Andrew Wirth

Radiotherapeutic and surgical management for newly diagnosed brain metastasis(es): An American Society for Radiation Oncology evidence-based guideline

Purpose To systematically review the evidence for the radiotherapeutic and surgical management of patients newly diagnosed with intraparenchymal brain metastases. Methods and Materials Key clinical questions to be addressed in this evidence-based Guideline were identified. Fully published randomized controlled trials dealing with the management of newly diagnosed intraparenchymal brain metastases were searched systematically and reviewed. The U.S. Preventative Services Task Force levels of evidence were used to classify various options of management. Results The choice of management in patients with newly diagnosed single or multiple brain metastases depends on estimated prognosis and the aims of treatment (survival, local treated lesion control, distant brain control, neurocognitive preservation). Single brain metastasis and good prognosis (expected survival 3 months or more): For a single brain metastasis larger than 3 to 4 cm and amenable to safe complete resection, whole brain radiotherapy (WBRT) and surgery (level 1) should be considered. Another alternative is surgery and radiosurgery/radiation boost to the resection cavity (level 3). For single metastasis less than 3 to 4 cm, radiosurgery alone or WBRT and radiosurgery or WBRT and surgery (all based on level 1 evidence) should be considered. Another alternative is surgery and radiosurgery or radiation boost to the resection cavity (level 3). For single brain metastasis (less than 3 to 4 cm) that is not resectable or incompletely resected, WBRT and radiosurgery, or radiosurgery alone should be considered (level 1). For nonresectable single brain metastasis (larger than 3 to 4 cm), WBRT should be considered (level 3). Multiple brain metastases and good prognosis (expected survival 3 months or more): For selected patients with multiple brain metastases (all less than 3 to 4 cm), radiosurgery alone, WBRT and radiosurgery, or WBRT alone should be considered, based on level 1 evidence. Safe resection of a brain metastasis or metastases causing significant mass effect and postoperative WBRT may also be considered (level 3). Patients with poor prognosis (expected survival less than 3 months): Patients with either single or multiple brain metastases with poor prognosis should be considered for palliative care with or without WBRT (level 3). It should be recognized, however, that there are limitations in the ability of physicians to accurately predict patient survival. Prognostic systems such as recursive partitioning analysis, and diagnosis-specific graded prognostic assessment may be helpful. Conclusions Radiotherapeutic intervention (WBRT or radiosurgery) is associated with improved brain control. In selected patients with single brain metastasis, radiosurgery or surgery has been found to improve survival and locally treated metastasis control (compared with WBRT alone).

Fluorine-18 fluorodeoxyglucose Positron emission tomography, Gallium-67 scintigraphy, and conventional staging for Hodgkin's disease and non-Hodgkin's lymphoma

PURPOSE To compare fluorine-18 fluorodeoxyglucose positron emission tomography (PET) and gallium scanning with each other and with conventional staging, for patients with Hodgkins disease or non-Hodgkins lymphoma. SUBJECTS AND METHODS Fifty patients had PET, gallium scanning, and conventional staging of newly diagnosed or progressive Hodgkins disease or non-Hodgkins lymphoma. Disease sites, stage, and treatment plans were assessed retrospectively. RESULTS Positron emission tomography and gallium scanning each upstaged 14% of patients (n = 7). Management was altered by PET in 9 cases (18%) and by gallium scanning in 7 (14%, P = 0.6). Disease was evident in 117 sites in 42 patients. The case positivity rate for conventional assessment was 90%; for PET, 95%; for gallium scanning, 88%; for conventional assessment plus PET, 100%; and for conventional assessment plus gallium scanning, 98%. Site positivity rates for conventional assessment were 68%; for PET, 82%; for gallium scanning, 69% (conventional vs. PET, P = 0.01; conventional vs. gallium scanning, P = 0.9; PET vs. gallium scanning, P = 0.01); for conventional assessment plus PET, 96%; and for conventional assessment plus gallium scanning, 94%. Positron emission tomography and gallium scanning were entirely concordant in 31 patients; in the other 19 patients, PET identified 25 sites missed by gallium scanning, whereas gallium scanning identified 10 sites missed by PET. CONCLUSION In this retrospective study, PET demonstrated a higher site positivity rate than did gallium scanning, with similar case positivity rates. These data support the use of PET in place of gallium scanning for the staging of patients with Hodgkins disease or non-Hodgkins lymphoma.

