esmo consensus conference: interactive session on colorectal cancer guidelines a clinical case...
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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)
Alexander SteinUniversity Cancer Center Hamburg, Germany
Disclosure
• Honoraria from Roche and Merck
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/osteolytic
(left os ileum) – thickening of colonic wall (descendens)
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
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].
1. start pure palliative chemotherapy for metastatic disease
2. discuss patient within MDT according to clinical presentation and determine treatment aim and clinical grouping
Acc. to ESMO guidelines next step should be ...
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].
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
whichmight become resectable after induction chemotherapy±limited/localized metastases to other sites, e.g. locoregional lymphnodesphysically able to undergo major surgery (biological age, heart/lung condition)
maximum tumour shrinkage
upfront most active combination regimen
2 multiple metastases/sites, with
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 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 1+2)
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 osingle agent, or odoublet with low toxicityexceptional triplets
Clinical groups for first line treatment stratification
Clinical course
• Patient was considered potentially curative (group 1) by MDT despite the unclear single bone lesion.
Acc. to ESMO guidelines primary tumor should be managed by ...
1. resection of primary tumor before chemotherapy2. 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
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].
6 months postop FOLFOX
3 months postop FOLFOX
synchronous metastatic colon cancer with intact primary
unresectable metastases
3 months preop FOLFOX
R0/R1 resectable metastases
yes no
surgery of primary: individual decision (e.g. complications or
emergency)
intensive upfront chemotherapy
continue initial treatment for a
total of 6 months
yes no
continue chemotherapy
resectability achieved?
resectability achieved?
resection of primary and metastases (simultaneous or delayed)
single, <2cmliver met
Treatment algorithm for synchronous metastatic colon cancer
• 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
Clinical course
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.
Further management?
1. maintenance (5FU/Cape and/or bevacizumab)2. complete stop of treatment3. consider locally ablative procedure
• 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].
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)
Acc. to ESMO guidelines further treatment should be ...
1. restart FOLFOX + bevacizumab2. change to irinotecan based second line (FOLFIRI +/-
targeted agent)
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)
Further treatment?
1. FOLFIRI + panitumumab2. FOLFIRI/irinotecan + cetuximab3. FOLFIRI + bevacizumab (beyond progression - TML)4. FOLFIRI5. single agent EGFR antibody
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
Thank you