Tung-Hao Chang

Primary breast lymphoma: a pooled analysis of prognostic factors and survival in 93 cases.

BACKGROUND Primary breast lymphoma is a rare disease. The small number of patients and the paucity of data make large-series studies difficult. We conducted a pooled analysis to evaluate the treatment outcome and prognostic factors in patients with primary breast lymphoma. METHODS In a search of PUBMED and MEDLINE we found 7 observational studies with 93 patients that were eligible for inclusion. Treatments included single therapy or combined surgery, chemotherapy and radiotherapy. We analyzed the correlation between treatment protocols, tumor relapse and survival. Histopathology and cancer stage were analyzed to evaluate their significance in treatment outcome. RESULTS All 93 patients were female, with a mean age of 57 years. The histopathology of 63 patients (68%) was diffuse large cell lymphoma. According to Ann Arbor classification, 57% were stage I, 23% were stage II, 4% were stage III, and 16% were stage IV. Thirteen percent received surgery alone, 27% received chemotherapy alone, 7% received radiotherapy alone, 10% received surgery and chemotherapy, 10% received surgery and radiotherapy, 22% received chemotherapy and radiotherapy, and 11% received surgery combined with chemotherapy and radiotherapy. With a median follow-up duration of 34 months (mean, 53 months), 48% had relapse of disease, 50% had no relapse, while 2% had disease progression. The mean time to first tumor relapse after treatment was 20 months. The 3-year and 5-year overall survival rates were 70% and 56%, respectively. Radiotherapy was a significant prognostic factor predicting tumor relapse (P=0.044). Tumor stage was a significant prognostic factor affecting overall survival, disease-free survival and disease-specific survival (P=0.0231, 0.0015, 0.0124, respectively). CONCLUSION With a 3-year overall survival rate of 70%, the high relapse rate of 48% is a cause for concern. Patients who received chemotherapy and radiotherapy had better survival outcome and a lower relapse rate. We suggest that chemotherapy and radiotherapy be the initial treatment for patients with primary breast lymphoma.

Prognostic factors affecting the outcome of early cervical cancer treated with radical hysterectomy and post‐operative adjuvant therapy

The purpose of this study is to investigate the clinical and histological features that may affect the survival of the patients and to evaluate the impact of post-operative adjuvant therapy on the outcomes of patients with stage IB and IIA carcinoma of the cervix. From August 1998 to January 2005, 140 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer were treated with radical hysterectomy and post-operative pelvic radiation therapy with or without chemotherapy. The median age was 55 years (range, 29-86 years). Seventy-six patients had stage IB and 64 patients had stage IIA disease. Tumour size was <4 cm in 96 patients and > or = 4 cm in 44 patients. One hundred and eleven patients had histology of squamous cell carcinoma, 12 patients has adenocarcinoma and 17 patients had other histologic types. Depth of stromal invasion was <2/3 in 20 patients and > or = 2/3 in 120 patients. Twenty-three patients had parametrial invasion and 117 patients had no parametrial invasion. Thirteen patients had lymphovascular space invasion and 127 had no lymphovascular space invasion. Nine patients had positive surgical margin and 131 patients had negative margin. Twenty-seven patients had pelvic lymph node metastasis and 113 patients had no pelvic lymph node metastasis. Seventy-five patients received concurrent chemoradiotherapy and 65 patients received radiotherapy alone. The 5-year overall survival (OAS) and disease-free survival were 83% and 72% respectively. In the log rank test, tumour size (P = 0.0235), pararmetrial invasion (P = 0.0121), pelvic lymph node metastasis (P < 0.0001) and adjuvant chemotherapy + radiotherapy (P = 0.0119) were significant prognostic factors for OAS, favouring tumour size <4 cm, absence of parametrial invasion and pelvic lymph node metastasis, and those who received adjuvant chemoradiotherapy. The patients who received radiation with concomitant chemotherapy had a 5-year OAS rate of 90% versus those who received radiotherapy alone, with a rate of 76%. For patients with high-risk early stage cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy, adjuvant chemoradiotherapy resulted in better survival than radiotherapy alone. The addition of weekly cisplatin to radiotherapy is recommended. The treatment-related morbidity is tolerable.

Prediction of outcome of patients with metastatic breast cancer: evaluation with prognostic factors and Nottingham prognostic index.

