# Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study

Yanis Dahel, Brice Chanez, Christophe Zemmour, Gilles Piana, Emmanuel Mitry, Marc Giovannini

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Yanis Dahel, Brice Chanez, Christophe Zemmour, Gilles Piana, Emmanuel Mitry, et al.. Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study. Endoscopic Ultrasound, 2023, 12 (2), pp.273-276. 10.4103/eus-d-22-00040. inserm-04546987

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# Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study

Yanis Dahel¹, Brice Chanez², Christophe Zemmour³, Gilles Piana⁴, Emmanuel Mitry², Marc Giovannini¹

¹Department of Endoscopy, Paoli-Calmettes Institute, Marseille, France; ²Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France; ³Department of Clinical Research and Investigation, Biostatistics and Methodology Unit, Paoli-Calmettes Institute, Aix Marseille University, INSERM, IRD, SESSTIM, Marseille, France; ⁴Department of Radiology, Paoli-Calmettes Institute, Marseille, France

## ABSTRACT

EUS associated with contrast-enhanced harmonic EUS (CH-EUS) and EUS elastography (EUS-E) are used in clinical practice to assess pancreatic tumor at the diagnosis. In case of pancreatic ductal adenocarcinoma (PDAC) with liver metastasis, nab-paclitaxel combined with gemcitabine is a first-line treatment option. We aimed to assess the modification of PDAC microenvironment induced by the combination of nab-paclitaxel with gemcitabine, by endoscopic ultrasonography technics. This single center phase III study conducted between February 2015 and June 2016 included patients with pancreatic adenocarcinoma with mesurable liver metastasis and no prior cancer treatment fit for two cycles of nab-paclitaxel combined with gemcitabine. We aimed to perform EUS with CH-EUS and EUS-E of the pancreatic tumor, CT scan and contrast enhanced ultrasonogram (CE-US) of a reference liver metastasis, before and after the two cycles of chemotherapy. Primary end point was modification of vascularizaion of primary tumor and a reference liver metastasis. Secondary end points were modification of stromal content, safety profile of drug combination and tumor response rate. Sixteen patients were analyzed, but only 13 received two cycled of chemotherapy (CT) (toxicity [n = 1] or death [n = 2]). There was no statistical modification induced by CT concerning vascularity of primary tumor (time to maximum intensity P = 0.24, value of maximum intensity P = 0.71, hypoechoogenic aspect generated by injection of contrast enhancing agent), vascularity of a reference liver metastasis (time to maximum intensity P = 0.99, value of maximum intensity P = 0.71) and tumor elasticity (P = 0.22). Eleven patients had tumor response assessment, 6/11 (54%) had measurable disease response 4/11 (36%) with partial responses and 2/11 (18%) with stable disease. All other patients showed disease progression. No serious side effects occurred, 6/11 patients had a dose adjustment. We did not show significant modification of vascularity and elasticity but these results should be taken with caution because of important limitations.

**Key words:** Chemotherapy, contrast enhanced ultrasonography, elastography, pancreatic adenocarcinoma

### Access this article online

Quick Response Code:

<figure><img src="image_1.png" /></figure>

Website:

www.eusjournal.com

DOI:

10.4103/EUS-D-22-00040

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

**How to cite this article:** Dahel Y, Chanez B, Zemmour C, Piana G, Mitry E, Giovannini M. Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study. Endosc Ultrasound 2023;12:273-6.

## Address for correspondence

Dr. Yanis Dahel, Department of Endoscopy, Paoli-Calmettes Institute, Marseille, France.

