Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

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 Nutritional Parameters and Thrombosis Risk in Cancer Patients.

Venous thromboembolism which consists of pulmonary embolism and deep venous thrombosis is one of the most important problems in cancer patients. The mechanisms of cancer-associated thrombosis are multi-factorial and still unclear. Nutrition is an important factor in the treatment and prognosis of cancer. Assessment of the nutritional status of cancer patients is multifactorial and it should be performed at each visit. We aimed to assess the relationship between nutritional status and thrombosis risk in various cancer types. It was a cross-sectional and single-center study and 582 cancer patients were included. Patients nutritional status was evaluated with their height, weight, BMI, triceps skinfold thickness, waist circumference, and upper arm circumference. It was found that there was a statistically significant relationship between the thrombosis risk and nutritional parameters such as weight, BMI, and waist circumference which are important anthropometric measurements. As a result, thrombosis is an important cause of morbidity and mortality in cancer patients. Obesity and cachexia are both important conditions in cancer patients and should be well evaluated. It has been shown that increased weight, BMI, and waist circumference indicating obesity are important risk factors for thrombosis risk in cancer patients.

Real-Life Analysis of Efficacy and Safety of Everolimus Plus Exemestane in Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor-2-Negative Metastatic Breast Cancer Patients: A Turkish Oncology Group (TOG) Study.

PURPOSE: This study evaluated the efficacy and safety of everolimus (EVE) plus exemestane (EXE) in hormone-receptor positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) metastatic breast cancer (MBC) patients in real-life settings. METHODS: Overall, 204 HR+, HER2- MBC patients treated with EVE + EXE after progressing following prior endocrine treatment were included. Overall survival (OS) and progression-free survival (PFS) and safety data were analyzed. RESULTS: The objective response rate, median PFS, and median OS were 33.4%, 8.9 months, and 23.4 months, respectively. Multivariate analysis revealed that negative progesterone receptor status was a significant determinant of poor treatment response (p = 0.035) and PFS (p = 0.024). The presence of bone-only metastasis was associated with better treatment response (p = 0.002), PFS (p < 0.001), and OS (p = 0.001). CONCLUSION: We confirmed the favorable efficacy and safety profile of EVE + EXE for HR+, HER - MBC patients.

Bevacizumab in recurrent ovarian cancer.

PURPOSE: The cost-effectiveness of bevacizumab has been the subject of debate, and we aimed to present our own retrospective data on its effect on survival in recurrent epithelial ovarian cancer. METHODS: Patients with recurrent ovarian, tubal and primary peritoneal cancer between October 2007 and June 2018 were grouped according to the platinum-free interval. The progression-free and overall survivals of the patients who had received chemotherapy only and chemotherapy with bevacizumab were calculated. RESULTS: Eighty patients had received chemotherapy (CT) only, and 65 had received CT+BV. In platinum-sensitive recurrent epithelial ovarian cancer (PSREOC) patients, the median progression-free survival (PFS) months was 7 months (95% CI; 5.5-8.4) in the group who had received CT only and 13 months (95% CI; 5.8-20.1) in the group who had received CT+BV (p=0.001) and for CT+BV HR (Hazard Ratio):0.39 (95% CI; 0.24-0.64) (p=0.001). The median PFS of platinum-resistant recurrent epithelial ovarian cancer (PRREOC) patients who had received CT only was determined as 2 (95% CI; 1.4-2.5) and as 10 (95% CI; 6.8-13.1) months for patients who had received CT+BV (p=0.001), for patients who had received CT+BV HR: 0.31 (95% CI; 0.17-0.58) (p=0.001). In both PSREOC and PRREOC patients, there was no difference between CT + BV and CT group in terms of overall survival (p=0.978 and p=0.738, respectively). CONCLUSION: A significant effect of bevacizumab on the progression-free survival of both platinum-sensitive and platinum resistant recurrent ovarian cancers has been demonstrated; however, this effect failed to impact overall survival. Therefore, it could be recommended to use bevacizumab, considering the cost-effectiveness in undeveloped and developing countries.

MicroRNAs as biomarkers for breast cancer.

