Analysis and Impact of a Multidisciplinary Lymphoma Virtual Tumor Board

Abstract

Objective:

To prospectively evaluate the impact of a multidisciplinary lymphoma virtual tumor board.

Background:

The utility of multi-site interactive lymphoma-specific tumor boards has not been reported. The Mayo Clinic Lymphoma Tumor Board is a component of the International Mayo Clinic Care Network (MCCN). The format includes the clinical case presentation, presentation of radiology and hematopathology findings by the appropriate subspecialist, proposed treatment options, review of the literature pertinent to the case, pharmacy contributions, and discussion followed by recommendations.

Patients and Methods:

309 consecutive highly selected real-time cases with a diagnosis of lymphoma were presented at the Mayo Clinic Lymphoma Tumor Board from January 2014 to June 2018 and decisions were prospectively tracked to assess its impact on the treatment decisions.

Results:

A total of 309 cases were prospectively evaluated. 140 (45.3%) cases had some changes made or recommended. The total changes suggested were 179, as some cases had more than one recommendation. There were 93 (30%) clinical management recommendations, 45 (14.6%) additional testing recommendations, 29 (9.4%) pathology changes, and 6 (1.9%) radiology changes. In an electronic evaluation process, 93% of the responders reported an improvement in knowledge and competence, and 100% recommended no change in format of the board.

Conclusion:

A multidisciplinary lymphoma tumor board approach was found to have a meaningful impact on lymphoma patients while enhancing interdisciplinary interactions and education for multiple levels of the clinical care team.

Introduction:

Management of cancer patients is becoming increasingly complex with ongoing advances in drug development, diagnostic approaches, local therapy options, emerging clinical data from multiple trials and constantly evolving clinical practices and guidelines. Furthermore, a wide range of health-care professionals involved in patient care creates room for miscommunication and arduous care coordination issues. Multidisciplinary teams (MDTs) or tumor boards are commonly conducted in oncology to implement evidence-based recommendations, providing opinions for complex cases, and conducting patient-centered care in a time-effective manner by bringing various specialists together.¹ MDT based care is becoming a standard practice worldwide. Typical method entails a description of the patient’s presentation, a review of relevant radiologic and histopathologic data, and then a discussion of treatment strategies by relevant disciplines. Several single-center studies have investigated the impact of an MDT based approach in various solid tumor malignancies.^2,3 Effective implementation of MDT requires a regular schedule and a team comprising of medical hematology-oncology, radiation oncology, pathology, radiology, and surgical specialists. Depending on the tumor type and institutional setting, tumor boards may also include palliative medicine, research coordinators, clinical research nurses and pharmacists with each providing their unique inputs based on circumstance.⁴ The American College of Surgeon’s Commission on Cancer Program accreditation, in fact, requires cancer programs to have multidisciplinary cancer conference that routinely reviews cases and discusses management options.⁶ American Society of Clinical Oncology (ASCO) also promotes tumor boards that are integrated into multidisciplinary cancer management courses. Attendees of these courses, especially in the middle- and low-income countries, have reported starting new MDT based patient approach in their own countries.⁷

Evaluation of the impact of MDTs for cancer patients suggest changes made to staging/diagnosis, management plans, higher rates of surgical resection, and adherence to evidence-based guidelines.^8,9,10,11,12 While some show an overall improvement in meaningful patient outcomes, including survival, other more extensive studies contradict this observation.^{13,14,15,16,3} MDTs are resource-intensive and thus it is essential to assess their impact. It is an arduous and complicated task which is currently under debate. It requires incorporation of measures of structure, adherence to recommendations, processes to provide feedback and to assess the patient-reported quality of care.¹⁷ Solid tumors such as lung, breast, and colon cancer have MDTs established more commonly, while hematologic malignancies are either discussed in general tumor boards or have disease-specific tumor boards in larger academic centers. A systematic review conducted by Pillay et al. evaluated the impact of MDTs on patient assessment, management, and patient outcomes, screened 1067 articles of which 27 met the inclusion criteria. Of these only two studies recruited patients with a range of oncologic diagnosis, the remainder were specific to solid tumors only.³ Lymphoma-specific tumor board outcomes have not been reported in recent years. In addition, the utility of multi-site, interactive tumor boards using videoconference technology is not widely reported. We prospectively evaluated the outcomes of a multidisciplinary multi-site lymphoma tumor board that included a change in the revision of the World Health Organization Classification first published in 2016, new genomic observations, and reports of new therapeutic interventions.¹⁸

