Course Of Chemoradiotherapy Research Articles

1773P - Effect of yoga on chemo-radiotherapy induced diabetes and hypertension (CRID-H) among cervical cancer patients at a regional cancer institute in south India

Background: Prior studies suggest the benefits of yoga in maintaining Diabetes and Hypertension. In this study we aim to evaluate the effect of yoga on Chemo-Radiotherapy induced Diabetes and Hypertension (CRID-H) in cervical cancer patients. Methods: 60 cervical cancer subjects (stage II - IV) undergoing chemo-radiation therapy were randomized into yoga (n = 30) and control group (n = 30). Yoga group was given loosening, breathing, chanting and meditation for 5 days/ week for 6 weeks. Weekly assessment of Random Blood Sugar and blood pressure was recorded from baseline to discharge. Appropriate statistical analysis was conducted. Results: 6 yoga and 6 non-yoga patients were found to be known case of hypertension and on medications. During the course of chemo-radiation 4 yoga and 6 non-yoga patients developed hypertension. The systolic pressure among the yoga group remained constant with a mean difference of just 11.3mm of Hg while non-yoga group recorded 37.2mm of Hg Comparative analysis between the two groups show Systolic BP attained significance of p = 0.3 and Diastolic BP, p = 0.11. Diastolic BP in non-hypertensive patients of yoga group (p = 0.01) achieved good significance while hypertensive patients (p = 0.14) and all patients (p = 0.11) the results incline towards significance. Thus, yoga is effective to maintain BP among non-hypertensive patients and attain moderate control in hypertensive ones. RBS data reveals 5 yoga and 6 non-yoga subjects had pre-existing diabetes. 4 yoga and 6 non-yoga subjects developed diabetes with chemo-radiation by the 3rd week of treatment. Good significance was achieved between the two groups as a whole (p = 0.02). The difference was highly significant at p = 0.009 among pre-existing diabetic patients. Conclusions: Adjuvant yoga therapy helps to control CRID-H in cervical cancer efficiently. The control achieved in RBS is highly significant. Considerable effect in hypertension was also observed. The above direction can be employed in future studies with larger sample size. Acknowledgement- Ministry of AYUSH, Government of India. Legal entity responsible for the study: Ministry of Ayush, Government of India. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Identification of Predictors of Recurrence in Patients with Lower Rectal Cancer Undergoing Neoadjuvant Chemotherapy: A Direct Comparison of Short-Course and Long-Course Chemoradiotherapy

Objective: This study aimed to investigate clinicopathological responses and oncological outcome in patients receiving short- or long-course chemoradiotherapy (CRT) and to assess the predictive factor for recurrence in each treatment. Methods: A total of 118 rectal cancer patients receiving preoperative CRT were enrolled. Clinicopathological responses and oncological outcome in patients receiving short- or long-course CRT were investigated. Results: Despite there being no significant differences in the prognosis of disease-free survival (DFS) based on TNM stage classification in patients receiving long-course CRT, patients with advanced stage demonstrated poor DFS after short-course CRT. The presence of lymph node metastasis was a predictor of poor DFS in short-course CRT, whereas poor pathological response was a predictor of recurrence in long-course CRT. Conclusions: Distinct predictors of recurrence depending on the CRT course might be needed to discriminate candidates from rectal cancer patients receiving preoperative CRT who might benefit from more intensive adjuvant therapy after surgery.

Use of 18F-FDG PET/CT to predict short-term outcomes early in the course of chemoradiotherapy in stage III adenocarcinoma of the lung.

The purpose of the present prospective study was to evaluate the use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in the assessment of therapy response and the prediction of short-term outcomes by maximum and mean standardized uptake values (SUVmax and SUVmean, respectively), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) following chemoradiotherapy (CRT) in patients with stage III adenocarcinoma of the lung. The study included a total of 15 patients, all of whom underwent two serial 18F-FDG PET/CT scans prior to and following 60-Gy radiotherapy with a concurrent cisplatin/pemetrexed combined chemotherapy regimen. SUVmax, SUVmean, MTV and TLG were determined. Short-term outcomes were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) and the PET Response Criteria in Solid Tumors (PERCIST). Post-CRT SUVmax, ΔSUVmax, ΔMTV and ΔTLG varied significantly between responders and non-responders (P=0.009, P=0.015, P=0.006 and P=0.004, respectively). The differences in SUVmax, SUVmean, carcinoembryonic antigen, MTV and TLG between the responders and the non-responders at the initial 18F-FDG PET/CT scans were not statistically significant (P>0.05). The overall response rate was significantly higher (P=0.01) when evaluated using PERCIST compared with evaluation using RECIST. It was concluded that post-CRT SUVmax, ΔSUVmax, ΔMTV and ΔTLG may be used to differentiate the responders from the non-responders following CRT for stage III adenocarcinoma of the lung. This would aid in deciding whether or not to increase dosages or to incorporate a boost treatment without the requirement to suspend therapy.

