The Outcome of Patients with Triple Negative Breast Cancer: The Turkish Oncology Group Experience.

OBJECTIVE: Triple negative breast cancer (TNBC) is generally considered as a poorer prognostic subgroup, with propensity for earlier relapse and visceral involvement. The aim of this study is to evaluate the outcome of non-metastatic TNBC patients from different centers in Turkey and identify clinical and pathologic variables that may effect survival. MATERIALS AND METHODS: Between 1993-2007, from five different centers in Turkey, 316 nonmetastatic triple negative breast cancer patients were identified with follow-up of at least 12 months. The data was collected retrospectively from patient charts. The prognostic impact of several clinical variables were evaluated by the Kaplan-Meier and Cox multivariate anayses. RESULTS: Mean age at diagnosis was 49 years (range: 24-82). The majority of the patient group had invasive ductal carcinoma (n: 260, 82.3%) and stage II disease (n: 164; 51.9%). Majority of the patients (87.7%) received adjuvant chemotherapy. 5 year overall survival (OS) and disease-free survival (DFS) rates were 84.6% and 71.6%, respectively. Univariate analysis revealed locally advanced disease (p: 0.001), advanced pathological stage (p: 0.021), larger tumor size (T1&T2 vs T3&T4) (p<0.001), nodal positivity (p: 0.006), and extensive nodal involvement (p<0.001) as significant factors for DFS; whereas, advanced pathological stage (p: 0.017), extensive nodal involvement (p<0.001) and larger tumor size (p: 0,001) and presence of breast cancer-affected member in the family (p=0.05) were identified as prognostic factors with an impact on OS. Multivariate analysis revealed larger tumor size (T3&T4 vs T1&T2) and presence of lymph node metastases (node-positive vs node-negative) as significant independent prognostic factors for DFS (Hazard ratio (HR): 3.03, 95% CI: 1.71-5.35, p<0.001 and HR: 1.77, 95% CI: 1.05-3.0, p=0.03, respectively). Higher tumor stage was the only independent factor affecting overall survival (HR: 2.81; 95% CI, 1.27-6.22, p=0.01). CONCLUSION: The outcome of patients with TNBC in this cohort is comparable to other studies including TNBC patients. Tumor size and presence of lymph node metastasis are the major independent factors that have effect on DFS, however higher tumor stage was the only negative prognostic factor for OS.

Breast conservation therapy: the influence of molecular subtype and margins.

PURPOSE: To evaluate treatment results and prognostic factors, especially margin status and molecular subtype, in early-stage breast cancer patients treated with breast conservation therapy (BCT). METHODS AND MATERIALS: The records of 1,058 Stage I or II breast cancer patients treated with BCT (surgical excision plus radiotherapy) at Duke University Medical Center, Durham, North Carolina, from 1985-2005 were retrospectively reviewed. Conventional receptor analyses were used as surrogate markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal like). Actuarial estimates of overall survival (OS), cause-specific survival (CSS), failure-free survival, and locoregional control (LRC) were computed by use of Kaplan-Meier plots. We analyzed prognostic variables for significance using Cox proportional hazards univariate and multivariate analysis. The study was approved by the Duke University Medical Center Institutional Review Board. RESULTS: The median age of the patients was 56 years (range, 18-89 years). Of the patients, 80% had T1 disease and 66% N0 disease pathologically. With a median follow-up of 9.8 years, an in-breast recurrence developed in 53 patients and 10 patients had nodal failure. For all patients, the 10-year CSS rate was 94%; LRC rate, 94%; and failure-free survival rate, 88%. Luminal A patients had a CSS rate of 95% and LRC rate of 99%. Basal-type patients appeared to do worse, with regard to both CSS rate (74%) and LRC rate (76%), but the numbers were small and the difference was not statistically significant. LRC rates of patients with negative margins (widely negative, close, and extent of margin not known) were virtually identical (93%, 96%, and 94%, respectively). Those with positive margins appeared to fare slightly worse based on LRC rate (88%), but again, the numbers were small and the difference was not statistically significant. CONCLUSIONS: BCT remains the treatment of choice for early-stage breast cancer patients irrespective of molecular subtype. Negative margins of excision are desirable, but the width of the negative margin does not influence outcome.

Validation of the Turkish versions of EORTC QLQ-C30 and BR23 modules in breast cancer patients.

