Comparisons of dosimetric approaches for fractionated radioimmunotherapy of non-Hodgkin lymphoma.

AIM: The aim of this study was to compare different dosimetric approaches on therapy naïve patients enrolled in a multicentre fractionated radioimmunotherapy trial, to determine which methodological approach correlates with bone marrow toxicity. METHODS: Twenty-height non-Hodgkin lymphoma patients were treated with one or two fractions of 90Y-Ibritumomab-Tiuxetan (11.1 MBq/kg) 8 to 12 weeks apart in four different institutions. Quantitative imaging with 111In-Ibritumomab-Tiuxetan (185 MBq) was performed at 0, 1, 4 and 7 days after infusion, starting two weeks before the therapeutic administration. A whole-body (WB) CT scan was also acquired prior to the 111In-Ibritumomab injection, for attenuation correction purposes and was segmented to derive patient-specific organ masses. All dosimetry processing was centralized in a single institution. The first method (M_2D) was based on geometric mean WB scans, corrected for attenuation, scatter and organs superposition. The second method (M_2.5D) was based on the computed assisted matrix inversion approach and used segmented CT scans. The third method (M_3D) used iterative reconstruction of tomographic scans, corrected for attenuation, scatter and collimator response. Absorbed doses were estimated for lungs, liver, kidneys and spleen using MIRD S values adjusted for organ masses. Bone marrow (BM) absorbed doses were evaluated according to imaging methods (3) and compared to blood-based approaches. RESULTS: For some patients, organ masses such as liver or spleen significantly differed from male/female reference masses, whereas lungs and kidneys masses were relatively constant. Except for lungs, absorbed doses estimated by M_2D were higher than those from M_2.5D and these, in turn, were higher that those calculated from M_3D (Wilcoxon P<8.6e-4). Median organ absorbed dose estimates were equivalent for both fractions except for the spleen. In fact, spleen absorbed doses for the second fraction were lower than those for the first fraction, regardless of the approach. Possible explanations are that patient spleen masses were kept constant for analysis of both fractions and/or that spleen uptake was lowered after the first fraction. Estimation of BM absorbed doses from blood sampling was unable to predict platelet toxicity, but image-based methods performed better. Additionally, for most organs, the absorbed dose delivered by the first fraction could predict that delivered by the second fraction. CONCLUSION: These results confirm that different acquisition/processing protocols will lead to statistically different absorbed doses. Additionally, image-based dosimetric approaches are needed in order to correlate absorbed dose to bone marrow toxicity.

A retrospective analysis of selective internal radiation therapy (SIRT) with yttrium-90 microspheres in patients with unresectable hepatic malignancies.

AIM: To evaluate the efficacy and safety of selective internal radiation therapy (SIRT). MATERIALS AND METHODS: A retrospective analysis was undertaken of all patients who underwent SIRT at a single institution. Diagnostic and therapeutic angiograms, computed tomography (CT) images, positron-emission tomography (PET) images, and planar isotope images were analysed. The response to SIRT was analysed using radiological data and tumour markers. Overall survival, complications, and side effects of SIRT were also analysed. RESULTS: The initial 12 patients were included on an intention-to-treat basis, between 21/09/2005 and 07/05/2008. All patients had advanced disease and multiple prior courses of chemotherapy. One patient did not receive yttrium-90 due to complex vascular anatomy; the remaining 11 patients underwent 13 SIRT treatment episodes following work-up angiography. A response was seen using PET in 80% of patients. Using CT, the response of the tumour to therapy in the treated hepatic segments demonstrated a 20% partial response, stable disease in 50%, and progressive disease in 30%. Estimated median survival was 229 days, with 64% of patients still alive at the time of writing. No major complications were observed, although 82% of patients experienced side-effects following SIRT, mainly nausea, vomiting, and abdominal pain. CONCLUSIONS: There have been no complications in the 12 SIRT patients. Tumour response was seen in four out of five patients who underwent PET. Objective CT response rates were mixed and are perhaps partially explained by advanced disease and limitations of using measurements to assess response. This complex and potentially hazardous service has been successfully and safely established.

Breast disease and undergraduate medical education: a randomized trial to assess the effect of a home study module on medical student performance.

BACKGROUND: This study sought to demonstrate the effectiveness of a home study module (HSM) on student performance at a large urban medical school. METHOD: Second-year students were randomized to receive: 1) a HSM in addition to regular teaching of clinical breast examination or, 2) the regular teaching alone. The HSM included adult learning principles, problem-based learning, and practice guidelines. Students completed a pretest, a post-test, and course evaluation. The pre- and post-tests examined students' knowledge and comfort levels. RESULTS: Of 176 students, 136 agreed to participate and 127 completed both pre- and post-tests. Baseline pretest indicated no significant difference between the intervention and control groups. Post-test showed that students receiving the HSM gained significantly more knowledge than had the control group, and their comfort levels shifted nonsignificantly more. Student evaluations indicated perceived value of the HSM. INTERPRETATION: Student performance can be enhanced and comfort levels increased by providing a critical core of knowledge in the form of a HSM. This approach may be applicable to other important subjects.