A prospective biomarker trial of microbiome, immune, and genomic markers as predictors of radiation response in anal squamous cell carcinoma.

TPS869 Background: Preclinical evidence suggests that the microbiome plays a significant role in carcinogenesis and in response to immunotherapy and chemotherapy, but little is known about the role of the microbiome in response to radiation. Our group previously demonstrated that in patients with cervical squamous cell carcinoma (SCC), radiation response and immune response to radiation are improved with increased rectal microbial diversity. Methods: We are currently enrolling patients with local anal SCC undergoing definitive chemoradiation on a prospective biomarker trial evaluating changes in the gastrointestinal microbiome, immune microenvironment, and whole genome sequencing using a novel, non-invasive swab biopsy technique in addition to serial blood collections. This biopsy technique allows novel evaluation of dynamic changes throughout the course of chemoradiation. Microbiome sequencing is performed using 16s rRNA sequencing. Immune profiling is done using multiparametric flow cytometry for T-cell activation and exhaustion phenotypes and T-cell receptor sequencing. Inclusion criteria are biopsy proven HPV-related SCC of the anus, with no evidence of metastatic disease, and undergoing definitive chemoradiation. Our population is uniquely treated with cisplatin/5-FU based chemotherapy, rather than lymphotoxic mitomycin-C, allowing unique evaluation of immune populations. The primary endpoint of this study is complete tumor response based on pelvic MRI and digital rectal exam at three weeks. Secondary endpoints include FDG-avid diseases at 3 months and disease recurrence. To date we have accrued 10 patients out a planned 30 patient pilot cohort. We expect the remainder of these patients to be accrued by December 2017.

ADVANTAGES OF SHORT-TERM AND PROLONGED COURSES OF PREOPERATIVE RADIATION THERAPY FOR RECTAL CANCER

Results of preoperative radiation therapy for 119 patients with resectable rectal T3-4N0-1M0 cancer were analyzed. 52 patients received a short-term course of the large-fraction radiation therapy and 67 patients received a prolonged course of chemoradiation therapy. The results demonstrated that the prolonged course reduced clinical signs of the disease twice as much as the short course, it reduced the tumor size and increased the distance to the anorectal line (p

Continuous Infusion of Cilengitide Plus Chemoradiotherapy for Patients With Stage III Non–Small-cell Lung Cancer: A Phase I Study

IntroductionBecause of our previous preclinical results, we conducted a phase I study associating the specific αvβ3/αvβ5 integrin inhibitor cilengitide, given as a continuous infusion, with exclusive chemoradiotherapy for patients with stage III non–small-cell lung cancer. Patients and MethodsA standard 3+3 dose escalation design was used. Cilengitide was given as a continuous infusion (dose levels of 12, 18, 27, and 40 mg/h), starting 2 weeks before and continuing for the whole course of chemoradiotherapy (66 Gy combined with platinum/vinorelbine), and then at a dose of 2000 mg twice weekly in association with chemotherapy. 2-Deoxy-2-[fluorine-18]fluoro-d-glucose positron emission tomography (PET) and computed tomography scans were performed before and after the first 2 weeks of cilengitide administration and then every 3 months. ResultsOf the 14 patients included, 11 were evaluable for evaluation of the dose-limiting toxicities (DLTs). One DLT, a tracheobronchial fistula, was reported with the 40 mg/h dose. No relevant adverse events related to cilengitide were observed overall. At the PET evaluation 2 months after chemoradiotherapy, 4 of 9 patients had a complete response and 4 had a partial response. The median progression-free and overall survival was 14.4 months (95% confidence interval [CI], 8.4 to not reached) and 29.4 months (95% CI, 11.73 to not reached), respectively. ConclusionCilengitide, given continuously with chemoradiotherapy, showed acceptable toxicity and gave encouraging clinical results.

