presentation of three challenging clinical cases and faculty … · 2018. 5. 31. · –1st stage...

ESMO Preceptorship Programme

Presentation of three challenging clinical cases

and Faculty discussion

Andrés Cervantes

Colorectal Cancer– Valencia – 18 & 19 May 2018

ESMO PRECEPTORSHIP PROGRAMME

CLINICAL CASE 1

63 years old male

Personal history: Good controlled diabetes mellitus

and hypertension. Verruciform epidermodysplasia.

Symptoms: Diarrhea and rectal bleeding

PS 1. No physical alterations. DRE: no palpable

tumor


Diagnosis

Complete colonoscopy: Tumor mass at 20 cm

from anal margin.

Biopsy: Moderately differenciated adenocarcinoma

CT scan: No metastasis

CEA 8.1 ng/mL


Treatment and evolution

Low anterior resection on November 2014.

Pathological report:

Rectosigmoid adenocarcinoma that invades through the

subserosa (pT3), G2, LVI +.

Metastasis in 3 of 10 assessed lymph nodes (pNx).

R0 resection.

Stage IIIB

Adjuvant chemotherapy: CAPOX (8 cycles)



May 2016 (DFS 18 months): CEA elevation (15 ng/mL)

CT scan



65 years old, liver only disease, ECOG 0

Lab tests: CEA 15,2 ng/dL. No other alterations

Molecular study: RAS wt, BRAF wt, MSS, Her 2 neg.

Left side primary tumor

Multidisciplinary team evaluation:Non resectable multiple and bilobar liver relapse

9

1. FOLFOX or FOLFIRI + anti-EGFRs

2. FOLFOXIRI + BEV

3. FOLFOX

4. Cape plus Bev

5. FOLFIRI or FOLFIRI +BEV

Your treatment plan:



✓ FOLFIRI-Cetuximab



FOLFIRI-Cetuximab

After 4 cycles: Partial response



5th cycle on August 30th

Multidisciplinary team evaluation:Resectable liver metastasis



21th October 2016:

– Bisegmentectomy liver sg II-III

– Metastasectomy of sg V, VII and VIII lesions

– Intraoperative radiofrecuency of sg V-VIII and sg IX metastasis


3 liver metastasis free margin resected.

Post-operative treatment: FOLFIRI-Cetuximab (6 cycles)



October 2017 (DFS 12 months):

CT scan



ECOG 0

Very good previous response to FOLFIRI-Cetuximab

Multidisciplinary team evaluation:Unresectable liver only relapse (vascular involvement)

17

1. FOLFOXIRI + BEV

2. FOLFOX BEV

3. Reintroduce FOLFIRI CETUXIMAB

4. Cape plus Bev





Retreatment FOLFIRI-Cetuximab

After 4 and 8 cycles: Partial response

….but persistent vascular involvement


CLINICAL CASE 2

69 years old male

Personal history: Arterial hypertension. Mitral valve

prolapse. No ischemic cardiomyopathy.

Oct-16: Rectal bleeding and G1 anorexia.

PS 1. No physical alterations. DRE: no palpable

tumor


Diagnosis

Complete colonoscopy: Vegetative mass at hepatic

colon (1) and ulcerated neoplasia at 10 cm from anal

verge (2).

Biopsies: Moderately differenciated adenocarcinoma

Rectal MRI: Polypoid tumor on the left posterior side

of the rectum, at 9 cm from the pectinate line. No

infiltration of the muscle layer (cT1). One

lymphadenopathy near the mesorectal fascia (cN1)


Diagnosis Rectal MRI:


Diagnosis

CT scan: Numerous low attenuation liver lesions compatible with metastasis. Nodules of small size in omental fat that do not allow to rule out peritoneal carcinomatosis. No lung metastasis.

Lab tests:

- CBC normal.

- Biochemistry: Normal liver and renal function.

ALP x 2 ULN.

- CEA 4.265 ng/mL


Diagnosis-CT scan 1


Diagnosis-CT scan 2


Diagnosis

Mutational status….. ¿where?

Double synchronous colorectal carcinoma (right and left side).

Stage IV (liver metastasis and suspected carcinomatosis)


Diagnosis

Mutational status….. ¿where?