E-mail: dahely@ipc.unicancer.fr

Received: 2022-02-19; Accepted: 2023-01-18; Published online: 2023-04-28
# Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study

Yanis Dahel<fnref n="1" />, Brice Chanez², Christophe Zemmour³, Gilles Piana⁴, Emmanuel Mitry², Marc Giovannini<fnref n="1" />

## ABSTRACT

EUS associated with contrast-enhanced harmonic EUS (CH-EUS) and EUS elastography (EUS-E) are used in clinical practice to assess pancreatic tumor at the diagnosis. In case of pancreatic ductal adenocarcinoma (PDAC) with liver metastasis, nab-paclitaxel combined with gemcitabine is a first-line treatment option. We aimed to assess the modification of PDAC microenvironment induced by the combination of nab-paclitaxel with gemcitabine, by endoscopic ultrasonography technics. This single center phase III study conducted between February 2015 and June 2016 included patients with pancreatic adenocarcinoma with mesurable liver metastasis and no prior cancer treatment fit for two cycles of nab-paclitaxel combined with gemcitabine. We aimed to perform EUS with CH-EUS and EUS-E of the pancreatic tumor, CT scan and contrast enhanced ultrasonogram (CE-US) of a reference liver metastasis, before and after the two cycles of chemotherapy. Primary end point was modification of vascularizaion of primary tumor and a reference liver metastasis. Secondary end points were modification of stromal content, safety profile of drug combination and tumor response rate. Sixteen patients were analyzed, but only 13 received two cycled of chemotherapy (CT) (toxicity [n = 1] or death [n = 2]). There was no statistical modification induced by CT concerning vascularity of primary tumor (time to maximum intensity P = 0.24, value of maximum intensity P = 0.71, hypoechoogenic aspect generated by injection of contrast enhancing agent), vascularity of a reference liver metastasis (time to maximum intensity P = 0.99, value of maximum intensity P = 0.71) and tumor elasticity (P = 0.22). Eleven patients had tumor response assessment, 6/11 (54%) had measurable disease response 4/11 (36%) with partial responses and 2/11 (18%) with stable disease. All other patients showed disease progression. No serious side effects occurred, 6/11 patients had a dose adjustment. We did not show significant modification of vascularity and elasticity but these results should be taken with caution because of important limitations.

**Key words:** Chemotherapy, contrast enhanced ultrasonography, elastography, pancreatic adenocarcinoma

### Access this article online

Quick Response Code:

<figure><img src="image_2.png" /></figure>

Website:

www.eusjournal.com

DOI:

10.4103/EUS-D-22-00040

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

For reprints contact: WKHLRPMedknow_reprints@wolterskluwer.com

**How to cite this article:** Dahel Y, Chanez B, Zemmour C, Piana G, Mitry E, Giovannini M. Assessment of biological effect of nab-paclitaxel combined with gemcitabine, using contrast enhanced ultrasonography and elastography, in advanced pancreatic ductal carcinoma: A single-center pilot study. Endosc Ultrasound 2023;12:273-6.

## Address for correspondence

Dr. Yanis Dahel, Department of Endoscopy, Paoli-Calmettes Institute, Marseille, France.

E-mail: dahely@ipc.unicancer.fr

Received: 2022-02-19; Accepted: 2023-01-18; Published online: 2023-04-28

<footnote n="1">¹Department of Endoscopy, Paoli-Calmettes Institute, Marseille, France; ²Department of Medical Oncology, Paoli-Calmettes Institute, Marseille, France; ³Department of Clinical Research and Investigation, Biostatistics and Methodology Unit, Paoli-Calmettes Institute, Aix Marseille University, INSERM, IRD, SESSTIM, Marseille, France; ⁴Department of Radiology, Paoli-Calmettes Institute, Marseille, France</footnote>
INTRODUCTION

Pancreatic ductal adenocarcinoma (PDAC) is the most
fatal malignancy among gastrointestinal cancer, with
increasing incidence over years and with a 5-year overall
survival rate of 5%–7%.[1,2]

New therapeutics and new technics to analyze early
tumor response are highly needed.

When metastases are detected, which the most frequent
being liver metastases, only palliative chemotherapy
computed tomography (CT) are validated;[3] however,
first-line regimen, mainly poly-CT based, depend on
the country and health system.[4] Nab-paclitaxel, an
albumin bound paclitaxel nanoparticle, is combined with
gemcitabine as first-line treatment option for advanced
PDAC.[5] The combination of the taxane drug with the
albumin bound compound has shown in a preclinical
study improvement of intratumoral concentration of
gemcitabine in mice treated with the combination
and this could be related to the modification of the
desmoplastic micro environment of the pancreatic tumor.