Tumor volume regression during preoperative chemoradiotherapy for rectal cancer: a prospective observational study with weekly MRI

Purpose: Few data is available on rectal tumor shrinkage during preoperative chemoradiotherapy (CRT). This regression pattern is interesting to optimize timing of dose escalation on the tumor.Methods: Gross tumor volumes (GTV) were contoured by two observers on magnetic resonance imaging (MRI) obtained before, weekly during, 2–4 weeks after, and 7–8 weeks after a 5-week course of concomitant CRT for rectal cancer.Results: Overall, 120 MRIs were acquired in 15 patients. A statistically significant tumor volume reduction is seen from the first week, and between any two time points (p < .007). At the end of CRT, 46.3% of the initial tumor volume remained, and 32.4% at time of surgery. PTV measured 61.2% at the end of treatment. Tumor shrinkage is the fastest in the beginning of treatment (26%/week), slows down to 7%/week in the last 2 weeks of CRT, and finally to 1.3%/week in the last 5 weeks before surgery.Conclusions: The main rectal tumor regression occurs during CRT course itself, and mostly in the first half, with shrinking speed decreasing over the course. This suggests that a sequential boost is preferably done after the elective fields, yielding an average PTV-reduction of 39%. A simultaneous integrated boost strategy could benefit from adaptive planning during the course.

Transtracheal Cyanoacrylate Glue Injection for the Management of Malignant Tracheoesophageal Fistula

Introduction: Malignant tracheoesophageal fistula (TEF) is a devastating complication of esophageal cancer, lung cancer or other carcinoma associated with high mortality, short survival, and poor quality of life. Covered metallic stents placement either in trachea/esophagus or both are used for the palliative treatment. Other endoscopic modalities rarely attempted for benign and malignant TEF includes use of over the scope clip, transesophageal glue injection, electrocautery and laser. Case description: A 56-year-old man presented with complain of intractable cough on swallowing for last 3 months. He had completed a course of chemo radiotherapy for carcinoma of middle one third of the oesophagus four months back. The upper gastrointestinal endoscopy showed a stricture with superficial ulceration at 23 cm from lower incisor in the oesophagus. A small (˜ 4 mm diameter) fistula was noted just above the stricture. Application of over-the-scope clip was failed. A hydrophilic guide wire (0.032” inches diameter) was placed through the ERCP cannula into the fistula. Bronchoscopy revealed the presence of guidewire coming out from a fistulous tract in the posterior wall of the trachea above the tracheal bifurcation. The guide wire was grasped with a biopsy forceps. The guide wire was removed along with the scope from the mouth. The fluoroscopic image showed a curved course (length of the fistula was about 2.5 cm) of the guide wire. After assessment of the fistula by the track of the guidewire, two routes of glue injection were considered, Trans-tracheal and Trans-esophageal. Transesophageal route was considered risky due to an expected spillage of the glue within the trachea. Hence, the option of transtracheal glue injection was selected. The cannula and the scope were reintroduced through the trachea. The presence of the markers on the cannula were used to assess the depth of insertion of cannula within the fistula and to plan the site of injection of the glue.1 ml of cyanoacrylate glue was injected while pulling the cannula out. 1 ml of distilled water was injected while pulling out the rest of the cannula to the tip of the fistula. After one hour, the patient started swallowing liquids without any cough. Patient has remained asymptomatic till now.Figure: Arrow showing the location of fistula.Figure: Hydrophilic wire inserted into the fistula.Conclusion: Transtracheal glue placement may be safer than transoesophageal glue placement. This appears to be first report of transtracheal glue injection of malignant TEF. Watch the video: https://goo.gl/46aJ9F

Comparison of Conventional Versus Hyperfractionated Chemoradiation for Bladder Preservation Treatment of Muscle Invasive Bladder Cancer in the National Cancer Database