PURPOSE: To test the validity and reliability of The European Organization for Research and Treatment of Cancer (EORTC) core (QLQ-C30) and breast cancer module (QLQ-BR23) for Turkish breast cancer patients. PATIENTS AND METHODS: A total of 127 patients treated with radiotherapy (RT) enrolled to this prospective study. EORTC QLQ-C30 and QLQ-BR23 modules applied to patients before initiation of RT and at follow-up period. Statistical analyses were performed by SPSS 13.0. RESULTS: Questionnaires' were found reliable and valid for Turkish breast cancer patients. Six of the 8 multi-item scales of QLQ-C30 had a high reliability (Cronbach's ? >0.7); where physical functioning and pain scores were less reliable (Cronbach's ? of 0.66 and 0.68 respectively). In the QLQ-BR23, 3 of 5 multi-item scales were reliable; less reliable were breast and arm symptoms scale (Cronbach's ? of 0.65 and 0.61 respectively). In our analysis the most determinative subscales of QLQ-C30 on global health was emotional functioning followed by fatigue, role functioning and appetite loss (respectively p=0.002, p=0.01; p=0.03 and p=0.08). Among QLQ-BR23 scales systemic therapy SIDE effects, future perspective and upset by hair loss subscales had high impact on global health status (respectively p=0.006; p=0.01 and p=0.03). CONCLUSIONS: The Turkish version of EORTC QLQ-C30 and QLQ-BR23 modules are reliable and valid tools to assess quality of life of Turkish breast cancer patients.

The interaction between antioxidant status and cervical cancer: a case control study.

AIMS AND BACKGROUND: To compare the antioxidant status of cervical cancer patients with healthy controls and to assess the antioxidant levels before and after radiotherapy or radiochemotherapy. METHODS AND STUDY DESIGN: Antioxidant levels (glutathione, glutathione peroxidase, superoxide dismutase, and malondialdehyde) were measured in 35 patients with cervical cancer and 35 age-matched healthy controls. Blood samples were collected twice (before and after treatment) from cervical cancer patients and once from healthy control subjects. RESULTS: In the patient group, pre-radiotherapy glutathione and glutathione peroxidase levels were significantly lower (P <0.01 and P <0.0001, respectively) than the control group. Pre-radiotherapy levels of superoxide dismutase were significantly higher in cancer patients (P <0.01). In general, no difference was observed between pre- and post-radiotherapy antioxidant levels in cancer patients. However, when post-radiotherapy glutathione levels were analyzed, patients who did not respond to treatment had significantly higher levels than those who did respond (P <0.01). CONCLUSIONS: Levels of antioxidants significantly differed between the patients with cervical cancer and the controls, and no change in antioxidant levels was observed after treatment. Moreover, further studies evaluating the predictive value of glutathione levels on treatment response are warranted.

Does the prognosis of nasopharyngeal cancer differ among endemic and non-endemic regions?

CONCLUSION: The survival rates and prognostic factors for nasopharyngeal cancer (NPC) were found to be similar to the published series from endemic regions. OBJECTIVES: The purpose of this retrospective study was to evaluate treatment outcome and prognostic factors of NPC patients treated with radiotherapy or chemoradiotherapy in a non-endemic region. METHODS: We analyzed clinical characteristics, treatment outcome, and prognostic factors of NPC patients in a non-endemic region, and compared our institution's results with the published literature including a similar patient population from endemic and non-endemic regions. Among 248 NPC patients, 71 (28.6%) were female and 177 (71.4%) were male with a median age of 48 years. RESULTS: Within a median 59 months (range 22-178) of follow-up, local recurrence developed in 22 (8.9%), regional recurrence in 2 (0.8%), locoregional recurrence in 5 (2%), distant metastases in 21 (8.5%), and both locoregional recurrence and distant metastases in 8 (3.2%) patients. Five-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) rates were 83.7%, 73%, 78.5%, and 71.1%, respectively. In multivariate analysis for LRC, cranial nerve involvement (CNI) (p = 0.009) and tumor response (p = 0.004); for DFS, age (p = 0.003), CNI (p = 0.02), AJCC T classification (p = 0.05), and tumor response (p = 0.01); for DSS, age (p = 0.003), CNI (p = 0.04), AJCC T classification (p = 0.04), and tumor response (p = 0.01); for OS, age (p < 0.001), AJCC T classification (p = 0.005), and tumor response (p < 0.001) were significant prognostic factors.

A comparison of clinical and dosimetric outcomes in patients receiving partial breast irradiation with photon-only versus mixed photon/electron treatment plans.

