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ESMO Preceptorship on Colorectal Cancer 2018

18-19 May 2018. Valencia, Spain

Co-Chairs:

Andrés CERVANTES (Spain) Dirk ARNOLD (Portugal)

Summary and highlights by Dr. Med. Mac RAMOS

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Friday, 18 May 2018 Session 1: Early colorectal cancer. Chair: Robert Glynne Jones (UK) Frédéric Bibeau (FR): The point of view of the pathologist

o Quality and Rules of a good pathology report o Histo-prognostic factors: Number of lymph nodes, neural/lymphatic invasion,

lymphocytic infiltration, MSH expression

Morphological and molecular level analyses (Grading, MSI status, serosa involvement, immuno microenvironment, tumor deposits, distant extension (Venous invasion, Perineural invasion), margins, molecular profile (MSI, KRAS, BRAF), liquid biopsy (ctDNA)) may have prognostic and predictive impact (DFS, OS).

Regina Beets-Tan (NL): Optimal loco regional staging for rectal cancer

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o Detailled MRI (better, rather than CT) identify mesorectal fascia tumor involvement with

aceptable both, sensitivity and specificity, allow radiotherapist, surgeon and oncologist to plan therapeutic strategy and re- staging.

o Integrated Diffusion Imaging (DWI) before Endoscopy allowes 8 weeks after Chemoradiotherapy better assessment (for complete response or residual tumor).

Eduardo Garcia Granero (SP) - State of the art: Standard of surgical practice for resectable colorectal cancer (special issues on rectal cancer, laparoscopy, transanal TNME and robotic-assisted surgery)

o Anterior Resection or (in lower third Rectum Cancer) Abdomino Perineal Escision, may let achieve short term (prevent complications, good pathological outcomes) and long term (Hr QoL, Local Recurrence, DFS, OS) outcomes.

o Open mesorectal excision vs. Laparoscopic interventions or robotic assisted surgery show similar clinical outcomes.

o Transanal Total Mesorectal Excision needs adequate patient selection and surgeon training.

Robert Glynne Jones (UK) - State of the art: Standard(s) of care in the pre-operative treatment for rectal cancer

ESMO Guidelines standard of care stickst o a risk adaptative strategy

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Andrés Cervantes (SP) – The role of chemotherapy of localized rectal cancer

o In advanced loco regional, MRI high risk staged, Rectal Cancer, chemo (radio) therapy impact survival outcome.

o Neoadjuvant score may impact, as surrogate parameter, the final outcome. Session 2: Metastatic colorectal cancer, liver limited metastases. Chair: Andrés Cervantes (SP) Chiara Cremolini (IT) - Review of the ESMO consensus conference on metastatic colorectal cancer – Basic strategies and groups (RASwt/mut, BRAF mut) – Chemotherapy and targeted agents in 1st line

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o Drivers of 1st Line Choice are patient clinical (PS), treatment (intention: cytoreduction or disease stabilization), tumor (molecular: KRAS, BRAF, sidedness, MSI high) characteristics.

o For early, marginally and potentially resectable tumors, the treatment aim should be the cure.

o Based on presence of prognostic factors, an (oxaliplatin based doublet) peri operative approach may be chosen.

o Through surgical, loco regional and systemic approaches, nowadays, previous never resectable may become technically (potentially) resectable tumors.

Dirk Arnold (PT) – Oligometastatic colorectal cancer: what to know about and how to treat it

Treatment may be selected from a ‘toolbox’ of procedures according to localisation, treatment goal (‘the more curative, the more surgery’/ higher importance of local/complete control), treatment-related morbidity, local expertise and availability, and patient-related factors such as comorbidity/ies and age.

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Session 3: Adjuvant settings of colorectal cancer. Chair: Dirk Arnold (PT) Frédéric Bilbeau (FR) – RAS, BRAF: Microsatellite instability and other molecular markers- how useful are they? Pitfalls in diagnostic?

In daily oncologic practice: CIN (conventional cancers) RAS mutation (predictive factor) pathway, CIMP (serrated and elderly cancer) prognostic factor pathway and MSI pathway may be useful biomarkers.

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Michel Ducreux (FR) – Adjuvant treatment for colon cancer II and III

o Adjuvant chemotherapy is indicated for stage III (N+) FOLFOX / CapeOx o Capecitabine or (inf.) FU/LV as an option for some patients FOLFOX/CapeOx for

patients < 70y, use with caution for pts > 70y. o Antibodies (EGFR, VEGF) are not indicated. o The decision for an adjuvant treatment should balance the risk of cancer mortality and

that of comorbidities. Demetris Papamichael (CY) – Adjuvant treatment for elderly patients: how to address it

o 40% CRC patients are Stadium III. 40% CRC patients are ≥ 75 y.