Breast cancer is the most common type of cancer among women and the most frequent cause of death due to cancer among women. The lack of standard biomarkers in the early diagnosis of breast cancer, microRNAs (miRNA) have been of interest recently. Although, miRNAs are 19-24 nucleotide-long non-coding RNA species, they have crucial roles in many areas from organogenesis to carcinogenesis. This study has been conducted to investigate miR 21, miR 27b, miR 125a, miR 155, miR 200c, miR 335 miR373 as biomarkers in the early diagnosis of breast cancer; a selection based on the literature. Two miRNAs, miR 181 and miR 192 were selected as the endogenous control. MiRNAs were obtained from 5 cc blood samples taken from 20 breast cancer patients and 20 healthy people. 10 microRNAs were studied using Real Time PCR method. As a result, the quantities of miR 21, miR155 and miR125 ​​were significantly higher in the breast cancer group than in healthy controls. We suggest that performing validation studies in wider populations can help the use of miRNAs as biomarkers in the early diagnosis of breast cancer.

Assessment of Prognostic Factors and Adjuvant Treatment Modalities in Adult Head and Neck Soft Tissue Sarcoma Patients Treated With Upfront Surgery.

Objectives Head and neck soft tissue sarcomas (HNSTSs) are a heterogeneous group of rare tumors. Surgical resection with negative margins remains the standard primary treatment for patients with HNSTS. The role of chemotherapy (CT) and radiotherapy (RT) remains controversial. In this multicenter study, we aimed to demonstrate the real-world assessing prognostic factors and the effect of adjuvant treatment modalities in adult patients with HNSTS treated with upfront surgery. Methods We included a total of 47 patients who underwent curative-intent resection of a primary HNSTS between 2000 and 2019. Results The median follow-up was 29 months. The median age of patients was 51 years, and 66% of patients were male. The median relapse-free survival (RFS) of the study population was 31 months (range: 1.0-61.1 months), and the median overall survival (OS) was 115 months (range: 60.8-169.2 months). The univariable analysis revealed that treatment modalities showed a significant impact on RFS (p = 0.021); however, no difference was found in its impact on OS (p = 0.137). R0 resection did not showed impact on RFS (p = 0.130), but a significant association was found with OS (p = 0.004). In multivariable analysis, T stage of the tumor (hazard ratio [HR]: 3.834; 95% CI: 1.631-9.008; p = 0.002) and treatment with surgery and sequential RT and CT (HR: 0.115; 95% CI: 0.035-0.371; p < 0.001) were independent factors associated with RFS. R0 resection was independently associated with OS (HR: 4.902; 95% CI: 1.301-18.465; p = 0.019). Conclusion Our study revealed that R0 resection improved OS, and T3-4 stage of tumor was a negative independent factor for RFS in surgically resected HNSTS patients. The use of sequential CT and RT after resection was associated with a better RFS, which emphasizes the importance of multidisciplinary evaluation of the treatment of HNSTS. Randomized prospective studies are needed.

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.

Worse patient-physician relationship is associated with more fear of cancer recurrence (Deimos Study): A study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

OBJECTIVE: Fear of cancer recurrence (FCR) is an important psychological trauma associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study was to evaluate the impact of patient-physician relationship on FCR. METHODS: The study was designed as a multicentre survey study. The cancer survivors, who were under remission, were evaluated with structured questionnaires. Patient-physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory was used. RESULTS: Between January and April 2019, 1,580 patients were evaluated. The median age was 57.0 (19-88), and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r = -.134, p < .001). In multivariate analysis, young age, female gender, history of metastasectomy and worse PPR were associated with high levels of FCR. CONCLUSION: It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practised. In addition, the cancer survivors, who are under the risk of FCR, should be evaluated and managed.

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.

68Ga-PSMA Uptake by Dermatofibroma in a Patient With Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a typ. 2 transmembrane protein that is highly expressed in prostate cancer cells. Ga-PSMA PET/CT imaging is a modality used to determine the extent of prostate cancer. Various other neoplasias may also express PSMA, which appears as Ga-PSMA uptake in PET/CT imaging. A 71-year-old man with prostate cancer underwent Ga-PSMA PET/CT imaging for restaging after having an elevated prostate-specific antigen level. Subcutaneous lesions showing focal PSMA uptake were detected, one of which was excised. The histopathologic diagnosis was dermatofibroma.

