Prognostic implications of response to neoadjuvant chemotherapy in breast cancer subtypes.

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by 18F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

Predictive significance of inflammatory markers and mGPS in metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

BACKGROUND: Prostate cancer is a prevalent cancer in men worldwide, and castration-resistant prostate cancer (CRPC) is characterized by disease progression despite androgen deprivation therapy. While clinical and prognostic biomarkers have been identified in CRPC, the significance of serum inflammatory markers remains unclear. MATERIALS AND METHODS: This retrospective study included 79 CRPC patients treated with abiraterone or enzalutamide. Inflammatory markers, including the modified Glasgow prognostic score (mGPS), systemic immune-inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR), were assessed as predictive tools for treatment response. Patient data were obtained from medical charts, and statistical analyses were performed. RESULTS: The median age of the patients was 67 years, with most having a Gleason score of 8-10. The median values for NLR, PLR, and SII were 2.9, 168.5, and 713.5, respectively. The objective response rate (ORR) to abiraterone or enzalutamide therapy was 55.1%. mGPS showed a significant association with ORR, with the mGPS 0 group having the highest response rate (59.5%). Median progression-free survival (PFS) was 12.8 months, and median overall survival (OS) was 35.4 months. Palliative radiotherapy during therapy and PSA doubling time were independent prognostic factors for PFS. CONCLUSIONS: mGPS and PSA doubling time significantly impacted survival, and mGPS significantly predicted the treatment response in mCRPC, which may lead to further prospective studies.

Platelet to lymphocyte ratio is associated with tumor localization and outcomes in metastatic colorectal cancer.

ABSTRACT: The aim of this study was to investigate the predictive and prognostic value of PLR, and the relationship between PLR and tumor localization.A total of 229 patients with de-novo metastatic CRC were retrospectively analyzed. The cutoff value for PLR was defined by the receiver operating characteristic (ROC) curve analysis and threshold value of 196.5 as best cut-off value was found.The higher rate of BRAF mutation was significantly detected for patients with PLRhigh (> 196.5) compared to those with PLRlow (≤196.5) (P = .001). PLR was significantly higher in tumors located on the right colon (P = .012). PLR, tumor localization, the presence of surgery for primary tumor, the presence of curative surgery, the presence of metastasectomy for progression-free survival (PFS) and PLR, gender, BRAF mutation, tumor localization, the presence of surgery for primary tumor, the presence of metastasectomy for overall survival (OS) were found to be prognostic factors by univariate analysis. Multivariate analysis showed that PLR, the presence of curative surgery and the presence of metastasectomy for both PFS and OS were found to be independent prognostic factors. Moreover, a logistic regression analysis indicated that PLR and tumor localization were found to be an independent factors for predicting response to systemic treatment (P < .001 and P = .023 respectively).Our results showed that pretreatment PLR was readily feasible and simple biomarker predicting response to treatment and survival, in addition it was significantly associated with tumor localization.

Prognostic significance of primary tumor localization in patients with metastatic colorectal cancer: Is it beneficial to select targeted treatment? Real-life experience from Turkey.

PURPOSE: The purpose of this study was to investigate the prognostic value,and the effect of primary tumor location on targeted therapy selection in patients with metastatic colorectal cancer (mCRC). METHODS: A total of 201 patients with de novo mCRC who received first line treatment were retrospectively analyzed. Clinicopathological features, treatment outcomes, the primary tumor surgery, metastasectomies/local therapies and survivals were evaluated in terms of both RAS mutation status and primary tumor sidedness. RESULTS: Tumor localization showed 140 (69.7%) patients with left-sided and 61 (30.3%) with right-sided tumors. Median progression-free survival (PFS) and overall survival (OS) were significantly shorter in patients with right-sided tumor than those with left-sided tumors (10.1 vs 12.9 months, p=0.005; 25 vs 44.4 months, p=0.008, respectively). In addition,the median OS interval of patients receiving anti-VEGF containing regimen was better than those treated with anti-EGFR containing regimen (50.7 vs. 26.9 months, p=0.001). Multivariate analysis indicated that age (HR:0.41,p=0.045), primary tumor resection (HR:0.41,p=0.037) and primary tumor localization (HR:0.38,p=0.021) for PFS and age (HR:0.39, p=0.09), the presence of BRAF mutation (HR:0.59,p=0.019) and the type of targeted therapy (HR:3.16,p=0.025) for OS were independent prognostic factors. CONCLUSIONS: Our results showed that primary tumor location is a prognostic factor in mCRC patients regardless of RAS status. Primary tumor location before treatment decision may be a simple indicator predicting survival and in choosing targeted agent.