It is unclear whether hyperfractionated (HF) chemoradiation therapy (CRT) results in a different overall survival (OS) outcomes compared to conventional daily fractionated CRT for bladder preservation treatment of muscle invasive bladder cancer. We compared these two treatment strategies using data from the National Cancer Database (NCDB). Using data from the NCDB between 2004 and 2013, we identified 3010 patients with bladder cancer treated with CRT for bladder preservation. Patients with stage T2-T4a transitional cell or squamous cell carcinoma of the bladder who received trans-urethral resection of bladder tumor (TURBT) and CRT were included. Average number of fractions delivered per week was calculated based on the total number of fractions of radiation, and the time interval between the first and last fraction in the NCBD. Conventional CRT was defined as five or fewer fractions per week, on average, over the course of CRT, and HF CRT was defined as more than five fractions a week on average. We compared the OS outcomes between the conventional CRT and HF CRT using the Kaplan-Meier method with log-rank statistics, and Cox univariate and multivariate analysis. Of the 3010 patients analyzed, 2822 (93.8%) received conventional CRT and 188 (6.2%) received HF CRT. The median age was 78 (range, 37-90), and 2208 (73.4%) were males and 802 (26.6%) were females. The median follow up time was 42.2 months (range, 2.5-143 months) for surviving patients. The pathology was transitional cell carcinoma in 2,919 (97%) and squamous cell carcinoma in 91 (3%). Distribution of stages was 2,360 (78.4%) for T2, 371 (12.3%) for T3, and 279 (9.3%) for T4a. 5-year OS in patients treated with standard fractionation was 28.9% vs. HF treatment with 22.7% (p=0.86). HF RT was associated with a similar hazard for death when compared to the standard radiation, which was 1.02 (95% CI 0.853-1.208, p=0.863). Several variables were associated with improved OS on univariate analysis including: age, Charlson/Deyo comorbidity score, histology, T stage, N stage and total dose. After adjusting for these factors in a step-wise model, standard fractionation vs. HF was not significant (p=0.396). Additionally, HF RT was not associated with improved OS compared to standard fractionated RT in subsets including patients with: stage T2 (p=0.507), T3 (p=0.331), and T4a (p=0.208). HF CRT resulted in similar overall survival when compared to standard fractionated CRT in patients with T2-T4a bladder cancer receiving bladder preservation therapy.

Dynamic Changes in Cell-Free DNA During Chemoradiation for Non–small Cell Lung Cancer

Cell-free DNA (cfDNA), of which circulating tumor DNA (ctDNA) is a subset, is a promising potential biomarker. Tumor cells apoptose or necrose and release DNA into the circulation which can be readily quantified, and cfDNA possesses a wide dynamic range which correlates with tumor burden. The release of cfDNA during a course of fractionated radiotherapy has not been systematically characterized, and to our knowledge, no studies have examined cfDNA during chemoradiation (CRT) for locally advanced thoracic malignancies. We hypothesized that there would be quantifiable change in cfDNA during a course of CRT for non-small cell lung cancer (NSCLC). We obtained patient plasma on an Institutional Review Board-approved trial from 24 patients treated with concurrent cisplatin/etoposide-based CRT for locally advanced NSCLC to a mean dose of 66 Gy (range 58-74 Gy). Plasma was obtained prior to therapy, at week 2, week 5, and at 6-week post-treatment follow-up, unless patients refused phlebotomy. Samples were single-spun at acquisition and subsequently processed via the Maxwell RSC ccfDNA Plasma Kit and quantified using the QuantiFluor ONE dsDNA system (Promega) according to the manufacturer’s protocols. A novel next generation sequencing (NGS) technique employing targeted-amplicon sequencing (InVision) was performed on a subset of samples. The cfDNA concentration was normalized by plasma volume and statistical associations were assessed via ANOVA and two sample t-test. Ninety total samples were examined. The median time between the baseline and post-treatment follow-up sample acquisition was 92 days. The mean normalized concentration of cfDNA isolated from baseline, week 2, week 5, and post-treatment follow-up was 10.1 pg/μl (σ = 8.9), 11.1 pg/μl (σ = 10.0), 11.1 pg/μl (σ = 7.2), and 18.7 pg/μl (σ = 18.5), respectively. There was a statistically significant increase in cfDNA between the baseline and post-treatment follow-up sample (P = 0.05). NGS was performed on a subset of samples to monitor specific genomic alterations in ctDNA, and it was possible to track putatively etiologic driver mutations. For example, in one patient a missense mutation was detected in the tumor suppressor gene p53 at a known pathologic site, V143M, and additional mutations were observed at subsequent time points. The concentration of cfDNA increases after CRT in patients with locally advanced NSCLC, and mutations specific to a tumor and present in ctDNA can be identified and tracked with NGS. Further work is required to determine whether the kinetics of cfDNA change over longer periods of time; whether NGS can be used to track the efficacy of CRT; or whether cfDNA-related endpoints correlate with patient outcomes. The system that we have established could potentially be adopted for future prospective clinical trials.