PATIENTS AND METHODS

The Mayo Clinic Lymphoma Tumor Board is a component of the International Mayo Clinic Care Network (MCCN). This comprises of over 40 hospitals both nationally and internationally. The format is comprised of a clinical case presentation, radiology review of images, presentation of hematopathology findings by the appropriate subspecialist, proposed treatment options, review of the literature pertinent to the case, discussion and recommendations (see Figure 1). The requirement for presentation involved having an established or suspected diagnosis of lymphoma with pathology reviewed at Mayo Clinic, Rochester, MN (MCR). Relevant pathology and radiology materials were required to be reviewed at MCR and presented by MCR hematopathologists and radiologists. Patients were presented prospectively with active clinical issues or questions to be addressed. Four cases were presented at each 60-minute meeting. Case selection was based on the managing physicians’ discretion both from MCR, and its affiliate centers when there was a clinical question that needed to be addressed. This could be related to clinical management such as next treatment of choice, exploring clinical trial possibilities when all the approved or standard treatment options had been exhausted, confirmation or clarification of the diagnosis, or discussion and management of unusual patient presentation. The referring physicians were provided the knowledge that at least 2 weeks was required for acquisition and review of the pathology material and radiological images. We ensured that the managing physicians were aware of this requirement via email notifications that were sent out once a week for request of cases so as not to delay patient care where urgent management was needed. Meeting was conducted every 2 weeks except for holidays, and during annual hematology-oncology meetings such as American Society of Hematology, and ASCO when the staff is limited.

Figure 1.

Illustration depicting the workflow of our multidisciplinary tumor board meeting.

309 consecutive highly selected cases with an established or suspected diagnosis of lymphoma at the Mayo Clinic Lymphoma Tumor Board were presented from 2014 to 2018. The pathology material was independently reviewed by the presenting hematopathologists and radiology material by the presenting radiologist. Participants outside of Mayo Clinic were office-based or hospital-based, and included multiple members of the health care team which included pharmacists, clinical research associates, and physicians-in-training. Recommendations were prospectively tracked for changes in radiology interpretation, pathologic diagnosis, and treatment approaches. Actual follow-up of all patients after the meeting was not allowed in the MCCN; therefore, the data on actual patient treatment and survival is not available. Participation in the meeting was either via in-room attendance at MCR, video conference at a participating MCCN site, or via non-participatory live-stream online. Video was available internally for fourteen days for review. Approval for this study was obtained from the Mayo Clinic Institutional Review Board. To acquire feedback from the participants, an anonymous online survey was conducted annually from 2017 onwards.

RESULTS

A total of 309 cases were presented from January 2014 to June 2018. 258 (83%) cases were from MCR, and 51 (17%) were not physically evaluated at MCR. Sixteen cases were presented at a subsequent meeting for further recommendations in the course of their disease after the initial presentation and discussion. Cases presented included a mix of new diagnosis, relapsed and refractory disease. 45% (140/309) of the cases presented had changes in some aspect of their care resulting in a total of 179 overall changes owing to the MDTs discussions. Clinical management changes comprised 30% (n = 93) of the changes, 14.6% (n = 45) for additional testing recommendations, 9.4% (n = 29) had pathology changes, and 1.9% (n = 6) had radiology changes (see Table 1). Of the cases that required change in care, 68.5% (n = 96) were newly diagnosed and 31.5% (n = 44) had relapsed/refractory disease (Figure 2). The clinical management changes suggested included one systemic treatment to another regimen, change in diagnosis based on the pathology review, both change in diagnosis based on pathology review and change in systemic treatment, the recommendaton of autologous stem cell transplant for consolidation and the addition of radiation to the systemic treatment (see Table 2).

Table 1:

Categories of changes recommended based on tumor board discussion.

Category	Number	% of 309 Cases
Radiologic Interpretation	6	1.9%
Pathologic Diagnosis	29	9.4%
Additional testing Recommended	45	14.6%
Clinical Management	93	30%

^*No consensus was reached: 6 (1.9%)

Figure 2.

Pie chart showing distribution of various lymphoma types presented in the lymphoma tumor board during the study period.