Prognostic Significance of Metastatic Lymph Node Ratio in Patients with pN3 Gastric Cancer Who Underwent Curative Gastrectomy.

BACKGROUND: Lymph node involvement is an important prognostic factor in patients with gastric cancer. The aim of this study was to determine the prognostic significance of metastatic lymph node ratio (MLNR) and compare it to the number of lymph node metastasis in pN3 gastric cancer. METHODS: We retrospectively analyzed 207 patients with pN3 gastric cancer who had undergone radical gastrectomy. Prognostic factors and MLNR were evaluated by univariate and multivariate analysis. RESULTS: An MLNR of 0.75 was found to be the best cut-off value to determine the prognosis of patients with pN3 gastric cancer (p = 0.001). The MLNR was significantly higher in patients with large-sized and undifferentiated tumors, vascular, lymphatic and perineural invasion, and total gastrectomy. In multivariate analysis, MLNR (p = 0.041), tumor differentiation (p = 0.046), and vascular invasion (p = 0.012) were found to be independent prognostic factors for disease-free survival, while both MLNR (p < 0.001) and pN stage (p = 0.002) were independent prognostic indicators, as was tumor size, for overall survival. There was significant difference with respect to the recurrence patterns between MLNR groups. Lymph node and peritoneal recurrences were significantly higher in patients with MLNR > 0.75 compared to the MLNR < 0.75 group (p < 0.05). However, recurrence patterns were similar between pN3a and pN3b. CONCLUSION: Our results showed that MLNR was a useful indicator to determine the prognosis and recurrence patterns of patients with radically resected gastric cancer. Moreover, MLNR is a beneficial and reliable technique for evaluating lymph node metastasis.

Anti-Ri-associated paraneoplastic neurological syndrome: Initial symptom of breast cancer with HER2 overexpression and treatment by dual HER2 blockade.

Paraneoplastic neurological syndrome is associated with anti-Ri antibodies, which are typically present with opsoclonus-myoclonus-ataxia. Human epidermal growth factor receptor 2 (HER2) overexpression is present in 15%-25% of breast cancer and is associated with poor prognosis. There are a few reports of paraneoplastic neurological syndrome associated with HER2-positive breast cancer in the literature, of which most are anti-Yo-associated paraneoplastic neurological syndrome. We present herein the case of a female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus-myoclonus paraneoplastic neurological syndrome. Following the diagnosis of paraneoplastic syndrome, chemotherapy with dual HER2 blockade and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri antibodies, there was partial clinical improvement and her neurological deficit persisted. To our knowledge, this is the first case report of female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus-myoclonus paraneoplastic neurological syndrome and treated with dual HER2 blockade.

Late relapse of testicular cancer: Recurrence after 24 years and treatment with chemotherapy alone.

Late relapse of testicular cancer, defined as >2 years interval between initial treatment and recurrence, is a rare disease with the incidence rate of 2.6%. Due to its chemoresistant features, treatment options of late relapses are controversial while surgical approach and cisplatin-based chemotherapies can be considered. We report here a patient with nonseminomatous germ cell tumor who experienced relapse 24 years after his first diagnosis. After detecting left supraclavicular lymphadenopathy and absence of any other malignant lesion in positron emission tomography-computerized tomography, patient was treated with three cycles of VeIP regimen (vinblastine/ifosfamide/cisplatin). Second complete response to this treatment was achieved with chemotherapy alone.

