The prognostic and predictive role of class III ß-Tubulin and hENT1 expression in patients with advanced pancreatic ductal adenocarcinoma.

BACKGROUND: FOLFIRINOX and gemcitabine-nabpaclitaxel (GnP) are standard first-line treatment regimens for advanced pancreatic ductal adenocarcinoma (PDAC). However, currently, there is a lack of predictive biomarkers to aid in the treatment selection. We aimed to explore the prognostic and predictive value of class III ß-Tubulin (TUBB3) and human equilibrative nucleoside transporter 1 (hENT1) expression, which have previously been shown to be associated with taxane and gemcitabine resistance in advanced PDAC. METHODS: We conducted a retrospective analysis of 106 patients with advanced PDAC treated with GnP and/or FOLFIRINOX at our institution. TUBB3 and hENT1 immunohistochemical staining was performed on tumor specimens and subsequently evaluated based on the intensity and percentage of expression. RESULTS: In patients who received the GnP regimen, a high combined score (TUBB3low/hENT1high) was associated with a higher DCR and longer PFS compared to those with intermediate (TUBB3high/hENT1high or TUBB3low/hENT1low) and low score (TUBB3high/hENT1low). In the multivariate analysis, a high combined score was an independent predictor of higher DCR (OR:11.96; 95 % CI:2.61-54.82; p = 0.001) and longer PFS (HR:0.33; 95%CI:0.18-0.60; p < 0.001). However, there was no difference in response rates or PFS based on TUBB3 and hENT1 expression among patients receiving the FOLFIRINOX regimen. CONCLUSION: Our findings indicate that tumor TUBB3 and hENT1 expression may predict the efficacy of the GnP regimen, and low TUBB3 and high hENT1 expression (TUBB3low/hENT1high) are associated with a higher DCR and longer PFS in patients treated with GnP. Evaluating TUBB3 and hENT1 jointly can identify the patients most (as well as least) likely to benefit from GnP chemotherapy.

PILE: a candidate prognostic score in cancer patients treated with immunotherapy

Background Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. Methods A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. Results The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2–3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450–3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263–2.954, p = 0.002) compared to PILE low-risk group (PILE score 0–1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. Conclusion In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy. (AU)

PILE: a candidate prognostic score in cancer patients treated with immunotherapy.

BACKGROUND: Although the immune checkpoint inhibitors (ICIs) became a vital part of cancer care, many patients do not respond to treatment, indicating need for biomarkers. The Pan-Immune-Inflammation Value (PIV) is a recently developed peripheral blood count-based biomarker. Herein, we evaluated a PIV-based candidate scoring system as a prognostic biomarker in ICI-treated patients. METHODS: A total of 120 advanced cancer patients treated with anti-PD-1 or anti-PD-L1 inhibitors for any cancer type were included in this study. The PILE scoring system incorporating the PIV (< median vs. ≥ median), lactate dehydrogenase levels (normal vs. > normal) and Eastern Cooperative Oncology Group performance status (0 vs. ≥ 1) was constructed from the multivariate analyses and used for stratification. The association between overall survival (OS), progression-free survival and PILE risk category was evaluated with multivariate analysis. RESULTS: The median follow-up was 9.62 months and the median OS of all cohort were 12.42 ± 2.75 months. Patients with higher PIV had significantly decreased OS (7.75 ± 1.64 vs. 18.63 ± 4.26 months, p = 0.037). The patients in the PILE high-risk group (PILE score 2-3) had decreased OS (18.63 ± 4.02 vs. 5.09 ± 1.23 months, HR: 2.317, 95% CI: 1.450-3.700, p < 0.001) and PFS (7.69 ± 1.30 vs. 2.69 ± 0.65 months, HR: 1.931, 95% CI: 1.263-2.954, p = 0.002) compared to PILE low-risk group (PILE score 0-1). The Harrell C-Index values were 0.65 and 0.61 for OS and PFS prediction, respectively. CONCLUSION: In this study, we demonstrated a decreased overall survival in ICI-treated patients with a higher PILE score. If prospective studies validate our results, PILE score could be a biomarker for immunotherapy.

Nivolumab for the salvage treatment of desperate germ cell tumor: A case report.