In a phase III trial, the combination demonstrated superior overall survival, progression-free survival and response rate compared with gemcitabine alone in metastatic untreated PDAC;[6] however, reimbursement of nab paclitaxel through public health policies is not equal across European countries. In France, the French Agency for the Safety of Health product has classified nab-paclitaxel as an important therapy in advanced PDAC and its use is approved by French authorities. However, the medical service improvement has been evaluated as “low” and the molecule is not reimbursed by social security.[7]

EUS is a key procedure allowing fine-needle aspiration
biopsies of the tumor and precise staging. Recently,
contrast-enhanced harmonic EUS (CH-EUS)[8,9] and
EUS elastography (EUS-E)[10,11] became available. These
modalities, done at the same time with conventional
EUS, allow an excellent evaluation of the stromal tissue.
CH-EUS allows visualization of micro vasculature
and assessment of parenchymal perfusion, useful for
characterizing pancreatic lesions and detecting PDAC
with a sensitivity of 94% and specificity of 89% as a
result of the hypo-enhancement of these lesions. PDAC
is usually not enhanced after injection of ultrasound
contrast agent (SonoVue®, Bracco, Italy) and 5–10 times
stiffer than normal tissue.

EUS-E is an ultrasound-based method for the
visualisation of relative strain distribution. By
calculating the elasticity of tissue we're able to
differentiate benign (soft) tissue from malignant (hard)
tissue. Comparison should be made between the
pancreatic mass and the duodenal or the gastric wall
elasticity; using this technique a ratio > 17 is always
correlated with a malignant pancreatic mass, a ratio
of < 7.8 is associated in 93% of cases with an
inflammatory mass.

In 2013, a mechanism of action trial in 16 resectable patients has been published.[12] Conclusions are that the combination of nab-paclitaxel + gemcitabine decreased tumor stiffness (assessed by EUS-E), and tumor stromal content (when compared with patients resected without preoperative CT or another CT).

It seems then of peculiar interest to try to confirm
these and to check if these tumor modifications are
limited to the PDAC itself or will be also noticed in
liver metastases. It is obvious that a decrease in stromal
content associated with an increase in tumor vascularity
allows for an increase in drug delivery to the tumor
cells. This is of major interest and can lead to test
combinations of nab-paclitaxel with other efficient
treatments.

The main objective were to assess if, compared to
baseline, the combination of nab-paclitaxel with
gemcitabine induces modification of the PDAC
microenvironment particularly in vascularization of the
primary tumor as well liver metastasis after two cycles
of treatment and second to assess the modification of
tissue's elasticity. We also evaluated overall response rate
and toxicity profile.

METHODS

In this single-center pilot study, we included patients
with pancreatic adenocarcinoma with measurable liver
metastasis, no prior pancreatic or liver surgery, no
radiotherapy and/or CT, with life expectancy longer than
2 months and a performance status (PS) 0–2. Tumors
other than ductal adenocarcinoma were excluded. Patients
were treated with two cycles of nab-paclitaxel (Abraxane®)
125 mg/m² intraveinous (IV) and gemcitabine 1 g/m² IV
on days 1, 8, and 15 every 4 weeks.

The treatment was continued after the two cycles until
progression or unacceptable toxicity occurred (Common
INTRODUCTION

Pancreatic ductal adenocarcinoma (PDAC) is the most
fatal malignancy among gastrointestinal cancer, with
increasing incidence over years and with a 5-year overall
survival rate of 5%–7%.[1,2]

New therapeutics and new technics to analyze early
tumor response are highly needed.

When metastases are detected, which the most frequent
being liver metastases, only palliative chemotherapy
computed tomography (CT) are validated;[3] however,
first-line regimen, mainly poly-CT based, depend on
the country and health system.[4] Nab-paclitaxel, an
albumin bound paclitaxel nanoparticle, is combined with
gemcitabine as first-line treatment option for advanced
PDAC.[5] The combination of the taxane drug with the
albumin bound compound has shown in a preclinical
study improvement of intratumoral concentration of
gemcitabine in mice treated with the combination
and this could be related to the modification of the
desmoplastic micro environment of the pancreatic tumor.