Prognostic factors in clinical stage T4N2 locally advanced non-small cell lung cancer.

PURPOSE: Relatively few studies have focused on T4N2 (stage IIIB) locally advanced non-small cell lung cancer (NSCLC). In this study, we tried to identify prognostic factors for patients with clinical stage T4N2 NSCLC. METHODS: We retrospectively identified 223 patients, of which 168 met the inclusion criteria. Patients treated with curative intent using concurrent chemoradiotherapy (CRT) with or without adjuvant chemotherapy, or concurrent CRT after induction chemotherapy, were included in this study. Relevant patient, treatment, and disease factors were evaluated for their prognostic significance in both univariate and multivariate analyses using the Cox proportional hazards model. RESULTS: The median progression-free survival (PFS) was 13 months (95% confidence interval [CI], 10.6-15.4). The median overall survival (OS) was 20 months (95% CI, 16.8-23.1), and 71, 40.3 and 28.2% of the patients survived for 1, 2 and 3 years after diagnosis, respectively. Multivariate analysis showed Eastern Cooperative Oncology Group (ECOG) performance status (PS) was independent predictor of PFS (hazard ratio [HR], 0.24; 95% CI, 0.13-0.43; p=0.001), and OS [HR, 0.48; 95% CI, 0.26-0.87; p=0.015). Absence of multifocal T4 tumors was also associated with a significantly longer OS (HR, 046; 95% CI, 0.31-0.7; p=0.001). There was no statistically significant difference in OS and PFS between treatment modalities. CONCLUSION: PFS and OS were significantly shorter in patients with poor ECOG PS. OS was also significantly shorter in patients with multifocal T4 tumors. There were no differences between the two therapeutic approaches with respect to outcome.

Use of chemotherapy at the end of life in Turkey.

BACKGROUND: An increasing number of patients receive palliative chemotherapy near the end of life. The aim of this study is to evaluate the aggressiveness of chemotherapy in Turkish individuals near the end of life. METHODS: Patients diagnosed with solid tumors and died from 2010 to 2011 in the medical oncology department of Akdeniz University were included in the study. Data about the diagnosis, treatment details and imaging procedures were collected. RESULTS: Three hundred and seventy-three people with stage IV solid tumors died from 2010 to 2011 in our clinic. Eighty-nine patients (23.9%) patients underwent chemotherapy in the last month of life while 39 patients (10.5%) received chemotherapy in the last 14 days. The probability of undergoing chemotherapy in the last month of life was influenced by: age, 'newly diagnosed' patients, and performance status. There was no significant association of chemotherapy in the last month of life with gender and tumor type. Having a PET-CT scan did not alter the chemotherapy decision. CONCLUSION: In conclusion, chemotherapy used in the last month of life in a tertiary care center of Turkey is high. Increasing quality of life should be a priority near the end of life and physicians should consider ceasing chemotherapy and direct the patient to early palliative care.

Prolonged progression-free survival with maintenance metronomic oral cyclophosphamide and etoposide treatment in macroscopic residual disease or recurrent/advanced stage ovarian cancer.

PURPOSE: In ovarian cancer permanent remission may be provided with optimal cytoreductive surgery and adjuvant chemotherapy. However survival is short in patients with residual macroscopic disease after surgery or recurrent ovarian cancer. Applicable maintenance therapies with low toxicity are required to prolong progression-free survival (PFS) for patients with no curative treatment options. In this study, we investigated the effect of maintenance metronomic oral cyclophosphamide and etoposide (CE) in ovarian cancer patients with post operative residual or recurrent disease. METHODS: Forty five patients that received metronomic oral CE (cyclophosphamide 50 mg/daily and etoposide 50 mg for 1-5 days, every 21 days) as maintenance therapy for residual disease due to incomplete surgical resection or recurrent advanced-stage ovarian cancer were evaluated. The time between the beginning of oral CE and disease progression was also evaluated. RESULTS: The mean patient age was 58 years, the vast majority had serous adenocarcinoma (78%) and received a mean of 2 (range 1-4) lines of various intravenous regimens for postoperative residual or recurrent disease. Mean duration of oral CE was 11.3 months (range 2.9-29). Median PFS was 10.3 months (range 7.9-12.8). Only 5 patients discontinued treatment due to intolerance and grade 3-4 toxicity was recorded in 3 patients (7%). CONCLUSION: Maintenance metronomic oral CE treatment was found effective, minimally toxic and sustainable in patients with macroscopic residual or recurrent advanced-stage ovarian cancer. However, randomized and placebo-controlled well designed studies are required.

