Research 1

Retrospective Review of Chemotherapy Treatment for Locally Advanced and Metastatic Penile Cancer in the North West of England

Aims: To examine current practices in the UK in the use of chemotherapy in advanced penile cancer and investigate the treatment outcomes of this group of patients.
Study Design: Retrospective series.
Place and Duration of Study: The study population received chemotherapy at Clatterbridge Cancer Centre, The Christie Hospital or Lancashire Teaching Hospital between January 1999 and January 2009.
Methodology: Patients undergoing chemotherapy for histologically confirmed squamous cell carcinoma of the penis within the designated time period were identified retrospectively.
Through case note review, data were collected on chemotherapy regimens, tolerability, response to treatment and survival. Response to chemotherapy was categorized by the investigators according to RECIST (version 1.0) criteria.
Chemotherapy given concurrently with radiotherapy was excluded.
Results: 40 patients were treated with chemotherapy for locally advanced or metastatic penile cancer. Prior to the inception of a Supra-regional Multidisciplinary Team (SMDT), seven different chemotherapy regimens were used first line. After introduction of the SMDT Cisplatin/5-Fluoruracil (5FU) was almost exclusively prescribed outside of clinical trials.
12/40 (30%) patients completed the planned course of chemotherapy. 27/40 (67%) discontinued treatment prematurely, 14/40 (35%) due to progressive disease, and 13/40 (32%) due to declining performance status and/or toxicity.
Response to chemotherapy was assessed radiologically in 23/40 patients and categorised by the investigators according to RECIST criteria. There were three complete responses and eight partial responses (objective response rate 28%). Median survival was 15 months from diagnosis and 5 months from commencing first line chemotherapy.
Conclusion: This supra-regional collaboration highlighted varying use of chemotherapy historically in penile cancer. Development of a supra-regional MDT has reduced much of the variability. Response rates are modest and survival outcomes are poor. This reinforces the urgent need for clinical trials to establish a framework for novel, more active regimens and to guide patient selection.

Research 2

Gemcitabine and Carboplatin in Inoperable, Loco-Regionally Advanced and Metastatic Gallbladder Cancer- A Study from Northern Indian Cancer Institute

Aims: The primary objective of this study was to determine the response rates of the gemcitabine and carboplatin combination chemotherapy in treatment naïve patients with inoperable gall bladder cancer. The secondary objectives were to evaluate the toxicity, progression free survival (PFS), and overall survival (OS).

Methodology: Treatment naïve patients with histologically proven inoperable gall bladder cancer treated with gemcitabine and carboplatin chemotherapy between February 2011 and December 2014 were included in this study. The dose of gemcitabine was 1 gm/m2 on day 1 and 8, and carboplatin [target AUC (area under the concentration versus time curve in mg/ml) of 5] on day 1, in a 21 day cycle. CT scan was used for response assessment.

Results: There were 32 men and 92 women with a median age of 59 years (range 26-75 years). Of the 124 patients, 9 (7.3%) patients achieved a complete response and 54 (43.5%) patients achieved a partial response for an overall response rate of 50.8%. The median PFS was 4.6 months [95% confidence interval (CI) 4–5.5 months], with 1-year survival rate of 20.2%. Common toxicity criteria (CTC) grade 3 anaemia was seen in 6 (4.8%) patients. Grade 3 and 4 neutropenia was observed in 11 (8.9%) and 4 (3.2%) patients respectively, whereas 9 (7.3%) patients experienced Grade 3 thrombocytopenia.

Conclusion: The combination of gemcitabine and carboplatin is active in advanced gall bladder carcinoma with mild toxicity.

Research 3

Triple-Negative Breast Cancer in Brazilian Women without Metastasis to Axillary Lymph Nodes: Ten-Year Survival and Prognostic Factors

Aims: To determine the 10-year overall survival (OS) in triple-negative (TN) and non-TN breast cancer (BC) patients, and to identify associated independent prognostic factors.
Study Design: Descriptive and survival.
Place and Duration of Study: Pathology Division at National Cancer Institute, Rio de Janeiro, Brazil, between 1992-1996.
Methodology: Population: 348 women patients with invasive ductal carcinoma without lymph node metastasis. Analyzed variables: age, treatment, surgery type, tumor size, skin involvement, histological grade, vascular invasion, estrogen and progesterone receptors, HER-2, Ki-67 and p53. Statistical analysis performed: Kaplan-Meier survival curves, log rank test, and multivariate Cox models.
Results: 27% of the studied women were categorized as TNBC and 73%, as non-TNBC. The former showed higher frequency of age <50yr, preoperative chemotherapy, tumors >5cm, high grade, vascular invasion, and positive p53, (P=.05). Ten-year OS among TNBC patients was 61.6%, and 70.1% for non-TNBC patients (P=.058). Survival was higher in TNBC patients treated with partial surgeries, tumors ≤5cm, without skin involvement, low grade, and Ki-67 negative (P=.05). Among non-TNBC patients, higher survival was observed in patients without skin involvement, low grade, no vascular invasion, and p53 negative, (P=.05). Cox modelization showed a 2-fold higher death risk for TNBC patients aged ≥50yr, about 2.5-fold higher risk related to preoperative chemotherapy, high grade tumor and skin involvement, and a 3.0-fold higher risk for Ki-67 positive patients (P=.05). For non-TNBC patients, a 2.0-fold increased death risk was verified in patients with skin involvement and vascular invasion (P=.05).
Conclusion: TNBC patients showed a worse prognosis and survival when compared to non-TNBC patients. A worse 10-yr survival among TNBC patients was associated with age ≥50yr, preoperative chemotherapy, skin involvement, high histological grade, and Ki-67 positive tumors. For non-TNBC patients, the worst prognosis was related to skin involvement and vascular invasion. These predictors need to be further validating by other studies.

 

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