Andrew O. Wahl

Use of Molecular Imaging to Predict Clinical Outcome in Patients With Rectal Cancer After Preoperative Chemotherapy and Radiation

PURPOSE To correlate changes in 2-deoxy-2-[18F]fluoro-d-glucose (18-FDG) positron emission tomography (PET) (18-FDG-PET) uptake with response and disease-free survival with combined modality neoadjuvant therapy in patients with locally advanced rectal cancer. METHODS AND MATERIALS Charts were reviewed for consecutive patients with ultrasound-staged T3x to T4Nx or TxN1 rectal adenocarcinoma who underwent preoperative chemoradiation therapy at Fox Chase Cancer Center (FCCC) or Robert H. Lurie Comprehensive Cancer Center of Northwestern University with 18-FDG-PET scanning before and after combined-modality neoadjuvant chemoradiation therapy . The maximum standardized uptake value (SUV) was measured from the tumor before and 3 to 4 weeks after completion of chemoradiation therapy preoperatively. Logistic regression was used to analyze the association of pretreatment SUV, posttreatment SUV, and % SUV decrease on pathologic complete response (pCR), and a Cox model was fitted to analyze disease-free survival. RESULTS A total of 53 patients (FCCC, n = 41, RLCCC, n = 12) underwent pre- and postchemoradiation PET scanning between September 2000 and June 2006. The pCR rate was 31%. Univariate analysis revealed that % SUV decrease showed a marginally trend in predicting pCR (p = 0.08). In the multivariable analysis, posttreatment SUV was shown a predictor of pCR (p = 0.07), but the test results did not reach statistical significance. None of the investigated variables were predictive of disease-free survival. CONCLUSIONS A trend was observed for % SUV decrease and posttreatment SUV predicting pCR in patients with rectal cancer treated with preoperative chemoradiation therapy. Further prospective study with a larger sample size is warranted to better characterize the role of 18-FDG-PET for response prediction in patients with rectal cancer.

ACR Appropriateness Criteria® pretreatment evaluation and follow-up of endometrial cancer.

Endometrial cancer is the most common gynecologic and the fourth most common malignancy in women in the United States. Cross-sectional imaging plays a vital role in pretreatment assessment of endometrial cancers and should be viewed as a complementary tool for surgical evaluation and planning of these patients. Although transvaginal US remains the preferred examination for the screening purposes, MRI has emerged as the modality of choice for the staging of endometrial cancer and imaging assessment of recurrence or treatment response. A combination of dynamic contrast-enhanced and diffusion weighted MRI provides the highest accuracy for the staging. Both CT and MRI perform equivalently for assessing nodal involvement or distant metastasis. PET-CT is more appropriate for assessing lymphadenopathy in high-grade FDG-avid tumors or for clinically suspected recurrence after treatment. An appropriate use and guidelines of imaging techniques in diagnosis, staging, and detection of endometrial cancer and treatment of recurrent disease are reviewed.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR appropriateness criteria® management of locoregionally advanced squamous cell carcinoma of the vulva

Objectives: Locoregionally advanced vulvar cancer (LRAVC) is a rare disease that presents many challenging medical decisions. An expert panel was convened to reach consensus on the most appropriate pretreatment assessment and therapeutic interventions in LRAVC patients. Methods: The American College of Radiology Appropriateness Criteria are evidenced-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journal and the application of a well-established consensus methodology (modified Delphi) to rate appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to formulate recommendations. Results: Three clinical variants were developed to address common scenarios in the management of LRAVC. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches, with numerical ratings and descriptive commentary. Conclusions: In combining available medical literature and expert opinion, this manuscript may serve as an aid for other practitioners in the appropriate management of patients with LRAVC.

Incidence of tissue toxicities in gamma ray and fission neutron-exposed mice treated with Amifostine.

