Prognostic Utility of Prechemoradiotherapy Albumin-to-Alkaline Phosphatase Ratio in Unresectable Locally Advanced Pancreatic Carcinoma Patients

Background. We investigated the prognostic usefulness of prechemoradiotherapy (CRT) albumin-to-alkaline phosphatase ratio (AAPR) in unresectable locally advanced pancreatic adenocarcinoma (LAPAC) patients managed with definitive concurrent CRT (CCRT). Methods. A sum of 136 LAPAC patients who consecutively underwent definitive CCRT was retrospectively analyzed. The AAPR (serum albumin (g/dL)/serum alkaline phosphatase (IU/L)) was calculated by using the parameters obtained from the routine biochemistry tests on the first day of the CCRT. Ideal AAPR cutoff was sought by utilizing receiver operating characteristic (ROC) curve analysis. The primary and secondary endpoints were the impact of the AAPR on the overall survival (OS) and progression-free survival (PFS) results, respectively. Results. At a median follow-up of 14.8 months (range: 3.2-85.7), the median PFS and OS times were 7.5 (95% confidence interval (CI): 6.0-9.0) and 14.9 months (95% CI: 11.9-17.9), respectively. The ideal common AAPR cutoff was identified at the rounded 0.46 (area under the curve: 72.3%; sensitivity: 71.2%; specificity: 70.3%) point that dichotomized the patients into two groups: low AAPR (L-AAPR; N = 71 ) and high AAPR (H-AAPR; N = 65 ) groups, respectively. Comparative survival analyses showed that the L-AAPR cohort had significantly shorter median PFS (6.8 (95% CI: 5.7-7.9) versus 11.3 (95% CI: 9.9-12.7) months; P = 0.005 ) and OS (12.8 (95% CI: 10.6-15.0) versus 19.2 (95% CI: 16.9-21.5) months; P = 0.001 ) durations than their H-AAPR counterparts, separately. Albeit the N1-2 ( P = 0.004 ) and CA 19 ‐ 9 > 90 U / mL ( P = 0.008 ) were also found to be associated with inferior outcomes, yet the results of the multivariate analyses ascertained the L-AAPR as an independent indicator of diminished PFS ( P = 0.003 ) and OS ( P = 0.002 ) results. Conclusion. The present results proposed that the pretreatment AAPR < 0.46 was a novel independent indicator of adverse PFS and OS in unresectable LAPAC patients undergoing definitive CCRT.

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Delta-volume radiomics of induction chemotherapy to predict outcome of subsequent chemoradiotherapy for locally advanced hypopharyngeal cancer

Tumori Journal ◽

10.1177/03008916211039018 ◽

2021 ◽

pp. 030089162110390

Author(s):

Che-Wei Su ◽

Jehn-Chuan Lee ◽

Yi-Fang Chang ◽

Nai-Wen Su ◽

Pei-Hsuan Lee ◽

...

Keyword(s):

Induction Chemotherapy ◽

Concurrent Chemoradiotherapy ◽

Locally Advanced ◽

Area Under The Curve ◽

Progression Free Survival ◽

Hypopharyngeal Cancer ◽

Imaging Biomarker ◽

Free Survival ◽

Before And After ◽

Selection Operator

Introduction: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is recommended for larynx-preserving treatment of locally advanced hypopharyngeal cancer (LAHC). However, the conventional evaluation of response is not robust enough to predict the outcome of subsequent treatments. This study aimed to develop an imaging biomarker using changes in radiomic features in invasive tumor front (ITF) by IC to predict treatment outcome of subsequent CCRT in LAHC. Methods: From 2006 to 2018, 59 computed tomography (CT) scan images before and after IC in patients with LAHC were used to contour the gross tumor volumes (GTVs). A total of 48 delta-volume radiomics features were acquired from the absolute spatial difference of GTVs (delta-GTV) before and after IC, conceptually representing a consistent portion of ITF. Least absolute shrinkage and selection operator regression (LASSO) was used to select features for establishing the model generating radiomic score (R score). Results: A model including 5 radiomic features from delta-GTV to predict better progression-free survival (PFS) of patients receiving subsequent CCRT was established. The R score was validated with all datasets (area under the curve 0.77). Low R score (<–0.16) was associated with improved PFS ( p < 0.05). Conclusions: The established radiomic model for ITF from radiomic features of delta-GTV after IC might be a potential imaging biomarker for predicting clinical outcome of subsequent CCRT in LAHC.

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Radiotherapy Scheme Effect on PD-L1 Expression for Locally Advanced Rectal Cancer

Cells ◽

10.3390/cells9092071 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2071

Author(s):

Jihane Boustani ◽

Valentin Derangère ◽

Aurélie Bertaut ◽

Olivier Adotevi ◽

Véronique Morgand ◽

...

