Combination of p16 levels and pre-radiotherapy factors predicts outcome in patients treated for oropharyngeal carcinoma.

PURPOSE: To explore whether tumor biomarkers and pre-treatment factors correlate with treatment outcome in patients with oropharyngeal squamous cell carcinoma (SCC). METHODS: Fifty-seven consecutive patients diagnosed with oropharyngeal SCC were treated using intensity modulated radiotherapy (IMRT). Thirty-four (60%) patients were treated with definitive chemoradiotherapy to a median total dose of 70 Gy and 23 (40%) were treated with postoperative RT to a median total dose of 66 Gy. Concurrent platinum- based chemotherapy was used in 51 patients (90%) and cetuximab in 3 (5%) patients. RESULTS: Forty-four (77%) cases were positive and 13 (23%) were negative for p16 expression. Eighty-eight percent of non-smokers, 87% of smokers in their remote past and 56% of active smokers were diagnosed with p16-positive cancer. After 22 months median follow up, 51 (89%) patients were alive. Forty-five (77%) patients were without evidence of disease at their last follow up, 82% of the patients with p16-positive tumors vs 58% of those with p16-negative cancer, respectively (p= 0.04). Locoregional disease-free survival was 82% for the entire cohort, 91% for patients treated postoperatively and 76% for patients treated with definitive chemoradiotherapy. Five (9%) patients developed distant metastases, and 3 (5%) developed new malignancies. One third of the patients with pre-RT hemoglobin level of ≤ 11 g/dL experienced persistent/recurrent disease; 80% of patients with hemoglobin ≤ 11 g/dL were smokers and 42% had p16-negative tumors. CONCLUSIONS: Smoking, p16 expression and pre-RT anemia are interrelated and influence outcome in oropharyngeal cancer patients and should be evaluated as stratifying variables in further clinical trials.

Dosimetric consequences of pancreatic tumor motion when predetermined treatment margins are employed during intensity-modulated radiation therapy.

PURPOSE: To quantify the dosimetric consequences of pancreatic tumor motion on the pancreatic intensity-modulated radiation therapy (IMRT) plans. METHODS: Dose map of IMRT plans for 5 patients with pancreatic cancer were measured using a 2D diode array placed on a computer-controlled platform to simulate 2D pancreatic tumor motion. Dosimetric analysis was then performed to obtain IMRT quality assurance (QA) passing rates. The convolution method, which used a motion kernel to simulate 2D pancreatic motion, was also applied to the treatment and phantom verification plans for a wide range of magnitudes of motion (0.8-2.0 cm). The resulting motion-convolved verification dose maps (VDMs) were compared with the dynamic measurements to evaluate IMRT QA passing rates as well as the dose-volume histogram, the V95% of the planning target volume (PTV) and V98% of the clinical target volume (CTV). RESULTS: While CTV coverage was maintained when the simulated pancreatic tumor drifted inside the PTV with magnitudes of 1.0 cm and 1.5 cm, the V95% of the PTV was reduced by 10% and 17%, respectively. We also found that the differences between the measurements and the static VDMs increased proportional to the amplitude of motion, while the agreement between the measurements and the motion-convolved VDMs was excellent for any magnitude of motion. CONCLUSIONS: When the 4D technique is not available, predetermined margins must be used carefully to avoid possible under-dose to the target. Additionally, the phantom results show that the kernel convolution method provides an accurate evaluation of the dosimetric impact due to tumor motion and it should be employed in the planning process.

Toxicity data for preoperative concurrent chemoradiotherapy with oxaliplatin and continuous infusion 5-fluorouracil for locally advanced esophageal cancer.

The purpose of this retrospective analysis was to characterize the feasibility and tolerability of oxaliplatin/5-fluorouracil (5-FU) given concurrently with radiotherapy for patients with locally advanced esophageal cancer. Between July 2005 and March 2009, 15 patients with clinical stage T3/T4 and/or N1/M1a lower esophageal or gastroesophageal junction adenocarcinoma were treated with preoperative chemoradiotherapy using oxaliplatin every 2 weeks and continuous infusion 5-FU. The main treatment-related toxicities were oral mucositis and dysphagia. During the first 2 weeks of treatment, 20% of patients presented with grade 1-2 oral mucositis, and one patient developed grade 1 dysphagia. In weeks 3-4, 53% of the patients experienced grade 1-2 mucositis, and 40% experienced grade 1-2 dysphagia. One patient only experienced grade 3 mucositis in week 4. Three patients (20%) had grade 3-4 dysphagia in weeks 3-4 and were continued on intravenous fluids and pain medications. During the last 2 weeks of chemoradiotherapy, 53% of patients reported grade 1-2 oral mucositis, mostly grade 1 and 73% of patients experienced grade 1-2 dysphagia and 26% patients experienced grade 3-4 dysphagia. Other toxicities included fatigue, nausea, neuropathy, and diarrhea. Only one patient experienced > 10% weight loss. The whole group was treated with aggressive supportive care during radiotherapy. Five (33%) patients achieved a pathological complete response. No patients developed locoregional failure. Sixty percent of the patients developed distant metastases and the 2-year disease-free survival was 53%. The median survival was 3.2 years with the 2-year overall survival of 73%. Preoperative oxaliplatin/5-FU-based chemoradiotherapy for locally advanced esophageal cancer is feasible, but associated with substantial gastrointestinal toxicity. A careful attention to nutrition and hydration throughout the course of therapy is required.

