Phase i study of \u27dose-dense\u27 pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma.

BACKGROUND: This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC). METHODS: Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m2. Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m2, but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m2) q3 weeks × 2 -3 cycles. RESULTS: Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients. CONCLUSIONS: Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m2 with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC

Phase i study of 'dose-dense' pemetrexed plus carboplatin/radiotherapy for locally advanced non-small cell lung carcinoma

<p>Abstract</p> <p>Background</p> <p>This phase I study investigates the feasibility of carboplatin plus dose-dense (q2-week) pemetrexed given concurrently with radiotherapy (XRT) for locally advanced and oligometastatic non-small cell lung cancer (NSCLC).</p> <p>Methods</p> <p>Eligible patients had Stage III or IV (oligometastatic) NSCLC. Patients received XRT to 63 Gy in standard fractionation. Patients received concurrent carboplatin (AUC = 6) during weeks 1 and 5 of XRT, and pemetrexed during weeks 1, 3, 5, and 7 of XRT. The starting dose level (level 1) of pemetrexed was 300 mg/m². Following the finding of dose limiting toxicity (DLT) in dose level 1, an amended dose level (level 1A) continued pemetrexed at 300 mg/m², but with involved field radiation instead of extended nodal irradiation. Consolidation consisted of carboplatin (AUC = 6) and pemetrexed (500 mg/m²) q3 weeks × 2 -3 cycles.</p> <p>Results</p> <p>Eighteen patients were enrolled. Fourteen patients are evaluable for toxicity analysis. Of the initial 6 patients treated on dose level 1, two experienced DLTs (one grade 4 sepsis, one prolonged grade 3 esophagitis). There was one DLT (grade 5 pneumonitis) in the 8 patients treated on dose level 1A. In 16 patients evaluable for response (4 with oligometastatic stage IV disease and 12 with stage III disease), the median follow-up time is 17.8 months. Thirteen of 16 patients had in field local regional response. The actuarial median survival time was 28.6 months in all patients and 34.7 months (estimated) in stage III patients.</p> <p>Conclusions</p> <p>Concurrent carboplatin with dose-dense (q2week) pemetrexed at 300 mg/m²with involved field XRT is feasible and encouraging in patients with locally advanced and oligometastatic NSCLC.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00330044">NCT00330044</a></p

Evaluating changes in radiation treatment volumes from post-operative to same-day planning MRI in High-grade gliomas.

BACKGROUND: Adjuvant radiation therapy (RT) with temozolomide (TMZ) is standard of care for high grade gliomas (HGG) patients. RT is commonly started 3 to 5 weeks after surgery. The deformation of the tumor bed and brain from surgery to RT is poorly studied. This study examined the magnitude of volume change in the postoperative tumor bed and the potential impact of RT planning. METHOD AND MATERIALS: This study includes 24 patients with HGG who underwent craniotomy and adjuvant RT with TMZ at our institution. All patients had immediate postoperative MRI and repeat MRI during the day of RT simulation. Gross tumor volumes (GTV), clinical target volumes (CTV) of initial 46 Gy (CTV1) and boost to 60 Gy (CTV2) were contoured on both sets of MRIs according to RTOG (Radiation Therapy Oncology Group) guidelines. For patients who recurred after RT, the recurrence pattern was evaluated. RESULTS: An average of 17 days elapsed between immediate and delayed MRIs. GTV1 (FLAIR abnormality and tumor bed) decreased significantly on the delayed MRI as compared to immediate post-operative MRI (mean = 30.96cc, p = 0.0005), while GTV2 (contrast-enhanced T1 abnormality and tumor bed) underwent a non-significant increase (mean = 6.82cc, p = 0.07). Such changes lead to significant decrease of CTV1 (mean decrease is 113.9cc, p CONCLUSION: The postoperative tumor bed of HGGs undergoes substantial volumetric changes after surgery. Treatment planning based on delayed MRI significantly reduces the volume of treated brain tissue without local control detriment. The marked reduction of volume treated to 46 Gy based on delayed MRI scan, could result in increased sparing of organs at risk. There may be a small risk of inadequate radiation field design if radiation planning is based on immediate post-operative MRI

Radiation Oncology Utilization in the IMRT Era

We evaluated long-term changes in the volume and payments for radiation oncology services in the intensity modulated radiation therapy (IMRT) era from 2000 to 2010, using a database of Medicare claims files. We used the Medicare Physician/Supplier Procedure Summary Master File (PSPSMF) for each year from 2000 to 2010 to tabulate the volume and payments for radiation oncology services. This database provides a summary of each billing code submitted to Medicare part B. We identified all codes used in radiation oncology services and categorized billing codes by treatment modality and place of service. We focused our analysis on office-based practices, which provide approximately half of all radiation oncology services. Total office-based patient volume increased 8.2% from 2000 to 2010, while total payments increased 217%. Increase in overall payments increased dramatically from 2000 to 2007, but subsequently plateaued. IMRT accounted for 52% of external beam treatment delivery, and 70% of treatment delivery payments by 2010. Increases in complexity of care, and image guidance in particular, have also increased cost. Office-based practices have greater utilization of IMRT than hospital-based outpatient practices. Cost of radiation oncology services increased from 2000 to 2010, mostly due to IMRT, but also with significant contribution from increased overall complexity of care. A bend in the cost curve occurred after 2007, limiting further growth of payments. Future health policy studies should explore the potential for further cost containment, including differences in utilization between free standing and hospital outpatient facilities. Presentation: 26 minute

Opportunities for use of radiation therapy in penile cancer based on patterns of care in the United States from 2007 to 2013

