Chemoradiation Therapy In Patients Research Articles

Who Will Benefit From Adjuvant Chemoradiation Therapy in Patients With Locally Advanced Gastric Cancer Following D2 Dissection: Do N3 Patients Need Additional Radiation?

Who Will Benefit From Adjuvant Chemoradiation Therapy in Patients With Locally Advanced Gastric Cancer Following D2 Dissection: Do N3 Patients Need Additional Radiation?

Feasibility and Efficacy of Preoperative Chemoradiation Therapy in Patients With Locally Advanced Gastric Cancer

Feasibility and Efficacy of Preoperative Chemoradiation Therapy in Patients With Locally Advanced Gastric Cancer

Correlation of Aurora-A expression with the effect of chemoradiation therapy on esophageal squamous cell carcinoma.

BackgroundChemoradiation therapy (CRT) is one of the most useful treatments for esophageal squamous cell carcinoma (ESCC). However, because some patients respond well to CRT and others do not, it is important to be able to predict response to CRT before beginning treatment by using markers. Aurora-A encodes a cell cycle regulated serine/threonine kinase that has essential functions in centrosome maturation and chromosome segregation. In this study, we investigated the relationship between the expression of Aurora-A and the response to CRT in patients with ESCC.MethodsWe immunohistochemically investigated the expression of Aurora-A in biopsy specimens of untreated primary tumors of 78 patients with ESCC and determined the relationship between Aurora-A levels and patient responses to CRT, which consisted of 5-fluorouracil plus cisplatin and 40 Gy of radiation.ResultsTumors were judged as Aurora-A positive when more than 10% of the cancer cells displayed a distinct positive nuclear anti-Aurora-A immunoreaction by immunohistochemical evaluation. The tumors of 46 of 78 patients (58.9%) displayed positive expression of Aurora-A. In terms of clinical response the percentage of patients showing complete response (CR), incomplete response/stable disease of primary lesion (IR/SD), and progressive disease (PD) was 19.2, 69.2, and 11.5%, respectively. In terms of histological response the tumor grade of the 41 patients who underwent surgery was as follows: grade 1, 48.8%; grade 2, 29.2%; grade 3, 22.0%. CRT was effective for patients who had Aurora-A (+) tumors (clinically: P = 0.0003, histologically: P = 0.036).ConclusionsOur results suggest that Aurora-A expression in biopsy specimens of primary tumors is associated with CRT efficacy in patients with ESCC. Assessment of Aurora-A expression in biopsy specimens maybe useful for regarding the potential utility of CRT therapy for patients with ESCC before treatment.

Association of beclin 1 expression with response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma.

Beclin 1 is an essential regulator of autophagy that is induced in response to cellular stress and serves to maintain cell survival in established tumors. We recently demonstrated that Beclin 1 suppression can sensitize colorectal cancer cells to radiation-induced DNA damage and apoptosis. Therefore, we hypothesized that the level of Beclin 1 expression may be associated with radiation sensitivity in vivo. We determined the association of Beclin 1 expression in pretreatment rectal cancer tissues with response to neoadjuvant chemoradiation in surgical resection specimens. Stages II and III (n = 96) rectal adenocarcinoma patients were treated with neoadjuvant chemoradiation followed by surgical resection with curative intent. Beclin 1 was analyzed by immunohistochemistry and the expression level was dichotomized at the median value with categorization into low and high groups. We identified 56 (58.3%) and 40 (41.7%) patients whose tumors had high- versus low-level Beclin 1 expression, respectively. Rectal cancers with high versus low Beclin 1 expression were significantly less likely to be downstaged after chemoradiation treatment (45% [25/55] vs. 58% [22/38]; p = 0.02). In a multivariable analysis adjusted for age, sex, histological grade and baseline tumor node metastasis (TNM) stage, the impact of Beclin 1 expression on tumor downstaging remained statistically significant (p = 0.03). The association of the level of Beclin 1 expression with the rate of tumor downstaging after chemoradiation is consistent with in vitro data, and suggests that Beclin 1 may be a predictive biomarker for the efficacy of chemoradiation in patients with rectal cancer.

