Michael Smith

Could more effective use of kidneys recovered from older deceased donors result in more kidney transplants for older patients

In the face of a severe shortage of kidneys from deceased organ donors that limits access to transplantation for many patients, about one of every seven kidneys (more than 1,500 each year) recovered from deceased donors in the United States are not transplanted. Eurotransplant, which coordinates organ distribution for six countries and a population of about 118 million, discards only one of every 20 kidneys procured for transplantation. We compared kidney procurement, transplants, and discards between January 2000 and June 2003 in the United States and in the Eurotransplant region using the Organ Procurement and Transplantation Network/United Network for Organ Sharing and Eurotransplant databases to examine differences that might account for this wide disparity.

The Current Role of Androgen Deprivation in Patients Undergoing Dose-Escalated External Beam Radiation Therapy for Clinically Localized Prostate Cancer

Purpose. To review existing literature on the role of androgen deprivation therapy (ADT) with dose escalated radiation therapy. Methods and Materials. A PubMed search was undertaken to identify relevant articles. Results. Multiple recent studies were identified examining the role of ADT in the current era of radiation dose-escalation. Among the reviewed studies, varying radiation doses and techniques, ADT regimens, and patient selection criteria were utilized. Conflicting results were reported, with some studies demonstrating a benefit of delivering a higher radiation dose with ADT. Other studies failed to show significant benefits with the addition of ADT to dose-escalated RT. Conclusions. The benefit of adding ADT to dose-escalated RT is still uncertain. Prospective randomized trials, several of which are ongoing, are necessary to more adequately examine this issue. In the interim, physicians and patients should continue to utilize the existing data to weigh the risks and benefits of each approach to therapy.

The Addition Of Low Dose Total Body Irradiation To Fludarabine And Melphalan Conditioning In Haplo-Cord Transplantation For High Risk Hematological Malignancies.

Background Preliminary evidence indicates that the addition of low-dose total body irradiation (TBI) (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high-risk patients receiving combination haploidentical single-unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection. Methods We retrospectively reviewed the posttransplant outcomes of patients who underwent haplocord stem cell transplant between May 2013 and March 2015 and who received fludarabine 30 mg/m2 day (D)−7 to −3, melphalan 140 mg/m2 D−2, and 2 Gy TBI D−4 and −3. Results All 25 patients achieved primary neutrophil engraftment after a median of 12 days. The median time to platelet engraftment was 27 days. The cumulative incidence of nonrelapse mortality was 16% by D+100 and 33% by 1 year. The cumulative incidence of grade III to IV acute graft-versus-host disease was 36% by D+100. The CIR was 13% by D+100 and 29% by 1 year. The estimated 1-year overall survival and progression-free survival were 40% and 37%, respectively. In a subgroup analysis, we compared the outcome of 13 acute myeloid leukemia patients receiving this conditioning regimen with age and disease risk index–matched acute myeloid leukemia patients receiving fludarabine-melphalan without TBI. The TBI group had lower incidence of relapse at 1 year (15% vs 54%, P = 0.05). Conclusions Overall, combination fludarabine-melphalan with low-dose TBI after haplocord stem cell transplant assures good engraftment and leads to acceptable toxicity and disease control in the setting of high risk, heavily pretreated patients. These findings warrant further investigation at a larger-scale, prospective level.

Role of radiation therapy for renal tumors.

Renal cell carcinoma (RCC) is an aggressive malignancy that carries a poor prognosis, especially in patients presenting with advanced stage. Primary treatment for localized RCC is surgical resection however, a significant number of patients still develop locoregional and distant metastasis after curative resection. In metastatic disease, radiation therapy (RT) has been used for palliation routinely for brain and other extracranial lesions with respectable response rates. However, RT for primary RCC has questionable benefit. In this article, the authors discuss the evidence with regards to the role of RT in primary RCC either as a primary treatment, adjuvant treatment, or preoperatively to improve resection outcomes. In addition, novel RT techniques such as stereotactic body radiation therapy and its use in RCC management are also addressed. Finally, the authors discuss the techniques and doses of RT for primary RCC.

Is there a tradeoff in using modified high tangent field radiation for treating an undissected node-positive axilla?