LIVER BIOPSY

Double synchronous colorectal carcinoma (right and left side).

Stage IV (liver metastasis and suspected carcinomatosis)


Treatment decision

69 years old male with controlled comorbidities.

ECOG 1

Double synchronous adenocarcinoma (right and left)

stage IV.

High volume liver metastasis and ↑↑ CEA

Unknown mutational status


Treatment decision


Treatment decision

1st line of treatment:

– CT doublet: FOLFOX (1st cycle December 27th , 2016)

– Biological agent (according to mutational status…unk)


Treatment decision

1st line of treatment….after 3 cycles:

– CT doublet: FOLFOX (1st cycle December 27th , 2016)

– Biological agent: Cetuximab

Liver biopsy results: Metastatic adenocarcinoma with colonic origin.

RAS/RAF wt


Evolution 1st line of treatment: FOLFOX-Cetuximab

– Toxicities: Rash (G2) and neurotoxicity.

– Partial response after 8 cycles.

Initial CT scan After 8 cycles



– Toxicities: Rash (G2) and neurotoxicity (G1).

– Very good partial response after 8 cycles.

– ….but unresectable.



– After 12 cycles:


– Very good partial response.

.



– After 12 cycles:


– Very good partial response.

….but unresectable.



– After 12 cycles (June 2017):

– Very good partial response …..but unresectable.

– G2 Neurotoxicity

– Stop Oxaliplatin and continue 5FU-LV+ Cetuximab

.

CEA evolution


EvolutionMay 2018 : 1st line of treatment - PFS 18 months

➢31th cycle May 9th . CEA: 5 ng/dL

.


CLINICAL CASE 3

63 years old female

No comorbidities

Jan-13: Rectal bleeding and depositional rhytm

alteration.

PS 1. DRE: Tumoral mass at 5 cm.


Diagnosis

Complete colonoscopy: Excrecent tumor at 5 cm

from the anal verge, partialy stenosing, but allowing

colonoscope surpass (gigant polyp).

Biopsy: Moderately differenciated adenocarcinoma

Rigid rectoscopy and US: Fixed tumor at 5 cm that

invades through the muscularis propria, without

peritoneum involvement. No lymphadenopaties.

uT3 N0


Diagnosis

Rectal MRI: Neoplasia at 4 cm from the pectineal line on the

right lateral side, that invades the subserosa (less than 5 mm

beyond muscularis propria) cT3b. No EMVI or malignant

lymph nodes cN0. Mesorectal fascia not involved.


Diagnosis

CT scan:

- Multiple bilobar liver

metastasis up to 62x44

mm (sg VII-VI)

- Mesosigma implant

(26x17 mm)

- No lung metastasis


Diagnosis

➢ Lower third of rectum adenocarcinoma with liver

metastasis cT3b cN0 M1

Lab tests: CEA 68 ng/dL. LDH 1.5x ULN

Mutational status: KRASm

63 yo female without comorbidities

ECOG 1


Treatment decision


metastasis cT3b cN0 M1

Lab tests: CEA 68 ng/dL. LDH 1.5x ULN

Mutational status: KRASm

63 yo female without comorbidities

ECOG 1

✓ Liver only✓ KRASm✓ “Fit” patient


Treatment decision


metastasis cT3b cN0 M1✓ Liver only✓ KRASm✓ “Fit” patient



1st line of treatment: FOLFOXIRI (Feb-13)

After 4 cycles: Partial response

Toxicity: G3 neutropenia (no febrile)

After 10 cycles:



1st line of treatment: FOLFOXIRI (Feb-13)

Very good PARTIAL RESPONSE after 10 cycles.

Multidisciplinar approach

Treatment plan:

– Radiation therapy to complete local treatment (5x5 Gy)

– Two stages surgery:

• Primary tumor and left liver lobe (+ right liver embolization)

• Right hepatectomy



Two stages surgery:

– 1st stage (Aug 2013):

Ultra low anterior resection (TME)+ ileostomy +left love

metastasectomy + right portal embolization


- Rectum adenocarcinoma that invades into the subserosa (ypT3),

G2, LVI +. 22 non infiltrated lymph nodes (ypN0).Nearly complete

mesorrectal excision. R0 resection.

- 0.7 cm free margin liver metastasis.



