Arzu Oguz

An Unusual Case: Gastric Metastasis of Hepatocellular Carcinoma

Introduction: Gastrointestinal tract involvement of hepatocellular carcinoma (HCC) is a rare entity with a poor prognosis and can occur via hematogenous route or direct invasion. Here we report a case with de novo HCC after liver transplantation who had rising alfa-fetoprotein (AFP) levels and was found to have gastric metastases incidentally. Case: A 62 year old man underwent liver transplantation with a diagnosis of hepatocellular carcinoma Three years after the liver transplantation, bone and liver metastasis developed and palliative treatment plan was made. During follow-up AFP levels began to rise subsequently and computed tomography of chest and abdomen revealed stable liver lesions and a suspicious gastric luminal nodule. Upper endoscopy showed polypoid lesions in stomach and the pathology of the biopsies taken from these lesions were consistent with HCC metastasis. Discussion: Patterns of metastases in patients with recurrent HCC after liver transplantation might be different. Immunsuppressive treatment in transplant patients might have a negative effect on disease biology and may result in more disseminated disease and atypical sites of metastases as in our case. In patients with rising AFP in the absence of progressive disease on radiologic evaluation, gastrointestinal system metastases via hematogenous route should be kept in mind and upper endoscopy should be considered even in the absence of gastric symptoms, particularly if the presence of extrahepatic disease will change treatment decisions.

Good Outcomes of Patients with Stage IB Endometrial Cancer with Surgery Alone

BACKGROUND Most patients with endometrial cancer have stage I disease. Adjuvant therapy in stage IB (formerly IC) endometrial cancer is controversial, treatment options including observation or brachytherapy/ radiotherapy in grade 1-3 patients with or without chemotherapy. The purpose of this study was to assess the outcomes of our patients with stage IB endometrioid endometrial cancer. MATERIALS AND METHODS Sixty two patients with stage IB endometrial cancer and endometrioid histology were retrospectively evaluated. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy, bilateral pelvic and paraaortic lymph node dissection and omentectomy. Adjuvant radiotherapy was discussed with patients and utilized by those who accepted. Adjuvant chemotherapy was not given to any of the patients. RESULTS Median age was 62 (range, 42-95). Ninety percent of the patients had grade 1-2 disease. Thirteen patients (21%) received intra vaginal brachytherapy (IVBT) and one received whole pelvic radiotherapy (WPRT). Median follow-up time was 46 months (range, 9-77 months). Three patients experienced recurrence (4.8%), two of them died on follow-up and one was still alive at last visit. Two patients with recurrence had FIGO grade 2 tumors and one had a grade 3 tumor. Two patients (3.2%) died without evidence of recurrent disease. Relapse free survival at 5 years was 94.4% and overall survival was 93.1%. CONCLUSIONS Patients with stage IB disease in our study demonstrated relatively low recurrence rates although the majority of them received no adjuvant treatment. Surgery alone may be sufficient for most patients with this stage of endometrial cancer.

Is Human Kallikrein 11 in Non-small Cell Lung Cancer Treated Chemoradiotherapy Associated with Survival?

Purpose Involvement of human kallikreins (hKs) in human cancers has been reported and several hKs are promising biomarkers of various cancers. The aim of this study was to evaluate the prognostic significance of hK11 expression in patients with non-metastatic non-small cell lung cancer (NSCLC). Materials and Methods The study included 44 patients with NSCLC. hK11 expression was determined by immunohistochemical staining. Results The estimation of disease-free and overall survival by Kaplan-Meier was 11 months and 17 months, respectively. The estimation of overall survival by Kaplan-Meier was significantly higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (20 months vs. 11 months, p=0.032). Although not statistically different, the estimation of disease-free survival by Kaplan-Meier was higher in patients with hK11 strongly positive (2+) than in those with hK11 weakly positive (1+) (12 months vs. 9 months, p=0.113). Multivariate Cox regression analysis showed that the overall survival rates were significantly associated with response to chemoradiotherapy and the degree of staining with hK11. Conclusion The stronger hK11 expression in NSCLC appears to be associated with better survival rates. hK11 may be a prognostic biomarker of NSCLC.

