**4. Classic and modified Glasgow prognostic score in pancreatic ductal adenocarcinoma**

Glasgow prognostic score is based on the evaluation of the prototypic acute phase protein, C-reactive protein; and albumin levels in blood serum. CRP is a nonspecific, but sensitive marker of systemic inflammatory reaction, produced in response to pro-inflammatory cytokines (IL-1, IL-6, TNF alpha). Hypoalbuminemia is induced by malnutrition, cancer cachexia or SIR. GPS represents a summary estimate of two crucial pathogenetic processes: the humoral SIR and cancer cachexia therefore it benefits from considerable sensitivity [14].

mGPS of 0, 1 and 2 classified the patients in three distinct groups by overall survival: 37.5

Systemic Inflammatory Response in Pancreatic Ductal Adenocarcinoma

http://dx.doi.org/10.5772/intechopen.78954

17

Elevated classic GPS (0 versus 1 and 2), was not associated with cancer-specific survival in 110

Despite the controversies, standard preoperative assessment of mGPS is recommended in cases of borderline resectable pancreatic cancer by consensus statement by the International

In 261 patients with inoperable pancreatic cancer (including both metastatic and locally advanced cases), elevated GPS (0 versus 1 and 2) was significantly associated with worse cancer-specific survival, as confirmed by p < 0.029. However, by multivariate analysis, GPS was not an independent prognostic factor in this cohort [25]. Nevertheless, the next level of evidence has been reached: mGPS was an independent prognostic factor in 187 patients with inoperable pancreatic cancer [67]. GPS is associated with survival in patients with unresectable pancreatic cancer treated with gemcitabine [68]. In 96 patients who underwent chemoradiotherapy for histologically confirmed, locally advanced PDAC, Glasgow prognostic score (of 2) was an independent predictor of worse overall survival and progression free survival [69]. In 40 patients undergoing adjuvant chemotherapy by gemcitabine after curative resection, elevated GPS (defined as 1 or 2 in contrast to 0) was associated both with worse disease-

mGPS shows specific associations with response to treatment. Comparing the efficacy of JAK/ STAT inhibitor ruxolitinib or placebo in combination with capecitabine (in both groups) for second-line treatment of metastatic pancreatic cancer, ruxolitinib showed trend to survival benefit only in those patients who had elevated mGPS (1 or 2) or CRP. Thus, in patients who had mGPS of 1–2, treatment by ruxolitinib resulted in hazard ratio HR = 0.60; 95% CI: 0.35–1.03; p = 0.063. In contrast, mGPS of 0 was associated with HR = 0.91; 95% CI = 0.46–1.74; p = 0.77. The trend reached statistical significance when the groups were compared by C-reactive protein level. Thus, the HR for overall survival in ruxolitinib group was HR = 0.47; 95% CI: 0.26–0.85; p = 0.011 in patients whose CRP was above the median value (>13 mg/L) contrasting with HR = 0.89; 95% CI: 0.47–1.65; p = 0.70 in those who had CRP ≤ 13 mg/L. The biological differences were minor: the median survival was 2.7 months receiving ruxolitinib versus 1.8 months in controls. The overall survival rates at 3, 6 and 12 months were 48 versus 29%; 42 versus 11% and 11 versus 0% in the ruxolitinib versus placebo groups [71]. In contrast, high mGPS was associated with poor outcome in patients with gemcitabine-refractory

Modified Glasgow prognostic score was evaluated in 56 patients who underwent preoperative chemoradiotherapy followed by surgical resection of pancreatic cancer, thus ensuring the option to assess the treatment efficacy by morphology. By this design, mGPS did not predict the response to treatment. However, only five patients presented with mGPS of 1 or 2, while most of the cohort (51 cases) had mGPS of 0. All five patients exhibiting elevated mGPS

responded poorly, but this was insufficient to reach statistical significance [34].

surgically treated pancreatic cancer patients, as confirmed by p < 0.585 [25].

months, 11.5 months and 7.3 months [66].

Study Group of Pancreatic Surgery [26].

free survival (p = 0.001) and overall (p = 0.035) survival [70].

advanced pancreatic cancer treated by salvage chemotherapy [72].

Two alterations of Glasgow prognostic score are known: the modified GPS and the high sensitivity GPS. In the modified GPS, albumin level influences the score only if CRP is increased. High sensitivity GPS differs from the original GPS by lower cut-off level for CRP [14].