Modern Radiation Therapy for Nodal Non-Hodgkin Lymphoma—Target Definition and Dose Guidelines From the International Lymphoma Radiation Oncology Group

Radiation therapy (RT) is the most effective single modality for local control of non-Hodgkin lymphoma (NHL) and is an important component of therapy for many patients. Many of the historic concepts of dose and volume have recently been challenged by the advent of modern imaging and RT planning tools. The International Lymphoma Radiation Oncology Group (ILROG) has developed these guidelines after multinational meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the ILROG steering committee on the use of RT in NHL in the modern era. The roles of reduced volume and reduced doses are addressed, integrating modern imaging with 3-dimensional planning and advanced techniques of RT delivery. In the modern era, in which combined-modality treatment with systemic therapy is appropriate, the previously applied extended-field and involved-field RT techniques that targeted nodal regions have now been replaced by limiting the RT to smaller volumes based solely on detectable nodal involvement at presentation. A new concept, involved-site RT, defines the clinical target volume. For indolent NHL, often treated with RT alone, larger fields should be considered. Newer treatment techniques, including intensity modulated RT, breath holding, image guided RT, and 4-dimensional imaging, should be implemented, and their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control.

Modern Radiation Therapy for Extranodal Lymphomas: Field and Dose Guidelines From the International Lymphoma Radiation Oncology Group

Extranodal lymphomas (ENLs) comprise about a third of all non-Hodgkin lymphomas (NHL). Radiation therapy (RT) is frequently used as either primary therapy (particularly for indolent ENL), consolidation after systemic therapy, salvage treatment, or palliation. The wide range of presentations of ENL, involving any organ in the body and the spectrum of histological sub-types, poses a challenge both for routine clinical care and for the conduct of prospective and retrospective studies. This has led to uncertainty and lack of consistency in RT approaches between centers and clinicians. Thus far there is a lack of guidelines for the use of RT in the management of ENL. This report presents an effort by the International Lymphoma Radiation Oncology Group (ILROG) to harmonize and standardize the principles of treatment of ENL, and to address the technical challenges of simulation, volume definition and treatment planning for the most frequently involved organs. Specifically, detailed recommendations for RT volumes are provided. We have applied the same modern principles of involved site radiation therapy as previously developed and published as guidelines for Hodgkin lymphoma and nodal NHL. We have adopted RT volume definitions based on the International Commission on Radiation Units and Measurements (ICRU), as has been widely adopted by the field of radiation oncology for solid tumors. Organ-specific recommendations take into account histological subtype, anatomy, the treatment intent, and other treatment modalities that may be have been used before RT.

Primary central nervous system lymphoma: age and performance status are more important than treatment modality

PURPOSE To assess prognostic factors and treatment modalities of patients with primary central nervous system lymphoma (PCNSL) in terms of response rates, patterns of failure and overall survival. METHODS AND MATERIALS Sixty-two patients presenting with PCNSL between 1982 and 1994 at Peter MacCallum Cancer Institute with no evidence of human immunodeficiency virus infection were included in the study. Their median age was 60 years; World Health Organisation (WHO) performance status was > or = 2 in 85%. All patients were planned to receive whole brain irradiation; 7 also received spinal irradiation. The median planned dose to the target volume was 50.4 Gy. Twenty patients were planned to receive chemotherapy as well. Patients were followed up to June 20, 1995, giving a median follow-up for 14 surviving patients of 5.4 years, range 0.3 to 10.2 years. RESULTS The clinical response rate to treatment was 77% [95% confidence interval (CI) 65 to 87%]. The estimated median overall survival was 20.6 months (CI 12.4 to 33.4 months). On univariate analysis male gender, age <60 years, WHO performance status < or = 1, treatment to the target volume > or = 45 Gy, and treatment with additional chemotherapy, were associated with a significantly better overall survival (p < 0.05). On multivariate analysis only age and performance status remained significant prognostic variables. Relapse involved the central nervous system or cerebrospinal fluid (CSF) in all patients with known sites of relapse except three who had ocular relapse only. There was a low incidence of relapse in the initial brain site (23% of known cases) and a high incidence (50%) of CSF/spinal cord relapse. Of 48 deaths, 15 were related to initial or subsequent treatment. CONCLUSIONS Patient outcome is strongly influenced by age and performance status. Studies suggesting better survival for patients treated with chemoradiation may reflect patient selection rather than treatment variables. Optimal management remains to be defined. The high CSF/spinal relapse rate deserves particular attention.