Table 2:

Different types of clinical management changes suggested during tumor board discussion

Category	Number	% of 309 Cases
Systemic treatment to different systemic treatment	11	3.6%
Pathology Change with No Change in Management	11	3.6%
Pathology Change with Treatment Change	11	3.6%
Systemic Treatment Alone to Systemic Treatment Plus Radiation Therapy	5	1.6%
Observation to More Testing	7	2.3%
Systemic Treatment to Autologous Stem Cell Rescue	5	1.6%
Other	43	14%

Various lymphoma types were discussed over this time period (Figure 3). Of these, the most common was diffuse large B-cell lymphoma (DLBCL), followed by follicular lymphoma (FL). We further categorized the cases presented based on year and classification, which demonstrates the diversity of cases presented (see Table 3). Average site in-room average attendance (internal/external) was 16.8/8.6. The non-participatory live-stream presence was not possible to track.

Table 3:

Different case diagnoses discussed with changes suggested from 2014–2018 based on lymphoma classification and disease status (new vs. relapsed/refractory disease)

Year	Number of Cases with change	Lymphoma classification	New/Relapsed diagnosis	Site of origin
2014	10	DLBCL- 3 FL- 3 cHL – 1 Mantle cell – 1 PTCL NOS – 1 Histiocytic disorder – 1	New – 4 Relapsed/Refractory - 6	MCR – 7 Outside - 3
2015	34	DLBCL – 9 EN- MZL – 5 FL – 2 cHL – 3 High-grade B cell- DHT – 2 EBV + LPD – 2 PTCL NOS – 1 PTLD – 2 NK/T Cell, nasal type – 1 Primary CNS – 1 Splenic MZL – 1 Nodal MZL – 1 Mantle cell - 1 Other - 3	New - 23 Relapsed/Refractory - 11	MCR - 30 Outside - 4
2016	33	DLBCL – 8 Mantle cell – 4 FL – 3 Primary CNS – 2 Other – 3 High-grade B cell NOS – 1 MF with large cell trans – 1 EN – MZL – 1 cHL – 1 HGBL – DHT – 1 EBV+ LPD – 1 Histiocytic disorder – 1 Nodal MZL – 3 NLPHL – 1 WM/LPL - 2	New – 23 Relapsed/Refractory - 10	MCR – 22 Ouside 11
2017	42	DLBCL – 10 cHL – 6 FL – 6 Other – 6 EN – MZL – 3 Primary CNS – 2 Mantle cell – 2 Burkitt’s – 1 PTCL NOS – 1 Mycosis fungoides – 1 Histiocytic disorder – 1 PTLD – 1 NLPHL – 1 WM/LPL - 1	New – 30 Relapsed/Refractory - 12	MCR-30 Outside −12
2018	21	DLBCL – 5 FL – 4 cHL – 2 EN MZL – 2 Other – 2 NLPHL – 1 Primary CNS – 1 Mantle cell – 1 WM/LPL – 1 EBV + LPD – 1 NK/T- cell, nasal - 1	New – 16 Relapsed/Refractory - 5	MCR – 17 Outside - 4

Abbreviations: DLBCL – Diffuse large B-cell lymphoma; FL- Follicular lymphoma; cHL- classical hodgkin’s lymphoma; PTCL-NOS – Peripheral T-cell lymphoma- not otherwise specified; EN-MZL – Extranodal marginal zone lymphoma; EBV+ LPD – EBV+ lymphoproliferative disorder; PTLD – post transplant lymphoproliferative disorder; HGBL NOS – High grade B-cell lymphoma not otherwise specified; MF- mycosis fungoides; NLPHL – nodular lymphocyte predominant hodgkin’s lymphoma; WM/LPL – waldenstrom’s macroglobulinemia/lymphoplasmacytic lymphoma

To evaluate the MTDs further, annual feedback surveys were incorporated in 2017. Anonymous online surveys were sent out to gauge the perception of the participants and to attain any feedback for improvement in the team structure, process, and outcomes. This was a 15-questions online survey which was distributed to all the attendees of the MDTs including clinicians, nurse practitioners, research staff, clinical nursing staff, and learners (lymphoma and general hematology-oncology fellows). On a 5-point rating scale, overall activity was rated excellent by 100% of participants both in 2017 and 2018. All participants responded that the objectives of the meeting were met, the tumor board was free of commercial bias, and that appropriate references and teaching slides were included for educational purposes. 93% of attendees perceived improvement in their overall knowledge, competence, performance, and patient outcomes (see Figure 4). 100% recommended no changes to the format of the conference. Optional fields were left in the survey to obtain general comments for feedback. Based on the feedback provided, enhancements over time included Continuous Medical Education (CME) credit, an in-room microscope, and real-time radiology images.

