Quality of life study of patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma treated with gemcitabine+nab-paclitaxel versus gemcitabine alone: AX-PANC-SY001, a randomized phase-2 study.

BACKGROUND: Combination of gemcitabine and nab-paclitaxel has superior clinical efficacy than gemcitabine alone. Nevertheless, health-related quality of life. (QoL) associated with this combination therapy when administered at first-line in advanced pancreatic adenocarcinoma is unknown. METHODS: A total of 125 patients were randomized to combination therapy (1000 mg/m2 gemcitabine + 125 mg/m2 nab-paclitaxel) and single-agent gemcitabine (1000 mg/m2) arms to take treatment weekly for 7 of 8 weeks, and following 3 of 4 weeks, until progression or severe toxicity. Primary endpoints were three-months of definitive deterioration free percent of patients, and QoL. RESULTS: Overall QoL analyses showed that 34 and 58.3% of cases in gemcitabine and gemcitabine+nab-P arms had no deterioration in 3rd month QoL scores (p = 0.018). These proportions were 27.3 and 36.6% in 6th month assessments, respectively (p = 0.357). Median overall survivals in combination and single-agent arms were 9.92 months and 5.95 months, respectively (HR: 0.64, 95% CI: 0.42-0.86, p = 0.038). Median progression free survivals in these treatment arms were 6.28 and 3.22 months, respectively (HR: 0.58, 95% CI: 0.39-0.87, p = 0.008). Median time-to-deterioration were 5.36 vs 3.68 months, and objective response rates were 37.1% vs 23.7% (p = 0.009), respectively in combination and single-agent arms. CONCLUSIONS: Combination therapy with gemcitabine + nab-paclitaxel had better overall and progression-free survival than gemcitabine alone. Also, combination therapy showed increased response rate without toxicity or deteriorated QoL. Combination treatment with gemcitabine and nab-paclitaxel may provide significant benefit for advanced pancreatic cancer. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov as NCT03807999 on January 8, 2019 (retrospectively registered).

Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation of pathological response with diffusion-weighted MRI and apoptotic markers.

PURPOSE: In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers. METHODS: The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed. RESULTS: No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72). CONCLUSIONS: Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.

Can complementary 68Ga-DOTATATE and 18F-FDG PET/CT establish the missing link between histopathology and therapeutic approach in gastroenteropancreatic neuroendocrine tumors?

UNLABELLED: Gastroenteropancreatic neuroendocrine tumors (GEPNETs) are indolent neoplasms presenting unpredictable and unusual biologic behavior that causes many clinical challenges. Tumor size, existence of metastasis, and histopathologic classification remain incapable in terms of treatment decision and prognosis estimation. This study aimed to compare (68)Ga-DOTATATE and (18)F-FDG PET/CT in GEPNETs and to investigate the relation between the complementary PET/CT results and histopathologic findings in the management of therapy, particularly in intermediate-grade patients. METHODS: The relation between complementary (68)Ga-DOTATATE and (18)F-FDG PET/CT results of 27 GEPNET patients (mean age, 56 y; age range, 33-79 y) and histopathologic findings was evaluated according to grade and localization using standardized maximum uptake values and Ki67 indices. Grade 2 (G2) patients were further evaluated in 2 groups as G2a (3%-9%) and G2b (10%-20%) according to Ki67 indices. RESULTS: The sensitivity of (68)Ga-DOTATATE and (18)F-FDG PET/CT was 95% and 37%, respectively, and the positive predictive values were 93.8% and 36.2%, respectively. The sensitivity in detecting liver metastasis, lymph nodes, bone metastasis, and primary lesion was 95%, 95%, 90%, and 93% for (68)Ga-DOTATATE and 40%, 28%, 28%, and 75% for (18)F-FDG, respectively. Statistically significant differences were found between grades 1-2, 2a-2b, and 1-2b with respect to (68)Ga-DOTATATE PET/CT as well as between 1-2a and 1-2b with respect to (18)F-FDG PET/CT. However, no statistical differences were found between 1 and 2a (P > 0.05) for (68)Ga-DOTATATE and 2a and 2b (P = 0.484) for (18)F-FDG. The impact of the combined (18)F-FDG and (68)Ga-DOTATATE PET/CT on the therapeutic decision was 59%. CONCLUSION: Combined (68)Ga-DOTATATE and (18)F-FDG PET/CT is helpful in the individual therapeutic approach of GEPNETs and can overcome the shortcomings of histopathologic grading especially in intermediate-grade GEPNETs.

Synuclein-gamma predicts poor clinical outcome in esophageal cancer patients.

