Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with R-CHOP and the impact of an end-of-treatment (EOT) FDG-PET scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent R-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP +RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT - 78% in RT era, 28% in PET era. The 5-year time to progression (TTP) and OS for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D) scored PET scans (n=103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3,DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, p=0.0002). Outcomes for R-CHOP treated PMBCL patients treated with R-CHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.

Consolidative radiation therapy (RT) for advanced-stage diffuse large B-cell lymphoma (DLBCL) remains controversial with routine practice continuing to include RT in patients with initial bulky disease or residual masses. PET-CT is a sensitive modality for detecting the presence of residual disease at end-of-treatment (EOT). A PET-guided approach to selectively administer RT has been policy in BC since 2005. Patients with advanced-stage DLBCL diagnosed between January 2005 - March 2017 treated with at least 6 cycles of R-CHOP that underwent EOT-PET were included in this analysis. Those with complete metabolic response (PET-NEG) were observed; those with PET-positive scans (PET-POS) were offered consolidative RT, when feasible. 723 patients were identified with median follow-up of 4.3 years: 517 (72%) were PET-NEG; 206 (28%) were PET-POS. Time-to-progression (TTP) and overall survival (OS) at 3 years were 83% v 56% and 87% v 64%, for PET-NEG and PET-POS patients, respectively. Non-progressing PET-POS patients treated with consolidative RT (109/206, 53%) had outcomes approaching those of PET-NEG patients, with 3-year estimates of 76% and 80% for TTP and OS. PET-NEG patients with bulky disease (≥10 cm) at diagnosis, had outcomes indistinguishable from those without bulk, despite omitting RT. These data suggest that patients with advanced-stage DLBCL that are PET-NEG at EOT and receive no RT have excellent outcomes. FDG-PET can reliably guide selective administration of consolidative RT, even for patients with initially bulky disease.

ObjectivesThis study sought to establish by expert review a consensus‐based, focused ultrasound curriculum, consisting of a foundational set of focused ultrasound skills that all Canadian medical students would be expected to attain at the end of the medical school program.MethodsAn expert panel of 21 point‐of‐care ultrasound and educational leaders representing 15 of 17 (88%) Canadian medical schools was formed and participated in a modified Delphi consensus method. Experts anonymously rated 195 curricular elements on their appropriateness to include in a medical school curriculum using a 5‐point Likert scale. The group defined consensus as 70% or more experts agreeing to include or exclude an element. We determined a priori that no more than 3 rounds of voting would be performed.ResultsOf the 195 curricular elements considered in the first round of voting, the group reached consensus to include 78 and exclude 24. In the second round, consensus was reached to include 4 and exclude 63 elements. In our final round, with 1 additional item added to the survey, the group reached consensus to include an additional 3 and exclude 8 elements. A total of 85 curricular elements reached consensus to be included, with 95 to be excluded. Sixteen elements did not reach consensus to be included or excluded.ConclusionsBy expert opinion‐based consensus, the Canadian Ultrasound Consensus for Undergraduate Medical Education Group recommends that 85 curricular elements be considered for inclusion for teaching in the Canadian medical school focused ultrasound curricula.