Platelet to lymphocyte ratio as a new prognostic for patients with metastatic renal cell cancer.

AIM: The objective of this study was to evaluate the blood platelet-lymphocyte ratio (PLR) for its prognostic value in patients with metastatic renal cell cancer (RCC). METHODS: We retrospectively reviewed 100 patients diagnosed with metastatic RCC previously treated with tyrosine kinase inhibitors from three centers. We assessed the prognostic value of pretreatment PLR and other clinical and laboratory parameters based on univariate and multivariate analyses. RESULTS: Median progression-free survival (PFS) was 7.3 months and median overall survival (OS) was 15.3 months. Multivariate analysis revealed that PFS is significantly affected by ECOG PS (P = 0.047), PLR (P = 0.029) and calcium level (P = 0.023). Median PFS was 13.9 versus 5.3 months in patients with PLR ≤ 210 versus PLR > 210 (log rank; P = 0.001). Median OS was 25.9 versus 10.9 months with PLR ≤ 210 versus PLR > 210 (log rank; P = 0.013). CONCLUSIONS: This study shows that increased pretreatment PLR is an independent prognostic indicator in patients with metastatic RCC who use tyrosine kinase inhibitors.

Modified docetaxel and cisplatin in combination with capecitabine (DCX) as a first-line treatment in HER2-negative advanced gastric cancer.

BACKGROUND: Docetaxel and cisplatin in combination with fluorouracil (DCF) regimen is accepted to be one of the standard regimens in the treatment of advanced gastric cancer. However, substantial toxicity has limited its use in daily clinical practice. Therefore, modification of DCF regimens, including introduction of capecitabine has been investigated to improve the safety profiles. In the present study, the efficacy and toxicity of a regimen with a modified dose of docetaxel and cisplatin in combination with oral capecitabine (DCX) was evaluated in untreated patients with HER2-negative advanced gastric cancer. MATERIALS AND METHODS: Fifty-four patients with HER2-negative locally advanced or metastatic gastric cancer were included in this cohort. Patients received docetaxel 60 mg/m2 plus cisplatin 60 mg/m2 (day 1) combined with capecitabine 1650 mg/m2 (days 1-14) every 3 weeks. Treatment response, survival, and toxicity were retrospectively analyzed. RESULTS: The median age was 54 years (range: 24-76). The majority of patients (70%) had metastatic disease, while 11 patients (21%) had recurrent disease and underwent curative gastrectomy, and 5 patients (9%) had locally advanced disease (LAD). The median number of DCX cycles was 4. There were 28 partial responses and 11 complete responses, with an overall response rate of 72%. Curative surgery could be performed in four patients among five with LAD. At the median follow-up of 10 months, the median progression-free survival (PFS) and overall survival (OS) of the entire cohort of patients were 7.4 and 12.1 months, respectively. Dose modification was done in 12 patients due to toxicity in 8 and noncompliance in 4 patients. The most common hematological toxicity was neutropenia, which occurred at grade 3-4 intensity in 10 of 54 patients (27.7%). Febrile neutropenia was diagnosed only in two cases. CONCLUSIONS: DCX regimen offers prominent anti-tumor activity and considered to be effective first- line treatment with manageable toxicity for patients with HER2-negative advanced gastric cancer.

Severe liver dysfunction and safe use of 5-fluorouracil leucovorin and oxaliplatin in one patient with metastatic colorectal carcinoma.

The liver is the most frequent site of metastases in colorectal cancer. Commonly used anticancer drugs in colorectal cancer are 5-fluorouracil, oxaliplatin and irinotecan 5-fluorouracil (5-FU) and oxaliplatin have very few numbers of studies that support their safety in hepatic dysfunction, but pharmacokinetic studies of anticancer drugs focused on the single-agents; however, there is lack of data about drug combinations such as 5-fluorouracil leucovorin and oxaliplatin (FOLFOX) and 5-fluorourocil, leucovorin and irinotecan (FOLFIRI) regimens. We demonstrated one patient with colorectal cancer and severe liver dysfunction secondary to hepatic metastases. Laboratory investigation on admission showed total bilirubin 22.5 mg/dl, alkaline phosphatase 1137 IU/l, aspartate amino transferase 254 IU/l, alanine aminotransferase 164 IU/l and carcinoembryonic antigen levels 863 ng/ml. We initiated a 5-FU/oxaliplatin-based combination chemotherapy. Our data supports the safety and feasibility of FOLFOX regimen in patients with severe liver dysfunction secondary to liver metastases of colorectal cancer.

