ESMO Consensus Conference: Interactive Session on Colorectal Cancer Guidelines A clinical case presentation on advanced colon cancer (first and second line therapy) - PowerPoint PPT Presentation

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ESMO Consensus Conference: Interactive Session on Colorectal Cancer Guidelines A clinical case presentation on advanced colon cancer (first and second line therapy)

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Title: ESMO Consensus Conference: Interactive Session on Colorectal Cancer Guidelines A clinical case presentation on advanced colon cancer (first and second line therapy)


1
ESMO Consensus Conference Interactive Session on
Colorectal Cancer GuidelinesA clinical case
presentation on advanced colon cancer (first and
second line therapy)
  • Alexander Stein
  • University Cancer Center Hamburg, Germany

2
Disclosure
  • Honoraria from Roche and Merck

3
Case presentation
  • male, 64 years of age, ECOG 0
  • no relevant comorbidity
  • routine abdominal ultrasound revealed suspicious
    liver lesions
  • CT chest/abdomen
  • 3 liver lesions up to 2.5cm
  • 3 suspicious pulmonary lesions up to 1cm
  • single bone lesion 1.8cm mixed osteoplastic/osteol
    ytic (left os ileum)
  • thickening of colonic wall (descendens)

4
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5
Case presentation
  • colonoscopy non obstructive tumor without
    bleeding signs colon descendens
  • histology adenocarcinoma
  • CEA value 245 ng/ml
  • ?colon carcinoma with synchronous liver and lung
    metastates and potential bone involvement

6
Further diagnostics
  • PET scan ? liver and lung lesions positive, bone
    lesion negative
  • bone scan ? weakly positive
  • determination of KRAS status ? wildtype

ESMO consensus guidelines for management of
patients with colon and rectal cancer 2012. KRAS
mutation precludes efficacy of treatment with
anti-EGFR antibodies and KRAS status
determination is therefore mandatory before
treatment I, A.
7
Acc. to ESMO guidelines next step should be ...
  1. start pure palliative chemotherapy for
    metastatic disease
  2. discuss patient within MDT according to clinical
    presentation and determine treatment aim and
    clinical grouping

8
Definition of treatment strategy
The optimal strategy should be developed
according to the characteristics of the patient
and be discussed in the multidisciplinary team
and should incorporate the (potential) view of
the patient as well. Patients can be
individually divided into the 4 clinical groups,
by parameters describing localization, extent,
and resectability of the disease, tumour
dynamics, co-morbidity, potential of the patient
to tolerate chemotherapy and secondary surgical
treatment IV, B.
9
Clinical groups for first line treatment
stratification
group clinical presentation treatment aim treatment intensity
0 clearly R0-resectable liver and/or lung metastases cure, decrease risk of relapse nothing or moderate (FOLFOX)
1 liver and/or lung metastases only liver and/or lung metastases only liver and/or lung metastases only
1 which might become resectable after induction chemotherapy limited/localized metastases to other sites, e.g. locoregional lymphnodes physically able to undergo major surgery (biological age, heart/lung condition) maximum tumour shrinkage upfront most active combination regimen
2 multiple metastases/sites, with multiple metastases/sites, with multiple metastases/sites, with
2 rapid progression and/or tumour-related symptoms/risk of rapid deterioration co-morbidity allows intensive treatment clinically relevant tumour shrinkage as soon as possible at least achieve control of progressive disease upfront active combination at least doublet
3 multiple metastases/sites, with multiple metastases/sites, with multiple metastases/sites, with
3 never option for resection and/or no major symptoms or risk of rapid deterioration and/or severe comorbidity (excluding from later surgery and/or intensive systemic treatment, as for groups 12) abrogation of further progression tumour shrinkage less relevant low toxicity most relevant treatment selection according to disease characteristics and patients preference re toxicity and efficacy watchful waiting sequential approach start with single agent, or doublet with low toxicity exceptional triplets
10
Clinical course
  • Patient was considered potentially curative
    (group 1) by MDT despite the unclear single bone
    lesion.