DISCUSSION

The disease-specific histology-based tumor board provided for a rich, in-depth review of the full context of the patient’s care that included regional and international input. The review of the history, physical examination, radiology findings, pathology findings, unique aspects of the individual case resulted in changes and recommendations in 45% of patients. The environment provides for broad educational opportunities and participation for all involved including individuals at different aspects of training; visiting fellows, pharmacists, clinical research associates involved in the University of Iowa/Mayo Clinic Specialized Program of Research Excellence (SPORE) program and the Lymphoma Epidemiology Outcomes (LEO) Consortium. New data from studies from these federally funded grants were included regularly into the discussion, applied to cases and incorporated into clinical decisions. Therapeutic options were vetted, including level of evidence supporting different treatment approaches, comorbidities, dosing considerations in hepatic or renal insufficiency, blood brain barrier access, drug-drug interactions, patient’s access to therapy and pharmaco-economic impact in the presence of a multi-disciplinary team to determine the optimal diagnosis and most effective and appropriate treatment approaches.

Several single centers have investigated the impact of MDTs on patient outcomes. Between 4 and 45% of patients with malignancies discussed at MDTs experience changes in the diagnosis or staging (including pathologic grade, the primary site of the tumor, histology, and extent of disease spread).^{3, 19, 20} Brannstrom et al. reported that rectal cancer patients discussed in MDT meetings had complete pre-operative staging in 96% of the cases compared to 63% not presented.²¹ Similar studies in other solid tumors (esophageal, lung, gynecological and prostate) suggest more accurate and complete staging and changes in surgical strategies after discussion in MDTs.^22,23,24 Recommendations for chemotherapy, radiation, and surgical resection were also reported to be impacted. Prospective and retrospective studies reported changes in the management plan in the range of 4.5–52% of cases.^25,26,8,27 Newman et al. showed that 17% of management plans changed in breast cancer patients due to review of pathology and radiology, as compared to 34% made only based on the discussion in MDT.²⁸ Additional testing and consultations ordered after case review in MDT meeting have been reported.²⁹ More patients received neo-adjuvant or adjuvant treatments, and even had more downstaging of their tumors, resulting in curative surgeries.^16,24,30,21 Greater adherence to clinical practice guidelines was noted in MDTs based care, along with fewer mean days from diagnosis to treatment and increased referral to palliative care.^24,31 Similar to the mentioned data, our study highlights changes in all aspects of care in the lymphoma patients presented which has not been previously described. About 45% of patients had changes in their management after discussion in this virtual tumor board. Our lymphoma MDT’s construct is unique in that it also included cases from low volume centers and was both regional and international. In concert with this, our format also necessitated a review of literature or evidence-based guidelines in a powerpoint based presentation with the goal of education for all the team members. The specifics of change in management included the transition from one systemic treatment to another, the incorporation of radiation therapy, the recommendation for transplant or cell therapy approaches and change in pathological diagnosis leading to change in systemic treatment. Since the cases were selected and likely more complex it provided for an exceptional environment which had an educational impact on all involved especially the learners. Further more, when the cases are challenging to diagnose, have rare presentations or issues in management not commonly encountered in daily practice, it generates enthusiasm to learn. Tumor boards are usually implemented in one of two ways. First, all patients with a new diagnosis of a particular malignancy are discussed or second, only selected, more complex, and high-yield cases are presented. MDTs provide second or expert opinion regarding complex cases and potentially screen patients for clinical trial enrollment. MDTs also provide evidence-based recommendations to satellite sites or lower volume centers through virtual tumor boards or a venue for education regarding new developments and guidelines for tumor type. We chose to implement our MDT in the latter manner for 2 reasons. One this provided more educational value to the participants, and two it gave the opportunity to the lower volume centers to discuss their most complex cases at such a venue and seek expert opinion. This process has demonstrated that three to four cases can be presented efficiently with appropriate discussion resulting in recommendations within 60 minutes with respect to the time of all participants. These cases were also generalizable since they represented genuine questions in the diagnosis, complications and management of lymphoma that are encountered by physicians routinely in practice. Lymphomas are a heterogenous group of disorders, and the variety of the cases discussed in the tumor board is consistent with the prevalence of various lymphoma types in the United States. Diffuse large B-cell lymphoma and follicular lymphoma were the most common lymphoma types that were discussed