The necessity of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma using antiangiogenic targeted therapy after interferon alfa-2b.

BACKGROUND: Targeted therapy has improved the survival of patients with metastatic RCC. In the present study, we evaluated whether there was an effect of cytoreductive surgery on prognosis of patients with metastatic RCC using antiangiogenic tyrosine kinase inhibitor (TKI) agents. PATIENTS AND METHODS: A total of 52 patients with metastatic RCC from Akdeniz University, Afyon Kocatepe University, and Medipol University participated in the study. All the patients had received targeted antiangiogenic therapy after interferon alfa-2b. According to previous CRN, the patients were divided into 2 groups as CRN (+) and CRN (-). RESULTS: The CRN (+) group was younger than the CRN (-) group (P < .001) and the hemoglobin levels were significantly higher in the CRN (+) group (P = .023). The median progression-free survival time from the date of starting TKIs were 8.5 and 3.0 months for the CRN (+) and CRN (-) groups, respectively (P = .104). The median overall survival was 15.1 and 5.4 months for the CRN (+) and CRN (-) groups, respectively (P = .034). CONCLUSION: We speculate that CRN is still an important part of treatment modalities in patients with metastatic RCC in modern era targeted therapy, which is currently the best systemic therapy. However, the indications of CRN might be limited to good-risk patients with metastatic RCC. Further randomized studies are warranted to clarify the necessity of CRN in patients with metastatic RCC.

PET-CT changes the management and improves outcome in patients with recurrent colorectal cancer.

BACKGROUND: The present study aims to analyze the impact of positron emission tomography/computed tomography (PET/CT) on management change in patients with suspected or proven colorectal cancer recurrence, and to assess the effect of this management change on progression-free survival (PFS) and overall survival (OS). MATERIALS AND METHODS: We retrospectively evaluated 122 patients with suspected potentially resectable recurrent colorectal cancer who underwent PET/CT scan. We determined management plans for these patients before and after the PET/CT examination. RESULTS: While previous conventional imaging studies had revealed solitary metastases, additional sites of disease were determined by PET/CT scan in 52/122 (42%) patients. PET/CT examination results changed the treatment plan to curative intent in 35 (37%) patients. While the median PFS was 22 months (95% CI, 11.2-32.6 months) among the patients planned to receive curative treatment after the PET/CT scan, it was 11 months (95% CI, 8.1-13.9 months) in patients planned to receive curative treatment before the PET/CT examination, and the difference between median PFS durations was statistically significant (HR, 0.51 [95% CI, 0.32 - 0.88], P = 0.004). Furthermore, OS was significantly longer in patients planned to receive curative treatment after the PET/CT scan (27 months [95% CI, 22.1-31.9]) compared with those who received curative treatment before the PET/CT scan (21 months [95% CI, 15.6 - 26.4]), and the difference was statistically significant (HR, 0.63 [95% CI, 0.42 - 0.89], P = 0.045). CONCLUSION: The present study demonstrates the significant impact of PET/CT on the management and outcome in patients with recurrent colorectal cancer.

What is the optimal treatment in clinical stage T3N0M0 rectal cancer?