Assessment of treatment response during chemoradiation therapy for pancreatic cancer based on quantitative radiomic analysis of daily CTs: An exploratory study.

PurposeIn an effort for early assessment of treatment response, we investigate radiation induced changes in quantitative CT features of tumor during the delivery of chemoradiation therapy (CRT) for pancreatic cancer.MethodsDiagnostic-quality CT data acquired daily during routine CT-guided CRT using a CT-on-rails for 20 pancreatic head cancer patients were analyzed. On each daily CT, the pancreatic head, the spinal cord and the aorta were delineated and the histograms of CT number (CTN) in these contours were extracted. Eight histogram-based radiomic metrics including the mean CTN (MCTN), peak position, volume, standard deviation (SD), skewness, kurtosis, energy and entropy were calculated for each fraction. Paired t-test was used to check the significance of the change of specific metric at specific time. GEE model was used to test the association between changes of metrics over time for different pathology responses.ResultsIn general, CTN histogram in the pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the 1st to the 26th fraction in MCTN ranged from -15.8 to 3.9 HU with an average of -4.7 HU (p<0.001). Meanwhile the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less peaked). The changes of MCTN, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response is associated with the changes of MCTN, SD, and skewness. In cases of good response, patients tend to have large reductions in MCTN and skewness, and large increases in SD and kurtosis.ConclusionsSignificant changes in CT radiomic features, such as the MCTN, skewness, and kurtosis in tumor were observed during the course of CRT for pancreas cancer based on quantitative analysis of daily CTs. These changes may be potentially used for early assessment of treatment response and stratification for therapeutic intensification.

Residual tumour detection in post-treatment granulation tissue by using advanced diffusion models in head and neck squamous cell carcinoma patients

PurposeTo evaluate the detectability of the residual tumour in post-treatment granulation tissue using parameters obtained with an advanced diffusion model in patients with head and neck squamous cell carcinoma (HNSCC) treated by chemoradiation therapy. Materials and methodsWe retrospectively evaluated 23 patients with HNSCC after the full course of chemoradiation therapy. The diffusion-weighted image (DWI) acquisition used single-shot spin-echo echo-planar imaging with 11 b-values (0–1000). We calculated 10 DWI parameters using a mono-exponential model, a bi-exponential model, a stretched exponential model (SEM), a diffusion kurtosis imaging (DKI) model and a statistical diffusion model (SDM) in the region of interest (ROI) placed on the post-treatment granulation tissue. The presence of residual tumour was determined by histological findings or clinical follow-up. ResultsAmong the 23 patients, seven patients were revealed to have residual tumour. The univariate analysis revealed significant differences in six parameters between the patients with and without residual tumour. From the receiver operating characteristic curve analysis, the highest area under curve was detected in the center of the Gaussian distribution of diffusion coefficient (Ds) obtained by the SDM. The multivariate analysis revealed that the Ds and diffusion heterogeneity (α) obtained by the SEM were predictors for the presence of residual tumour. ConclusionDWI parameters obtained by advanced fitting models will be one of the diagnostic tools for the detection of residual tumour.

Phase I study of neoadjuvant 5-fluorouracil (5FU) chemoradiation (CRT) and trametinib in patients with locally advanced rectal cancers (LARC).

685 Background: RAS/BRAF mutations constitutively activate the MAPK pathway in colorectal cancer, and may promote resistance to CRT. We propose that trametinib, a MEK1/2 inhibitor, in combination with 5FU CRT for patients with LARC will improve outcome. Methods: Phase I study with standard 3+3 design in patients with Stage II/III rectal cancer with 3 dose levels of trametinib: 0.5, 1, and 2mg daily with 5FU 225mg/m2/day and 50.4 Gy. Trametinib was given over a 5-day lead-in and continued through the course of CRT. Patients undergo surgery 6-10 weeks after the completion of CRT. An expansion cohort at the maximum tolerated dose (MTD) with 12 patients is ongoing. Tumor tissue is collected prior to therapy, at day 4/5 of trametinib, and at surgery. The primary endpoint is to determine the MTD of trametinib with CRT. Results: 15 patients (10 males, 5 females) have been enrolled and 14 patients are evaluable for toxicities to date. Median age is 53 years (range 35-74). Patients have completed enrollment to all dose levels, with 1 dose-limiting toxicity of diarrhea attributed to 5FU CRT. No grade 4/5 toxicities, and toxicities are shown in the table. Generalized skin rash led to trametinib discontinuation after 2 weeks of therapy for 1 patient, and was held 3 days for 2 patients. At the trametinib dose level of 2mg, 3 out of 7 (43%) patients had a pathological complete response and the average neoadjuvant rectal (NAR) score is 8.1. Tumor RAS/BRAF mutation status is determined. Analysis of tumor tissue shows dose-dependent decrease in phosphorylated-ERK1/2 with increasing doses of trametinib. Conclusions: Initial evaluation shows that the combination of trametinib with 5FU CRT is tolerable and effective, and warrants further investigation in LARC. Clinical trial information: NCT01740648. [Table: see text]

