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.

First-line treatment of patients with HER2-positive metastatic gastric and gastroesophageal junction cancer.

Fluoropyrimidine+cisplatin/oxaliplatin+trastuzumab therapy is recommended for the first-line treatment of HER2-positive metastatic gastric adenocarcinoma. However, there is no comprehensive study on which platinum-based treatment should be preferred. This study aimed to compare the treatment response and survival characteristics of patients with HER2-positive metastatic gastric or gastroesophageal junction (GEJ) cancer who received fluorouracil, oxaliplatin, and leucovorin (mFOLFOX)+trastuzumab or cisplatin and fluorouracil (CF)+trastuzumab as first-line therapy. It was a multicenter, retrospective study of the Turkish Oncology Group, which included 243 patients from 21 oncology centers. There were 113 patients in the mFOLFOX+trastuzumab arm and 130 patients in the CF+trastuzumab arm. The median age was 62 years in the mFOLFOX+trastuzumab arm and 61 years in the CF+trastuzumab arm (P = 0.495). 81.4% of patients in the mFOLFOX+trastuzumab arm and 83.1% in the CF+trastuzumab arm had gastric tumor localization (P = 0.735). The median progression-free survival (PFS) was significantly higher in the mFOLFOX+trastuzumab arm (9.4 months vs. 7.3 months, P = 0.024). The median overall survival (OS) was similar in both groups (18.4 months vs. 15.1 months, P = 0.640). Maintenance trastuzumab was continued after chemotherapy in 101 patients. In this subgroup, the median OS was 23.3 months and the median PFS was 13.3 months. In conclusion, mFOLFOX+trastuzumab is similar to CF+trastuzumab in terms of the median OS, but it is more effective in terms of the median PFS in the first-line treatment of HER2-positive metastatic gastric and GEJ cancer. The choice of treatment should be made by considering the prominent toxicity findings of the chemotherapy regimens.

Comparison of 68Ga-FAPI PET/CT and 18FDG PET/CT Modalities in Gastrointestinal System Malignancies with Peritoneal Involvement.

PURPOSE: In this study, we aimed to investigate the utilization of 68Ga-FAPI PET/CT in comparison to 18FDG PET/CT to evaluate the peritoneal involvement of the gastrointestinal malignancies alongside primary lesions and other metastatic foci. PROCEDURES: A total of 37 patients with various gastrointestinal malignancies with accompanying peritoneal involvement who underwent 68Ga-FAPI PET/CT and 18FDG PET/CT imaging between September 2020 and June 2021 were included in this retrospective study. SUVmax values of 68Ga-FAPI and 18FDG were compared according to lesion locations. Also, the lesion localization ability of both imaging was compared in patient basis. RESULTS: Of the 37 patients with peritoneal involvement (23 males and 14 females; median age, 62.8 ± 12.7 years), 35.1% (n = 13) had colorectal cancer, 37.8% (n = 14) gastric cancer, and 27.0% (n = 10) pancreaticobiliary cancer. While 45.9% of them were operated, the remaining did not have surgery. The mean time interval between two studies was 3.2 days (range: 2-6 days). The mean SUVmax value of peritoneal metastases (p < 0.001) was significantly higher with 68Ga-FAPI PET/CT compared to that with 18FDG PET/CT, as in primary lesions (p < 0.001), lymph node metastases (p = 0.006), liver metastases (p = 0.002), and bone metastases (p = 0.018). A total of 185 lesions was detected in the initial assessment with 18FDG PET/CT. Of the total lesions detected with 18FDG PET/CT, 5 of them were evaluated as benign lesions with 68Ga-FAPI PET/CT also in accordance with the reference standard. In addition to 180 lesions detected with 18FDG PET/CT, a total of 37 additional malignant lesions, 12 of which were peritoneal metastases, were detected with 68Ga-FAPI PET/CT. CONCLUSION: 68Ga-FAPI PET/CT was determined to be superior to 18FDG PET/CT in terms of detection of peritoneal involvement with high image quality as well as primary tumor and other metastatic foci. Consequently, 68Ga-FAPI PET/CT can be used as a complementary imaging modality especially for inconclusive 18FDG findings due to the lack of accuracy of 18FDG PET/CT in some of the metastatic regions, especially in the liver.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

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.

Is SUVmax a useful marker for progression-free survival in patients with metastatic GEP-NET receiving 177Lu-DOTATATE therapy?