PURPOSE: Some previous studies suggested that certain rectal cancer patients with stage T3N0 and favorable features may be adequately treated with surgery and adjuvant chemotherapy. However, the optimal management of clinical (c) T3N0 rectal adenocarcinoma based on preoperative imaging is unclear. In this study, we aimed to determine the frequency of lymph node metastases in patients clinically staged as T3N0 rectal adenocarcinoma following preoperative chemoradiotherapy (CTR). METHODS: The medical records of 105 patients with clinico- imaging stage T3N0M0 rectal cancer who received preoperative CRT between 2004-2011 were retrospectively analyzed. Chemotherapy used concurrently with preoperative radiotherapy (RT) was protracted 5-fluorouracil (5FU) infusion. RESULTS: Twenty-seven percent of the patients clinically staged as T3N0 before preoperative CRT had pathological (p) lymph node involvement on surgical material. The rate of pathological lymph node involvement was 0% in pT1, 20% in pT2 , 35% in pT3 and 34% in pT4 patients. A significant association was demonstrated between pT stages and pN status (p=0.03). CONCLUSION: Our study demonstrated that the accuracy of preoperative imaging for staging rectal cancer is limited because at least 27% of the patients may have undetected lymph node involvement after preoperative CRT in surgical material.

Preoperative versus postoperative chemoradiotherapy in stage T3, N0 rectal cancer.

BACKGROUND: The study populations of previous preoperative chemoradiotherapy (pre-CRT) studies have consisted of mixed clinical stages, such as cT3-cT4 and/or cN positive. For this reason, it has not been possible to demonstrate whether pre-CRT is of benefit for individual subgroups. METHODS: The medical records of 137 rectal cancer patients with clinical stage T3, N0 disease who received either pre-CRT or postoperative chemoradiotherapy (post-CRT) between 2002 and 2011 were retrospectively analyzed. The regimen of pre-CRT consisted of slow fluorouracil (5FU) infusion and that of post-CRT consisted of bolus 5FU and leucovorin concurrent with radiation. RESULTS: Following pre-CRT, significant downstaging was achieved. However, administration of pre-CRT did not influence the type of surgical resection in tumours ≤5 cm distant from the anal verge (p = 0.14). Pathological complete response was achieved in 16 % of the patients in the pre-CRT group. The local recurrence rate (LRR) at 5 years was 5.7 % in the pre-CRT and 11.1 % in the post-CRT groups (p = 0.04). The distant recurrence rate (DRR) at 5 years was 76 % and 77 % in the pre-CRT and post-CRT groups, respectively (p = 0.1). Overall survival was similar in two groups (74.8 % vs. 75.3 %, p = 0.3). CONCLUSIONS: The treatment of stage T3, N0 rectal cancer patients with pre-CRT followed by surgery decreased LRR, but did not improve DRR or OS as compared with surgery followed by post-CRT in our patient cohort.

The relation between pathological complete response and clinical outcome in patients with rectal cancer.

BACKGROUND/AIMS: Preoperative chemoradiotherapy (CRT) is the standard treatment modality in locally advanced rectal cancer. The primary aim was to correlate pathological complete response (pCR) with patient outcome, and the secondary objective was to identify predictive factors of pCR. METHODOLOGY: Patients with clinical stage II/III rectal cancer who received preoperative CRT between 2002 and 2010 were retrospectively studied.The median radiotherapy dose was 54 Gy (range, 45 to 64 Gy), and all patients received concurrent infusional 5-fluorouracil-based chemotherapy. RESULTS: Median follow-up time was 48.3 months (range, 24 to 96 months) and 51 months (range, 44 to 110 months) for no-pCR and pCR groups, respectively. Eighteen patients (18.6%) had pCR. The 5-year overall survival was 95% for patients with pCR and 74.8% in patients without pCR (p=0.009). The 5-year local relapse free survival was 87.5% and 95% for the no-pCR and pCR groups, respectively (p=0.09). The 5-year distant relapse free survival was 93% in pCR group and 79.8% in no-pCR group (p=0.02). The 5-year distant free survival was 94% and 66% in patients with and without pCR, respectively (p=0.017). The clinical T4 (p=0.043) and pretreatment carcinoembryonic antigen level (CEA) >5ng/mL (p=0.012) were significantly associated with a lower pCR rate. In the multivariate logistic regression analysis, pretreatment CEA level >5ng/mL (p=0.008) was the only independent factor associated with a lower pCR rate. CONCLUSIONS: Patients with pCR after preoperative CRT had a significantly improved outcome. Furthermore, the pretreatment CEA level was independently associated with pCR.