In a phase III trial, the combination demonstrated superior overall survival, progression-free survival and response rate compared with gemcitabine alone in metastatic untreated PDAC;[6] however, reimbursement of nab paclitaxel through public health policies is not equal across European countries. In France, the French Agency for the Safety of Health product has classified nab-paclitaxel as an important therapy in advanced PDAC and its use is approved by French authorities. However, the medical service improvement has been evaluated as “low” and the molecule is not reimbursed by social security.[7]

EUS is a key procedure allowing fine-needle aspiration
biopsies of the tumor and precise staging. Recently,
contrast-enhanced harmonic EUS (CH-EUS)[8,9] and
EUS elastography (EUS-E)[10,11] became available. These
modalities, done at the same time with conventional
EUS, allow an excellent evaluation of the stromal tissue.
CH-EUS allows visualization of micro vasculature
and assessment of parenchymal perfusion, useful for
characterizing pancreatic lesions and detecting PDAC
with a sensitivity of 94% and specificity of 89% as a
result of the hypo-enhancement of these lesions. PDAC
is usually not enhanced after injection of ultrasound
contrast agent (SonoVue®, Bracco, Italy) and 5–10 times
stiffer than normal tissue.

EUS-E is an ultrasound-based method for the
visualisation of relative strain distribution. By
calculating the elasticity of tissue we're able to
differentiate benign (soft) tissue from malignant (hard)
tissue. Comparison should be made between the
pancreatic mass and the duodenal or the gastric wall
elasticity; using this technique a ratio > 17 is always
correlated with a malignant pancreatic mass, a ratio
of < 7.8 is associated in 93% of cases with an
inflammatory mass.

In 2013, a mechanism of action trial in 16 resectable patients has been published.[12] Conclusions are that the combination of nab-paclitaxel + gemcitabine decreased tumor stiffness (assessed by EUS-E), and tumor stromal content (when compared with patients resected without preoperative CT or another CT).

It seems then of peculiar interest to try to confirm
these and to check if these tumor modifications are
limited to the PDAC itself or will be also noticed in
liver metastases. It is obvious that a decrease in stromal
content associated with an increase in tumor vascularity
allows for an increase in drug delivery to the tumor
cells. This is of major interest and can lead to test
combinations of nab-paclitaxel with other efficient
treatments.

The main objective were to assess if, compared to
baseline, the combination of nab-paclitaxel with
gemcitabine induces modification of the PDAC
microenvironment particularly in vascularization of the
primary tumor as well liver metastasis after two cycles
of treatment and second to assess the modification of
tissue's elasticity. We also evaluated overall response rate
and toxicity profile.

METHODS

In this single-center pilot study, we included patients
with pancreatic adenocarcinoma with measurable liver
metastasis, no prior pancreatic or liver surgery, no
radiotherapy and/or CT, with life expectancy longer than
2 months and a performance status (PS) 0–2. Tumors
other than ductal adenocarcinoma were excluded. Patients
were treated with two cycles of nab-paclitaxel (Abraxane®)
125 mg/m² intraveinous (IV) and gemcitabine 1 g/m² IV
on days 1, 8, and 15 every 4 weeks.

The treatment was continued after the two cycles until
progression or unacceptable toxicity occurred (Common
Toxicity Criteria for Adverse Events version 4.03, National Institutes of Health, 2010, USA) or discontinued per patient's request.

Before and 2 months after initial CT we performed CH-EUS and EUS-E of the primary tumor during general anesthesia. We also conducted a contrast-enhanced ultrasonogram (CE-US) of a reference liver metastasis and CT scan tumor measurement according to RECIST v1.1 as well as density measurement according to Choi criteria.

Based on empirical considerations, a total of 16 patients are planned to be evaluated.

The primary end point was to evaluate if two cycles of nab-paclitaxel combined with gemcitabine-induced modifications in vascularization of pancreatic adenocarcinoma measured by CH-EUS. We also assessed these modifications by C-US in a reference liver metastasis.