11
Acc. to ESMO guidelines primary tumor should be
managed by ...
  1. resection of primary tumor before chemotherapy
  2. upfront chemotherapy and delayed resection in
    case of major response (but still unresectable
    mets)
  3. upfront chemotherapy and resection only in case
    of local symptoms

12
Clinical course
  • primary tumor was left in situ

Potentially resectable metastatic disease after
chemotherapy (group 1) For initially unresectable
metastatic disease, most active available
induction treatment should be chosen V, C. If
metastases become resectable surgery for primary
and metastases should be performed. Palliative
surgery, stenting, laser ablation, or
(chemo)radiation in case of unresectable disease,
even after systemic treatment should be confined
to bleeding or obstruction and as minimal
invasive as possible and non invasive measures
applied first V, C.
13
Treatment algorithm for synchronous metastatic
colon cancer
synchronous metastatic colon cancer with intact
primary
unresectable metastases
R0/R1 resectable metastases
3 months preop FOLFOX
intensive upfront chemotherapy
single, lt2cm liver met
resectability achieved?
yes
no
resection of primary and metastases (simultaneous
or delayed)
continue chemotherapy
resectability achieved?
6 months postop FOLFOX
3 months postop FOLFOX
continue initial treatment for a total of 6 months
yes
no
surgery of primary individual decision (e.g.
complications or emergency)
14
Clinical course
  • FOLFOX bevacizumab
  • restaging after 2/4 months partial response
    (RECIST)
  • restaging after 6 months (PET/CT)
  • liver mets one remaining with 1.4cm (PET
    positive)
  • lung lesions complete response
  • bone lesion unchanged
  • colonoscopy witout macroscopic evidence of
    residual primary tumor, biopsy negative (local
    CR)
  • decreased tolerability with peripheral neuropathy
    G2 and asthenia G1

15
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16
Clinical course
  • ? major response liver and complete response
    lung-metastases and primary tumor
  • Decision was made by MDT to classify the patient
    as potentially curative based on age, ECOG, major
    response and unchanged bone lesion. However,
    resection or RFA of remaining central liver met.
    seemed technically difficult.

17
Further management?
  1. maintenance (5FU/Cape and/or bevacizumab)
  2. complete stop of treatment
  3. consider locally ablative procedure

18
  • helical tomotherapy with 10x 4Gy for liver
    metastasis and as a precaution for the bone
    lesion
  • followed by complete stop of treatment

If metastases are not resectable due to their
location additional measures like radiofrequency
ablation or stereotactic body radiotherapy (in
specialized institutions) should be considered,
although the benefit is not formally proven III,
B.
19
Clinical course
  • no evidence of disease for 10 months, followed by
    progressive disease with 4 new liver and
    disseminated pulmonary lesions, single bone
    lesion unchanged
  • remaining toxicity PNP G1 (12 months after last
    oxaliplatin administration)

20
Acc. to ESMO guidelines further treatment should
be ...
  1. restart FOLFOX bevacizumab
  2. change to irinotecan based second line (FOLFIRI
    /- targeted agent)

21
Reinduction
  • reinduction FOLFOX bevacizumab

In first line treatment patients should be
treated as long as possible by restart of the
former first line regimen (reinduction), when the
toxicity (especially neurotoxicity) allows such
reinduction.
  • restaging after 2 months stable disease
  • restaging after 4 months progressive disease
    (multiple new liver lesions)

22
Further treatment?
  1. FOLFIRI panitumumab
  2. FOLFIRI/irinotecan cetuximab
  3. FOLFIRI bevacizumab (beyond progression - TML)
  4. FOLFIRI
  5. single agent EGFR antibody

23
Course of second line
  • FOLFIRI panitumumab
  • restaging after 3 months stable disease (SLD
    -25), dose reduction FOLFIRI 80 due to
    neutropenia
  • restaging after 6 months partial response (SLD
    -8)
  • side effects asthenia G2, cutaneous tox. G1

24
Thank you
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