Goals of workThe purpose of this study is to analyze the survival rate of patients with metastatic breast cancer and to evaluate the outcome of these patients using prognostic factors and Nottingham prognostic index.Materials and methodsFrom February 1992 to August 2008, 135 patients with metastatic breast cancer were treated at the Changhua Christian Hospital. In these patients, we evaluated the significance of the following factors in predicting the survival rate after the occurrence of metastasis: age, initial stage at primary diagnosis, histological grade, Karnofsky performance status (KPS), estrogen receptor (ER), progesterone receptor status, human epidermoid growth factor receptor 2 overexpression status, number of axillary lymph node metastasis, history of adjuvant radiotherapy and/or chemotherapy, disease-free interval, status of local recurrence, status of various sites of distant metastases, number of distant metastases, and Nottingham prognostic index.Main resultsThe 1-, 2-, and 5-year survival rates were 53.3%, 25.2%, and 1.5%, respectively. In the univariate analysis, KPS, histological grade, ER status, initial stage at primary diagnosis, number of axillary lymph node metastasis, liver metastasis, disease-free interval, first-/second-/third-line chemotherapy for recurrence or metastasis, number of metastases, and Nottingham prognostic index had significant impact on survival. The median survival of patients determined as corresponding to Nottingham low-risk group, intermediate-risk group, and high-risk group was 29.3, 17.9, and 4.6 months, respectively. In our multivariate analysis, Karnofsky performance status (p = 0.030) and Nottingham prognostic index (p ≤ 0.0001) were significant prognostic factors for survival, while first-/second-/third-line chemotherapy for recurrence or metastasis (p = 0.002) was a significant predictor for the outcome of the treatment.ConclusionsThe prognosis of patients with metastatic breast cancer is poor. In spite of the fact that many advances in treatment have been made, numerous additional questions have arisen; new drugs and therapeutic regimens are needed to improve the outcomes of patients, and further well-designed randomized trials are warranted.

Successful Treatment of Adult Type Granulosa Cell Tumor of the Ovary - A Case Report and the Literature Review

Introduction: Granulosa cell tumor (GCT) of the ovary is classified as a sex cord stromal tumor, representing approximately 2-5% of ovarian neoplasms, and adult type accounts 95% of all GCTs, usually occurs in women during 50-55 years old. The most important prognostic factor of this tumor is stage, with 10-year overall survival of 84-95% for stage I tumors, decreasing to 50-65% for stage II tumors, and to 0-22% for stage III and IV disease. Case report: A 56-year-old woman with left side ovarian granulosa cell tumor, at least clinical FIGO stage IIIa, underwent debulking operation on February 23rd, 2002. After surgery, she received four cycles adjuvant chemotherapy with the regimen of Bleomycin, Cisplatin and Etoposide. Then she received postoperative whole-abdomen and pelvis irradiation. The dose was given 2520 cGy in 21 fractions with liver and kidney shielding. After whole-abdomen and pelvis irradiation, she received pelvis boost with the dose of 1980 cGy in 11 fractions. Since then, she was regularly followed at our hospital until now without any signs of tumor recurrence nor tumor progression. Discussion: Until now there is no standard and proven treatment for GCT patients, especially when they suffered from advanced-stage or recurrent unresectable tumors. Complete tumor resection should be considered as the primary treatment. The optimal choice of combination platinum-based chemotherapy is still not well-defined. The role of adjuvant radiation therapy remains controversial. We suggested that adjuvant RT for patients with GCT might improve outcomes in selected patients.

Treatment Outcome in Women with Operable HER 2-Positive Breast Cancer: A single Institutional Report

