David B. Mansur

The Role of Postoperative Radiation and Chemoradiation in Merkel Cell Carcinoma: A Systematic Review of the Literature

Objective: A systematic review of the literature was undertaken to investigate whether adjuvant radiotherapy and/or chemotherapeutics offered any additional benefit than surgery alone in the treatment of Merkel Cell Carcinoma (MCC). Methods: A PubMed, MEDLINE search was conducted between 1995 and 2013, to identify reported cases of surgically treated MCC followed by either observation, radiation, or chemoradiation. Patient demographics and outcomes were recorded and compared in a systematic fashion. Results: Thirty-four studies (n = 4475) were included. The median age was 73 years, median follow up was 36 months and there was a 1.5:1 ratio of men to women. All 4475 patients had surgery, 1975 had no further treatment, 1689 received postoperative RT, and 301 received postoperative chemoRT. The most common site was face/head/neck, 47.8%. Stage 1 was the most common clinical stage at diagnosis (57%). Three-year local control was 20% (median 10%) in the observation cohort, compared to 65% (62%) with postoperative RT, and 67% (75%) with postoperative chemoRT; these findings were statistically significant (P < 0.001). Recurrence was found to be 38% (60%) in the observation cohort, compared to 23% (20%) with postoperative RT (P < 0.001). Three-year overall survival (OS) was found to be 56% (57%) in the observation cohort, compared to 70% (78%) with postoperative RT and 73% (76%) with postoperative chemoRT (P < 0.001). The observation cohort had a median OS of 44 months compared with 64 months (P < 0.001) in the postoperative RT cohort. There was no statistically significant difference in any parameters assessed between postoperative radiation and postoperative chemoradiation arms. Conclusion: The comprehensive collection of retrospective data suggests a survival and control benefit for postoperative radiation in MCC. No differences were noted between adjuvant radiation and chemoradiation. This analysis indicates the need for prospective trials with patients stratified by known prognostic factors.

Splenic marginal zone lymphoma: excellent outcomes in 64 patients treated in the rituximab era

ABSTRACT Objectives and methods: Splenic marginal zone lymphoma (SMZL) is a rare non-Hodgkin lymphoma. We sought to identify prognostic factors and define outcomes in a cohort of 64 patients with SMZL who were treated at two large academic medical centers in North America in the rituximab era. Results: Over a median follow-up of 37.8 (range 6–167.1) months, Kaplan–Meier estimate of median OS was 156.3 months and median PFS was 52.9 months. On univariate analysis, baseline hemoglobin <12 g/dl was associated with inferior OS (p = 0.045). High-risk FLIPI score was associated with inferior PFS when compared with intermediate/low risk (p = 0.05) and marginally significant with regard to OS (p = 0.056). Splenectomy was not predictive of OS or PFS (p = 0.563 and 0.937, respectively). Transformation to diffuse large B-cell lymphoma occurred in four (6.3%) patients during the observation period. OS was comparable to contemporaneous cohorts of patients with extranodal and nodal marginal lymphomas and FLIPI score was highly predictive for inferior PFS and OS when all three cohorts were analyzed together. Conclusion: Outcomes of SMZL, in our series, were excellent, with a median OS of >13 years. Low hemoglobin and high-risk FLIPI were associated with inferior outcomes.

Dual institution experience of nodal marginal zone lymphoma reveals excellent long-term outcomes in the rituximab era

Nodal marginal zone lymphoma (NMZL) is a rare non‐Hodgkin lymphoma that arises from mature B‐cells. We delineate outcomes, prognostic factors and treatment trends among a large cohort of patients with NMZL in the rituximab era. We identified 56 such patients treated at our institutions. The majority presented with advanced stage disease (78·6%). Over a median follow‐up of 38·2 months, median progression‐free survival (PFS) was 42·4 months and median overall survival (OS) was not reached. Kaplan–Meier estimates of OS at 120 months after diagnosis was 71·9%. High‐risk follicular lymphoma international prognostic index (FLIPI) was associated with inferior PFS. Age >60 years and elevated serum lactate dehydrogenase (LDH) were associated with inferior OS. Transformation to diffuse large B‐cell lymphoma occurred in 7 patients, 6 of who presented with advanced disease. OS was comparable to our previously reported extranodal MZL cohort. FLIPI score predicted for inferior PFS and OS when both cohorts were analysed together (n = 267). In summary, outcomes in NMZL are favourable with a large majority of patients surviving at 120 months. High risk FLIPI, age >60 years, and elevated serum LDH were associated with inferior outcomes.