OBJECTIVE: The prognostic potential of pretreatment maximum standardized uptake volume (SUVmax) on gallium-68-DOTATATE was evaluated with positron emission tomography/computed tomography (68Ga-DOTATATE PET/CT) in 37 patients with G1/G2 gastroenteropancreatic neuroendocrine tumors (NET) who received peptide receptor radionuclide therapy (PRRT) with lutetium-177-[DOTAo,Tyr3] octreotate (177Lu-DOTATATE) after the failure of somatostatin analogues. METHODS: The mean and total SUVmax were used in 68Ga-DOTATATE PET/CT before 177Lu-DOTATATE treatment to assess the progression-free survival (PFS). RESULTS: The responses of the patients were evaluated as partial response in 8 (32%) patients, stable disease in 12 (48%), and progressive disease in 5 (20%). The median PFS was 18 months; longer than this threshold in 14 patients (26.0 months) and shorter in 11 (8.4 months). The mean SUVmax of metastases in the liver (34.15±17.89 vs. 14.69±9.17, P=0.004) and mean SUVmax of all body metastatic lesions (33.05±14.32 vs. 15.26±4.84, P=0.001) were higher in patientswith longer PFS. The tumor grade, the origin of the tumor, Ki67 status, and previous somatostatin treatment history were not significantly different between the two PFS groups. CONCLUSION: The pre-treatment SUVmax values of 68Ga-DOTATATE PET/CT in lesions are a potential prognostic factor for PFS in well-differentiated gastroenteropancreatic neuroendocrine tumors undergoing 177Lu-DOTATATE treatment, and could be a useful parameter for the treatment selection.

Superiority of 68Ga-FAPI PET/CT scan in detecting additional lesions compared to 18FDG PET/CT scan in breast cancer.

PURPOSE: We compared the ability of 68Ga-FAPI PET//CT with 18FDG PET/CT imaging techniques to detect additional lesions in breast cancer patients that may affect further chemotherapy options. METHODS: A total of 48 patients with breast cancer underwent concurrent 68Ga-FAPI-04 and 18FDG PET/CT regardless of whether they had received chemotherapy or not in the last month before imaging. Both modalities were compared according to various parameters: clinical/pathological features, number of lesions detected, activity uptake (SUVmax), and the effect on the evaluation of response to treatment in the post-chemotherapy group. RESULTS: This retrospective study included 48 patients with breast cancer (mean age 53.3 ± 11.7 years; IDC 89.6%; ILC 10.4%). In the comparison of both modalities, no statistical significance was obtained in terms of the pathological characteristics of the patients. More lesions were demonstrated in all categorized regions in 68Ga-FAPI PET/CT imaging with higher uptake values compared to 18FDG PET/CT in this study. In the treatment response evaluation of the post-chemotherapy group, 12 cases (12/24) who were evaluated as PMR, CMR, or SD according to 18FDG PET/CT results were later accepted as PD due to newly detected lesions in complementary 68Ga-FAPI PET/CT imaging and treatment of patients was managed accordingly by clinicians. CONCLUSION: It was determined that 68Ga-FAPI PET/CT was superior to 18FDG PET/CT in terms of accuracy and it was thought that 68Ga-FAPI PET/CT could be utilized as an additional complementary imaging to 18FDG PET/CT. Moreover, 68Ga-FAPI PET/CT, with its significant theranostic potential, could become a key element in predicting the pathological response of breast cancer patients in further researches.

The mean platelet volume may predict the development of isolated bone metastases in patients with breast cancer: a retrospective study of the Young Researchers Committee of the Turkish Oncology Group (TOG).

PURPOSE: To determine the predictive value of the mean platelet volume (MPV) and the MPV/platelet count ratio on the development of isolated bone metastasis in patients with breast cancer. METHODS: A total of 121 previously untreated female patients with isolated bone metastases from breast cancer (group 1) were included in this retrospective cohort study. The patients enrolled in this study had similar age, biological subtypes, and duration of follow-up after diagnosis. Group 1 was compared with both 71 previously untreated women with breast cancer with no metastases at all (group 2) and 39 healthy women (group 3). Demographic data, laboratory tests and histological features of all of the patients in groups 1 and 2 were recorded and the study variables from each of the three groups were compared. RESULTS: In group 1, the cut-off value (9.2 fL) for the MPV was determined and patients were stratified into 4 subgroups. The MPV was higher in group 1 than in either group 2 or group 3. Group 1 patients had a MPV of 8.8±3.1 fL (mean 5.1, range: 6.1-15.6) and the cut-off value for MPV was 9.2 fl. For patients in group 1, the MPV distribution was stratified into 4 groups as follows: group A included MPV values <6.08 fL, in group B values ranged from 6.09 to 8.46 fL, group C included values from 8.47 to 10.05 fL, and group D included patients with MPV values >10.06 fL. MPV and the presence of lymphovascular invasion were found to be independent risk factors for the development of isolated bone metastases. CONCLUSION: We concluded that MPV can be used to predict the development of isolated bone metastases.