Background: Treatment practices for patients with limited-stage DLBCL are varied and include combined-modality treatment (3 cycles immunochemotherapy + radiation therapy) or immunochemotherapy alone. Since 2005, patients (pts) in BC with limited-stage DLBCL (stage I/II, no B-symptoms, mass < 10cm) have been treated according to a PET-guided algorithm. Following 3 cycles of R-CHOP, pts undergo FDG-PET/CT scan; PET-negative pts receive one additional cycle of R-CHOP, while PET-positive pts receive involved-site radiation therapy (RT). We present long-term follow-up of this population-based experience. Methods: Using the BC Cancer Lymphoid Cancer Database we identified all pts who were diagnosed with limited-stage DLBCL from Mar 2005 to February 2019 and underwent a PET/CT after 3 cycles of curative-intent R-CHOP, in keeping with the PET-guided policy. Pts with primary CNS, primary testicular, PMBCL, PTLD, and transformed/discordant/composite lymphoma were excluded. Pts with evidence of progressive disease prior to or on mid-treatment PET/CT were also excluded. All PET/CT scans were performed and reviewed centrally. Prior to 2014, interpretation was based on the International Harmonization Project (IHP) criteria, and subsequently according to Deauville criteria. Importantly, uptake greater than the mediastinal blood pool was consistently used to determine PET-positivity (ie. PET-positive by IHP, or D3-5 by Deauville). Results: Clinical characteristics of the 319 pts identified are as follows: median age, 68 y (range 19-92); 48%, male; 59%, stage I; 41%, stage II; 8%, PS>1; 13%, elevated LDH; 52%, at least 1 extranodal site; 37%, mass size ≥ 5cm. Stage-modified IPI risk score: 19%, 0; 45%, 1; 27%, 2; 9%, 3-4. Median follow-up is 6.25 yrs (range 0.42-14.25). After 3 cycles of R-CHOP: 254 pts (80%) were PET-negative; 59 pts (18%) were PET-positive; and 6 pts (2%) were considered PET-indeterminate (by IHP). Elevated serum LDH (p<0.001), mass size ≥ 5cm (p=0.008) and stage-adjusted IPI (p=0.025) were predictive of PET-positive status. Of the 254 PET-negative pts, 234 (92%) completed treatment with one additional cycle of R-CHOP, 7 (3%) stopped treatment after 3 cycles R-CHOP and 13 (5%) received RT due to poor chemotherapy tolerance or physician choice. 21/254 PET-negative pts have relapsed and 2/254 died of treatment-related toxicity. 8/21 (38%) PET-negative relapses were late, occurring more than 4 years post initial diagnosis. 55/59 (93%) PET-positive pts received RT, 2 pts refused RT and received only 3 cycles R-CHOP, and 2 pts received 1 additional cycle of R-CHOP alone due to physician preference. 13/59 PET-positive pts have relapsed, only 2/13 (15%) relapses were late >4 years from diagnosis. Of the 6 PET-indeterminate patients, 2 received RT and 3/6 have relapsed. Overall 5-year time-to-progression (TTP) censoring deaths from unrelated causes is 89% (92% for PET-negative and 80% for PET-positive pts). Overall 5-year PFS is 84% (88% for PET-negative and 74% for PET-positive pts) and 5-year OS is 87% (90% for PET-negative and 77% for PET-positive pts). On univariate analysis, age>60, PS>1, stage-modified IPI, and PET status were significant predictors of TTP. On multivariate analysis controlling for age>60, stage, PS, LDH, presence of extranodal involvement, mass size ≥ 5cm, and PET status, only age (p=0.002) and PET status (p=0.004) remained independent predictors of TTP. Conclusion: Using a PET-guided approach to treatment, the majority of patients with limited-stage DLBCL have negative PET scans after 3 cycles of R-CHOP. Patients with negative PET scans have an excellent outcome when treated with 4 cycles of R-CHOP alone, without exposure to radiation. Patients with a positive PET scan who complete treatment with radiation therapy have a slightly less favorable outcome, and may be appropriate for alternative approaches. A detailed analysis of patterns of relapse, as well as efforts to identify clinical factors, PET parameters and biomarkers associated with poor outcome and delayed relapse are ongoing. Figure Disclosures Sehn: Acerta: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; TG Therapeutics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; TEVA Pharmaceuticals Industries: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria; Janssen-Ortho: Honoraria; Janssen-Ortho: Honoraria; Merck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; F. Hoffmann-La Roche/Genentech: Consultancy, Honoraria, Research Funding; Acerta: Consultancy, Honoraria. Scott:NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding; Roche/Genentech: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy. Gerrie:Lundbeck, Seattle Genetics: Consultancy, Honoraria. Freeman:Seattle Genetics, Janssen, Amgen, Celgene, Abbvie: Consultancy, Honoraria. Pickles:TarSera: Honoraria, Other: Participated in advisory board meeting; Abbvie, Sanofi: Consultancy, Honoraria; Astellas Inc.: Research Funding. Savage:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding; BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria.

Abstract:The abscopal effect is a rare phenomenon in the setting of radiation therapy (RT) for metastatic cancer where tumor regression occurs distant from the site of treatment. A proposed mechanism of the abscopal effect is the activation of a systemic antitumor immune response by localized RT. We report the first case, to our knowledge, of the abscopal effect in squamous carcinoma of the anal canal with metastases to pelvic lymph nodes, liver and bone. After palliative RT to the pelvis with sensitizing chemotherapy, complete response was observed not only in the primary tumor but also in bone and multiple liver metastases at 4 months after treatment, an effect that remained durable at 4-year follow-up. Understanding of the abscopal effect and the immune mechanisms associated with anal cancer may lead to new avenues of research to improve outcome for patients with this rare disease.