Several series evaluating external-beam partial breast irradiation (PBI) have linked negative cosmetic outcomes to large normal tissue treatment volumes. We compared patients treated with PBI whose treatment plans included only photons to those whose plans incorporated electrons. Twenty-seven patients were identified: median age 67 years, pT1 82%, pN0 56%, margin negative 100%. All received 38.5 Gy using 3-5 noncoplanar photon beams (6-15X). Electrons (9-20 MeV) were included in 59%. Median follow-up was 22 months. Ninety percent experienced good/excellent cosmetic outcomes. Two patients had fair cosmesis, and both were treated with a mixed photon/electron approach. Median conformity index for photon-only treatment plans was 1.7 (range, 0.9-2.0) and for photon/electron plans, 1.0 (0.3-1.4). Median percent ipsilateral breast volume receiving 100% and 50% of prescription dose was 19 and 50 for photon-only plans vs. 10 and 38 for photon/electron plans (p < 0.05). Median percent target volume receiving 100% and 95% of prescription dose was 93 and 98 for photon-only plans vs. 75 and 94 for photon/electron plans (p < 0.05). A mixed photon/electron, noncoplanar technique decreases the volume of treated normal breast tissue at the cost of slightly decreased tumor bed coverage. Further study is needed to determine whether this results in a more favorable therapeutic ratio than photon-only approaches.

Postoperative gemcitabine alone and concurrent with radiation therapy in locally advanced pancreatic carcinoma.

AIMS AND BACKGROUND: To evaluate the treatment results of gemcitabine alone and concurrent with radiotherapy after R0/R1 resection of locally advanced pancreatic cancer. METHODS AND STUDY DESIGN: From 1999 to 2005, 55 patients with stage II resected pancreatic cancer treated with gemcitabine-based radiochemotherapy were retrospectively evaluated. Initially, one cycle of induction gemcitabine was administered and followed by weekly gemcitabine concurrent with radiotherapy. After the completion of radiochemotherapy, patients received 3 additional courses of gemcitabine. RESULTS: Thirteen patients were stage IIA and 42 were stage IIB. Forty-six patients (83.6%) had R0 and 9 patients (16.4%) had R1 resection. All of the patients received induction chemotherapy and radiotherapy, all but 3 received concurrent radiochemotherapy, and 46 (84%) patients received maintenance chemotherapy. During induction, concurrent and maintenance phases of the protocol, 11%, 13.5% and 19.5% of the patients had at least one > or = grade 3 toxicity, respectively. Within a median 47 months (range, 34-105) of follow-up, 4 (7.3%) patients had isolated local recurrence, 5 (9%) patients had local recurrence and distant metastases, and 27 (49%) had only distant metastases. Median disease-free survival and overall survival were 13 (range, 4-105) and 19 months (range, 6-105), respectively. In multivariate analysis, nodal stage, AJCC stage and number of lymph nodes dissected were the significant factors affecting disease-free survival whereas Karnofsky performance status was the only significant factor for overall survival. CONCLUSIONS: The prognosis for pancreatic cancer remains poor despite adjuvant radiochemotherapy. More aggressive treatments should be considered in patients with unfavorable prognostic factors.

Postoperative radiotherapy in rectal cancer: long-term results of 290 patients.

BACKGROUND/AIMS: To evaluate treatment results and to identify prognostic factors affecting local-relapse-free (LRFS), disease-free (DFS) and overall survival (OS) in patients treated with postoperative radiotherapy (RT) for rectal cancer. METHODOLOGY: A retrospective review was performed in 290 patients treated between January 1990 and December 2005. Median RT dose was 54 Gy. A total of 220 (75.8%) patients also received 5-fluorouracil based chemotherapy. RESULTS: During a median follow-up of 56 months (range 9-216 months), 68 patients (23.4%) developed local recurrence and 96 patients (33.1%) developed distant metastases. Five-year LRFS, DFS, and OS rates were 74.6%, 52.6%, and 53.7%, respectively. On multivariate analysis, significant prognostic factors for LRFS were age, pathologic T stage (pT), and distance from anal verge; for DFS were pT stage, and positive surgical margin; for OS were pT and pathologic N (pN) stages. One hundred and fifty-two node-positive patients whose number of retrieved and metastatic nodes are known were evaluated according to the lymph node ratio (LNR). OS and DFS rates significantly decreased with increasing LNR (p = 0.005, and p = 0.023 respectively). RT related Grade 3-4 late morbidity rate was 3.1%. A second primary malignancy developed in 4.8% of patients. CONCLUSION: Among several prognostic factors, pT stage significantly predicted for LRFS, DFS and OS on multivariate analysis, while pN stage was significant for all three only on univariate analysis. LNR which affected DFS and OS could be an important tool for prognostic prediction for node-positive patients.

