcitonin in infection-related mortality of cancer patients.

PURPOSE: Infectious diseases are a major cause of morbidity and mortality in cancer patients. Tumor-induced inflammatory responses may increase the value of classical inflammatory markers in blood, so these markers may not be as useful in cancer patients as in non-cancer patients. Serum procalcitonin (PCT) is a sensitive and specific biomarker for severe infection, and has been shown to be unaffected by tumor-induced inflammatory response. In this study we aimed to evaluate the possible role of PCT in mortality in cancer patients with infection. METHODS: In total, 104 consecutive adult cancer patients who presented with fever (body temperature ≥ 38.3° C or ≥ 38° C on two consecutive measurements) during follow-up and needing hospitalization for infection were enrolled in this study. RESULTS: The majority (72%) of the patients were male. The most common diagnosis and type of infection were lung cancer (40.4%) and pneumonia (56.7%), respectively. The overall mortality rate was 17%. Statistical analysis showed a significant relationship between PCT levels and mortality (p=0.001), but not between classical inflammatory markers and mortality (p>0.05). The mortality rate of patients with a PCT value > 2 ng/mL was 34.3%, compared with 9.6% in patients with a PCT below this value (p=0.005). Furthermore, PCT predicted in-ward cancer patient mortality with a sensitivity of 66% and a specificity of 76%. CONCLUSION: PCT is a unique serum biomarker significantly related to infection-related mortality and predicts mortality with a relatively high sensitivity and specificity.