The effect of anticancer therapy on anti-hepatitis B antibody titres in patients with haematological malignancies and solid tumours.

OBJECTIVE: To investigate the effect of immunosuppressive anticancer therapy on titre levels of anti-hepatitis B surface antibodies (anti-HBs) in hepatitis B surface antigen (HBsAg) negative and anti-HBs positive patients with haematological malignancies or solid tumours. METHODS: This retrospective study reviewed the medical records of patients with haematological malignancies or solid tumours. Pretreatment HBsAg negative and anti-HBs positive patients were included in the analysis. Anti-hepatitis B core antibody status was used to evaluate vaccinated patients and those with resolved HBV infections. RESULTS: The medical records of 237 patients were reviewed retrospectively. The median anti-HBs titre decreased significantly after anticancer therapy compared with the pretreatment median anti-HBs titre in all patients (71 mIU/ml versus 57 mIU/ml). Anti-HBs titre decreased significantly in patients with haematological malignancies (70 mIU/m versus 37 mIU/ml) and in patients administered rituximab-based chemotherapy (67 mIU/ml versus 33 mIU/ml) following chemotherapy, whereas there was no significant change in patients with solid tumours. After chemotherapy, patients with low pretreatment anti-HBs titres (<100 mIU/ml) were more likely to become seronegative (<10 mIU/ml). CONCLUSION: High levels of anti-HBs may have a protective effect against the reactivation of HBV especially in patients with haematological malignancies who received immunosuppressive anticancer therapy.

Quality of life in colorectal cancer patients during chemotherapy in the era of monoclonal antibody therapies.

PURPOSE: Colorectal cancer (CRC) survivors are currently living longer due to better therapies but they also need to maintain their quality of life (QoL). QoL is increasingly being used as primary outcome measure in clinical studies. This study was designed to gain knowledge about QoL during chemotherapy across different lines and different regimens. METHODS: The study comprised 101 CRC out patients receiving chemotherapy who completed the EORTC QLQ-C30 questionnaire. The Shapiro-Wilk, Kruskal-Wallis, and Mann-Whitney U tests were used for statistical analyses. RESULTS: The demographics of the patients were evaluated for QoL. Prior surgery, prior radiotherapy, working status, stage, comorbidity and sex had no effect on global health status in CRC patients, although some other demographics such as education, monthly income, age and type of chemotherapy regimen did have an effect on global health status. Role functioning was worse in older than in younger ones (p<0.05). Adjuvant chemotherapy did not affect the QoL scores negatively but palliative chemotherapy negatively affected the cognitive function, appetite loss and nausea/vomiting scores (p<0.05). According to chemotherapy regimen, the best QoL was observed with adjuvant FUFA regimen. In the palliative setting FOLFOX/Bevacizumab was associated with the best QoL scores whereas FOLFIRI/Cetuximab were associated with the worst QoL scores. CONCLUSIONS: Palliative chemotherapy maintained QoL irrespective of the chemotherapy line in metastatic CRC (mCRC) patients. Some demographics affect QoL and different chemotherapy regimens showed different QoL scores.

The value of red blood cell distribution width in endometrial cancer.

BACKGROUND: Red cell distribution width (RDW) is a routinely examined parameter with the complete blood count. In recent studies, RDW levels have been associated with cardiovascular, liver and renal diseases and solid tumors. The aim of this study was to evaluate the alterations of RDW levels in benign and malignant causes of postmenopausal bleeding and to investigate the association of RDW levels with clinicopathological parameters of endometrial cancer (EC) patients. METHODS: A retrospective study was made of a total of 884 females who were admitted to hospital for postmenopausal bleeding between May 2009 and December 2013. After inclusion and exclusion criteria were applied, 222 patients remained. Complete blood count data was obtained from the recorded computerized database. After pathological evaluation, the patients were divided into two groups, benign and malignant (EC). RESULTS: The EC group (n=113) had significantly higher RDW levels compared to the benign group (14.78±2.02 vs. 13.88±1.05; p=0.000). Grade II and above EC patients had higher levels of RDW than Grade I patients (15.2±2.3 vs. 14.1±1.00; p=0.005). Correlation analyses also revealed a negative correlation between RDW and hemoglobin levels (p=0.000), RDW and mean corpuscular volume (p=0.000), RDW and lymphocyte count (p=0.035) but a positive correlation between RDW and platelet to lymphocyte ratio (p=0.030). CONCLUSIONS: The results of the current study revealed the potential predicitve role of RDW in patients with postmenopausal bleeding. Significant associations were also determined between RDW and clinicopathological characteristics in EC patients.