Dual institution experience of extranodal marginal zone lymphoma reveals excellent long-term outcomes

Extranodal marginal zone lymphoma (EMZL) is a B‐cell lymphoma arising from mucosa‐associated lymphoid tissue (MALT). The disease characteristics, clinical course and treatment vary considerably based on site of involvement. Because long‐term outcome data for EMZL are limited, we sought to describe the clinical details of a large number of patients with EMZL evaluated at the Case Comprehensive Cancer Center over a 12‐year period to identify prognostic markers including the impact of site of involvement. We identified 211 cases of EMZL involving the stomach (30%), ocular adnexa (19%), lungs (16%) and intestines (9%). Initial treatment included antibiotics (18%), radiation (21%), rituximab (20%), chemotherapy (3%), rituximab + chemotherapy (7%), surgery (17%) or observation (8%). After a median follow‐up of 44·3 months (range 2·2–214·9), median progression‐free survival (PFS) was 68·2 months (95% confidence interval [CI] 54·5–111·3) and median overall survival (OS) has not been reached. Age >60 years, elevated lactate dehydrogenase level (LDH), ≥4 lymph node groups involvement, and high follicular lymphoma international prognostic index (FLIPI) were associated with inferior PFS/OS. In summary, patients with EMZL have excellent prognosis with median OS in excess of 10 years. Age, elevated LDH, advanced disease, and high FLIPI score are associated with worse outcomes.

Extra-CNS metastasis from glioblastoma: a rare clinical entity

Extra-CNS metastasis from glioblastoma (ECMGBM) is an emerging but little known clinical entity. We review pre-clinical and translational publications assessing the ability of GBM to spread locally and outside the CNS. Reported cases demonstrating ECMGBM are reviewed providing a summary of presentations for the entity. Special attention is placed on transmission of GBM through organ transplantation. Finally, predictions are made as to the future significance of ECMGBM, especially in the context of better outcomes in CNS GBM.

Incorporating a compact proton therapy unit into an existing National Cancer Institute-designated comprehensive cancer center.

Proton beams offer specific dosimetric advantages for radiation therapy. Their depth-dose relationship is characterized by the Bragg peak beyond which no dose is deposited. The elimination of exit dose for passively scattered proton beams results in greatly reduced low and intermediate doses to distant uninvolved normal tissues, but little or no difference in conformality of higher prescription doses immediately surrounding the targeted tissue. This approach is highly desirable in certain clinical scenarios such as the treatment of pediatric patients with curable malignancies for whom protons will theoretically reduce the risk of treatment related late effects. However, typical proton facilities are too large to be well integrated into most existing urban cancer centers where space is at a premium. The use of a new compact proton facility can more feasibly be incorporated into existing medical center space. In addition, they are associated with much lower cost than the typical mega-facility. The smaller capacity of this type of proton facility is quite reasonable as long as this limited and relatively expensive technology is reserved for those patients who stand to benefit the most.