Neutrophil to lymphocyte ratio associated with prognosis of lung cancer.

PURPOSE: Many studies recently focus on complicated and expensive genomic tests, but the prognostic values of biochemical markers which are easily obtained in clinics are largely overlooked and without further exploration. This study assesses the association of neutrophil-lymphocyte-ratio (NLR) with prognosis of lung cancer patients. METHODS: In 1032 patients with histologically confirmed lung cancer, the association of pretreatment NLR values with overall survival (OS) was evaluated using a Cox proportional hazards model and the temporal relationship of longitudinal NLR was assessed using a mixed effects model. RESULTS: Compared to the patients with a low pretreatment NLR value, those with elevated NLR exhibited a statistically significant worse OS with a hazard ratio (HR) of 1.50 (P < 0.0001) after adjusting for age, gender, race, smoking status, drinking status, tumor stage, tumor grade, histology, and treatments. A significant trend of increasing HRs along with increasing NLR values was observed. The increased risk of death conferred by pretreatment NLR values reached a peak level around 2 years after diagnosis. Moreover, in longitudinal analysis, we observed a trend of dramatically increased NLR values in patients who died during follow-up, but stable NLR values in those who were still alive, with a significant interaction of death-alive status with follow-up time (P < 0.0001). CONCLUSIONS: Elevated NLR is a potential biomarker to identify lung cancer patients with poor prognosis and should be validated in a future clinical trial.

Current controversies in sentinel lymph node biopsy for breast cancer.

Despite the widespread use of sentinel lymph node biopsy (SLNBx) in the surgical management of breast cancer patients, several areas remain controversial. The following controversies are reviewed: Learning curves and validation studies. There clearly is a learning curve, and a completion ALND should be done until adequate proficiency is exhibited, both in terms of identification and false-negative rates. Location of injection. Intradermal injection offers superior identification rates compared with peritumoral injection, with comparable false-negative rates. Subareolar injection is as accurate as peritumoral injection. The value of scintigraphy. Routine scintigraphy does not enhance identification or false-negative rates. Mapping agents. Blue dye and radioactive tracer combined to provide a higher identification rate than either used alone.SLNBx in DCIS. In patients with a high risk of microinvasion, such as large tumors, a mass or high-grade DCIS-SLNBx is justified.SLNBx following neoadjuvant chemotherapy. Although there is evidence that SLNBx after neoadjuvant chemotherapy may be accurate, these data should be applied cautiously. Implications of non axillary SLN, especially internal mammary nodes. Data do not support routine resection of internal mammary sentinel lymph nodes outside a clinical trial. Implications of micrometastases in the sentinel lymph node seen only on immunohistochemistry. Since the significance of such metastases is unclear, decisions regarding treatment of these patients should be individualized. The value of completion axillary lymph node dissection. Is being addressed in clinical trials. Until those studies mature, completion ALND should be performed for patients with SLN metastases, but may be abandoned for patients with a negative SLN.

Neutrophil to lymphocyte ratio associated with prognosis of lung cancer

Purpose. Many studies recently focus on complicated and expensive genomic tests, but the prognostic values of biochemical markers which are easily obtained in clinics are largely overlooked and without further exploration. This study assesses the association of neutrophil-lymphocyte-ratio (NLR) with prognosis of lung cancer patients. Methods. In 1032 patients with histologically confirmed lung cancer, the association of pretreatment NLR values with overall survival (OS) was evaluated using a Cox proportional hazards model and the temporal relationship of longitudinal NLR was assessed using a mixed effects model. Results. Compared to the patients with a low pretreatment NLR value, those with elevated NLR exhibited a statistically significant worse OS with a hazard ratio (HR) of 1.50 (P < 0.0001) after adjusting for age, gender, race, smoking status, drinking status, tumor stage, tumor grade, histology, and treatments. A significant trend of increasing HRs along with increasing NLR values was observed. The increased risk of death conferred by pretreatment NLR values reached a peak level around 2 years after diagnosis. Moreover, in longitudinal analysis, we observed a trend of dramatically increased NLR values in patients who died during follow-up, but stable NLR values in those who were still alive, with a significant interaction of death-alive status with follow-up time (P < 0.0001). Conclusions. Elevated NLR is a potential biomarker to identify lung cancer patients with poor prognosis and should be validated in a future clinical trial (AU)

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