Secondary end points were to evaluate if this combination induces a modification in stromal content of the pancreatic primary tumor by assessing stiffness with E-EUS and density of liver metastases by CTs. The safety profile of the drug combination and the tumor response rate were also evaluated.

## RESULTS

Between February 2015 and June 2016 19 patients were evaluated with a mean age of 69 year (range, 49–78), 10 were women (52%). Three patients were excluded, one neuroendocrine tumor, one because of PS 3 and another patient at the discretion of the principal investigator. Finally, 16 patients were analyzed in the study.

Thirteen patients (81.25%) received two cycles of CT. Two patients died before the beginning of the second cycle and one patient did not start the second cycle because of toxicity. Eleven patients had tumor response assessment before and after CT.

### Vascularity and elasticity of primary tumor

Assessment of vascularity of the primary tumor was performed by CH-EUS in 13 patients before CT and in 12 patients after CT. There was no statistically significant difference of time to maximum intensity (P = 0.24, paired t-test), value of maximum intensity (P = 0.71) and hypoechoogenic aspect generated by injection of contrast enhancing agent (12/13 before and 12/12 after).

Assessment of vascularity of a reference liver metastatic lesion was performed by CE-US on 8 patients before and after CT. There was no statistically significant difference of time to maximum intensity (P = 0.99) or value of maximum intensity (P = 0.71).

Pancreatic tumor elasticity assessment done by E-EUS in 11 patients before CT and 12 patients after CT showed no statistical significant difference (P = 0.22).

### Tumor response assessment

Eleven patients evaluated by Choi and Recist: 6/11 (54%) had measurable disease response with 4/11 (36%) partial responses and 2/11 (18%) had stable disease. All other patients showed disease progression.

### Toxicity profile

No serious side effects occurred and 6/11 patients had a dose adjustment because of hematologic toxicity (5/6) or asthenia (1/6).

## CONCLUSION

Our pilot study is the first to evaluate the effect of gemcitabine in combination with nab-paclitaxel in advanced PDAC utilizing EUS techniques (CH-EUS and E-EUS). We aimed to assess if CT increased tumor vascularity to improve drug diffusion but we did not see any increase of vascularity of PDAC or liver metastasis after two cycles of CT in patient without prior treatment.

Our results should be taken with caution and reasons for the absence of variation in elasticity or vasculature can be multiple. First of all, the small sample of patients associated with known heterogeneity of pancreatic adenocarcinoma had probably led to heterogeneous measurements. Second, endoscopic ultrasound techniques are innovative techniques but operator dependent that could lead to variation of values. Moreover, we had technical difficulty with endoscopic ultrasound. The data extracted from contrast-enhanced imaging and elastography showed missing data.

A recent study described the decrease of tumor vascularity, assessed by CH-EUS and chemotherapies in 23 patients treated by gemcitabine alone. They showed modification of the pancreatic tumor with appearance of avascular areas in 11/23 patients.[13]
Toxicity Criteria for Adverse Events version 4.03,
National Institutes of Health, 2010, USA) or
discontinued per patient's request.

Before and 2 months after initial CT we performed
CH-EUS and EUS-E of the primary tumor
during general anesthesia. We also conducted
a contrast-enhanced ultrasonogram (CE-US) of a
reference liver metastasis and CT scan tumor
measurement according to RECIST v1.1 as well as
density measurement according to Choi criteria.

Based on empirical considerations, a total of 16 patients
are planned to be evaluated.

The primary end point was to evaluate if two cycles
of nab-paclitaxel combined with gemcitabine-induced
modifications in vascularization of pancreatic
adenocarcinoma measured by CH-EUS. We also assessed
these modifications by C-US in a reference liver metastasis.

Secondary end points were to evaluate if this
combination induces a modification in stromal content
of the pancreatic primary tumor by assessing stiffness
with E-EUS and density of liver metastases by CTs.
The safety profile of the drug combination and the
tumor response rate were also evaluated.