Two stages surgery:

– Liver re-evaluation after 1st surgery:



Two stages surgery:

– 2nd stage (Nov 2013):

Right hepatectomy


- 4 intestinal origin liver metastasis

- Larger lesion (4.5 cm) reaches the resection border.



➢ Jan-14:

7 months without chemotherapy

Asymptomatic patient and completely recovered

CT scan (1st complete post-surgery evaluation):

– Milimetric bilateral pulmonary nodules compatible with metastasis

– No liver relapse


Treatment and evolution ➢ Jan-14: Multiple and small size asymptomatic lung progression

➢ April-15 (22 months without chemotherapy):

- Indolent growth of pulmonary M1- Ileostomy closure surgery: Nov.13th, 2014


Treatment and evolution ➢ April-15:

22 months without chemotherapy

Multiple bilateral lung progression. KRASm

ECOG 1.

FOLFOX-Bev


Treatment and evolution ✓ April-15: FOLFOX-Bev

1st cycle: April 15th

Partial response after 5 cycles

Stop oxaliplatin after 8 cycles (neurotoxicity)

5FU/LV-Bevacizumab maintenance.

➢ April-16 (PFS 12m- 8 m without Oxal): Pulmonary PD


Treatment and evolution ✓ April-15: FOLFOX-Bev

1st cycle: April 15th

Partial response after 5 cycles

Stop oxaliplatin after 8 cycles (neurotoxicity)

5FU/LV-Bevacizumab maintenance.

➢ April-16 (PFS 12m- 8 m without Oxal.): Pulmonary PD

Oxaliplatin reintroduction:

2nd cycle: Infusion reaction during oxaliplatin administration

(positive cutaneous sensibilization test)

Oxaliplatin administration with desensitizing regimen

After 7th cycle (July-16): Stop treatment (neurotoxicity).



➢ October-16 (PFS 6 m- 3 m without Ox.): Pulmonary PD


Treatment and evolution ➢ October-16 (PFS 6 m- 3 m without Ox.): Pulmonary PD

FOLFIRI treatment:

1st cycle October 31th

Toxicity: G1-2 diarrhea and no febrile neutropenia

Long radiological and clinical stability of the disease


Treatment and evolution ➢ October-16 (PFS 6 m- 3 m without Ox.): Pulmonary PD

FOLFIRI treatment:

1st cycle October 31th

Toxicity: G1-2 diarrhea and no febrile neutropenia

Long radiological and clinical stability of the disease

➢ September-17 (PFS 11 m-20 cycles): Pulmonary PD

✓ TAS-102 treatment:

1st cycle September 9th

Toxicity: No febrile neutropenia (G3-4)→ cycles delays and dose modif.

Stable disease after 2 cycles



➢ January -18:

4 complete cycles of TAS-102

Respiratory deterioration related with PD.

Stop TAS-102 and start BSC

† Exitus: 28th April 2018 (OS: 64 months)


Jan-13: Liver only KRASm rectal carcinoma: FOLFOXIRI

Aug-Nov 13: Two stages surgery

Apr-15: FOLFOX-Bev → Maint

Apr-16: Ox. Retreat.

Oct-16:FOLFIRI

OS 64 months

Sep-17:TAS-102

Jan-18:BSC

63

• Woman 33 years old.

• Pregnacy in the 17th week.

• Complains about rectal bleeding and

hypertransaminasemia.

• Abdominal-pelvic MRI: Multiple liver metastasis.

Thickening of sigma.

• CEA 82 ng/mL

• LDH 2450 IU/ml AlK Ph 285 IU/ml

• Colonoscopy: Tumor at 25 cm of anal margin.

BiopsyAdenocarcinoma. RAS/BRAF wt.

CLINICAL CASE

MARCH 2015

Abdominal CT-scan

65

1. Surgery for the primary followed by CT

2. FOLFOX or FOLFIRI + anti-EGFRs

3. FOLFOXIRI + BEV

4. Cape plus Bev



02/15

Diag.

Abortion

03/15

FOLFOXIRI-BEVA

08/15

8 cycles

PR(-50%)

Non resect.

->

FOLFIRI-

Beva.

