David C. Hodgson

Localized Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy Has Excellent Clinical Outcome

PURPOSEnExtranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct lymphoma with unique clinicopathologic features. We report the clinical outcome of stage I and II MALT lymphoma treated with involved field radiation therapy (RT).nnnPATIENTS AND METHODSnFrom 1989 to 2000, 103 patients with stage IE and IIE disease were referred. Their median age was 60 years, with a 2:1 female predominance. Presenting sites were stomach (17 patients), orbital adnexa (31 patients), salivary glands (24 patients), thyroid gland (13 patients), and other sites (18 patients). Ninety-three patients received RT--85 received RT alone, and eight received chemotherapy and RT--with a median dose of 30 Gy. The median follow-up time was 5.1 years.nnnRESULTSnA complete response (CR) to RT alone was achieved in 84 of 85 patients. Among CR patients, 14 experienced relapse. Relapse sites were mostly contralateral paired-organ or distant MALT locations and, infrequently, lymph nodes. The crude local control rate with RT was 95.3% (81 of 85 patients). No relapses were observed in patients with stomach or thyroid lymphoma, whereas 14 of 63 patients (22%) experienced relapse in the other sites. The overall 5-year survival rate was 98%, and the disease-free survival rate was 77%. Transformed lymphoma was observed in 14% of patients (two of 14) experiencing relapse.nnnCONCLUSIONnModerate-dose RT achieved excellent local control in localized MALT lymphomas and had curative potential for three fourths of the patients. Gastric and thyroid MALT lymphomas had better outcome, whereas distant failures were common for other sites. Despite relapse, the disease often maintained an indolent course.

Solitary plasmacytoma treated with radiotherapy: Impact of tumor size on outcome

PURPOSEnSolitary plasmacytoma (SP) is a rare presentation of plasma cell neoplasms. In contrast to multiple myeloma, long-term disease-free survival and cure is possible following local radiotherapy (RT), particularly for soft tissue presentations. In this study, we attempt to identify factors that predict for local failure, progression to multiple myeloma, and disease-free survival (DFS) in patients mainly managed with local RT.nnnMETHODS AND MATERIALSnWe identified 46 patients referred to the Princess Margaret Hospital between 1982 and 1993. The median age was 63 years (range 35-95), with a male:female ratio of 1.9:1. All patients had biopsy-proven SP (osseous: 32, soft tissue: 14). M-protein was abnormal in 19 patients (41%). All patients were treated with local RT (median dose 35 Gy), with 5 patients (11%) also receiving chemotherapy. Maximum tumor size pre-RT ranged from 0 to 18 cm (median 2.5).nnnRESULTSnThe 8-year overall survival, DFS, and myeloma-free rates were 65%, 44%, and 50%, respectively. The local control rate was 83%. Factors predictive of progression to myeloma (and poorer DFS) included bone presentation and older age. However, these two factors did not influence local control, which was affected by tumor size. All tumors < 5 cm in bulk (34 patients) were controlled by RT. Anatomic location did not predict outcome; however, 3 of the 5 tumors arising in paranasal sinuses did not achieve local control. Lower RT dose (< or =35 Gy) was not associated with a higher risk of local failure.nnnCONCLUSIONnSolitary plasmacytomas are effectively treated with moderate-dose RT, although osseous tumors have a high rate of recurrence as systemic myeloma. Large tumor bulk locally (> or =5 cm) predicts for local failure. Combined chemotherapy and RT should be investigated in these high-risk patients to increase the local control rate and the cure rate.

Stage I and II MALT lymphoma : results of treatment with radiotherapy

PURPOSEnMucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following involved field radiation therapy (RT).nnnPATIENTS AND METHODSnSeventy patients with Stage IE (62) and IIE (8) disease were treated between 1989 and 1998. Patients with transformed MALT were excluded. The median age was 62 years (range, 24--83 years), M:F ratio 1:2.2. Presenting sites included stomach, 15; orbital adnexa, 19; salivary glands, 15; thyroid, 8; lung, 5; upper airways, 3 (nasopharynx, 2; larynx, 1); urinary bladder, 3; breast, 1; and rectum, 1. Staging included site-specific imaging, CT abdomen in 66 patients (94%) and bone marrow biopsy in 54 (77%). Sixty-two patients received radiation therapy: 52 received RT alone, 7 received chemotherapy and RT, and 3 received antibiotics followed by RT. Median RT dose was 30 Gy (range, 17.5--35 Gy). Most frequently used RT prescriptions were 25 Gy (26 patients-18 orbit, 6 stomach, and 2 salivary glands), 30 Gy (23 patients), and 35 Gy (8 patients). Five patients had complete surgical excision of lymphoma and no other treatment (stomach 1, salivary 2, lung 2), whereas 2 patients with gastric lymphoma received antibiotics only. One patient refused treatment and was excluded from the analysis of treatment outcome, leaving 69 patients with a median follow-up of 4.2 years (range, 0.3-11.4 years).nnnRESULTSnA complete response was achieved in 66/69 patients, and 3 patients had partial response (2 lung, 1 orbit). The 5-year disease-free survival (DFS) was 76%, and the overall survival was 96%. No relapses were observed in patients with stomach and thyroid lymphoma. The 5-year DFS for these patients was 93%, in contrast to 69% for patients presenting in other sites (p = 0.006). Among the 5 patients treated with surgery only, 2 relapsed locally (lung, and minor salivary gland). Among 62 patients who received RT, 8 relapsed (2 salivary, 3 orbit, 1 nasopharynx, 1 larynx, 1 breast). Three patients relapsed in the nonirradiated contralateral paired organ, 4 in distant sites, and 1 in both local and distant sites. The overall local control rate with radiation was 97% (60/62 patients).nnnCONCLUSIONnLocalized MALT lymphomas have excellent prognosis following moderate-dose RT. Gastric and thyroid MALT lymphomas have better early outcome, as compared to the other sites where distant failure is more common. Relapses were observed in nonirradiated paired organs or distant sites. Further follow-up is required to assess the impact of failure on survival.