Clinical Significance of Circulating Tumor Cells in Peripheral Blood of Patients with Esophageal Squamous Cell Carcinoma.

BackgroundEsophageal squamous cell carcinoma is an aggressive gastrointestinal tract cancer. To date, the presence of circulating tumor cells (CTC) has been reported as a prognostic factor in peripheral blood from patients with gastrointestinal cancers.MethodsThe CellSearch system was used to isolate and enumerate CTCs. A total of 90 patients with esophageal squamous cell carcinoma who received chemotherapy or chemoradiotherapy were enrolled. Peripheral blood specimens were collected before and after treatments.ResultsAt baseline analysis, CTCs were detected in 25 patients (27.8 %). Overall survival was significantly shorter in patients with than without CTCs. Follow-up blood specimens were obtained from 71 patients. Partial response, stable disease, and progressive disease after treatment were seen in 32, 12, and 27 patients, respectively. CTC positivity after treatment in the progressive disease group (40.7 %) was significantly higher than that of the partial response group (6.3 %). Patients with a change in CTC status from positive to negative had a good prognosis as well as patients without baseline CTCs.ConclusionsEvaluation of CTCs may be a promising indicator for predicting tumor prognosis and the clinical efficacy of chemotherapy or chemoradiation therapy in patients with esophageal squamous cell carcinoma.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-015-4392-8) contains supplementary material, which is available to authorized users.

Effectiveness of the apparent diffusion coefficient for predicting the response to chemoradiation therapy in locally advanced rectal cancer: a systematic review and meta-analysis.

The efficacy of the different apparent diffusion coefficients (ADCs) in predicting different responses to preoperative chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC) is controversial. We did this meta-analysis to evaluate the efficacy of different ADCs predicting different responses to CRT in patients with LARC.We systematically searched the MEDLINE, Embase, and Cochrane Library databases for articles published from January 1, 1990, to June 3, 2014. Pooled estimates were calculated using a bivariate random-effects model for the ADCs before and after CRT (pre- and post-ADC), as well as the change between the pre- and post-ADC (ΔADC). The values of the 3 ADCs for judging different response endpoints, which were defined according to the tumor grading (TRG) system and downstaging of T (tumor) or N (nodal) stages (TN downstaging), were assessed.We included 16 studies with a total of 826 patients. The sensitivity, specificity, DOR, and AUC were 75% (95% CI 57%-87%), 70% (95% CI 50%-84%), 6.81 (95% CI 2.46-18.88), and 0.79 (95% CI 0.75-0.82), respectively, for the pre-ADC in predicting a good response; 76% (95% CI 63%-85%), 87% (95% CI 78%-92%), 20.68 (95% CI 11.76-36.39), and 0.89 (95% CI 0.86-0.91), respectively, for the post-ADC; and 78% (95% CI 65%-87%), 77% (95% CI 62%-87%), 11.82 (95% CI 4.65-30.04), and 0.84 (95% CI 0.81-0.87), respectively, for the ΔADC. The post-ADC demonstrated the highest specificity and DOR (P < 0.001), although sensitivity did not differ between the 3 types of ADC (P = 0.380, 0.192, and 0.214). For predicting a pathological complete response (pCR), the post-ADC had the highest specificity (P < 0.001and 0.030) but lowest sensitivity (P < 0.001). The ΔADC had the highest DOR; however, this difference was not statistically significant (P = 0.146).The ADC is a reliable and reproducible measure and could serve as a promising noninvasive tool for evaluating the response to CRT in patients with LARC; the post-ADC and ΔADC are particularly promising. The ΔADC had the highest diagnostic performance to predict a pCR compared with the pre-ADC and post-ADC. The value of the ADCs to predict T or N downstaging requires further investigation.