Imaoka et al. evaluated the prognostic value of mGPS across all stages of pancreatic cancer. After adjustment, both mGPS values 1 and 2 showed prognostic significance reflected in the hazard ratios: mGPS of 1 was associated with HR = 1.772; 95% CI: 1.417–2.215, but mGPS of 2 yielded HR = 2.033; 95% CI: 1.284–3.219. However, the biological significance was remarkable between mGPC of 0 and elevated values: the median survival was 15.8 months versus 5.8 versus 4.8 months in those presenting with mGPS 0, 1 or 2, respectively. In this study, the prognostic value of mGPS was not demonstrated in patients who had localised tumours and underwent surgical resection. Instead, mGPS was important in advanced pancreatic cancer [63]. Similarly, in advanced pancreatic cancer, high mGPS was a significant independent prognostic marker for shorter survival. The median survival by mGPS (2 versus 1 versus 0) was 1.8 months versus 9.6 versus 8.3 months [31]. As will be discussed further, most scientists agree on prognostic role of mGPS in advanced pancreatic cancer. The findings in resectable cases are more controversial.

Matsumoto et al reported significant prognostic value of mGPS in resectable pancreatic cancer. However, the role of mGPS in this study was to predict recurrence. According to their findings, mGPS (2 versus 0 or 1) was an independent predictive factor for tumour recurrence within 6 months, along with CA 19-9 (at least 300 U/mL) and tumour diameter (at least 30 mm). To detect survival, the number of these risk factors was significant, as it was associated with significantly (p < 0.001) different median survival: 35.5 versus 26.3 versus 15.9 months in those having 0, 1 or 2 or the identified factors, respectively [64].

mGPS (of 2) predicted postoperative pneumonia in 46 patients subjected to pancreaticoduodenectomy for pancreatic cancer. However, mGPS was not associated with overall survival contrasting with NLR and PLR [22].

Still, several researchers and teams have reported on the association between elevated mGPS and survival in surgical PDAC patients. In resectable PDAC, longer overall survival is observed in patients having mGPS of 0: 27–37 months contrasting with less than 18 months in patients with elevated mGPS [65]. In 101 patients treated by pancreatic resection for PDAC, mGPS of 0, 1 and 2 classified the patients in three distinct groups by overall survival: 37.5 months, 11.5 months and 7.3 months [66].

**4. Classic and modified Glasgow prognostic score in pancreatic** 

SIR and cancer cachexia therefore it benefits from considerable sensitivity [14].

Glasgow prognostic score is based on the evaluation of the prototypic acute phase protein, C-reactive protein; and albumin levels in blood serum. CRP is a nonspecific, but sensitive marker of systemic inflammatory reaction, produced in response to pro-inflammatory cytokines (IL-1, IL-6, TNF alpha). Hypoalbuminemia is induced by malnutrition, cancer cachexia or SIR. GPS represents a summary estimate of two crucial pathogenetic processes: the humoral

Two alterations of Glasgow prognostic score are known: the modified GPS and the high sensitivity GPS. In the modified GPS, albumin level influences the score only if CRP is increased.

Imaoka et al. evaluated the prognostic value of mGPS across all stages of pancreatic cancer. After adjustment, both mGPS values 1 and 2 showed prognostic significance reflected in the hazard ratios: mGPS of 1 was associated with HR = 1.772; 95% CI: 1.417–2.215, but mGPS of 2 yielded HR = 2.033; 95% CI: 1.284–3.219. However, the biological significance was remarkable between mGPC of 0 and elevated values: the median survival was 15.8 months versus 5.8 versus 4.8 months in those presenting with mGPS 0, 1 or 2, respectively. In this study, the prognostic value of mGPS was not demonstrated in patients who had localised tumours and underwent surgical resection. Instead, mGPS was important in advanced pancreatic cancer [63]. Similarly, in advanced pancreatic cancer, high mGPS was a significant independent prognostic marker for shorter survival. The median survival by mGPS (2 versus 1 versus 0) was 1.8 months versus 9.6 versus 8.3 months [31]. As will be discussed further, most scientists agree on prognostic role of mGPS in advanced pancreatic cancer. The findings in resectable