Change in the management can be attributed to a certain extent to the emergence of new data from clinical trials. For instance, in Hodgkin lymphoma, clinical trial results emerged over our study period for both limited-stage disease and advanced-stage disease. In limited-stage disease, the German Hodgkin Study Group had reported a 90% disease-free survival with ABVD (Adriamycin, bleomycin, Velban®, and DTIC) for two cycles followed by 20Gy radiation therapy.³² The UK RAPID trial randomized negative PET patients after three cycles of ABVD to 20Gy radiation therapy versus observation and despite not being able to show non-inferiority of the observation approach, showed very good outcomes in PET negative cohort.³³ In advanced-stage disease, PET-based de-escalation of bleomycin chemotherapy to mitigate pulmonary toxicity was adopted based on results from RATHL study.³⁴ New laboratory assessments such as the TP53 mutation status in mantle cell lymphoma were routinely incorporated in our laboratory after a tumor board presentation.³⁵ New understanding of the natural history of follicular lymphoma, diffuse large B-cell lymphoma, and other subtypes were incorporated.^{36,37,38,39,40,41,42} New insights into treatment approaches, unusual lymphomas, rare presentations and management, the influence of physical activity, new biology and therapeutic approaches were reviewed.^{43,44,45,46,47,48,49,50,51} National and Mayo Clinic practice guidelines were incorporated into the discussions as many of these expert participants serve on the panel of these guidelines.^52,53,54,55

Effects of MDT based care on patient outcomes such as survival is complex. Several single-institution studies support its benefit, and positive impact, however larger studies and systematic reviews challenge this notion.^3,16 Keating et al. expanded the evaluation to a large integrated health system, the Veterans Health Administration (VA). They surveyed all of the 138 VA medical centers on the availability of MDTs for discussion of patients diagnosed in 2001–2004. The study inferred that the mere existence of tumor boards did not correlate with improvement in survival outcome measures.¹⁶ There was also little association between the MDTs and measures of utilization and quality of care. While several limitations of this study were emphasized after its publication, the authors stated their research did not imply that tumor boards had no benefits. Furthermore, it was suggested that tumor boards might provide limited benefit when performance is assessed using general measures of guideline-recommended care, but may be helpful to more complex patients. It also may be necessary for centers with limited resources and a low volume of physicians. Extensive debates since then have contemplated changing the tumor board conduct and improving measures of structure, process, and outcomes of tumor boards.¹⁷ A limitation of our study is that it did not allow for follow-up on the implementation of recommendations or assess survival metrics for patients. In addition, the majority of patients returned to their local facilities for treatment and detailed follow-up is not available. On the other hand, a strength of our tumor board is that there was representation from lower volume centers (17% of the cases presented were from outside MCR).

Process adherence measures are designed to predict future outcomes after the application of the process. The association between process adherence and better outcomes is yet to be proven in oncologic settings. Data remain scarce on actual adherence of the recommendations from the MDTs and its impact on outcomes. One study suggested that MDT consensus may be perceived as a validation of management plan even if no changes are made.²⁹ While we did not assess whether or not the recommendations made during MDTs were implemented or not, feedback on the conduct of our MDT meetings was obtained and changes were implemented. Participants in the online survey consistently reported the incorporation of evidence-based guidelines, significant improvement in knowledge of the most updated treatment strategies, change in treatment plans due to discussion in MDTs improved and efficient communication between clinicians, increased clinical trial participation evaluations and improved professional relationships between all team members (Figure 4).

CONCLUSION

In conclusion, our study assessed a selected group of real-time suspected or established lymphoma cases from multiple sites over four and one-half years, and noted new recommendations made in 45% of the cases presented. A multidisciplinary lymphoma tumor board approach was of value and substantially enhanced interdisciplinary interactions and education at multiple levels of clinical care. Lower volume centers benefitted from re-review of diagnosis and radiologic data, along with recommendations on most complex and rare diagnoses, and discussion of emerging data. Cost and time-effectiveness of MDTs are issues which may be overcome by selecting particularly controversial and complex cases for discussion rather than all new diagnoses as in our study. Future directions consist of appraising the impact of our MDT on patient outcomes, quality of life and experience, and process adherence.

Abbreviations and Acronyms:

MDTs

Multidisciplinary teams

MCR

Mayo Clinic, Rochester, MN

MCCN

Mayo Clinic Care Network

DLBCL

diffuse large B-cell lymphoma

FL

follicular lymphoma

CME

Continuous Medical Education