Value of unstructured time (breaks) during formal continuing medical education events.

BACKGROUND: Unstructured time (breaks) at formal continuing medical education (CME) events is nonaccredited in some jurisdictions. Program participants, however, perceive this time as valuable to their learning. The purpose of this research was to determine what activities occur during unstructured time in formal CME events and how these activities impact learning for physicians. METHODS: A qualitative method based on grounded theory was used to determine themes of behavior. Both individual and focus group interviews were conducted. Data were analyzed and coded into themes, which were then further explored and validated by the use of a questionnaire survey. RESULTS: One hundred ninety-seven family physicians were involved in the study. Several activities related to the enhancement of learning were identified and grouped into themes. There were few differences in the ranking of importance between the themes identified, nor were differences determined based on gender or type of CME in which the break occurred. FINDINGS: The results suggest that unstructured time (breaks) should be included in formal CME events to help physician learners integrate new material, solve individual practice problems, and make new meaning out of their experience. The interaction between colleagues that occurs as a result of the provision of breaks is perceived as crucial in aiding the process of applying knowledge to practice.

Family physicians' knowledge of malignant melanoma.

BACKGROUND: The incidence and mortality of melanoma have been increasing during the past two decades. Melanoma is relatively easy to detect and, when diagnosed early, is curable. OBJECTIVE: Our purpose was to assess the baseline knowledge of malignant melanoma among family practitioners and to identify their preferred method of learning new information about the skin. METHODS: The design was a randomized survey by mailed questionnaire. RESULTS: More than 50% of physicians stated they lacked confidence in being able to recognize melanoma. Family physicians were well informed on factors affecting prognosis, but knowledge deficits were identified on history, physical examination, and risk factors. The most effective method of learning new information about the skin was hands-on teaching demonstration. CONCLUSION: Many family physicians are not confident in their ability to recognize melanoma, and knowledge deficits were identified. In addition, some important risk factors were not well recognized. Thus, those at highest risk may not be receiving education on early detection that may help decrease the incidence and mortality of melanoma.

Using faculty and student perceptions of group dynamics to develop recommendations for PBL training.

BACKGROUND: In training faculty as tutors for problem-based learning (PBL), certain aspects (domains) of teaching methodology are highlighted in the medical education literature. These are content, cognitive processing, and group dynamics. The authors contend that the amounts of attention given to these domains in faculty and student development have not been equal and that group dynamics needs further attention. METHOD: In March 1993 the authors conducted a time-lapse study that involved 27 first-year students and three faculty in three PBL groups at the University of Toronto Faculty of Medicine. The purpose of the study was to determine faculty and student perceptions and knowledge of effective group dynamics, and to develop recommendations for student and faculty training. A qualitative approach was used that combined projective questions, post-tutorial questionnaires, and live and videotaped observations. RESULTS: Observations and analysis of the data revealed a generally low awareness of effective group dynamics and the absence of a mechanism for reflection that could help groups analyze and learn from their behaviors. The results also revealed a discrepancy between self-reported behavior and observed behavior. For example, the students and faculty perceived their groups as generally "working well as a team," but observers noted that several aspects of group productivity (such as the articulation of goals and planning for future sessions) were not addressed. CONCLUSION: The authors recommend that medical schools develop comprehensive training programs to teach group members to evaluate group performance and engage in open discussion of effective and ineffective behaviors.

Shifting students and faculty to a PBL curriculum: attitudes changed and lessons learned.

BACKGROUND: The University of Toronto Faculty of Medicine is implementing a new undergraduate curriculum that emphasizes active, self-directed learning. The aims of this study were to (1) evaluate shifts in students' attitudes after initial direct experience with problem-based learning (PBL), (2) describe faculty experiences, and (3) develop guidelines for further implementation of PBL. METHOD: Questionnaires were administered at the beginning of the first PBL session and at the close of the last session (five weeks later) to the 250 second-year students in 1992-93 and to their 15 faculty tutors. Quantitative data were analyzed using multivariate analysis of variance and univariate tests. Open-ended questions were categorized based on common patterns that emerged. RESULTS: Of the 250 students, 196 (78%) responded to the pretest, and 207 (83%) responded to the posttest. There was a statistically significant shift in the students' perceptions from pretest to posttest in agreeing that PBL is more effective than traditional teaching methods (increasing from 38% to 52%). The students rated traditional methods as better for knowledge acquisition, whereas PBL methods were rated better for improving teamwork and doctor-patient relationships. At pretest, the most common themes concerned a perceived danger that PBL would result in knowledge gaps, reinforce the wrong information, and make inefficient use of valuable time. Perceived advantages of PBL included that it is more stimulating and enjoyable, and it teaches students how to learn rather than to memorize. At posttest, there was an increase in favorable comments by the students. Virtually all of the attitudes expressed by the students were shared by the faculty. In addition, at pretest the faculty were anxious about the perceived lack of structure in PBL. CONCLUSION: Direct experience with PBL led to more favorable attitudes among the students and faculty. Recommendations are suggested for other schools and programs seeking to implement PBL curricula.