Extracorporeal Shock Wave Therapy for Breast Cancer–Related Lymphedema: A Pilot Study

OBJECTIVE To investigate the clinical effect of extracorporeal shock wave therapy (ESWT) in patients with secondary lymphedema after breast cancer treatment. DESIGN Prospective clinical pilot study. SETTING Education and research hospital. PARTICIPANTS Women with a diagnosis of lymphedema secondary to breast cancer (N=11). INTERVENTIONS Patients were treated for 12 sessions of ESWT with 2500 impulses each. The treatment frequency was 4Hz in multiple shock mode. The energy flow density during treatment was equal to a working pressure of 2 bar. MAIN OUTCOME MEASURES The primary outcome measure was volumetric measurements. The secondary outcome measures were the short version of the Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH) and the brief version of the World Health Organization Quality of Life (WHOQOL-BREF). Assessments were conducted by the same investigator at baseline, posttreatment, and at 1, 3, and 6 months after treatment for all patients. RESULTS Significant reduction was found in the amount of lymphedema with ESWT treatment in all patients, and this reduction was maintained for 6 months. A statistically significant reduction was observed in volumetric measurements for the follow-up period (P=.001). The mean volume displacement of the affected upper extremity before treatment was 870.45±384.19mL at 6 months, and after the treatment it was 604.54±381.74mL. In addition, improvements were observed in the QuickDASH functional assessment tool and in the physical health domain of the WHOQOL-BREF questionnaire (P=.002 and P=.007, respectively). CONCLUSIONS ESWT was shown to provide a reduction in the amount of lymphedema in patients with lymphedema secondary to breast cancer. Also, a marked improvement was observed in the functional status and quality of life of study patients. Treatment efficacy was maintained in the long term. As a noninvasive, novel, and effective method, ESWT is a promising treatment modality for the treatment of lymphedema, which is a chronic, progressive, and refractory condition.

Morphine: Patient Knowledge and Attitudes in the Central Anatolia Part of Turkey

BACKGROUND In Muslim majority countries (MMC) opioid use for pain management is extremely low. The underlying factors contributing to this are not well defined. AIM The aim of this study was to survey the attitudes of cancer patients towards morphine use for pain management in a MMC and identify the factors that influence patient decisions to accept or refuse morphine as treatment for cancer pain. SETTINGS/PARTICIPANTS Patients were questioned whether they had pain or not, the severity and the medications for pain management. Questions included what type of medication they thought morphine was, whether or not they would be willing to take morphine if recommended for pain management and the basis for their decision if they were against morphine use. RESULTS Four hundred and eighty-eight patients participated in the study. Some 50% of the patients who refused morphine use and 36.8% of the patients who would prefer another drug, if possible, identified fear of addiction as the basis for their decision. Reservation of morphine for later in their disease was the case for 22.4% of the patients who refused morphine use. Only 13.7 % of the patients refusing morphine and 9.7% of the patients who preferred another drug, if possible, cited religious reasons as the basis for this decision. CONCLUSIONS Identifying the underlying factors contributing to low opioid use for pain management in MMC is important. Once the underlying factors are identified, all efforts should be taken to overcome them as they are barriers to improving patient pain management.

Hepatitis B and C Seroprevalence in Solid Tumors - Necessity for Screening During Chemotherapy

BACKGROUND Hepatitis B and C are the leading causes of liver diseases worldwide. For hematological and solid malignancy patients undergoing chemotherapy, increases in HBV DNA and HCV RNA levels can be detected which may result in reactivation and hepatitis-related morbidity and mortality. The aim of this study was to determine the seroprevalence of Hbs ag and Anti HCV positivity in patients with solid malignancies undergoing chemotherapy and consequences during follow-up. MATERIALS AND METHODS The files of 914 patients with solid malignancies whose hepatitis markers were determined serologically at diagnosis were reviewed retrospectively. All underwent adjuvant/palliative chemotherapy. For the cases with HBV and/or HCV positivity, HBV DNA and HCV RNA levels, liver function tests at diagnosis and during follow-up and the treatment modalities that were chosen were determined. RESULTS Of 914 cases, Hbs Ag, anti Hbs and anti HCV positivity were detected in 40 (4.4%), 336 (36.8%) and 26 (2.8%) of the cases respectively. All of the Hbs ag positive patients received prophylactic lamuvidine before the start of chemotherapy. In the Hbs ag and anti HCV positive cases, liver failure was not detected during chemotherapy and a delay in chemotherapy courses because of hepatitis was not encountered. CONCLUSIONS Just as with hematological malignancies, screening for HBV and HCV should also be considered for patients with solid tumors undergoing chemotherapy. Prophylactic antiviral therapy for HBV reduces both the reactivation rates and HBV related mortality and morbidity. The clinical impact of HCV infection on patients undergoing chemotherapy is still not well characterized.