Background: Radiation therapy (RT) is an effective modality for the treatment of squamous cell carcinomas of the penis. The National Comprehensive Cancer Network recommends consideration of primary radiation for penile preservation, in surgically unresectable tumors, and as adjuvant therapy for positive margins, bulky groin nodes or pelvic nodes. We performed a population-based analysis to evaluate the usage of RT in penile cancer from 2007 to 2013. Methods: We used the Surveillance, Epidemiology and End Results ( SEER ) database to identify men diagnosed with squamous cell carcinoma of the penis from 2007 to 2013. Patients were grouped as early stage (T1–T2N0), locally advanced (T3–T4N0), node-positive (T1xN1–3) and metastatic. We used linear regression model to test for factors associated with adjuvant radiation in node-positive patients. Results: We identified 2200 men diagnosed with penile cancer between 2007 and 2013. Of these, 66.4% had early stage, 10.7% had locally advanced, 15.5% had node-positive, 3.2% had metastatic cancer. Among patient with early stage cancer, RT was used in 14 patients (1.0%) and postoperative radiation in an additional 45 patients (3.1%). Among 340 patients with node-positive cancer, 62.1% received surgery alone, 5.6% radiation alone, 21.8% surgery with adjuvant radiation, and 10.6% neither surgery nor radiation. Of patients who had surgery, 26.0% had adjuvant radiation. On univariate analysis, higher nodal stage (N2–3 versus N1) was associated with adjuvant radiation ( p = 0.02), while there was a trend for higher T-stage (T3/T4 versus T1/T2) ( p = 0.08) and history of prior malignancy ( p = 0.06). On multivariate analysis, only higher nodal stage (N2–3 versus N1) was associated with use of adjuvant radiation [hazard ratio (HR) 1.94, p = 0.03]. Conclusions: A small percentage of patient who are eligible for primary or adjuvant RT in the United States receive this treatment. Further work should be done to assess barriers to use of radiation in patients with penile cancer

The Efficacy of Conventionally Fractionated Radiation in the Management of Osseous Metastases from Metastatic Renal Cell Carcinoma

Background. There is little data regarding the effectiveness of palliative radiation with conventional fractionation for metastatic renal cell carcinoma (RCC), which has been described as radioresistant. We conducted a retrospective analysis of patients with metastatic bony disease from RCC treated with radiation therapy at our institution. Methods. Forty patients with histologically confirmed RCC with a total of 53 treatment courses were included. Pain response after radiotherapy was recorded and freedom from progression was generated using posttreatment radiographs. Patient data was analyzed to assess influence on local control. Results. Patients had a median age of 63. Median follow-up was 9.3 months. The most common radiation dose was 30 Gy in 10 fractions. Pain control after radiotherapy was achieved in 73.6% of patients. Increasing age was associated with nonresponse at the initial pain assessment post-RT (p=0.02). In lesions with initial pain response, nonclear cell histology was associated with increased pain recurrence (p=0.01) and a shorter duration to pain recurrence (p=0.01). Radiographic control at 1 year was 62%. Conclusions. Pain response and control rates for osseous metastatic disease in RCC are comparable to other histologies when treated with conventional fractionation. These appear to be inferior to reported control rates from stereotactic treatments

The Efficacy of Conventionally Fractionated Radiation in the Management of Osseous Metastases from Metastatic Renal Cell Carcinoma

Background. There is little data regarding the effectiveness of palliative radiation with conventional fractionation for metastatic renal cell carcinoma (RCC), which has been described as radioresistant. We conducted a retrospective analysis of patients with metastatic bony disease from RCC treated with radiation therapy at our institution. Methods. Forty patients with histologically confirmed RCC with a total of 53 treatment courses were included. Pain response after radiotherapy was recorded and freedom from progression was generated using posttreatment radiographs. Patient data was analyzed to assess influence on local control. Results. Patients had a median age of 63. Median follow-up was 9.3 months. The most common radiation dose was 30 Gy in 10 fractions. Pain control after radiotherapy was achieved in 73.6% of patients. Increasing age was associated with nonresponse at the initial pain assessment post-RT (p=0.02). In lesions with initial pain response, nonclear cell histology was associated with increased pain recurrence (p=0.01) and a shorter duration to pain recurrence (p=0.01). Radiographic control at 1 year was 62%. Conclusions. Pain response and control rates for osseous metastatic disease in RCC are comparable to other histologies when treated with conventional fractionation. These appear to be inferior to reported control rates from stereotactic treatments

Degradation of Ibuprofen by the Electro/Fe3+/Peroxydisulfate Process: Reactive Kinetics, Degradation Products and Mechanism

Ibuprofen (IBU), a nonsteroidal anti-inflammatory drug, is one of the most widely used and frequently detected pharmaceuticals and personal care products in water bodies. This study examined the IBU degradation in aquatic solutions via ferric ion activated peroxydisulfate (PDS) coupled with electro-oxidation (EC/Fe3+/PDS). The degradation mechanisms involved three synergistic reactions in the EC/Fe3+/PDS system, including: (1) the electro-oxidation; (2) SO4&bull;&minus; generated from the activation of PDS by ferrous ions formed via cathodic reduction; (3) SO4&bull;&minus; generated from the electron transfer reaction. The radical scavenging experiments indicated that SO4&bull;&minus; and &bull;OH dominated the oxidation process. The effects of the applied current density, PDS concentration, Fe3+ dosage, initial IBU concentration and initial pH as well as inorganic anions and humic acid on the degradation efficiency, were studied, and the degradation process of IBU followed the pseudo-first-order kinetic model. About 99.37% of IBU was removed in 60 min ((Fe3+ concentration) = 2.0 mM, (PDS concentration) = 12 mM, (initial IBU concentration) = 30 mg/L, current density = 15 mA/cm2, initial pH = 3). Finally, seven intermediate compounds were identified and probable IBU degradation pathways in the EC/Fe3+/PDS system were speculated