Keyword(s):

Rectal Cancer ◽

Tumor Regression ◽

Checkpoint Inhibitors ◽

Objective Response ◽

Locally Advanced ◽

Progression Free Survival ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Tumor Regression Grade ◽

The Impact

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.

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Neoadjuvant radiotherapy in the approach of locally advanced breast cancer

ESMO Open ◽

10.1136/esmoopen-2019-000640 ◽

2020 ◽

Vol 5 (2) ◽

pp. e000640 ◽

Cited By ~ 1

Author(s):

Cláudia Sousa ◽

Mafalda Cruz ◽

Ana Neto ◽

Kayla Pereira ◽

Marta Peixoto ◽

...

Keyword(s):

Breast Cancer ◽

Advanced Breast Cancer ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Progression Free Survival ◽

Complete Response ◽

Intrinsic Subtype ◽

Advanced Breast ◽

Neoadjuvant Radiotherapy ◽

The Impact

BackgroundApproximately 4% of European patients are diagnosed with locally advanced breast cancer (LABC), a clinical condition commonly associated with poorer prognosis. Systemic therapy is the recommended initial treatment and when inoperability criteria prevails, radiotherapy (RT) should be used for tumour downstaging. This study intends to evaluate the impact of neoadjuvant radiotherapy (NART) in the treatment of inoperable LABC.MethodsA retrospective study of female patients, submitted to the NART between January 2014 and December 2018 at our institution. The evaluation of pathological response (pR) was made based on Pinder criteria. Primary endpoint: pR. Secondary endpoints: overall survival (OS) and progression-free survival (PFS). OS and PFS were calculated using the Kaplan-Meier method. Differences between groups were compared using Student’s t-test, ANOVA (Analysis of variance) and χ2 test. The statistical analyses were performed using Stata (V.13).ResultsA total of 76 patients were included, 18% with breast complete response. The 5 years OS was 54% and PFS was 61%. Subgroup analysis showed that pR >90% is correlated with a better OS (p=0.004). Basal-like intrinsic subtype is correlated with worse OS and PFS (p<0.05). No relation was found between response and age, intrinsic subtype, treatment performed and clinical T stage.ConclusionOur study confirms that NART is an effective downsizing treatment in inoperable LABC, allowing for a surgical resection regardless of the systemic treatment performed. Response to NART is independent of the intrinsic subtype and pR >90% is correlated with a better OS. Prospective studies to explore predictive response biomarkers are necessary in order to improve patient selection and optimisation of the treatment.

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A randomized phase III study of gemcitabine (G) versus GV1001 in sequential combination with G in patients with unresectable and metastatic pancreatic cancer (PC)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.4601 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 4601-4601 ◽

Cited By ~ 5

Author(s):

T. Buanes ◽

J. Maurel ◽

W. Liauw ◽

M. Hebbar ◽

J. Nemunaitis

Keyword(s):

Overall Survival ◽

Performance Status ◽

Locally Advanced ◽

Peptide Vaccine ◽

Progression Free Survival ◽

Phase Iii ◽

Ecog Performance Status ◽

Delayed Treatment ◽

Sequential Combination ◽

The Impact

4601 Background: A phase I/II study with GV1001, a telomerase peptide vaccine, showed a median overall survival (OS) of 8.6 months in non-resectable PC (Bernhardt SL et al, Br J Cancer. 2006;95:1474–1482). This phase III trial was conducted to determine the impact on overall survival of G monotherapy vs. GV1001 in sequential combination with G in unresectable and metastatic PC. Methods: Eligible patients (pts) had chemotherapy-naive, advanced PC and ECOG performance status 0–1. Pts were randomized 1:1 to receive arm A: G (1,000 mg/m2 30 min i.v.) weekly for 7 weeks (w), 1w off and then 3w during 4-weekly cycles, or arm B: GV1001 0.56 mg s.c. plus GM-CSF as immune adjuvant on days 1, 3, 5, 8, 15, 22, 36, then every 4 weeks. Patients who progressed clinically or radiologically during GV1001 continued on GV1001 and concomitant gemcitabine. CT scans were performed every 8 weeks. The primary end-point was OS. A sample size of 520 patients allowed the detection of a hazard ratio (HR) of 0.73 (B/A), with 2α = 0.05 and 90% power. Results: Between June 2006 and May 2008, 365 pts were enrolled (A / B; 182 / 183). The study was stopped prematurely due to a preliminary analysis with 178 events showing no survival benefit of GV1001. Pts were well balanced for baseline characteristics: male 59.3% / 62.8%; median age 61y / 61y; ECOG PS 0 34.3% / 36.7%; locally advanced 22.4% / 20.7%. As of August 2008, 238 pts (A / B : 114 / 124) had died. Median OS was 7.3 / 5.9 months (HR 0.8; 95% CI 0.6–1.0). Median progression-free survival (PFS) was 3.7 / 1.9 months (HR 0.5; 95%CI 0.4–0.7). Grade 3–4 AEs: gastrointestinal 6% / 8%, infection 5% / 5%, vascular disorders 2% / 3%, neutropenia 6% / 3%. Conclusions: GV1001 did not show efficacy in sequential combination with G in advanced PC. The advantage of G monotherapy over the sequential combination may be due to the delayed treatment with G in arm B. [Table: see text]