Matsumoto et al reported significant prognostic value of mGPS in resectable pancreatic cancer. However, the role of mGPS in this study was to predict recurrence. According to their findings, mGPS (2 versus 0 or 1) was an independent predictive factor for tumour recurrence within 6 months, along with CA 19-9 (at least 300 U/mL) and tumour diameter (at least 30 mm). To detect survival, the number of these risk factors was significant, as it was associated with significantly (p < 0.001) different median survival: 35.5 versus 26.3 versus 15.9 months in

mGPS (of 2) predicted postoperative pneumonia in 46 patients subjected to pancreaticoduodenectomy for pancreatic cancer. However, mGPS was not associated with overall survival

Still, several researchers and teams have reported on the association between elevated mGPS and survival in surgical PDAC patients. In resectable PDAC, longer overall survival is observed in patients having mGPS of 0: 27–37 months contrasting with less than 18 months in patients with elevated mGPS [65]. In 101 patients treated by pancreatic resection for PDAC,

those having 0, 1 or 2 or the identified factors, respectively [64].

High sensitivity GPS differs from the original GPS by lower cut-off level for CRP [14].

**ductal adenocarcinoma**

16 Advances in Pancreatic Cancer

cases are more controversial.

contrasting with NLR and PLR [22].

Elevated classic GPS (0 versus 1 and 2), was not associated with cancer-specific survival in 110 surgically treated pancreatic cancer patients, as confirmed by p < 0.585 [25].

Despite the controversies, standard preoperative assessment of mGPS is recommended in cases of borderline resectable pancreatic cancer by consensus statement by the International Study Group of Pancreatic Surgery [26].

In 261 patients with inoperable pancreatic cancer (including both metastatic and locally advanced cases), elevated GPS (0 versus 1 and 2) was significantly associated with worse cancer-specific survival, as confirmed by p < 0.029. However, by multivariate analysis, GPS was not an independent prognostic factor in this cohort [25]. Nevertheless, the next level of evidence has been reached: mGPS was an independent prognostic factor in 187 patients with inoperable pancreatic cancer [67]. GPS is associated with survival in patients with unresectable pancreatic cancer treated with gemcitabine [68]. In 96 patients who underwent chemoradiotherapy for histologically confirmed, locally advanced PDAC, Glasgow prognostic score (of 2) was an independent predictor of worse overall survival and progression free survival [69]. In 40 patients undergoing adjuvant chemotherapy by gemcitabine after curative resection, elevated GPS (defined as 1 or 2 in contrast to 0) was associated both with worse diseasefree survival (p = 0.001) and overall (p = 0.035) survival [70].

mGPS shows specific associations with response to treatment. Comparing the efficacy of JAK/ STAT inhibitor ruxolitinib or placebo in combination with capecitabine (in both groups) for second-line treatment of metastatic pancreatic cancer, ruxolitinib showed trend to survival benefit only in those patients who had elevated mGPS (1 or 2) or CRP. Thus, in patients who had mGPS of 1–2, treatment by ruxolitinib resulted in hazard ratio HR = 0.60; 95% CI: 0.35–1.03; p = 0.063. In contrast, mGPS of 0 was associated with HR = 0.91; 95% CI = 0.46–1.74; p = 0.77. The trend reached statistical significance when the groups were compared by C-reactive protein level. Thus, the HR for overall survival in ruxolitinib group was HR = 0.47; 95% CI: 0.26–0.85; p = 0.011 in patients whose CRP was above the median value (>13 mg/L) contrasting with HR = 0.89; 95% CI: 0.47–1.65; p = 0.70 in those who had CRP ≤ 13 mg/L. The biological differences were minor: the median survival was 2.7 months receiving ruxolitinib versus 1.8 months in controls. The overall survival rates at 3, 6 and 12 months were 48 versus 29%; 42 versus 11% and 11 versus 0% in the ruxolitinib versus placebo groups [71]. In contrast, high mGPS was associated with poor outcome in patients with gemcitabine-refractory advanced pancreatic cancer treated by salvage chemotherapy [72].

Modified Glasgow prognostic score was evaluated in 56 patients who underwent preoperative chemoradiotherapy followed by surgical resection of pancreatic cancer, thus ensuring the option to assess the treatment efficacy by morphology. By this design, mGPS did not predict the response to treatment. However, only five patients presented with mGPS of 1 or 2, while most of the cohort (51 cases) had mGPS of 0. All five patients exhibiting elevated mGPS responded poorly, but this was insufficient to reach statistical significance [34].