Long-term outcome after radiotherapy alone for lymphocyte-predominant Hodgkin lymphoma: A retrospective multicenter study of the Australasian Radiation Oncology Lymphoma Group

The curative potential of radiotherapy (RT) alone as initial treatment for patients with Stage I–II lymphocyte‐predominant Hodgkin lymphoma (LPHL) has not been defined well.

Measurement of lung tumor volumes using three-dimensional computer planning software

PURPOSE To examine the interclinician variation in the definition of gross tumor volume (GTV) in patients undergoing radiotherapy for non-small-cell lung cancer (NSCLC), develop methods to minimize this variation, and test these methods. METHODS AND MATERIALS The radiotherapy planning computed tomography (CT) scans of 6 consecutive patients with NSCLC in which the radiologist was able to define and outline the GTV were used. Six oncologists independently contoured the tumors with the radiologists markings as a guide using a three-dimensional treatment planning system. Separate contours were prepared using only mediastinal window settings and using both mediastinal and lung window settings. The volumes were calculated using the planning system software (series 1). Factors that resulted in interclinician variation were determined, and, after a 3-year interval, 5 of the 6 clinicians redefined the GTVs using a revised protocol aimed at minimizing variation (series 2). RESULTS For series 1, the interclinician variation in the measurement of volumes ranged from 5%, in the most tightly measured tumor, to 42%, in the most variable, but was, on average, 20%. Statistically significant differences were noted among the clinicians (p = 0.002), that is, some clinicians tended to record relatively small and some relatively large volumes. The reasons for the variation among the oncologists included a tendency to include regions with a low probability of containing tumor, as if the oncologist were contouring a target volume; inclusion of adjacent atelectasis (ignoring the radiologists outline); and variable treatment of spicules. When the exercise was repeated using the revised protocol (series 2), the degree of interclinician variation was reduced, with a range of 7-22% (average 13%). In series 2, the differences among the clinicians were not statistically significant (p = 0.25). CONCLUSION Despite major radiologic input, significant variation occurred in the delineation of the three-dimensional GTVs of NSCLC among oncologists. Standardization of the approach with guidelines resulted in a reduction in this variation.

Radiotherapy in the management of solitary extramedullary plasmacytoma.

Abstract

Ocular Risks From Orbital and Periorbital Radiation Therapy: A Critical Review

Radiation therapy (RT) plays an essential role in the treatment of a wide range of tumors that arise in the orbit, invade the orbit, or are located in close proximity to it. Partial or total orbital irradiationmay cause awide spectrum of early and late toxicities, ranging from transient irritation to permanent blindness. Fastidious treatment planning and treatment delivery, informed by detailed knowledge of the effects of RTon ocular structures, can help minimize the risk of toxicity. The purpose of this article is to provide an overview of the potential complications of orbital radiotherapy and discuss their prevention and management. We discuss each major region of the orbit and globe in turn and where possible have made recommendations for the management of RTrelated toxicities. However, few prospective studies exist in this area of medicine, and therefore the evidence base is often weak. The authoritative QANTEC (1) reviews of normal tissue effects in the clinic, published recently in this journal (2) considered the effects of RT on the optic nerve but due to lack of high quality quantitative data did not consider other orbital subsites. We have confined our discussion largely to external beam RTwith photon or electron beams.

Primary testicular lymphoma

Primary testicular lymphoma (PTL) is a rare, clinically aggressive form of extranodal lymphoma. The vast majority of cases are histologically diffuse large B-cell lymphoma, but rarer subtypes are clinically important and must be recognized. In this review, we discuss the incidence, clinical presentation, and prognostic factors of PTL and present a summary of the recent advances in our understanding of its pathophysiology, which may account for the characteristic clinical features. Although outcomes for patients with PTL have historically been poor, significant gains have been made with the successive addition of radiotherapy (RT), full-course anthracycline-based chemotherapy, rituximab and central nervous system-directed prophylaxis. We describe the larger retrospective series and prospective clinical trials and critically examine the role of RT. Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 21 days with intrathecal methotrexate and locoregional RT is the current international standard of care, a substantial minority of patients progress, representing an unmet medical need. Finally, we discuss new treatment approaches and recent discoveries that may translate into improved outcomes for patients with PTL.