Pediatric clinical case of parameningeal undi erentiated pleomorphic sarcoma treated with chemoradiotherapy

Malignant fibrous histiocytoma (MFH) is a rare “NON-RMS-LIKE” pediatric tumor with highly malignant clinical behavior, high metastatic potential and overall 5-year survival around 65-70%. Soft tissue sarcoma diagnostic work-up and optimal combination of systemic therapy and local therapy approaches are one of the most challenging issues in modern pediatric oncology. To present a clinical case of parameningeal undifferentiated pleomorphic sarcoma in 7-year old child treated with adaptive conformal radiotherapy aimed at local tumor control. We describe a method of combined treatment of patient with parameningeal UPS consisting of the intensity-modulated radiotherapy (IMRT) in the form of volumetrically-modulated arc- therapy (VMAT) aimed at local tumor control. The radiotherapy course was completed at the planned total dose of 54 Gy. Acute skin and mucosal toxicity not more than Grade 2 (RTOG scale) was noted during the treatment. A good partial response was recorded after chemoradiotherapy course had been finished. Histological verification of UPS diagnosis is complicated as substantial amount of tumor tissue material is required for immunohistochemical and cytogenetical studies. An aggressive surgical approach is a method of choice for local control in parameningeal soft-tissue sarcomas. However the adaptive radiotherapy was the only possible treatment method of local tumor control with significant decrease of high doses to adjacent normal organs and tissues.

The Role of Baseline Inflammatory Response Biomarkers in Predictingthe Prognosis in No Metastatic Gastric Cancer Patients Treated with Preoperative Chemoradiation

Purpose: To evaluate the prognostic potential of inflammatory response biomarkers neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in predicting the outcome of gastric cancer patients undergoing neoadjuvant chemoradiation prior to surgical resection. Methods: Patients with localized, gastric adenocarcinoma received two cycles of induction chemotherapy of fluorouracil, docetaxel, and cisplatin (TPF) followed by 45 Gy of radiation and concurrent fluorouracil plus docetaxel then surgery for non-metastatic patients. Baseline NLR, dNLR, PLR and LMR calculated from peripheral blood cell count taken at pre-operation were compared with clinicopathological parameters. The prognostic value of baseline NLR, dNLR, PLR and LMR for disease free survival (DFS) and overall survival (OS) were assessed using Log rank and Cox regression. Results: The final analysis included 80 patient who had resection after neoadjuvant chemoradiation. The receiver operating curve (ROC) cut off values of baseline NLR, dNLR, LMR and PLR in predicting outcome were 2.4, 1.7, 5.1 and 130 respectively. Elevated NLR, dNLR, PLR, LMR, age of patients (≥ 50 years), stage III, grade 3 tumors, R1 resection and partial response to preoperative chemoradiation course with >10% residual tumor were significantly associated with decreased OS, and DFS. Multivariate analysis revealed that elevated NLR and dNLR were independent factors for worse OS and DFS hazard ratio (HR) 2.04 (95% CI=2.41-8.24), 6.63 (95% CI, 1.61- 10.32) and DSF with (HR) 1.84 (95% CI=3.27-7.36), 4.63 (95% CI=3.61-12.12) respectively. Conclusion: The baseline NLR, dNLR, LMR and PLR showed a significant association with different clinicopathological prognostic factors in gastric cancer patients receiving preoperative chemoradiation. Additionally, NLR, dNLR may be considered as potential independent prognostic indicators of clinical outcomes in this group of patients.