Diffusion-weighted imaging for evaluating lymph node eradication after neoadjuvant chemoradiation therapy in locally advanced rectal cancer.

As lymph node (LN) eradication is the prerequisite for clinical surveillance or local excision for patients who have achieved a complete response after preoperative chemoradiation therapy (CRT), the radiological evaluation of LN eradication is important. To evaluate the added value of diffusion-weighted imaging (DWI) in the evaluation of LN eradication after CRT in patients with locally advanced rectal cancer (LARC). Ninety-five consecutive patients (64 men, 31 women; mean age, 59 years; range, 32-82 years) who underwent pre- and post-CRT 1.5-T MRI with DWI (b = 0, 1000 s/mm(2)) were enrolled. To evaluate the added value of DWI in the evaluation of LN eradication after CRT, two radiologists first independently read the pre- and post-CRT T2-weighted (T2W) images and then read the combined T2W imaging set and the pre- and post-CRT DWIs with a 4-week interval. The radiologists recorded their confidence scores for LN eradication using a 5-point scale on a per-patient basis. The diagnostic performances were compared between the two reading sessions for each reader with pair-wise comparisons of receiver-operating characteristic curves. Histopathological reports served as the reference standards for LN eradication. The study population consisted of an LN-eradicated group (n = 66) and a non-eradicated group (n = 29). The diagnostic performances did not significantly differ between the two reading sessions for the two readers (AUCs for reader 1, 0.770 and 0.774, P = 0.8155; for reader 2, 0.794 and 0.798, P = 0.8588). Adding DWI to T2W imaging provided no additional diagnostic benefit for the evaluation of LN eradication following CRT in patients with LARC.

A comparison of survival with chemoradiation therapy alone versus surgery and post-esophagectomy chemoradiation in patients with esophageal carcinoma

Background: Esophageal cancer is usually incurable. Aggressive treatments involving multimodality therapies have been offered to improve overall survival rates. It seems that various therapeutic approaches can have a different outcome and survival. The aim of our study was to compare survival with chemoradiation therapy (CRT) alone versus surgery and post-esophagectomy chemoradiation therapy (CRT-S) in patients with esophageal carcinoma. Methods: This historical cohort study assigned 226 patients with stage I to III esophageal cancer who referred to Radio-oncology clinic of Razi hospital from 2005-2011 for oncology treatment. Patients were categorized into two groups. One group treated by chemoradiation therapy (CRT) alone and other group treated with surgery and post-esophagectomy chemoradiation. Overall survival of two groups was compared. For statistical analysis SPSS was used and the comparison of groups was performed with Kaplan-Meier analysis and Log-rank test. Results: Of 266 patients with stage I to III esophageal cancer, 222 patients were in the CRT group and 44 patients were in the CRT-S group. 22 patients had stage I, 82 had stage II and 118 had stage III. Median survival was 17 month for the CRT group and 18 month for the CRT-S group. There was no significant difference in survival rate between chemoradiation therapy alone (CRT) and post-esophagectomy chemoradiation therapy (CRT-S) (P>0.005). Conclusion: Based on these data, we concluded that patients with tumors, especially of squamous cell carcinoma, that respond to initial chemoradiotherapy did not derive any survival benefit from subsequent surgery and three-month mortality was significantly higher in the surgery group. Surgery imposes a major emotional trauma and an excessive and unnecessary cost on the patient and the community health system. We conclude that it is better to use CRT for patients with non-advanced esophageal cancer.

Continuous Intravenous Pumping of Recombinant Human Endostatin Combined With Concurrent Chemoradiation Therapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer: Preliminary Data of a Prospective Multicenter Phase 1/2 Clinical Trial (NCT01733589): Locally Advanced Non-Small Cell Lung Cancer

Preclinical models have shown that recombinant human endostatin can transiently normalize the tumor vasculature to make it more efficient for oxygen delivery, which provides a treatment window of enhancing tumor radiosensitivity. This study is to evaluate the safety and efficacy of continuous intravenous pumping of endostatin combined with standard concurrent chemoradiation therapy for unresectable stage III non-small cell lung cancer (NSCLC).