The synuclein gamma (SNCG) protein, a member of neuronal protein family synuclein, has been considered as a promising potential biomarker as an indicator of cancer stage and survival in patients with cancer. The present study was conducted to evaluate the prognostic value of SNCG in patients with esophageal carcinoma (EC). SNCG levels were assessed immunohistochemically in cancer tissues from 73 EC patients. Median age was 57 (range, 29-78) years old. Forty-seven percent of the patients were male. Thirty-seven percent of the patients had upper or middle localized tumor whereas 59 % had epidermoid carcinoma. More than half of the patients (61 %) had undergone operation where 57 % received adjuvant treatment including chemotherapy or chemotherapy plus radiotherapy. Median overall survival was 11.3 ± 1.8 months (95% confidence interval (CI): 7.7-14.9 months). SNCG positivity was significantly associated with the histological type of EC and inoperability (for SNCG positive vs. negative group; epidermoid 80 vs. 53 %; p = 0.05 and inoperable 59 vs.32 %; p = 0.04, respectively). Lymph node metastasis, inoperability and receiving no adjuvant treatment had significantly adverse effect on survival in the univariate analysis (p = 0.01, p < 0.001, and p = 0.001, respectively). SNCG positivity had significantly adverse effect on survival in both univariate and multivariate analysis (p = 0.02 and p = 0.01, respectively). Our results are the first to suggest that SNCG is a new independent predictor for poor prognosis in EC patients in the literature.

Comparison of two different adjuvant treatment modalities for pN3 gastric cancer patients after D2 lymph node dissection: can we avoid radiotherapy in a subgroup of patients?

Adjuvant chemoradiotherapy (CRT) is the standard of care for gastric cancer patients in the USA. However, in countries where D2 lymph node dissection is performed, the effect of radiotherapy on locoregional recurrence is controversial. The aim of this study is to compare the outcomes in pN3 gastric cancer patients following two adjuvant treatment modalities: chemotherapy (CT) and CRT after D2 lymph node dissection. Between 2005 and 2009, 71 gastric cancer patients who underwent D2 lymph node dissection and had pTanyN3M0 stage (according to AJCC 6th edition) were identified. Fifty-three patients were treated with CT and 18 patients received CRT. CRT consisted of bolus fluorouracil (FU) 425 mg/m(2) and leucovorin 20 mg/m(2) before, after, and during radiotherapy. For the CT arm, treatment protocols consisted of combination therapies involving FU and cisplatin as the backbone. Median overall survival (OS) and disease-free survival (DFS) rates for all patients were 26.3 months (15-37.7 months) and 12.5 months (8-17.1 months). Median OS in CT arm was 26.8 months and it was 34.2 months for CRT arm (p = 0.74). DFS rates did not differ statistically either (p = 0.56, 12.5 and 15.2 months for CT and CRT, respectively). Locoregional recurrence rates were also similar (p = 0.63). Only metastatic/dissected lymph node ratio (≥0.75) was identified as a prognostic factor in both univariate and multivariate analyses for DFS. Comparison of CT versus CRT for N3 stage gastric cancer patients with D2 lymph node dissection did not reveal any statistically significant difference in survival rates and locoregional recurrence.

Penile metastasis of cutaneous malignant melanoma: a true hematogenous spread?: Case report and review of the literature.

Penile involvement has been implicated as a metastatic site in several tumors; approximately 300 cases have been reported. Of these, only two cases showed cutaneous melanoma as the primary site. Our patient presented with a painless mass on the penile shaft together with other distant metastases. A magnetic resonance image demonstrated two sites of deposit in the subcutaneous tissue on the radix penis, and fine needle aspiration cytology of the mass confirmed the presence of melanoma cells. The patient died of systemic disease without any further treatment for penile involvement. This unusual involvement is presented with a review of the related literature.

Timing of death from tumor recurrence after curative gastrectomy for gastric cancer.

In Western literature, there are few studies investigating the predictors of early versus late recurrence after curative gastrectomy for gastric cancer. The current study analyzed (1) patients who died of recurrent gastric cancer and (2) prognostic factors, which can be applied to timing of death from tumor recurrence. Of 492 patients who underwent curative resection (R0) for gastric cancer in the Department of Surgery, Medical Faculty of Istanbul between 1994 and 2000, 142 patients who died of recurrence were included into study. None of the patients had received postoperative adjuvant treatment. The patients were divided into 2 groups: an early recurrence group that included 102 patients who recurred and died within 2 years after surgery, and a late recurrence group, which included 40 patients who died of recurrence more than 2 years after surgery. Clinicopathologic findings were compared between the early and late recurrence groups. Multivariate analysis was performed to investigate the independent factors, which are predictive for early versus late recurrence, and prognostic factors independently associated with the survival period. In multivariate analysis, the early recurrence group, when compared with the late recurrence group, was characterized by lymph node metastasis (N1-3 versus N0; P = 0.002). Overall survival was influenced by nodal status (N1-3 versus N0; P = 0.003), type of operation performed (radical total versus radical subtotal gastrectomy; P = 0.003), Eastern Cooperative Oncology Group performance status (PS 3-4 versus PS 1-2; P = 0.004), and tumor localization (cardia versus corpus and antrum; P = 0.046). In contrast, T stage of the disease was not prognostic for survival, although it was close to statistical significance (P = 0.066). Multivariate analysis showed that poorer performance status at initial presentation (P = 0.001) and lymph node metastasis (P = 0.032) independently correlated with overall survival (P = 0.002). Lymph node status was the most important factor predictive for early versus late recurrence and patients with lymph node metastases were at more risk of death within 2 years after curative operation for gastric cancer. Postoperative chemoradiotherapy should be especially recommended for patients at high risk of recurrence of adenocarcinoma of the stomach or who have undergone curative resection.