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Surgery Prolongs the Survival of Patients with Metastatic, Recurrent, or Unresectable Locally Advanced Gastrointestinal Stromal Tumors Response to Imatinib Mesylate Treatment: A Systematic Review and Meta-analysis

10.21203/rs.3.rs-212183/v1 ◽

2021 ◽

Author(s):

Weihao Li ◽

Jianhong Peng ◽

Xinyue Li ◽

Rongxin Zhang ◽

Binyi Xiao ◽

...

Keyword(s):

Imatinib Mesylate ◽

Gastrointestinal Stromal Tumors ◽

Locally Advanced ◽

Progression Free Survival ◽

Final Analysis ◽

Cochrane Library ◽

Stromal Tumors ◽

Pooled Data ◽

Surgery Group ◽

The Impact

Abstract Background The role of surgery in patients with metastatic, recurrent or unresectable locally advanced gastrointestinal stromal tumors (GIST) who respond to imatinib mesylate (IM) treatment is still not formally defined. Therefore, we systemically searched and analyzed the available literature to evaluate the oncologic benefits of surgery in this specific population. Methods A systematic literature search of the PubMed, Embase, and Cochrane Library databases was performed to identify relevant articles on July 16, 2020. Pooled data analysis was also performed using Review Manager. Results Totally 10 studies including 1188 patients (410 patients in the surgery group and 778 patients in the no surgery group) were included in the final analysis. No significant differences in baseline clinical characteristics were found except that patients in the surgery group were significantly younger (WMD, -5.02, 95% CI, -8.38 to -1.67, P = 0.003). In the overall population, pooled data showed a significant improvement in overall survival (OS) (HR, 0.62; 95% CI, 0.53 to 0.73; P < 0.0001) and progression-free survival (PFS) (HR, 0.57; 95% CI, 0.44 to 0.72; P < 0.0001) with surgery. In the subgroup analysis, the impact of surgery on patient response to IM treatment was further confirmed (OS: HR, 0.67; 95% CI, 0.55 to 0.81; P < 0.0001; PFS: HR, 0.62; 95% CI, 0.46 to 0.82; P = 0.009). Conclusions Surgery prolongs the OS and PFS of patients with metastatic, recurrent, or unresectable locally advanced GIST who respond to IM treatment. Future prospective, multicenter RCTs are warranted.

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The impact of trans-arterial embolization on the result of chemoradiotherapy in oral cavity cancer

Ear Nose & Throat Journal ◽

10.1177/01455613211054181 ◽

2021 ◽

pp. 014556132110541

Author(s):

Dang Nguyen Van ◽

Quang Le Van ◽

Nhung Nguyen Thi Thu ◽

Giang Bui Van ◽

To Ta Van

Keyword(s):

Oral Cavity ◽

Concurrent Chemoradiotherapy ◽

Oral Cavity Cancer ◽

Locally Advanced ◽

Arterial Embolization ◽

Progression Free Survival ◽

Bleeding Complications ◽

Selective Embolization ◽

Acute Bleeding ◽

The Impact

Objectives: Evaluation of the hemostatic effect of trans-arterial embolization on patients with advanced oral cavity cancer who had bleeding complications while undergoing definitive concurrent chemoradiotherapy (CCRT). Additionally, assess the effect of trans-arterial embolization on treatment response following concurrent chemoradiotherapy, as well as overall survival (OS) and progression-free survival (PFS) in the group of patients following the intervention. Method: From September 2018–June 2021, a retrospective descriptive study was conducted on 16 patients with inoperable, locally advanced oral cavity cancer who received definitive concurrent chemoradiotherapy, experienced acute bleeding complications, and received selective intravascular intervention with various embolization materials at Vietnam National Cancer Hospital. Results: After selective embolization, 16/16 patients ceased bleeding; 1 patient re-bled for the second time after 3 weeks. The average duration of chemoradiotherapy interruption due to intervention was 6.7 days. After CCRT, 15/16 (93.75%) patients achieved a response, with 9/16 (56.25%) patients achieving a complete response. The median OS was 14 months (range, 3–26 months), and the median PFS was 10 months (range, 3–20 months). There were no significant complications, particularly neurological side effects. ConclusionsTumor bleeding is a common and serious complication of CCRT treatment in patients with locally advanced oral cavity cancer. Embolization is a safe and effective method of controlling acute bleeding that has no adverse effect on the outcome of definitive concurrent chemoradiotherapy.