Purpose: To determine the effects of Amifostine or WR-151327 on the incidence of lethal and non-lethal toxicities in a large cohort of mice exposed to γ-ray or fission-spectrum neutron radiation. Methods: To analyze data from 4000 B6CF1 mice which received a single whole body irradiation (WBI) with 206 cGy or 417 cGy cobalt-60 gamma rays or 10 cGy or 40 cGy of fission-spectrum neutrons (average energy 0.85 MeV) produced by the Janus reactor at Argonne National Laboratory. In the neutron cohort, Amifostine, WR-151327, saline or nothing was injected once, intraperitoneally, 30 minutes before irradiation. In the cobalt-60 cohort, WR-151327 was omitted from the same protocol. At the time of natural death, tissue toxicities found in these mice were recorded, and these records were analyzed. While all previous studies focused on the modulation of life shortening effects of WBI by Amifostine, in this study we calculated changes in the frequencies of 59 tissue toxicities and changes in the total number of toxicities per animal. Results: Amifostine protected against specific non-tumor pathological complications (67% of the non-tumor toxicities induced by gamma irradiation, 31% of the neutron induced specific toxicities), as well as specific tumors (56% of the tumor toxicities induced by gamma irradiation, 25% of the neutron induced tumors). Amifostine also reduced the total number of toxicities per animal for both genders in the gamma ray exposed mice and in males in the neutron exposed mice. Conclusions: Amifostine was protective against many, but not all, tissue toxicities caused by WBI gamma and neutron irradiation.

ACR appropriateness criteria® definitive therapy for early-stage cervical cancer

Objectives:The definitive treatment of early-stage cervical cancer involves multidisciplinary decision making. This expert panel was convened to reach consensus on the selection of appropriate therapies based on patient and disease characteristics at presentation. Methods:The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or the treatment. Results:Three clinical variants were developed to represent common scenarios in the treatment of early-stage cervical cancer. Group members reached consensus on the appropriateness of therapeutic options. This process yielded numerical ratings and descriptive commentary. Conclusions:This manuscript represents the consensus opinion of an expert panel based on a survey of all available medical literature. This manuscript may be used to inform the clinical decision making of physicians involved in the treatment of early-stage cervical cancer.

Still equivalent for dose calculation in the Monte Carlo era? A comparison of free breathing and average intensity projection CT datasets for lung SBRT using three generations of dose calculation algorithms

Purpose Inhomogeneity dose modeling and respiratory motion description are two critical technical challenges for lung stereotactic body radiotherapy, an important treatment modality for small size primary and secondary lung tumors. Recent studies revealed lung density‐dependent target dose differences between Monte Carlo (Type‐C) algorithm and earlier algorithms. Therefore, this study aimed to investigate the equivalence of the two most popular CT datasets for treatment planning, free breathing (FB) and average intensity projection (AIP) CTs, using Type‐C algorithms, and comparing with two older generation algorithms (Type‐A and Type‐B). Methods Twenty patients (twenty‐one lesions) were planned using a Type‐A algorithm on the FB CT. Lung was contoured separately on FB and AIP CTs and compared. Dose comparison was obtained between the two CTs using four commercial dose algorithms including one Type‐A (Pencil Beam Convolution – PBC), one Type‐B (Analytical Anisotropic Algorithm – AAA), and two Type‐C algorithms (Voxel Monte Carlo – VMC and Acuros External Beam – AXB). For each algorithm, the dosimetric parameters of the target (PTV, Dmin, Dmax, Dmean, D95, and D90) and lung (V5, V10, V20, V30, V35, and V40) were compared between the two CTs using the Wilcoxon signed rank test. Correlation between dosimetric differences and density differences for each algorithm were studied using linear regression and Spearman correlation, in which both global and local density differences were evaluated. Results Although the lung density differences on FB and AIP CTs were statistically significant (P = 0.003), the magnitude was small at 1.21 ± 1.45%. Correspondingly, for the two Type‐C algorithms, target and lung dosimetric differences were small in magnitude and statistically insignificant (P > 0.05) for all but one instance, similar to the findings for the older generation algorithms. Nevertheless, a significant correlation was shown between the dosimetric and density differences for Type‐C and Type‐B algorithms, but not for the Type‐A algorithm. Conclusions With the capability to more accurately model inhomogeneity, Monte Carlo (Type‐C) algorithms are sensitive to respiration‐induced local and global tissue density changes and exhibit a strong correlation between dosimetric and density differences. However, FB and AIP CTs may still be considered equivalent for dose calculation in the Monte Carlo era, due to the small magnitude of lung density differences between these two datasets.