Purpose: Women with HER-2 overexpressing breast carcinoma benefit from trastuzumab-based systemic therapy despite the awareness of increasing risk of brain failure from this treatment modality among several studies. We report the treatment outcome and patterns of failure in women with operable HER2-positive breast cancer using trastuzumab as adjuvant setting at our institution, furthermore, focus on the incidence of central nervous system failure and the predictors for those with high risk of developing CNS relapse. Method and Material: We retrospectively identified 243 women with HER2-positive operable breast cancer diagnosed and treated at our institution between June 2002 and December 2011. All patients with tumor size more than two centimeters or any positive lymph node received adjuvant anthracycline-based chemotherapy with or without trastuzumab. Central nervous system failure was recognized through clinical symptoms and neuro-images during follow up. We estimated the event - free survival (EFS), overall survival (OS), and brain-metastasis free survival (BMFS) using Kaplan-Meier method, and performed cox-proportional hazards models to assess the impact of clinical-pathologic parameters on EFS, OS. The covariates for predicting CNS relapse either as first site or as sequential event during follow up were also analyzed. Results: With median follow up of 63.57 months (range 8.8~132.4months) of entire cohort, the five year event-free survival rate, overall survival rate, and brain-metastasis free survival was 72%, 85%, and 92%, respectively. Forty-three of sixty first events (71.7%) were distal relapse which remained the main failure type of our cohort. The five year cumulative incidence of different first events, included loco-regional recurrence, CNS relapse, distal non-CNS relapse, second primary, and non-cancer death, were 4.7%, 2.57%, 15.83%, 1.46%, and 0.4%. Central nervous system failure either as first site of recurrence or as a sequential event was noted in six and ten women. No adjuvant trastuzumab, positive lymph node number more than nine, and dermis involvement significantly predicted poorer event free survival on uni-and-multivariate analysis(p= 0.001, ＜ 0.001, 0.042, respectively). These factors also translated in predicting overall survival. No significant predictor was noted for the occurrence of CNS relapse as first site (5-year cumulative incidence: 1.86% and 3.02% in patients with or without adjuvant trastuzumab, p= 0.633). The negatively prognostic factors for brain-metastasis free survival were positive lymph node number more than nine, lymphovascular invasion, and high grade tumor (p= 0.043, ＜0.001, and ＜0.001, respectively). Conclusion: Using adjuvant trastuzumab improves event-free survival and overall survival in women with stage II /III HER2-positive breast cancer. The development of CNS relapse did not increase in our patients receiving trastuzumab based adjuvant therapy. Brain image as part of follow up might be considered, especially for those with positive lymph node number more than nine, high grade tumor, and with lymphovascular invasion. Larger prospective data or data from published randomized trials is needed for determining patients with high risks of developing CNS relapse.

Image-Guided Stereotactic Radiosurgery Using Volumetric Modulated Arc Therapy for Arteriovenous Malformation of the Brain: Experiences of a Single Institution

Purpose: To evaluate the therapeutic effects of brain arteriovenous malformation (AVM) treated with image-guided stereotactic radiosurgery using volumetric modulated arc therapy. Material and Methods: From March 2010 through November 2012, there were 20 patients with brain AVM treated with image-guided stereotactic radiosurgery in our institution. The median age at diagnosis was 40 years (ranged from 9 to 74 years). Fourteen patients were male (70%) and 6 were female (30%). Among all these 20 patients, 5 patients (25%) had previous surgery of craniotomy with excision, and 2 patients (10%) received previous endovascular embolization. No patients had been managed with observation only at the time of diagnosis. The median dose of stereotactic radiosurgery was 18 Gy (ranged from 12 to 20 Gy). The median clinical target volume was 3.6 c.c (ranged from 1.5 to 15.5 c.c). Results: The median follow-up period was 11.8 months (ranged from 4.7 to 35.4 months). Four patients (20%) had complete obliteration, 8 patients (40%) had partial obliteration, while 8 patients (40%) had stable diseases after treatments. The actuarial 1-year, 2-year and 3-year obliteration rates were 40%, 55% and 60%, respectively. Conclusion: The therapeutic effects of brain AVM treated with image-guided stereotactic radiosurgery using volumetric modulated arc therapy achieved 60% of both complete and partial obliteration rate within the median follow-up period of 11.8 months. The actuarial 1-year, 2-year and 3-year obliteration rates were 40%, 55% and 60%, respectively. The long-term follow-up duration should be warranted to evaluate the further treatment results.

Predictive Factors for Brain Metastases in Early-Stage Non-Small Cell Lung Cancer

Purpose: The risk of developing brain metastases in locally advanced non-small cell lung cancer (NSCLC) is approximately 22%-55% and has been discussed in many studies. However the risk for patients with early stage NSCLC is less defined. The purpose of this study is to evaluate the risk factors of developing brain metastases in early stage NSCLC. Materials and Methods: Patients diagnosed with early stage (clinical T1-2, N0-1, M0) NSCLC in our institution from Jan, 2007 to Jun, 2012 were surveyed. Exclusion criteria were (1) patients who did not received regular follow up at our hospital or those with missing data or who had a follow up time ＜ 3 months. (2) Double cancer (3) pathological ＞T2 or ＞N1 disease. Factors such as age at diagnosis, gender, cell type, histological grade, T stage, N stage, different pulmonary lobe, performance status and treatment modality were reviewed from their chart records and analyzed using Kaplan-Meier and Cox regression to estimate the association and significance with brain metastases. Results: From Jan, 2007 to Jun, 2012, 260 patients were diagnosed with early stage NSCLC. Eighty three patients were excluded and 177 were enrolled in this study. The median follow up time of all the patients was 28.4 months (range, 3-74 months). Brain metastases were identified in 18 patients. The 5-year risk of developing brain metastases was 19%. The median time from diagnosis to brain metastases was 17.8 months (range, 1.8-60.6 months) and the median age at diagnosis was 69.5 years. In univariate and multivariate analysis, stage (T2) and surgery status (without surgery) had strong associations with developing brain metastases (p= 0.007 and 0.001 in univariate, p= 0.028 and 0.007 in multivariate respectively). Age (＞60 y/o) showed a trend towards association with brain metastases in multivariate analysis (p= 0.053). Conclusions: Our results showed that the 5-year risk of developing brain metastases was 19% in early stage NSCLC. Tumor stage (T2) and surgery status (without surgery) were significant predictors for brain metastases.