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A multicenter randomized phase II study of full-dose gemcitabine and concurrent radiotherapy comparing gemcitabine alone for the unresectable locally advanced pancreatic adenocarcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15512 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15512-e15512

Author(s):

T. Ioka ◽

R. Takakura ◽

A. Nakaizumi ◽

S. Tanaka ◽

H. Iishi ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Concurrent Chemoradiotherapy ◽

Locally Advanced ◽

Progression Free Survival ◽

Free Survival ◽

Full Dose ◽

Concurrent Radiotherapy ◽

Pancreatic Cancers ◽

Randomized Phase Ii ◽

Locally Advanced Pancreatic Adenocarcinoma

e15512 Background: Some of locally advanced pancreatic cancers (LAPC) are considered to include a potential micro metastasis. We think that full-dose of gemcitabine (GEM) improve the outcome of LAPC. We report the efficacy of full-dose GEM and concurrent radiotherapy, comparing GEM alone for unresectable LAPC. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma were eligible for this study. We decide that LAPA which involved a major artery with CT imaging was unresectable. Patients were randomized into a concurrent chemoradiotherapy (CRT) group and a chemotherapy alone (CTX) group. GEM was given intravenously at a dose of 1,000 mg/msq over 30 min on days 1, 8 and 15 of each 28-day cycle and repeated until disease progression in both groups. Patients randomized into CRT group received a limited field irradiation with a total dose of 50 Gy in 25 sessions during first two cycles. The two groups were compared for mean survival, progression free survival and safety. Results: From September 2002 to April 2005, 80 patients were randomized at two institutions into the two arms of the trial (40 patients to CRT group and 40 patients to CTX group). The CRT group had better results than the CTX group as measured by mean survival time (391 vs 372 days, P< 0.02) and progression free survival (237 vs 128 days, P< 0.01). There were no differences in the safety between both groups. Conclusions: The concurrent chemoradiotherapy with full-dose GEM is effective and feasible in patients of LAPC compared with full-dose GEM alone. No significant financial relationships to disclose.

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Germline ATM mutations on survival in metastatic pancreatic cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e16746 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e16746-e16746

Author(s):

Arjan Gower ◽

Gillian Gresham ◽

Nanor Haladjian ◽

John Lee ◽

Camille Ng ◽

...

Keyword(s):

Pancreatic Cancer ◽

Metastatic Disease ◽

Cox Regression ◽

Locally Advanced ◽

Progression Free Survival ◽

Underlying Mechanism ◽

First Line ◽

Increased Risk ◽

Atm Protein ◽

The Impact

e16746 Background: Ataxia telangiectasia mutated (ATM) protein is a DNA damage repair enzyme and regulates normal cell-cycle mechanisms. Germline ATM mutations are associated with increased risk for developing pancreatic cancer (PC), occurring in approximately 2% of PC patients (pts). The role of germline ATM mutations in PC is not well defined. The objective of this study was to compare survival outcomes in patients with germline ATM mutations compared to somatic ATM mutations in PC. Methods: Tumor genomic profiling was completed in 144 PC patients at a single institution in the US, where pts were included in the analysis if they had either germline ATM mutations or somatic ATM mutations. Clinical outcomes were compared between pts with germline ATM mutations and pts with somatic ATM mutations only. Adjusted Cox regression models were fit to evaluate the impact of ATM mutation on overall survival (OS), calculated from treatment (tx) initiation to death, and progression free survival (PFS) calculated from tx initiation to first progression. Results: From 144 PC pts evaluated, 7 pts (4.9%) had germline ATM mutations, all of whom presented with metastatic disease, and 14 pts (9.7%) with somatic ATM mutations only, of whom 10 presented with metastatic disease and 4 who initially presented with locally advanced PC. The majority of pts (15/21), including all 7 pts with germline ATM mutations and 8 with somatic ATM mutations, were treated with first line gemcitabine and abraxane. Median OS was not reached in patients with germline mutations, and 11 months for patients with somatic mutations. Pts with germline ATM mutations had significantly higher OS (HR: 0.12, 95% CI 0.03-0.62, p = 0.01) and PFS (HR:0.26, 95%CI 0.07-0.91, p = 0.04) compared to patients with somatic ATM mutations only after adjusting for age, sex, and first-line tx. Conclusions: Pts with germline ATM mutations may experience greater survival benefit from tx compared to those with only somatic ATM mutations. Further research into the underlying mechanism is warranted.

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