Comparison of (18)F-FDG PET/CT methods of analysis for predicting response to neoadjuvant chemoradiation therapy in patients with locally advanced low rectal cancer.

The aim of this study was to prospectively investigate the predictive value of (18)F-FDG PET/CT semiquantitative parameters for locally advanced low rectal cancer (LARC) treated by neoadjuvant chemoradiation therapy (nCRT). 68 patients with LARC had (18)F-FDG PET/CT scans twice (baseline and 5-6 weeks post-nCRT). All patients underwent surgery with preservation of the sphincter 8 weeks later. (18)F-FDG PET/CT analysis was performed by visual response assessment (VRA) and semiquantitative parameters: SUVmax(baseline), SUVmean(baseline), MTV(baseline), TLG(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), TLG(post-nCRT); ΔSUVmax and mean and Response indexes (RImax% and RImean%). Assessment of nCRT tumor response was performed according to the Mandard's Tumor Regression Grade (TRG) and (y)pTNM staging on the surgical specimens. Concordances of VRA with TRG, and with (y)pTNM criteria were evaluated by Cohen's K. Results were compared by t student test for unpaired groups. ROC curve analysis was performed. VRA analysis of post-nCRT (18)F-FDG PET/CT scan for the (y)pTNM outcome showed sensitivity, specificity, accuracy, PPV, and NPV of 87.5%, 66.7%, 83.8%, 92.5%, and 53.3%, respectively. Concordances of VRA with TRG and with (y)pTNM were moderate. For the outcome variable TRG, the statistical difference between responders and non-responders was significant for SUVmax(post-nCRT) and RImean%; for the outcome variable (y)pTNM, there was a significant difference for MTV(baseline), SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. ROC analysis showed better AUCs: for the outcome variable TRG for SUVmax(post-nCRT), SUVmean(post-nCRT), and RImean%; for the outcome variable (y)pTNM for MTVbaseline, SUVmax(post-nCRT), SUVmean(post-nCRT), MTV(post-nCRT), RImax%, and RImean%. No significant differences among parameters were found. Qualitative and semiquantitative evaluations for (18)F-FDG PET/CT are the optimal approach; a valid parameter for response prediction has still to be established.

PET SUVmax as a Predictor of Pathologic Complete Response to Neoadjuvant Chemoradiation Therapy in Patients With Carcinoma of the Esophagus

PET SUVmax as a Predictor of Pathologic Complete Response to Neoadjuvant Chemoradiation Therapy in Patients With Carcinoma of the Esophagus

Concurrent Chemoradiation Therapy in Patients With Locally Advanced NSCLC: Toxicity and Clinical Assessment Using VMAT Technique

Concurrent Chemoradiation Therapy in Patients With Locally Advanced NSCLC: Toxicity and Clinical Assessment Using VMAT Technique

Is Marital/Partner Status Associated With Survival in Patients With Resectable Pancreatic Cancer Treated With Adjuvant Postoperative Multi-Modality Therapy?: Results of Secondary Analysis of RTOG 9704