INTRODUCTION: Testicular germ cell tumors (GCT) are the most common tumor in young men. Their distinctive feature is the exceptional response to platin based combination chemotherapy.Since the prognosis is poor in relapsed and refractory patients, the immune checkpoint inhibitors are candidate agents in these patients although clinical trials are mostly lacking. Herein, we describe a patient with a refractory nonseminomatous GCT using nivolumab as a last resort therapy and provided long term response without any significant toxicity. CASE REPORT: A 41-year-old male presented with the complaint of flank pain eleven years ago. The patient underwent a retroperitoneal lymph node excision and pathology reported as the mixed germ cell tumor. There were no mass in the testicles and the patient was diagnosed with a primary retroperitoneal GCT. Since the disease has progressed under multiple lines of chemotherapy and autologous stem cell transplantation, treatment was started with nivolumab. MANAGEMENT AND OUTCOME: The patient started to treatment with nivolumab 3 mg/kg two weekly as a last resort treatment. The nivolumab was continued and the patient's response to this treatment is ongoing and has been stable for 13 months. DISCUSSION: There are limited treatment options in platinum-refractory germ cell tumors. Recently, immune checkpoint inhibitors tried in this setting with some success in especially non-seminomatous GCTs. We see a good response and prolonged benefit with the use of nivolumab in our patient. Further research including prospective studies on the use of immune checkpoint inhibitors in platinum-resistant testicular cancer can further delineate the role of immunotherapy.

Monitoring the metabolic response to major surgery in neonates.

BACKGROUND: Visceral proteins and acute phase reactants have commonly been used as indicators of nutritional status, and metabolic response of surgical trauma. AIM: This study was undertaken to determine how some plasma proteins, alone or together reflect metabolic response in neonates recovering from major surgery. METHODS: Serum albumin, pre-albumin (PA), C-reactive protein (CRP), and alpha1-acid glycoprotein (AGP) levels were measured, and the prognostic inflammatory and nutritional index (PINI) was calculated for preoperative day 1 (-1) and postoperative (PO) days 1 (+1) and 7 (+7). RESULTS: PA, CRP, AGP and PINI were significantly different on day +1 from day -1. While AGP and PINI were still significantly higher than that of day -1, PA and CRP returned to the preoperative levels on day +7. CONCLUSION: PA, CRP and AGP measurements are superior to PINI for assessing postoperative metabolic changes in term neonates following uncomplicated major surgery on early and late phase. But this comparison must be performed in the management of more complex cases to determine which one is better to indicate morbidity and mortality.

Acute-phase changes in children recovering from minor surgery.

The metabolic response to surgical stress is a nonspecific increase in hepatic synthesis of some specialized acute-phase proteins and a decrease in plasma concentrations of visceral proteins following surgical trauma. This study was undertaken determine which specific proteins were the better clinical indices in monitoring the metabolic response to surgical stress in children recovering from minor surgery. Forty-four patients undergoing elective inguinal surgical procedures under general anesthesia were studied. Blood samples were collected preoperatively (-1) and at 1(+1) and 5(+5) days postoperatively to determine albumin (AL), Prealbumin (PA), C-reactive protein (CRP), and a1-acid glycoprotein (AGP) values, and to calculate the prognostic inflammatory and nutritional index (PINI). Mean AL values were the same on all days. Mean PA +1 was significantly lower than PA -1 and PA +5 (P < 0.001). Median CRP +1 and mean AGP +1 values were significantly higher than median CRP -1 and mean AGP -1 (P < 0.0001), respectively. Although there was a decrease after postoperative day 1, median CRP +5 and mean AGP +5 values were still significantly higher than preoperative values (P < 0.01 and P < 0.0001). Moreover, the median PINI +1 was also greater than PINI -1 and PINI +5 (P < 0.0001), but the median PINI+5 was significantly higher than PINI -1 (P < 0.01). Median percent changes of PINI values were significantly higher than those of the other parameters from both preoperatively to postoperative day 1 and preoperatively to postoperative day 5. Although several specific proteins (AL, PA, CRP, and AGP) have been evaluated as indicators of the acute metabolic response, we suggest that the PINI is more valuable for reflecting the response to surgical stress in patients recovering from minor surgery.