Treatment with capecitabine + bevacizumab following induction treatment with FOLFIRI + bevacizumab in metastatic colorectal carcinoma.

Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, and it has been found to increase both progression-free survival and overall survival when it is combined with chemotherapeutic agents in the first-line and subsequent treatment of metastatic colorectal carcinoma. The objective of this study was to show the efficacy of maintenance treatment with capecitabine plus bevacizumab in patients with metastatic colorectal cancer who responded to treatment with FOLFIRI plus bevacizumab. The study included patients with metastatic colorectal cancer who received FOLFIRI plus bevacizumab as a first-line treatment. Patients who had objective response with FOLFIRI plus bevacizumab treatment after an average period of 6 months received a maintenance treatment with capecitabine plus bevacizumab (capecitabine 2 x 1000 mg/m(2), 1 - 14 days, every 21 days, bevacizumab 7.5 mg/m(2), every 21 days) until disease progression or toxicity. The time to progression on bevacizumab treatment was evaluated. A total of 29 patients (15 male, 14 female) were included. The mean age was 62 years. The mean number of cycles for maintenance treatment with capecitabine plus bevacizumab was 12. The median PFS was 16 ± 3 months, and OS was 42 ± 11 months. PFS and OS were remarkably higher in patients with a complete or near complete response to induction treatment. Fourteen patients (48%) experienced hand-foot syndrome associated with capecitabine plus bevacizumab treatment, without any severe toxicity. Inselected patients with metastatic colorectal carcinoma who had a remarkable objective response to FOLFIRI plus bevacizumab treatment, a maintenance treatment with capecitabine plus bevacizumab following FOLFIRI plus bevacizumab until disease progression may be a suitable, effective and tolerable regimen, which requires further studies.

Basal proteinuria as a prognostic factor in patients with metastatic colorectal cancer treated with bevacizumab.

BACKGROUND: The beneficial effects of bevacizumab, a widely used agent in metastatic colorectal cancer (mCRC), on clinical survival have been proven. This study investigated the correlation of the clinical benefits and prognosis with proteinuria and other parameters. METHODS: The study included mCRC patients receiving bevacizumab. Hypertension, 24-hour urine proteinuria, and other routine parameters were recorded at baseline and at certain intervals during treatment. RESULTS: The study included 36 consecutive patients. The median progression-free survival (PFS) duration was 10.9±2.6months, and the median overall survival (OS) was 23±3.1months. The median PFS was 7.2months among patients with basal proteinuria above 114mg/day, whereas the median PFS was 12months among patients with an equal or lower level (P=0.010). Similarly, PFS was shorter in patients with high lactate dehydrogenase (LDH) or carcinoembryonic antigen (CEA) levels (LDH, P=0.022; CEA, P=0.014). Bevacizumab response's performance status was good (P=0.05) and was even better in patients with a single liver metastasis (P=0.034) or hypertension (P=0.034). CONCLUSIONS: We demonstrated that high basal proteinuria, LDH, or CEA levels may be negative prognostic factors in mCRC patients receiving bevacizumab.

Hepatitis B reactivation related to everolimus.

Reactivation of hepatitis B virus (HBV) during chemotherapy is a well known complication in patients with chronic hepatitis B and cancer. The clinical manifestations range from subclinical elevation of liver enzymes to severe, potentially fatal fulminant hepatitis. Reactivation can occur in a patient with previous inactive HBV infection; either an inactive carrier or a patient with resolved hepatitis. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved in renal cell carcinoma, neuroendocrine tumours and breast cancer. mTOR inhibitors are a new generation of drugs for targeted treatment; therefore, little about their side effects is known. Here, we report a patient with renal cell carcinoma who experienced a flare of hepatitis B infection during treatment with everolimus. Clinicians should be aware of HBV reactivation in patients who are undergoing treatment with everolimus, and screening for hepatitis B infection and prophylactic antiviral treatment should be considered.