Two recently published studies based on analyses of Surveillance, Epidemiology, and End Results (SEER) data disclosed a statistically significant survival advantage for married/partnered patients with pancreatic cancer. However, the SEER data base does not contain detailed treatment information and therefore neither study specifically looked at survival in patients with resected pancreatic cancer who underwent combined modality adjuvant therapy. Since the impact of marital/partner status on survival in this cohort of aggressively treated patients has not been reported, this study was undertaken. A secondary analysis of RTOG 97-04, a phase III clinical trial of post-operative adjuvant chemotherapy and chemo-radiation therapy for patients with resected pancreatic carcinoma, was performed. Socio-demographic co-variables analyzed with respect to survival included gender (male vs female), age (<60 years vs ≥ 60 years), and marital status (married/partnered vs single). Survival analysis was performed using the product limit method and compared using the log rank test. Multivariable analysis was performed using the Cox proportional hazards regression model. Of the 531 patients enrolled in RTOG 97-04, complete socio-demographic data was available for 451. At the time of the secondary analysis 368 (82%) of the patients had died. Median patient age was 61 years (range 33 to 85 years), 271 (74%) were married/partnered, and 256 (56%) were male. Multivariable analysis disclosed that marital/partner status was not statistically significantly (p = 0.52) associated with overall survival. This secondary analysis of data from RTOG 97-04 demonstrated no association between marital/partner status and survival in patients with resected pancreatic cancer who received adjuvant post-operative chemo-radiation therapy. This finding suggests that while married patients with pancreatic cancer in general have a survival advantage, being married/partnered does not provide a survival advantage for patients with resected pancreatic cancer who undergo aggressive post-operative adjuvant multi-modality therapy.

Trends in the use of evidence-based therapy for resectable gastric cancer.

Two pivotal randomized controlled trials (RCTs), the Intergroup (INT-0116) and Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trials, demonstrated a survival benefit of multimodality therapy in patients with resectable gastric cancer. The purpose of this study was to determine utilization rates of these treatment regimens in the United States and to identify factors associated with receipt of evidence-based care. We performed a retrospective cohort study of patients with Stage IB-IV (M0) gastric adenocarcinoma who underwent resection from 1991 to 2009 using the linked SEER-Medicare database. Only 19.1% of patients received post-operative chemoradiation therapy (CRT), and 1.9% received peri-operative chemotherapy; most patients underwent surgery alone (60.9%). Patients with more advanced stage, younger age, and fewer comorbidities were more likely to receive evidence-based care. We found no association between National Cancer Institute (NCI) designation and delivery of multimodality therapy. However, patients who underwent medical oncology consultation were much more likely to receive evidence-based treatment (OR 3.10, 95% CI 2.35-4.09). Rates of peri-operative chemotherapy and post-operative CRT in patients with resected gastric cancer remain remarkably low, despite high-quality RCT evidence demonstrating their benefit. Furthermore, NCI designation does not appear to be associated with administration of evidence-based treatment.

Assessment of interstitial lung disease associated with chemotherapy alone and chemoradiation therapy in patients with pancreatic cancer.

e15194 Background: For pancreatic cancer (PC), the regimens which have been approved in Japan are gemcitabine(G), S-1(S), erlotinib combined with G(GE),and GS. And we have conducted chemoradiation ...

Chromosomal instability portends superior response of rectal adenocarcinoma to chemoradiation therapy

Persistent chromosome segregation errors represent a conspicuous feature of human neoplasms. It is widely accepted that this chromosomal instability is associated with poor prognosis; however, its effect on therapeutic response is a matter of conjecture. Here, the role of chromosome segregation errors in the response of patients with rectal adenocarcinoma to chemoradiation therapy (CRT) was examined. Pretreatment samples from 62 patients were surveyed for evidence of chromosome mis-segregation and mis-segregation frequency was correlated to the pathological response to CRT as determined by the tumor regression grade after surgical resection of irradiated tumors. Surprisingly, it was found that errors in chromosome segregation predicted enhanced pathological response of rectal adenocarcinoma to CRT (odds ratio, 3.9; P = .02). Furthermore, tumor response inversely correlated with the frequency of cells that exhibited segregation errors during anaphase (correlation coefficient, 0.94; P < .05). Strikingly, elevated chromosome mis-segregation combined with decreased levels of the DNA damage repair protein Mre11 portended a markedly enhanced response (odds ratio, 54.0; P = .008). The results of the current study demonstrate that chromosomal instability is a favorable predictor of response to CRT in patients with locally invasive rectal adenocarcinoma. Therefore, the authors propose that downstream structural damage to chromosomes resulting from segregation errors potentiates the effect of DNA-damaging therapies and synergizes with deficiencies in the DNA repair machinery. This work identifies a novel mechanistic marker that foretells treatment response to CRT and suggests that concomitant targeting of whole-chromosome segregation and DNA repair may constitute an effective therapeutic strategy.