RESULTS

Between February 2015 and June 2016 19 patients were
evaluated with a mean age of 69 year (range, 49–78),
10 were women (52%). Three patients were excluded, one
neuroendocrine tumor, one because of PS 3 and another
patient at the discretion of the principal investigator.
Finally, 16 patients were analyzed in the study.

Thirteen patients (81.25%) received two cycles of CT.
Two patients died before the beginning of the second
cycle and one patient did not start the second cycle
because of toxicity. Eleven patients had tumor response
assessment before and after CT.

Vascularity and elasticity of primary tumor

Assessment of vascularity of the primary tumor was
performed by CH-EUS in 13 patients before CT and in
12 patients after CT. There was no statistically significant
difference of time to maximum intensity (P = 0.24,
paired t-test), value of maximum intensity (P = 0.71)
and hypoechogenic aspect generated by injection of
contrast enhancing agent (12/13 before and 12/12 after).

Assessment of vascularity of a reference liver metastatic
lesion was performed by CE-US on 8 patients before
and after CT. There was no statistically significant
difference of time to maximum intensity (P = 0.99) or
value of maximum intensity (P = 0.71).

Pancreatic tumor elasticity assessment done by E-EUS
in 11 patients before CT and 12 patients after CT
showed no statistical significant difference (P = 0.22).

Tumor response assessment

Eleven patients evaluated by Choi and Recist:
6/11 (54%) had measurable disease response with
4/11 (36%) partial responses and 2/11 (18%) had stable
disease. All other patients showed disease progression.

Toxicity profile

No serious side effects occurred and 6/11 patients had
a dose adjustment because of hematologic toxicity (5/6)
or asthenia (1/6).

CONCLUSION

Our pilot study is the first to evaluate the effect
of gemcitabine in combination with nab-paclitaxel
in advanced PDAC utilizing EUS techniques
(CH-EUS and E-EUS). We aimed to assess if CT
increased tumor vascularity to improve drug diffusion
but we did not see any increase of vascularity of
PDAC or liver metastasis after two cycles of CT in
patient without prior treatment.

Our results should be taken with caution and reasons
for the absence of variation in elasticity or vasculature
can be multiple. First of all, the small sample of
patients associated with known heterogeneity of
pancreatic adenocarcinoma had probably led to
heterogeneous measurements. Second, endoscopic
ultrasound techniques are innovative techniques but
operator dependent that could lead to variation of
values. Moreover, we had technical difficulty with
endoscopic ultrasound. The data extracted from
contrast-enhanced imaging and elastography showed
missing data.

A recent study described the decrease of tumor
vascularity, assessed by CH-EUS and chemotherapies in
23 patients treated by gemcitabine alone. They showed
modification of the pancreatic tumor with appearance
of avascular areas in 11/23 patients.[13]
Our global response rate is 54% and is slightly better
than those observed in the literature in particular in
the pivotal study,[6] but our patient sample was small
and selective.

In conclusion, we did not show significant modification
of vascularity and elasticity of pancreatic tumor and
liver metastasis after combination treatment with
nab-paclitaxel and gemcitabine, but these results should
be taken with caution because of important limitations.

Financial support and sponsorship

Nil.

Conflicts of interest

Marc Giovannini is a Founding Editor-in-Chief of the journal. This article was subject to the journal's standard procedures, with peer review handled independently of the editor and his research group.

REFERENCES

1. Ferlay J, Partensky C, Bray F. More deaths from pancreatic cancer than breast cancer in the EU by 2017. *Acta Oncol* 2016;55:1158-60.

2. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. *Cancer Res* 2014;74:2913-21.

3. Ducreux M, Cuhna AS, Caramella C, et al. Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. *Ann Oncol* 2015;26 Suppl 5:v56-68.

4. Taieb J, Prager GW, Melisi D, et al. First-line and second-line treatment of patients with metastatic pancreatic adenocarcinoma in routine clinical practice across Europe: A retrospective, observational chart review study. *ESMO Open* 2020;5:e000587.

5. Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. *J Clin Oncol* 2018;36:2545-56.

6. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. *N Engl J Med* 2013;369:1691-703.