Psychological factors impacting transition from paediatric to adult care by childhood cancer survivors

PurposeChildhood cancer survivors require life-long care focused on the specific late effects that may arise from their cancer and its treatment. In many centers, survivors are required to transition from follow-up care in a paediatric cancer center, to care provided in an adult care setting. The purpose of this study was to identify the psychological factors involved in this transition to adult care long-term follow-up clinics.MethodsQualitative interviews were conducted with ten paediatric survivors still in paediatric care, as well as 28 adult survivors of whom 11 had transitioned successfully to adult care (attended three long-term follow-up (LTFU) appointments consecutively); ten who failed to transition (attended at least one LTFU appointment as an adult, but were inconsistent with subsequent attendance); and seven who had never transitioned (did not attend any LTFU care as an adult). Line-by-line coding was used to establish categories and themes. Constant comparison was used to examine relationships within and across codes and categories.ResultsTwo overall categories and four subthemes were identified: (1) Identification with being a cancer survivor included the subthemes of ‘cancer identity’ and ‘cancer a thing of the past’ and; (2) Emotional components included the subthemes of ‘fear and anxiety’ and ‘gratitude and gaining perspective’. The analysis revealed that the same factor could act as either a motivator or a hindrance to successful transition in different survivors (e.g., fear of recurrence of cancer might be a barrier or a facilitator depending on the survivor’s life experience).ConclusionsPsychological factors are an important consideration when preparing cancer survivors for transition to adult long-term follow-up care. Identifying and addressing the individual psychological needs of childhood cancer survivors may improve the likelihood of their successful transition to adult care.

Current knowledge and future research directions in treatment-related second primary malignancies

Currently, 17–19% of all new primary malignancies occur in survivors of cancer, causing substantial morbidity and mortality. Research has shown that cancer treatments are important contributors to second malignant neoplasm (SMN) risk. In this paper we summarise current knowledge with regard to treatment-related SMNs and provide recommendations for future research. We address the risks associated with radiotherapy and systemic treatments, modifying factors of treatment-related risks (genetic susceptibility, lifestyle) and the potential benefits of screening and interventions. Research priorities were identified during a workshop at the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer. Recently, both systemic cancer treatments and radiotherapy approaches have evolved rapidly, with the carcinogenic potential of new treatments being unknown. Also, little knowledge is available about modifying factors of treatment-associated risk, such as genetic variants and lifestyle. Therefore, large prospective studies with biobanking, high quality treatment data (radiation dose–volume, cumulative drug doses), and data on other cancer risk factors are needed. International collaboration will be essential to have adequate statistical power for such investigations. While screening for SMNs is included in several follow-up guidelines for cancer survivors, its effectiveness in this special population has not been demonstrated. Research into the pathogenesis, tumour characteristics and survival of SMNs is essential, as well as the development of interventions to reduce SMN-related morbidity and mortality. Prediction models for SMN risk are needed to inform initial treatment decisions, balancing chances of cure and SMNs and to identify high-risk subgroups of survivors eligible for screening.

Added cancer yield of breast magnetic resonance imaging screening in women with a prior history of chest radiation therapy

Recommendation for breast magnetic resonance imaging (MRI) screening for women with a prior history of chest radiation is currently based on expert opinion, because existing data are very scant. The objective of this study was to evaluate added cancer yield of screening breast MRI in this population.

Methods to Assess Adverse Health-Related Outcomes in Cancer Survivors

Designing a study focused on adverse health-related outcomes among cancer survivors is complex. Similarly, reading and interpreting the findings of a survivorship-focused study requires an appreciation of the complexities of study design, potential biases, confounding factors, and other limitations. The topic areas are broad—study design, comparison populations, measures of risk, key health outcomes of interest, potential modifying factors to consider. With brevity, this article includes basic information to consider within these areas as well as examples and concepts intended to advance the science of survivorship research and encourage further reading and exploration. Cancer Epidemiol Biomarkers Prev; 20(10); 2022–34. ©2011 AACR.