Arginine deiminase: A novel radiosensitizer in pancreatic cancer in vitro and in vivo.

221 Background: The benefits of chemoradiation therapy in patients with locally advanced pancreatic cancer (LAPC) are limited due to the inherent radioresistance of pancreatic cancer (PC) and high systemic toxicity of current radiosensitizers (e.g., gemcitabine). Hence, the search for newer radiosensitizers with unique anticancer properties continues. Single amino acid arginine starvation is a new promising therapeutic approach for solid tumors (e.g., PC), that are auxotrophic for non-essential amino acids. Arginine degrading enzyme, arginine deiminase (ADI), deprives cells of arginine and thereby exerts its anti-proliferative effects, especially in cancer cells deficient in enzyme argininosuccinate synthase (ASS1). Here we evaluate the effects of ADI-polyethylene glycol formulation (ADI-PEG20) as a radiosensitizer in PC. Methods: The toxicity of ADI-PEG20 in vitro was evaluated using XTT. Effect of ADI-PEG20 as radiosensitizer was determined by clonogenic cell survival. For in vivo, mice with PC tumor xenografts (Panc1), randomized into four groups, were treated with vehicle (PBS), ADI-PEG20 (5 IU/mouse; twice weekly), radiation (IR; 2 Gy × 5 times), and ADI-PEG20 with IR. Tumors were measured following treatment and the tumor re-growth delay time for each group was calculated. Immunohistochemical analysis of Ki-67 and VEGF was done on tumor tissues (paraffin sections) by routine immunofluorescence. Results: ADI-PEG20 selectively sensitized ASS1 deficient PC cells to IR at low, non-toxic concentrations (0.04 and 0.08 μg/mL for 72 h; DER at 10% SF for Panc1 was 1.39 and 1.52; for Miapaca-2, 1.09 and 1.25 respectively), but not ASS1 positive cells (L3.6pl). In vivo, ADI-PEG20 profoundly sensitized PC cells to IR. IR treatment alone delayed the tumor doubling time (7.6 ± 1.7 days compared to the non-treated controls); however, combining ADI-PEG20 with IR delayed the tumor growth by an additional 10 ± 1.3 days (p&lt;0.05). Immunohistochemical analysis of tumor tissues suggested that ADI-PEG20 with IR down-regulates the expression of Ki-67 and VEGF. Conclusions: ADI-PEG20 potently radiosensitizes PC cells in vitro and in vivo. The detailed molecular mechanism of this radiosensitization warrants further investigations.

Study of Nimotuzumab With Concurrent Chemoradiation Therapy in Patients With Advanced Head-and-Neck Cancer: Definitive Management of Head-and-Neck Squamous Cell Carcinoma

Study of Nimotuzumab With Concurrent Chemoradiation Therapy in Patients With Advanced Head-and-Neck Cancer: Definitive Management of Head-and-Neck Squamous Cell Carcinoma

Reduction in Cardiac Volume During Chemoradiation Therapy for Patients With Esophageal Cancer: Magnitude and Possible Implications for Adaptive Radiation Therapy

Reduction in Cardiac Volume During Chemoradiation Therapy for Patients With Esophageal Cancer: Magnitude and Possible Implications for Adaptive Radiation Therapy

The Efficacy of CHOP Regimen-Based Concurrent Chemoradiation Therapy in Patients With Nasal Extranodal Natural Killer/T-Cell Lymphoma: A Comparison Among Treatment Modalities

The Efficacy of CHOP Regimen-Based Concurrent Chemoradiation Therapy in Patients With Nasal Extranodal Natural Killer/T-Cell Lymphoma: A Comparison Among Treatment Modalities