Treatment of Lymph Node-Negative, Early-Stage HER2-Positive Breast Cancer

TO THE EDITOR: O’Sullivan et al report a meta-analysis of five randomized trastuzumab trials with 4,221 patients who had early-stage breast cancers that were human epidermal growth factor receptor 2 (HER2) positive and 2 cm or smaller. The efficacy end points were disease-free and overall survivals. They concluded that patients with HER2positive, 2-cm or smaller tumors derive significant disease-free and overall survival benefits from the addition of trastuzumab to the treatment regimen. Although we appreciate this meta-analysis, several points warrant discussion. The prognosis of patients with T1a and T1b tumors that are node negative is uncertain even in cases of HER2 overexpression. Many studies have reported that HER2 overexpression is an independent factor of poor prognosis in patients with pT1abN0 breast tumors. The authors mentioned that the number of such occurrences had been too small to make a decision about efficacy end points and that almost all of the occurrences were obtained from the HERA trial, which used trastuzumab sequentially. In the whole study population, as in the T1a and T1b tumor groups, almost 50% of occurrences came from the HERA trial. Thus, the faith of this population may be declared, because this metaanalysis consisted of randomized trials. The same disputation is valid for the lymph node–negative group. The authors evaluated the clinical outcomes of the group of patients with one or fewer lymph nodes, including those in an N0 group. They stated that the reasons were that few events had occurred in this patient group and that greater than 90% of occurrences were from the HERA trial. We think that, because there were approximately 1,000 cases in this group, mostly from the largest prospectively designed adjuvant trastuzumab trial on which the backbone of the adjuvant treatment of HER2-positive breast cancer has been patterned, the results of this group also may be worth declaring for clinical practice. There are some conflicting data in the literature reported, not from randomized trials but instead from retrospective series. Fehrenbacher et al retrospectively investigated 234 patients with breast cancer that was HER2 positive, lymph node negative, and T1a or T1b; distant invasive recurrence was a primary end point, and locoregional recurrence was a secondary end point. They stated that the 5-year distant relapse–free interval was 98.2% for patients with T1a tumors, whereas it was 89.4% and 84.5% for those with T1b and 1-cm tumors, respectively. Of those patients, 174 (74%) did not receive any adjuvant treatment. This result raises the question of whether the use of adjuvant chemotherapy and trastuzumab is necessary in the T1a group of patients. However in the study by Rodriguez et al, 276 patients with node-negative and T1abHER2-positive breast cancer were evaluated retrospectively. A total of 47% of all patients were given adjuvant chemotherapy and trastuzumab. Of adjuvant chemotherapy protocols, 42.6% were antracycline and taxane based; 28.7% were antracycline based, and 27.9% were taxane-only based. The 40month disease-free survival was 93% for patients who had not received chemotherapy, whereas it was 99% for those who had received adjuvant therapy. In the multivariate analysis, tumor size was not associated with clinical outcomes, and the authors stated that adjuvant treatment should be discussed with all patients who have pT1ab node-negative HER2-positive breast cancer. Another important question is what type of chemotherapy is reasonable for this group of patients. The optimal regimen in patients in a T1abN0 HER2-positive group is still not precise. As was discussed in the meta-analysis, APT is a single-arm prospective study for the efficacy of adjuvant paclitaxel and trastuzumab in patients with HER2-positive, node-negative breast cancer of 3 cm or smaller. Because most of the patients in this meta-analysis received an anthracycline and taxane combination, it may be valuable, in our opinion, to compare these two patient groups (ie, those who receive paclitaxel and trastuzumab versus those who receive an anthracycline and a taxane) to decide whether it is necessary to add an anthracycline or whether it is reasonable to continue with just a taxane and trastuzumab, which could have a lower probability of adverse effects. It was stated that the number of patients who had T1abN0 tumors in the meta-analysis was low; however, the group of patients with 1to 2-cm tumors is a larger patient group, and it is also important to evaluate the chemotherapy regimens in this group. Finally, we agree that the results of APT trial do not apply to patients who have 2to 3-cmHER2-positive node-negative tumors, because the number of patients in this group is quite low. It may be possible to evaluate this subgroup from these adjuvant trials to decide upon a treatment suggestion for this subgroup. Still, the guidelines include both a regimen of anthracycline and taxane combinations with trastuzumab and a regimen of only a taxane with trastuzumab.