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o Sociodemographic, clinical, research (under- representation) characteristics of older

than 75 y CRC patients influence Safety and Efficacy of treatment. Session 4: Metastatic colorectal cancer. Special clinical situations. Chair: Andrés Cervantes (SP) Luis Sabater (SP) – How to integrate surgery in the treatment of patients with liver- only metastatic disease

o After pre- operative evaluation and imaging, surgical eligibility (resectable, fit) patient, open or laparoscopic (less complications, faster) approaches are available.

o Radiofrequency ablation or Chemoembolisation and 2 step hepatectomy (associated liver partition and vein ligation for staged hepatectomy) are rather suitable for unresctable M1 CRC patients.

Demetris Papamichael (CY) – How to deal with elderly patients or individual with comorbidities

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o G8 EORTC Geriatric assessment (functional (autonomy, cognition), psychological,

comorbidities, nutrition) may allow identify areas of vulnerability and predict survival.

o Overall Utility evaluation for CRC patients becomes relevant. Luis Sabater (SP) – How to deal with synchronous primary and liver metastases

Simultaneous liver metastasis and primary bowel Surgery (trend) or sequential bowel first or sequential liver first (always Neoadjuvant chemotherapy) considering advantages and disadvantages show similar efficacy and safety results.

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Michel Ducreux (FR) – How to deal with patients with isolated peritoneal metastases

The increased effectiveness of systemic chemotherapy (in combination with targeted chemotherapy) has improved the survival of patients with peritoneal metastases from colorectal cancer.

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Saturday, 19 May 2018 Session 5: Metastatic colorectal cancer. Maintenance and further lines. Chair: Dirk Arnold (PT) Dirk Arnold (PT) – The role of maintenance treatment, appropriate endpoints according to ESMO consensus

o After 6-8 weeks FOLFOX or CAPOX induction, maintenance should be considered.

o Patients with FOLFIRI induction, maintanence should continue as long as shrinkage is present.

Dirk Arnold (PT) – What to do after 1st line failure

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o 75% of patients entering 3. Line have PS 0-1 and Tumor Burden after 1. and 2. Line success is evident

o 3rd and 4th Line treatment with new agents (TAS-102 or Regorafenib) before Reintroduction or Rechallenge should be considered.

o In further later lines, Best Supportive Care is still an option. Michel Ducreux (FR) – Management of treatment related side-effects: GI toxicity, Neuropathy, skin toxicity, hypertension, hand-foot syndrome

Management of chemotherapy: • Neutropenia (Stop the 5-FU bolus first, then hematological growth factors or decrease of doses) • Thrombocypenia (Decrease of doses) • Mucositis (Decrease of doses) • Diarrhea (High dose of loperamide)

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Special Lecture: Immunotherapy in gastrointestinal cancer. Chair: Dirk Arnold (PT) Elizabeth Smyth (UK) – Immunotherapy in gastrointestinal cancer

o At this time, checkpoint blockade with PD-1 or anti-PD-L1 either alone or in combination

with anti-CTLA4 therapy has demonstrated the most promise for patients with gastroesophageal cancer.

o Integration of these therapies with currently used treatments such as chemotherapy and monoclonal anti-bodies such as trastuzumab and ramucirumab is yet to be optimized

Session 6: Anal canal tumours. Chair: Robert Glynne Jones (UK) Robert Glynne Jones (UK) – Standard of care for anal canal squamous carcinomas

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o Primary chemoradiotherapy is the standard treatment in anal squamous cell carcinoma

(ASCC).

o Radiotherapy dose escalation/de-escalation strategies are currently investigated in ASCC.

o HPV infection (70–90% of patients with ASCC are human papilloma virus (HPV) positive) renders ASCC more immunogenic and immunotherapies hold great promise in primary and metastatic ASCC.

o Biomarkers and modern imaging methods are needed for personalized treatment. ESMO Preceptorship on Colorectal Cancer. Valencia, Spain. 18th May - 19th May 2018. http://www.esmo.org/Conferences/Preceptorship-Courses/ESMO-Preceptorship-on-Colorectal-Cancer-2018-Valencia http://www.esmo.org/content/download/126475/2389184/file/ESMO-Preceptorship-on-Colorectal-Cancer-Valencia-2018-Programme.pdf

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Feedback from attendee 4 oncologists from Switzerland had the possibility to attend this ESMO Preceptorship on Colorectal cancer. Feedback from Dr. med. Elisabeth Schmidt-Weiss (University Hospital Zürich): Content

• Very nice overview over the whole topic of CRC (adjuvant & metastatic) • Good level

Organization

• Perfect organization (travel, flight, transfer to hotel, hotel room, food…) • Very nice hotel (beautiful rooms & sight) • Congress in same hotel as room (saved time for transfer…)

Suggestion(s) to improve the future CRC Preceptorship

• Leave more time for case discussions, this is where we learn most • Time management of speakers can be optimized (less is more) • Power point slides were often “overloaded” (less is more) • It would be good to have the slides at the time of presentation (not 2 weeks later) to be

able to better listen to the speaker & not be occupied with taking photos of the slides (because of not being sure if they really share them later…)