7. French High Authority of Health Committee. Abraxane Combined with Gemcitabine is Indicated as First Line Treatment of Adult with Metastatic Pancreatic Adenocarcinoma; HAS - Medical, Economic and Public Health Assessment Division 2014. p. 1-15.

8. Giovannini M. Contrast-enhanced and 3-dimensional endoscopic ultrasonography. *Gastroenterol Clin North Am* 2010;39:845-58.

9. Gheonea DI, Streba CT, Ciurea T, et al. Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer. *BMC Gastroenterol* 2013;13:2.

10. Giovannini M, Thomas B, Erwan B, et al. Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: A multicenter study. *World J Gastroenterol* 2009;15:1587-93.

11. Giovannini M. Clinical Pancreatology for Practicing Gastroenterologists and Surgeons. 2nd ed. USA: John Wiley & Sons Ltd; 2021. p. 449-59.

12. Alvarez R, Musteanu M, Garcia-Garcia E, et al. Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. *Br J Cancer* 2013;109:926-33.

13. Tanaka H, Kamata K, Takenaka M, et al. Contrast-enhanced harmonic endoscopic ultrasonography for evaluating the response to chemotherapy in pancreatic cancer. *Dig Liver Dis* 2019;51:1130-4.
Our global response rate is 54% and is slightly better
than those observed in the literature in particular in
the pivotal study,[6] but our patient sample was small
and selective.

In conclusion, we did not show significant modification
of vascularity and elasticity of pancreatic tumor and
liver metastasis after combination treatment with
nab-paclitaxel and gemcitabine, but these results should
be taken with caution because of important limitations.

Financial support and sponsorship

Nil.

Conflicts of interest

Marc Giovannini is a Founding Editor-in-Chief of the journal. This article was subject to the journal's standard procedures, with peer review handled independently of the editor and his research group.

REFERENCES

1. Ferlay J, Partensky C, Bray F. More deaths from pancreatic cancer than breast cancer in the EU by 2017. *Acta Oncol* 2016;55:1158-60.

2. Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: The unexpected burden of thyroid, liver, and pancreas cancers in the United States. *Cancer Res* 2014;74:2913-21.

3. Ducreux M, Cuhna AS, Caramella C, et al. Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. *Ann Oncol* 2015;26 Suppl 5:v56-68.

4. Taieb J, Prager GW, Melisi D, et al. First-line and second-line treatment of patients with metastatic pancreatic adenocarcinoma in routine clinical practice across Europe: A retrospective, observational chart review study. *ESMO Open* 2020;5:e000587.

5. Sohal DPS, Kennedy EB, Khorana A, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline update. *J Clin Oncol* 2018;36:2545-56.

6. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. *N Engl J Med* 2013;369:1691-703.

7. French High Authority of Health Committee. Abraxane Combined with Gemcitabine is Indicated as First Line Treatment of Adult with Metastatic Pancreatic Adenocarcinoma; HAS - Medical, Economic and Public Health Assessment Division 2014. p. 1-15.

8. Giovannini M. Contrast-enhanced and 3-dimensional endoscopic ultrasonography. *Gastroenterol Clin North Am* 2010;39:845-58.

9. Gheonea DI, Streba CT, Ciurea T, et al. Quantitative low mechanical index contrast-enhanced endoscopic ultrasound for the differential diagnosis of chronic pseudotumoral pancreatitis and pancreatic cancer. *BMC Gastroenterol* 2013;13:2.

10. Giovannini M, Thomas B, Erwan B, et al. Endoscopic ultrasound elastography for evaluation of lymph nodes and pancreatic masses: A multicenter study. *World J Gastroenterol* 2009;15:1587-93.

11. Giovannini M. Clinical Pancreatology for Practicing Gastroenterologists and Surgeons. 2nd ed. USA: John Wiley & Sons Ltd; 2021. p. 449-59.

12. Alvarez R, Musteanu M, Garcia-Garcia E, et al. Stromal disrupting effects of nab-paclitaxel in pancreatic cancer. *Br J Cancer* 2013;109:926-33.

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