Role of Comparative Effectiveness Research in Cancer Funding Decisions in Ontario, Canada

Recently, the evidence-based drug funding process in Ontario, Canada, was challenged by a young mother with a breast tumor too small, based on the evidence that existed at the time, to qualify for an expensive drug. In reality, this is only the latest in a number of challenges the publicly funded health care system has had to deal with in the face of an evolving drug policy landscape. This article defines comparative effectiveness research (CER), considering how it is viewed differently in the United States and Canada. It also reviews the role CER now plays in the Ontario drug funding process and concludes with a review of the challenges and opportunities of using observational data to conduct CER and incorporate it into policy making within a universal health care system. Many of the issues faced by Ontario are relevant beyond Canada, including in the United States during this period of health care reform.

Reconstruction of 3D lung models from 2D planning data sets for Hodgkin's lymphoma patients using combined deformable image registration and navigator channels

PURPOSEnLate complications (cardiac toxicities, secondary lung, and breast cancer) remain a significant concern in the radiation treatment of Hodgkins lymphoma (HL). To address this issue, predictive dose-risk models could potentially be used to estimate radiotherapy-related late toxicities. This study investigates the use of deformable image registration (DIR) and navigator channels (NCs) to reconstruct 3D lung models from 2D radiographic planning images, in order to retrospectively calculate the treatment dose exposure to HL patients treated with 2D planning, which are now experiencing late effects.nnnMETHODSnThree-dimensional planning CT images of 52 current HL patients were acquired. 12 image sets were used to construct a male and a female population lung model. 23 Reference images were used to generate lung deformation adaptation templates, constructed by deforming the population model into each patient-specific lung geometry using a biomechanical-based DIR algorithm, MORFEUS. 17 Test patients were used to test the accuracy of the reconstruction technique by adapting existing templates using 2D digitally reconstructed radiographs. The adaptation process included three steps. First, a Reference patient was matched to a Test patient by thorax measurements. Second, four NCs (small regions of interest) were placed on the lung boundary to calculate 1D differences in lung edges. Third, the Reference lung model was adapted to the Test patients lung using the 1D edge differences. The Reference-adapted Test model was then compared to the 3D lung contours of the actual Test patient by computing their percentage volume overlap (POL) and Dice coefficient.nnnRESULTSnThe average percentage overlapping volumes and Dice coefficient expressed as a percentage between the adapted and actual Test models were found to be 89.2 +/- 3.9% (Right lung = 88.8%; Left lung = 89.6%) and 89.3 +/- 2.7% (Right = 88.5%; Left = 90.2%), respectively. Paired T-tests demonstrated that the volumetric reconstruction method made a statistically significant improvement to the population lung model shape (p < 0.05). The error in the results were also comparable to the volume overlap difference observed between inhale and exhale lung volumes during free-breathing respiratory motion (POL: p = 0.43; Dice: p = 0.20), which implies that the accuracies of the reconstruction method are within breathing constraints and would not be the confining factor in estimating normal tissue dose exposure.nnnCONCLUSIONSnThe result findings show that the DIR-NC technique can achieve a high degree of reconstruction accuracy, and could be useful in approximating 3D dosimetric representations of historical 2D treatment. In turn, this could provide a better understanding of the biophysical relationship between dose-volume exposure and late term radiotherapy effects.

FDG PET/CT Response Assessment Criteria for Patients with Hodgkin's and Non-Hodgkin's Lymphoma at End of Therapy: A Multiparametric Approach

PurposeBased on the International Harmonization Project (IHP) criteria, positron emission tomography (PET) response assessment of residual nodal masses in patients with lymphoma after completion of therapy is performed visually using mediastinal blood pool as the reference. The primary objective of this study was to define the optimal reference for PET response assessment. Secondary aim was to assess if morphological criteria on computed tomography (CT) may improve performance of PET.MethodsThis institutional review board approved retrospective study included 137 patients, with Hodgkin’s (nu2009=u200943) or non-Hodgkin’s lymphoma (nu2009=u200994) assessed for residual masses (nu2009=u2009180) after completion of therapy with pathology and clinical and imaging surveillance data (mean, 19xa0months) as the standard of reference. Two readers independently assessed response by IHP and Deauville criteria. The addition of morphological parameters on CT was assessed in relation to therapy response.ResultsBased on the standard of reference, 36 patients (26.3xa0%) had residual lymphoma. For IHP and Deauville criteria, sensitivity, specificity and accuracy were 97.2xa0%, 97.2xa0% (pu2009=u20091); 79.2xa0%, 92.1xa0% (pu2009<u20090.001); and 83.9xa0%, 93.4xa0% (pu2009=u20090.001), respectively. Of the morphological parameters assessed, only change in size over course of therapy was significant (pu2009<u20090.003) and improved specificity for IHP-based interpretation to 90.4xa0% (pu2009=u20090.008).ConclusionsUsing liver as the visual reference to determine PET positivity for lymphoma patients being assessed for residual masses at the end of therapy improves specificity, yet maintains the high sensitivity of PET in identifying residual disease. The addition of change in size after therapy improves specificity of PET when using IHP-based but not Deauville-based interpretation.