A Case of Complete Response to Letrozol Treatment in a Postmenopausal Woman With Breast Cancer Who has Progressed After Multiple Lines of Chemotherapy.

Approximately 60% of all breast cancers are endocrine dependent. Postmenopausal patients who have positive hormone receptor status are eligible for aromatase inhibitor treatment. Letrozole is a potent, selective, non-steroidal, third-generation aromatase inhibitor which reduces oestrogen biosynthesis approximately 99% at the dose of 2.5 mg/day. We report a 54-years-old female patient diagnosed with grade 2 invasive ductal carcinoma of the breast. She received adjuvant chemotherapy, followed by 5 years of tamoxifen. After 8 years, recurrence appeared in lung, supraclavicular lymph nodes and brain. She had many cycles of cytotoxic chemotherapeutic agents, trastuzumab and lapatinib previously. After the progression (lung and brain), palliative therapy was thought due to very poor performance status of the patient. (ECOG: 3) Letrozole was added in the treatment and we obtained near-complete remission from her lung and brain metastasis with 2.5 mg/day dose of letrozole. This study might support successfully use of aromatase inhibitors in patients who has been previously treated with multiple lines of chemotherapy and had still progressive disease.

Increasing Role of FDG-PET/CT in Detecting Bone Marrow Metastasis of Solid Tumors in Adults: An Analysis of Ten Patients.

BACKGROUND: We aimed to test the hypothesis that whether FDG-PET/CT which was ordered for various purposes can predict suspected or particularly unsuspected bone marrow metastasis (BMM) from the complete blood count and therefore can change the management of these patients. METHODS: In this retrospective study, the study sample consisted of 68 subsequent patients presented to our institution's pathology department with bone marrow metastases of solid tumors. PET/CT was found to have been ordered in 10 out of 68 patients (6.8%) for various purposes. All patients gave informed consent about the PET/CT examinations and bone marrow biopsies. RESULT: FDG-PET/CT was ordered in 10 out of 68 solid tumor patients with pathologically proven BMM. Of these 10 patients, 3 were female and 7 were male; mean age was 54.7 years. While FDG PET/CT showed bone and BMM in 4 of 10 patients (40%), the rest of the patients had BMM without bone involvement. Five patients (50%) who had probable bone marrow involvement on their FDG PET/CT scans had unsuspected complete blood counts with regard to BMM. CONCLUSION: PET/CT has the ability to detect a substantial number of metabolically active tumor cells in the bone marrow in all of our patients which we proved by bone marrow biopsies. We think that this cohort of patients with solid tumors is hypothesis-generating with regard to detecting early bone marrow metastases by FDG PET/CT.

Olfactory neuroblastomas: an experience of 24 years.

Objective. The aim of this study was to evaluate clinicopathological findings and the efficacy of the treatment modalities used in patients with olfactory neuroblastomas. Study Design. Retrospective record review. Setting. Istanbul University, Cerrahpasa Medical Faculty, medical oncology outpatient clinic. Subjects and Methods. There were 3 stage A tumors, 5 stage B and 11 stage C according to the Kadish staging system. There were 5 grade I/II and 12 grade III/IV according to the Hyams' histopathologic system. Involvement to orbita was detected in eight patients at the time of diagnosis. Results. The median follow-up period was 23.7 months. The 5-year survival rate for the whole group was 26%. The stage A/B groups exhibited a better survival rate than the C group with 2-year survival rates being 25 versus 71% respectively (P = .008). The grade I/II groups exhibited a better survival rate than the grade III/IV groups with 2-year survival rates being 50 versus 16% respectively (P = .001). The group who had orbital involvement exhibited a poor survival rate than the group of patients who had no involvement of the orbital. Conclusion. In our study, tumor stage, histopathologic grading, involvement of the orbita, brain and bone marow metastases were the statistically significant prognostic factors.