ASCO GI 2018 Rectal Cancer Poster Review Filippo Pietrantonio INT Milan

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1 ASCO GI 2018 Rectal Cancer Poster Review Filippo Pietrantonio INT Milan Rome, 16 February 18

2 AGENDA rectal cancer data - Staging - Prognostic Factors - Management strategies

3 Staging AJCC 7 edition staging: internal iliac nodes III Common/external iliac nodes IV Clinical practice: internal and external/common iliac nodes uniform RT approach Prospective trials to standardize patients management Jehan Yahya et al

4 Staging Facility-level variations & rates of use of neoadjuvant therapy: 13% patient factors 30% inappropriate or missed use of pelvic MRI and EUS in preoperative staging Unadjusted rates and adjusted associations of clinical stage, neoadjuvant therapy, adjusted facility clinical staging rates and adjusted facility neoadjuvant therapy rates with positive margins and overall survival Better staging correlates with better patients outcome Douglas S. Swords et al

5 AGENDA rectal cancer data - Staging - Prognostic Factors - Management strategies

6 Systemic Inflammation White Blood Cell (WBC) ratio: Nadir WBC count/pre-crt WBC count Low WBC ratio n=641 Better tumor response to preoperative chemoradiotherapy 0.49 cut-off Improved recurrence-free survival in locally advanced rectal cancer Joo Hwan Lee et al

7 Systemic Inflammation n=50 LMR: lymphocyte-to-monocyte ratio NLR: neutrophil-to-lymphocyte ratio Recent study LMR, NLR highly prognostic for locally advanced rectal cancer high LMR: improved OS after short course neoadjuvant scrt + CT vs standard CRT LMR and NLR: significant intra-patient variability, especially if outside of range Cieszymierz Gawinski et al

8 Systemic Inflammation SIR: Systemic Inflammatory Response measured by scores and ratios of NLR (neutrophil/lymphocytes) PLR (platelets/lymphocytes) LMR (lymphocytes/monocytes) CAR (CRP/albumin) NPS (neutrophil Platelet Score) mgps (modified Glasgow Prognostic Score) n=393 SIR: prognostic value NPS, mgps, CAR: prognostic value independently of TNM stage Which is the functional meaning? Russ D. Dolan et al

9 Molecular Prognostic Factors n=260 Consensus molecular subtypes (CMS)/phenotypic subtypes are associated with local recurrence after rectal cancer surgery Stromal (CMS4) T4 serosal involvement R1 Selection of patients for neoadjuvant/intensified treatment Katrina Knight et al

10 Molecular Prognostic Factors Neoadjuvant chemoradiotherapy in locally advanced rectal cancer: 45% tumor downstaging 13% pathological complete response N=10 versus N=13 Unmet need for prognostic/predictive factors Next-generation expression analysis: TRG0 and TRG1-3 have different gene signatures Prospective validation needed Annalisa Milano et al

11 Molecular Prognostic Factors Is MSI-high a prognostic and/or predictive biomarker? MSI vs MSS in Locally Advanced Rectal Cancer (n=5448) NAR score: similar distribution ypcr rate: 9,9% vs 9,3% 3-y OS: 84 vs 83% No support for use of MSI status as a LARC-specific biomarker RM Shulman et al

12 Molecular Prognostic Factors Mucosal Microbiota Composition is associated with clinical features Treponema: pcr to neoadjuvant CRT Campylobacter: > chemoresistance Fusobacterium/Parvimonas: worse clinical tumor stage Streptococcus: Older age at diagnosis Prosepctive validation needed Michael S. Lee et al

13 AGENDA rectal cancer data - Staging - Prognostic Factors - Management strategies

14 TNT: total neoadjuvant therapy 82 patients with stage II/III rectal cancer CRT long course mfolfox6 x4 alongside RT mfolfox6 x4 TME Results: pcr in patients receiving full neoadjuvant regimen was 37.8% when compared to 30% in patients receiving <8 cycles of mfolfox6. Higher pcr for tumors located within 5 cm from the anal verge (46.7%). Deng Y et al

15 TNT: total neoadjuvant therapy 21 patients with stage II/III rectal cancer receiving TNT retrospectively reviewed TNT allows high rate of pcr (38%) without delays of surgery or toxicity worsening Pathologic response Friedrich T et al

16 Overall survival Disease specific survival Adjuvant treatment after preoperative CRT and surgery Retrospective study (n=649): CRT surgery adjuvant CT Adequate adjuvant treatment: 4 months of post operative CT Benefit in OS and DFS only for adequate treatment No benefit in multiagent vs single agent chemotherapy Daphna Y. Spiegel et al

17 Locally advanced rectal cancer with distant metastases Potentially resectable group n=105 Unresectable group Short course RT (SCRT) 5 Gy x 5 fractions Systemic chemotherapy Upfront SCRT followed by systemic chemotherapy in LAD + mrc is Feasible Effective: objective response rate, bridge to surgery and potential avoidance of palliative stoma Surgery of T Akhil Kapoor et al

18 Proton beam therapy for local relapses n=23 Proton Beam therapy is effective for local relapses of rectal cancer with manageable adverse events Therapeutic option for patients unsuitable for or declining surgery Ogi Y. et al

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