Bladder (ICRU) dose point does not predict urinary acute toxicity in adjuvant isolated vaginal vault high-dose-rate brachytherapy for intermediate-risk endometrial cancer

Purpose High-dose-rate brachytherapy (HDR-BT) alone is an adjuvant treatment option for stage I intermediaterisk endometrial cancer after complete surgical resection. The aim of this study was to determine the value of the dose reported to ICRU bladder point in predicting acute urinary toxicity. Oncologic results are also presented. Material and methods One hundred twenty-six patients were treated with postoperative HDR-BT 24 Gy (4 × 6 Gy) per ICRU guidelines for dose reporting. Cox analysis was used to identify variables that affected local control. The mean bladder point dose was examined for its ability to predict acute urinary toxicity. Results Two patients (1.6%) developed grade 1 gastrointestinal toxicity and 12 patients (9.5%) developed grades 1-2 urinary toxicity. No grade 3 or greater toxicity was observed. The mean bladder point dose was 46.9% (11.256 Gy) and 49.8% (11.952 Gy) for the asymptomatic and symptomatic groups, respectively (p = 0.69). After a median follow-up of 36.8 months, the 3-year local failure and 5-year cancer-specific and overall survival rates were 2.1%, 100%, and 94.6%, respectively. No pelvic failure was seen in this cohort. Age over 60 years (p = 0.48), lymphatic invasion (p = 0.77), FIGO histological grade (p = 0.76), isthmus invasion (p = 0.68), and applicator type (cylinder × ovoid) (p = 0.82) did not significantly affect local control. Conclusions In this retrospective study, ICRU bladder point did not correlate with urinary toxicity. Four fractions of 6 Gy HDR-BT effected satisfactory local control, with acceptable urinary and gastrointestinal toxicity.

Quantitative Analysis Tools and Digital Phantoms for Deformable Image Registration Quality Assurance

This article proposes quantitative analysis tools and digital phantoms to quantify intrinsic errors of deformable image registration (DIR) systems and establish quality assurance (QA) procedures for clinical use of DIR systems utilizing local and global error analysis methods with clinically realistic digital image phantoms. Landmark-based image registration verifications are suitable only for images with significant feature points. To address this shortfall, we adapted a deformation vector field (DVF) comparison approach with new analysis techniques to quantify the results. Digital image phantoms are derived from data sets of actual patient images (a reference image set, R, a test image set, T). Image sets from the same patient taken at different times are registered with deformable methods producing a reference DVFref. Applying DVFref to the original reference image deforms T into a new image R′. The data set, R′, T, and DVFref, is from a realistic truth set and therefore can be used to analyze any DIR system and expose intrinsic errors by comparing DVFref and DVFtest. For quantitative error analysis, calculating and delineating differences between DVFs, 2 methods were used, (1) a local error analysis tool that displays deformation error magnitudes with color mapping on each image slice and (2) a global error analysis tool that calculates a deformation error histogram, which describes a cumulative probability function of errors for each anatomical structure. Three digital image phantoms were generated from three patients with a head and neck, a lung and a liver cancer. The DIR QA was evaluated using the case with head and neck.

Multidisciplinary management of pediatric intracranial ependymoma

Pediatric intracranial ependymoma is a rare disease representing approximately 7% of brain tumors in children aged 15 years or younger. Due to the relative rarity of these tumors, a clear standard therapy has been difficult to establish. The mainstay of treatment is surgical resection and the majority of data demonstrate improved outcome with gross total resection. The standard of care also includes postoperative radiation therapy for most patients with grade II and III tumors. Chemotherapy has been used in many capacities in this disease; however, its optimal role is yet to be defined. Current controversies such as treatment with surgery alone in completely resected tumors, use of chemotherapy for subtotally resected tumors and use of adjuvant postradiation chemotherapy are incorporated into the design of the current Childrens Oncology Group clinical trial.

What is the most appropriate clinical target volume for glioblastoma

Glioblastoma is one of the most common primary brain tumors in adults and the prognosis is very poor. The standard treatment is gross total resection and postoperative radiotherapy with concurrent and adjuvant chemotherapy with temozolomide. Given its propensity to spread to areas of brain parenchyma surrounding the gross tumor volume (GTV), a generous margin is typically created around the GTV. Peritumoral edema is frequently included in the GTV, especially in the USA. The margin of expansion from GTV to clinical target volume also varies widely among different institutions. There is a lack of consensus as to what constitutes the most appropriate clinical target volume for glioblastoma.