Evolution and treatmentsDISEASE EVOLUTION AND

TREATMENT

MARCH 2015 AUGUST 2015

RESPONSE ASSESSMENT: PR

Evolution and treatments

02/15

Diag.

Abortion

03/15

FOLFOXI

RI-BEVA

08/15

8 cycles

PR(-50%)

Unresect.

->

FOLFIRI-

Beva.

01/16

6 cycles

PR maint.

Haematological

tox.

H. And F. Sind.

Diarreha.

03/16

10 cycles

PR maint.

->5-FU-Beva.

????

DISEASE EVOLUTION AND

TREATMENT

AUGUST 2015 JULY 2016

RESPONSE ASSESSMENT: PD

70

1. REINTRODUCE FOLFOX + BEV

2. FOLFIRI + anti-EGFRs

3. FOLFOX + BEV

4. IRINOTECAN + anti-EGFRs



AUGUST 2015 JULY 2016

RESPONSE ASSESSMENT: PD


02/15

Diag.

Abortion

03/15

FOLFOXI

RI-BEVA

08/15

8 cycles

PR(-50%)

Unresect.

->

FOLFIRI-

Beva.

01/16

6 cycles

PR maint.

Haematological

tox.

H. And F. Sind.

Diarreha.

03/16

10 cycles

PR maint.

->5-FU-Beva.

07/16

8 cycles

Liver PD

->FOLFOX-Beva.


TREATMENT

JANUARY 2017

• 11 cycles of FOLFOX-Bevacizumab.

• In CT scan no evidence of progression: increase of 20%

of metastasic lesions.

• LIVER PROGRESSIVE DISEASE

• Blood test:

– Hypertransaminasemia.

– LDH 1006 U/ml. ALP 321mU/ml.

– CEA 180 ng/ml (previous 93,7 ng/ml).


TREATMENT

74

1. REINTRODUCE FOLFIR + BEV

2. FOLFIRI + anti-EGFRs

3. CAPE + BEV

4. IRINOTECAN + anti-EGFRs

5. BEST SUPPORTIVE CARE



02/15

Diag.

Abortion

03/15

FOLFOXI

RI-BEVA

08/15

8 cycles

PR(-50%)

Unresect.

->

FOLFIRI-

Beva.

01/16

6 cycles

PR maint.

Haematological

tox.

H. And F. Sind.

Diarreha.

03/16

10 cycles

PR maint.

->5-FU-Beva.

07/16

8 cycles

Liver PD

->FOLFOX-

Beva.

11/16

8 cycles

SD

01/17

11 cycles

Liver PD

->CPT11-cetuximab

03/17

4 cycles

PR (-50%

liver met.)

JANUARY 2017 MARCH 2017


TREATMENT


02/15

Diag.

Abortion

03/15

FOLFOXI

RI-BEVA

08/15

8 cycles

PR(-50%)

Non resect.

->

FOLFIRI-

Beva.

10/15

3 cycles

PR

maintenance

01/16

6 cycles

PR maint.

Haematological

tox.

H. And F. Sind.

03/16

10 cycles

PR

->5-FU-Beva.

07/16

8 cycles

Liver DP

->FOLFOX-

Beva.

11/16

8 cycles

SD

01/17

11 cycles

Liver DP

->CPT11-

cetuximab

03/17

4 cycles

PR (-50%

liver met.)

05/17

8 cycles

PR maint.

1. REGORAFENIB

2. LONSURF

3. CAPE + BEV

4. TEST HER2 STATUS

5. BEST SUPPORTIVE CARE

OPTIONS FOR FUTURE

TREATMENTS

• Herceptest Positive 3+.

OPTIONS FOR FUTURE

TREATMENTS

Kavuri SM et al, Cancer Discovery 2015; 5:832-841

Anomalías moleculares de HER2 en cáncer de colon

Kavuri SM et al, Cancer Discovery 2015; 5:832-841

Anomalías moleculares de HER2 en cáncer de colon: Sesibilidad a Lapatinib + Trastuzumab

HERACLES treatment and assessments

Siena et al Lancet Oncol, 2016; 17:438-446.

Lapatinib/Trastuzumab en cáncer de colon HER2+++Estudio Heracles

presentation of three challenging clinical cases and faculty … · 2018. 5. 31. · –1st stage...

Documents