Primary Small Cell Carcinoma of the Ureter-A Case Report and Review of the Literature

Introduction: Small cell carcinoma usually arises in the lung but can also originate in a wide range of extrapulmonary sites. Extrapulmonary small cell carcinoma is rare, encompassing approximately 0.1-0.4 percent of all small cell carcinomas, and has been described in a variety of organs. Small cell carcinoma of the genitourinary tract is often found in the urinary bladder, and is extremely rare in the ureter. Case report: A 56-year-old man was admitted with a two-month history of the right flank pain. An abdominal computed tomography demonstrated an infiltrative mass lesion with size of about 8.5 × 7.6 cm in the right pelvis, arising from the right ureter, with severe right hydronephrosis and hydroureter. The patient received neoadjuvant chemotherapy with cisplatin and gemcitabine for 3 cycles, followed by right side hand-assisted retroneoscopic nephroureterectomy. Then adjuvant concurrent chemo-radiotherapy was given. The chemotherapy regimens were cisplatin and etoposide for 3 cycles. The irradiation course consisted of 64.8 Gy/36 fractions to the tumor bed. Discussion: The most common symptoms of this disease are gross hematuria and flank pain. The staging of this disease is according to small cell carcinoma of the lung. The treatment of ureter small cell carcinoma is not well established. Despite adjuvant chemotherapy or radiotherapy, most patients develop metastatic disease resulting in poor prognosis of this disease. Aggressive treatment is warranted to improve the outcome. However, the tolerance of the patients is still needed to be considered.

PET-CT Imaging for Radiotherapy: From Clinical Biologic Target Definition to Translational Research

Medical modalities for molecular imaging such as F-18 fluorodeoxyglucose positron emission tomography (FDG-PET), has become an important surrogate biomarker that reflects cellular glucose metabolism. It has been applied to the staging, re-staging, therapeutic monitoring and follow-up of patients with various tumors. Phenotypic information is being used to increase the accuracy of radiation treatment planning, by fusing CT planning images, which has resulted in better tumor control and fewer treatment related toxicities. Applications of PET-CT using biotracers other than FDG in clinical radiotherapy research and in translational research for radiotherapy are intensively investigated which may offer additional parameters in therapeutic targeting.

Prognostic Factor Affecting the Outcome of Bone Metastasis from Hepatocellular Carcinoma

Purpose: The purpose of this study is to analyze the overall survival rate of patients with bone metastasis from hepatocellular carcinoma (HCC) and prognostic factors affecting their outcomes.Materials and Methods: From June 1999 to January 2005, there were 69 patients with bone metastasis from HCC who were treated at our hospital. The variables, such as gender, age of diagnosis of bone metastasis, Pughs modification of Childs grading of cirrhosis Okuda staging system, performance status, serum level of α-fetoprotein at diagnosis of bone metastasis from HCC, methods of treatment for bone metastasis, site of bone metastasis and metastasis to organ other than bones were analyzed about their influence upon prognosis.Results: Fifty-two patients (75.4%) are male and 17 patients (24.6%) are female. The medium age of diagnosis of bone metastasis was 66 years old (range from 31 to 78 years old). The medium survival from diagnosis of bone metastasis was 3.06 months. The 6-month, 1-year and 2-year overall survival rates were 30.43%, 11.59% and 5.80%, respectively. In univariate analysis, Childs grading of cirrhosis (p=0.0022), Okuda staging system (p=0.0002), and performance status (p=0.0277) were statistically significant factors for survival. In multivariate analysis, performance status (p=0.003) was the only significant prognostic factor.Conclusion: The survival of patients with bone metastasis from HCC was poor. To improve the outcome, we should enroll more patients and arrange prospective trial by combination of locoregional and systemic therapy.