Trastuzumab in metastatic breast cancer after complete remission: How long is enough?

Anti-human epidermal growth factor receptor 2 (HER2) therapies added to standard chemotherapy agents have been shown to improve disease-free survival (DFS) and overall survival (OS) via either single or dual blockade in HER2-amplified metastatic breast cancer patients [1]. The approved anti-HER2-directed drugs are monoclonal antibodies as trastuzumab, pertuzumab; dual tyrosine kinase inhibitor lapatinib and an antibody–drug conjugate trastuzumab emtansine. As is customary, maintanence treatment with an anti-HER2 drug until progression of disease remains the standard after response to first-line combined treatment of chemo and anti-HER2 agent that is mostly trastuzumab. Since tumors classified as HER2 positive are a heterogenous group, the optimal duration of trastuzumab for patients achieving complete response and the predictive markers for such patients is still a matter of debate. The longest relapse-free period with trastuzumab maintenance after complete remission was reported to be almost 9 years in a 46-year-old, hormone-receptor-negative breast cancer patient with liver and bone metastases at diagnosis. The reported progression-free values are between 6 months to 9 years in the literature. Among the 7 published cases with prolonged complete remission periods, all but one had metastases in the liver and 5 of them were hormone receptor negative. Six patients were reported to be in complete remission, all but one with trastuzumab maintanence [2]. In the report by Yan et al., 2 triple-negative locally advanced breast cancer patients were found to have HER2-positive, hormone-receptor-negative metastases during the follow-up. Because of financial problems, they could not receive trastuzumab at the time of metastases and anti-HER2 agent was added to treatment approximately after 1 year. Despite multiple metastatic sites including brain, both patients continued maintenance trastuzumab treatment up to now. One is still on complete remission while on trastuzumab maintenance for 28 months, and the other patient has been reported to be doing quite well with a partial response and still being on trastuzumab maintenance for 15 months [3]. In all of these cases, cardiac toxicity was not reported to be a clinically relevant adverse event. In the phase II HERLAP study, the predictive biomarkers for long-term efficacy of anti-HER2 agents without addition of chemotherapy were evaluated [4]. Although closed early with only 19 patients being enrolled, median progression-free and overall survivals were 7.3 (1.6–38?) and 43 (14–81?) months, respectively, quite similar to that reported with combined chemotherapy and single-agent anti-HER2 therapy trials [1]. Gene expression data and protein expression analysis revealed that patients with HER2-enriched tumors and with increasing values of quantitative HER2/p95HER2 (H2T/p95HER2) protein expression ratios showed significant increases in persistence on protocol, compared to patients with luminal A & B tumors and with lower H2T/p95HER2 ratios [4]. This finding can be a clue for choosing patients that will benefit most from long-term trastuzumab maintenance after achieving complete response with first-line combined therapy. Furthermore, studies analyzing the clinical outcomes with second-line trastuzumab after progression on first-line & Arzu Oguz oguzarzu@yahoo.com

Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study

BACKGROUND For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. MATERIALS AND METHODS Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. RESULTS The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. CONCLUSIONS Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.

Metaplastic carcinoma of the breast: A rare carcinoma with chondroid metaplasia

Metaplastic breast carcinoma accounts for less than 1% of breast malignancies. Huvos et al. first introduced the term metaplastic carcinoma in 1974. It is usually seen together with poorly differentiated ductal carcinoma of the breast. Within its mesenchymal components, undifferentiated connective tissue cells, fibroblasts, osteoblasts and chondroblasts can be found. Metaplastic breast carcinoma is an aggressive disease with a poor prognosis. In this report, a case of a 45-year-old female patient who underwent segmental mastectomy with a diagnosis of metaplastic carcinoma of the breast is presented.