A case of gastric cancer with liver metastases had a complete response with cisplatin and capecitabine as third-line chemotherapy.

Advanced gastric cancer has a poor prognosis, and only chemotherapy improves survival. Further chemotherapy after progression is controversial. Eastern Cooperative Oncology Group performance status is an important indicator for new chemotherapy decision. Complete response (CR) after recurrent disease is very rare, but could occur in some cases with chemotherapy. The 68-year-old male received chemotherapy for metastatic gastric adenocarcinoma. He received epirubicin, cisplatin and fluorouracil in the first line, capecitabine in the second line and cisplatin-capecitabine in the third line. CR was observed after third-line chemotherapy with four courses. Mediastinal and abdominal metastases were completely resolved. We decided to report this patient because it is very unusual to achieve CR in a patient in whom the best supportive care might be reasonable.

Efficacy and safety of docetaxel or epirubicin, combined with cisplatin and fluorouracil (DCF and ECF), regimens as first line chemotherapy for advanced gastric cancer: a retrospective analysis from Turkey.

OBJECTIVES: Advanced gastric cancer (AGC) patients have a poor prognosis. The best benefit of chemotherapy is usually achieved by first line setting. Very few studies have compared combination regimens. This study was designed to compare two combination regimens. METHODS: Patients with advanced gastric cancer receiving first line chemotherapy were retrospectively collected, and divided into two groups, receiving DCF (docetaxel, cisplatin and fluorouracil) or ECF (epirubicin, cisplatin and fluorouracil) regimens. Data were collected for the retrospective analysis in a single center. RESULTS: Eighty-six patients were eligible for analysis. Median overall survival (OS) was 10.0 months in the ECF group and 11.0 months in the DCF group (p=0.31). Median progression free survival (PFS) for ECF and DCF was equal at 6.0 months. Second line chemotherapy were administered in more than one third of patients. Both regimens had similar toxicity. CONCLUSIONS: This is the first study investigating the outcomes of gastric cancer chemotherapy in this region. ECF and DCF regimens have similar efficacy and a similar tolerability profile for first line treatment of advanced gastric cancer. The decision of the first line chemotherapy in advanced gastric cancer could be improved with patient selection according to clinical parameters and molecular markers.

Elevated serum neutrophil to lymphocyte and platelet to lymphocyte ratios could be useful in lung cancer diagnosis.

BACKGROUND: Lung cancer (LC) is still the primary cause of cancer deaths worldwide, and late diagnosis is a major obstacle to improving lung cancer outcomes. Recently, elevated preoperative or pretreatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and mean platelet volume (MPV) detected in peripheral blood were identified as independent prognostic factors associated with poor survival with various cancers, including colon cancer, esophageal cancer, gastric cancer and breast cancer. OBJECTIVE: The aim of this study was to examine whether MPV, NLR and PLR could be useful inflammatory markers to differentiate lung cancer patients from healthy controls. An investigation was also made of the relationship between these markers and other prognostic factors and histopathological subgroups. MATERIALS AND METHODS: Retrospectively eighty-one lung cancer patients and 81 age-sexes matched healthy subjects included into the study. Patients with hypertension, hematological and renal disease, heart failure, chronic infection, hepatic disorder and other cancer were excluded from the study. The preoperative or pretreatment blood count data was obtained from the recorded computerized database. RESULTS: NLR and PLR values were significantly higher in the LC patients compared to the healthy subjects.( NLR: 4.42 vs 2.45 p=0.001, PLR: 245.1 vs 148.2 p=0.002) MPV values were similar in both groups (7.7 vs 7.8). No statistically significant relationship was determined between these markers (MPV, NLR and PLR) and histopathological subgroups and TNM stages. CONCLUSIONS: NLR and PLR can be useful biomarkers in LC patients before treatment. Larger prospective studies are required to confirm these findings.