Proton radiotherapy for gynecologic neoplasms

Abstract Background: Proton beam therapy (PBT) is increasingly being used globally to treat a variety of malignancies. This is the first review assessing PBT for gynecologic neoplasms. Dose distribution to organs-at-risk (OARs), particularly bone marrow (BM), is addressed. Clinical outcomes and toxicity data are detailed. Material and methods: Systematic searches of PubMed, EMBASE, abstracts from meetings of the American Society for Radiation Oncology, Particle Therapy Co-Operative Group, and American Society of Clinical Oncology were conducted for publications. There were no restrictions on publication dates. Sixteen original investigations were identified and analyzed for this review. Results: The available evidence for PBT in treating gynecologic cancers is of both low quantity and quality. The most studied scenarios for PBT include treatment of para-aortic lymph nodes, re-irradiation, and as an alternative to brachytherapy, and these also represent indications with the greatest opportunity for demonstrating as yet unproven toxicity reductions. Dosimetric studies have shown significantly decreased dose to OARs, such as the rectum, bladder, bowel, kidneys, BM, and femoral heads. This dose reduction to OARs with PBT is more pronounced within the low-dose volumes than the higher dose volumes, which radiobiologically could be expected to lower second malignancy rates. Clinical data, though no level 1 evidence, show appropriate stage-specific tumor control and outcomes with PBT treatment, along with low toxicity rates. Conclusion: The existing data, albeit limited, warrant and can help guide larger scale and higher quality studies addressing whether PBT could provide clinically meaningful differences in toxicities and outcomes in women with gynecologic neoplasms.

A new variable for SRS plan quality evaluation based on normal tissue sparing: the effect of prescription isodose levels

OBJECTIVE A new dosimetric variable, dose-dropping speed (DDS), was proposed and used to evaluate normal tissue sparing among stereotactic radiosurgery (SRS) plans with different prescription isodose lines. METHODS 40 plans were generated for 8 intracranial SRS cases, prescribing to isodose levels (IDLs) ranging from 50% to 90% in 10% increments. Whilst maintaining similar coverage and conformity, plans at different IDLs were evaluated in terms of normal tissue sparing using the proposed DDS. The DDS was defined as the greater decay coefficient in a double exponential decay fit of the dose drop-off outside the planning target volume (PTV), which models the steep portion of the drop-off. Provided that the prescription dose covers the whole PTV, a greater DDS indicates better normal tissue sparing. RESULTS Among all plans, the DDS was found to be the lowest for the prescription at 90% IDL and the highest for the prescription at 60% or 70%. The beam profile slope change in the penumbra and its field size dependence were explored and given as the physical basis of the findings. CONCLUSION A variable was proposed for SRS plan quality evaluation. Using this measure, prescriptions at 60% and 70% IDLs were found to provide best normal tissue sparing. ADVANCES IN KNOWLEDGE A new variable was proposed based on which normal tissue sparing was quantitatively evaluated, comparing different prescription IDLs in SRS.

ACR appropriateness criteria® advanced stage endometrial cancer

Objectives:Patients with advanced stage endometrial carcinoma constitute a heterogeneous group of patients with different stages, tumor histologic types, and involved sites. Hysterectomy, bilateral salpingo-ophorectomy, and surgical staging are the cornerstone of surgical management in these patients. The optimal adjuvant therapy is yet to be established. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients. Methods:The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. Results:Four clinical variants were developed to address common scenarios in the management of women with advanced-stage endometrial carcinoma. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings. Conclusions:In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with advanced-stage endometrial carcinoma.

Radiotherapy for rejection of renal transplant allografts refractory to medical immunosuppression.

Objective:To evaluate the outcome and prognostic factors of patients who underwent local graft irradiation for acute renal allograft rejection refractory to modern immunosuppressive medications. Methods:From 1996 to 2005, 33 patients received local graft irradiation (LGI), with 3 patients receiving 2 courses of radiation. Graft rejection was diagnosed when a rise in creatinine prompted a renal biopsy that demonstrated acute allograft rejection. Upon failure of medical immunosuppresion to resolve rejection, patients were then referred by the organ transplant team for LGI. The median dose was 800 cGy (range, 600–800 cGy), and was given in 200 cGy fractions generally using AP/PA fields. A retrospective review was conducted to determine dialysis-free survival, defined as the date from initiation of radiation therapy to date of hemodialysis placement, and to analyze potential factors that may predict dialysis free survival. Results:Median follow-up from date of radiation therapy to date of last follow-up was 25 months (range, 0.9-99.4 months). The median time between allograft transplantation and radiation therapy was 17.8 months. For the entire group of patients, 20.6% were alive with a functioning graft. The median dialysis-free survival for the entire group was 3.8 months. The median dialysis-free survival for those patients not on dialysis at time of irradiation versus those patients on dialysis was significantly different (5.6 versus 0 months, P = 0.02). Conclusion:In renal allograft transplant recipients who experienced acute rejection episodes refractory to modern chemical immunosuppression, LGI was well tolerated and remains a viable salvage treatment option.