Evaluation of burnout syndrome in oncology employees.

Burnout is an important occupational problem for health care workers. We aimed to assess the burnout levels among oncology employees and to evaluate the sociodemographic and occupational factors contributing to burnout levels. The Maslach Burnout Inventory, which is designed to measure the three stages of burnout-emotional exhaustion (EE), depersonalization (DP), and personal accomplishment (PA), was used. The study sample consisted of 90 participants with a median age of 34 (range 23-56). The mean levels of burnout in EE, DP and PA stages were 23.80 +/- 10.98, 5.21 +/- 4.99, and 36.23 +/- 8.05, respectively, for the entire sample. Among the 90 participants, 42, 20, and 35.6% of the employees had high levels of burnout in the EE, DP, and PA substage, respectively. Sociodemographic and occupational factors associated with higher levels of burnout included age of less than 35, being unmarried, being childless, >40 work hours per week, working on night shifts, and <10 years experience in the medicine/oncology field. Within all oncology clinics, medical oncology employees had the highest levels of burnout. Furthermore, employees who are not pleased with working in oncology field, who would like to change their specialty if they have an opportunity, and whose family and social lives have been negatively affected by their work experienced higher levels of burnout. Burnout syndrome may influence physical and mental health of the employee and affects the quality of health care as well. Therefore, several individual or organizational efforts should be considered for dealing with burnout.

Palliative radiotherapy for the skin metastasis of ovarian cancer: a case report and review of the literature.

Ovarian cancer which is the most common cause of death among all gynecological malignancies tends to metastasize through peritoneal cavity. Skin metastasis, however, is a very rare clinical entity and related with poor prognosis. We report a 43-year-old patient with recurrent ovarian cancer presented with extensive abdominal skin metastasis approximately 6 years after the initial diagnosis. Patient was treated with radiotherapy with electrons to a total dose of 37.5 Gy given in 2.5 Gy per fraction per day. Skin metastasis showed good response to radiotherapy, and the patient has been alive for 7 months after radiotherapy with no recurrences on abdominal skin. Radiotherapy might be considered as an efficient palliative treatment option for the skin metastasis of ovarian cancer.

Radiation-induced cardiac toxicity after therapy for breast cancer: interaction between treatment era and follow-up duration.

PURPOSE: Cardiac toxicity after breast radiotherapy (RT) has been widely described in "older" RT trials (i.e., using larger fraction sizes, wide RT fields, and orthovoltage energy). The results from more "modern" RT trials have shown less cardiac toxicity. The comparisons between the "older" and "modern" trials are confounded by the longer follow-up time in the "older" trials. We systematically assessed the effect of treatment era and follow-up duration on the reported rates of cardiac toxicity associated with RT. METHODS AND MATERIALS: The published data were surveyed using PubMed to identify studies using "breast cancer," "irradiation/radiotherapy," "cardiac/heart," and "toxicity/morbidity/mortality" in a keyword search. Relevant data were extracted from the identified trials. The trials were defined as "older" (patient accrual start year before 1980) and "modern" (patient accrual start year in or after 1980) to segregate the trials and assess the treatment era effect. A 10-year follow-up duration was used as a cutoff to segregate and analyze trials with varying lengths of follow-up. RESULTS: We analyzed 19 published reports of patients treated between 1968 and 2002 (5 randomized controlled trials, 5 single- or multi-institutional studies, and 9 national cancer registry database reviews). In the reviewed trials, all the older trials reported excess cardiac toxicity, typically with a median of >10-15 years of follow-up. However, the vast majority of modern RT trials had shorter median follow-up durations, typically

Multiple spinal metastases of cranial gliosarcoma: a case report and review of the literature.

Gliosarcoma is a rare brain tumor that consists of both glial and mesenchymal components. We report the case of a 68-year-old female with cranial gliosarcoma metastatic to the spinal cord. Initially, the patient was diagnosed with cranial gliosarcoma and treated with surgical resection followed by radiotherapy. Four months after she completed treatment, she presented with a sudden onset of hemiplegia. MRI (Magnetic Resonance Imaging) scan demonstrated two masses at the thoracic spinal cord. Immediate surgery was performed and the lesions were resected. No further therapy was recommended due to the poor condition of the patient. The patient subsequently died 3 months after diagnosis of the spinal cord metastases. There are about 20 reported cases of metastatic gliosarcoma and most focus on systemic metastases of gliosarcoma. Spinal cord metastases are, however, very rare and here we report such a case. Available literature on metastatic gliosarcoma was also reviewed.