INTRODUCTIONnRecent data are changing axillary management in patients with 1 to 2 positive sentinel nodes. The proposed omission of completion axillary node dissection calls into question the need for axillary nodal irradiation. This study evaluates the difference in dose to the lung and heart and risk of radiation pneumonitis (RP) for patients treated with standard tangent fields (STF) compared with modified high tangent fields (MHTF).nnnMATERIALS AND METHODSnPlans of 30 patients treated with STF were evaluated. A second plan (MHTF) was developed to include axillary levels I (Ax1) and II (Ax2). Ax1 and Ax2 volumes were contoured based on the RTOG (Radiation Therapy Oncology Group) Atlas guidelines. Dose-volume histograms of the 2 plans were used to compare doses received by Ax1, Ax2, lung, and heart volumes. The risk of RP was calculated using normal tissue complication probability (NTCP) modeling.nnnRESULTSnThe D95 (dose to 95% of volume) received by Ax1 and Ax2 volumes increased from 16.38 Gy and 5.71 Gy for STF to 49.38 Gy and 48.08 Gy for MHTF, respectively. Mean lung dose increased from 5.40 Gy for STF to 9.47 Gy for MHTF. Mean ipsilateral lung V5, V10, and V20 values increased from 19%, 14%, and 10%, respectively, for STF, to 32%, 24%, and 18%, respectively, for MHTF. Mean heart dose increased from 1.98 Gy for STF to 3.93 Gy for MHTF. Mean heart V25 and V30 values increased from 2% and 1%, respectively, for STF, to 4% and 3%, respectively, for MHTF. NTCP for RP increased from near 0% for STF to 1% for MHTF.nnnCONCLUSIONnModified high tangent fields are necessary for definitive coverage of Ax1 and Ax2. This technique increases mean ipsilateral lung and heart doses as well as the V5, V10, and V20 of ipsilateral lung and the V25 and V30 of the heart. Risk of RP remains low by use of MHTF.

Impact of a large breast separation on radiation dose delivery to the ipsilateral lung as result of respiratory motion quantified using free breathing and 4D CT-based planning in patients with locally advanced breast cancers: A potential for adverse clinical implications

PURPOSEnWe examined the effects of large breast separation (BS) on dosimetric and positional differences of radiation treatment plans of locally advanced breast cancers during a free-breathing respiratory cycle.nnnMATERIALS AND METHODSnComputed tomography (CT) datasets of 18 patients were acquired using 3D, 4D-0% (end-inspiration), and 4D-50% (end-exhalation). BS was examined in relation to the positional and dosimetric changes to organs-at-risk (OAR). Based on dosimetric analysis of all three plans, we compared 4D-0% and 4D-50% for V5, V10, and V20 to 3D for heart and ipsilateral lung. Using 4D-0% and 4D-50% CTs, we recorded positional variations of the organs centroid (centers of mass) and their effects on dosimetry.nnnRESULTSnMedian BS was 23.95 cm (range: 16.86-29.48 cm). There was a strong positive correlation between BS and dose to the ipsilateral lung for V5, V10, and V20, with the greatest linearity observed at V20 (R(2) = 0.23). At BS ≥ 27 cm, the dose increased during inspiration at V5, V10 , and V20 (P < 0.05). When comparing 4D and 3D for the heart, V5 and V10, decreased by average of 0.94% and 0.96% (P < 0.008), respectively.nnnCONCLUSIONSnThis study offers the first evidence of the impact of a large BS on radiation dose to the ipsilateral lung.

Comparison of primary radiation versus robotic surgery plus adjuvant radiation in high-risk prostate cancer: A single center experience

OBJECTIVEnThe objective of this study was to compare robotic-prostatectomy plus adjuvant radiation therapy (RPRAT) versus primary RT for high-risk prostate cancer (HRPCa).nnnMATERIALS AND METHODSnA retrospective chart review was performed for the HRPCa patients treated in our institution between 2000 and 2010. One hundred and twenty-three patients with high-risk disease were identified. The Chi-square test and Fishers exact test were used to compare local control and distant failure rates between the two treatment modalities. For prostate-specific antigen comparisons between groups, Wilcoxon rank-sum test was used.nnnRESULTSnThe median follow-up was 49 months (range: 3-138 months). Local control, biochemical recurrence rate, distant metastasis, toxicity, and disease-free survival were similar in the two groups.nnnCONCLUSIONSnPrimary RT is an excellent treatment option in patients with HRPCa, is equally effective and less expensive treatment compared with RPRAT. A prospective randomized study is required to guide treatment for patients with HRPCa.