Inter-observer agreement improves with PERCIST 1.0 as opposed to qualitative evaluation in non-small cell lung cancer patients evaluated with F-18-FDG PET/CT early in the course of chemo-radiotherapy.

BackgroundThe purpose of this study is to determine whether a qualitative approach or a semi-quantitative approach provides the most robust method for early response evaluation with 2′-deoxy-2′-[18F]fluoro-d-glucose (F-18-FDG) positron emission tomography combined with whole body computed tomography (PET/CT) in non-small cell lung cancer (NSCLC).In this study eight Nuclear Medicine consultants analyzed F-18-FDG PET/CT scans from 35 patients with locally advanced NSCLC. Scans were performed at baseline and after 2 cycles of chemotherapy. Each observer used two different methods for evaluation: (1) PET response criteria in solid tumors (PERCIST) 1.0 and (2) a qualitative approach. Both methods allocate patients into one of four response categories (complete and partial metabolic response (CMR and PMR) and stable and progressive metabolic disease (SMD and PMD)). The inter-observer agreement was evaluated using Fleiss’ kappa for multiple raters, Cohens kappa for comparison of the two methods, and intraclass correlation coefficients (ICC) for comparison of lean body mass corrected standardized uptake value (SUL) peak measurements.ResultsThe agreement between observers when determining the percentage change in SULpeak was “almost perfect”, with ICC = 0.959. There was a strong agreement among observers allocating patients to the different response categories with a Fleiss kappa of 0.76 (0.71–0.81). In 22 of the 35 patients, complete agreement was observed with PERCIST 1.0. The agreement was lower when using the qualitative method, moderate, having a Fleiss kappa of 0.60 (0.55–0.64). Complete agreement was achieved in only 10 of the 35 patients. The difference between the two methods was statistically significant (p < 0.005) (chi-squared).Comparing the two methods for each individual observer showed Cohen’s kappa values ranging from 0.64 to 0.79, translating into a strong agreement between the two methods.ConclusionsPERCIST 1.0 provides a higher overall agreement between observers than the qualitative approach in categorizing early treatment response in NSCLC patients. The inter-observer agreement is in fact strong when using PERCIST 1.0 even when the level of instruction is purposely kept to a minimum in order to mimic the everyday situation. The variability is largely owing to the subjective elements of the method.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0223-6) contains supplementary material, which is available to authorized users.

Adaptive Dose Escalation using Serial Four-dimensional Positron Emission Tomography/Computed Tomography Scans during Radiotherapy for Locally Advanced Non-small Cell Lung Cancer

AimsComputed tomography (CT)-based radiotherapy dose escalation for locally advanced non-small cell lung cancer (LA-NSCLC) has had limited success. In this planning study, we investigated the potential for adaptive dose escalation using respiratory-gated 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans (4DPET/4DCT) acquired before and during a course of chemoradiotherapy (CRT). Materials and methodsWe prospectively enrolled patients with LA-NSCLC receiving curative intent CRT. Radiotherapy was delivered using intensity-modulated radiotherapy (IMRT) using the week 0 4DCT scan. Three alternative, dose-escalated IMRT plans were developed offline based on the week 0, 2 and 4 4DPET/4DCT scans. The FDG-avid primary (PET-T) and nodal disease (PET-N) volumes defined by the 50% of maximum standard uptake value threshold were dose escalated to as high as possible while respecting organ at risk constraints. ResultsThirty-two patients were recruited, 27 completing all scans. Twenty-five patients (93%) were boosted successfully above the clinical plan doses at week 0, 23 (85%) at week 2 and 20 (74%) at week 4. The median dose received by 95% of the planning target volume (D95) at week 0, 2 and 4 to PET-T were 74.4 Gy, 75.3 Gy and 74.1 Gy and to PET-N were 74.3 Gy, 71.0 Gy and 69.5 Gy. ConclusionsUsing 18F-FDG-4DPET/4DCT, it is feasible to dose escalate both primary and nodal disease in most patients. Choosing week 0 images to plan a course with an integrated boost to PET-avid disease allows for more patients to be successfully dose escalated with the highest boost dose.

Having Your Cake and Eating It Too: Combining SBRT and Multi-agent Chemotherapy in Locally Advanced Pancreatic Cancer.

We read with great interest the results of the LAP07 study comparing capecitabine-based chemoradiation with gemcitabine-based therapy for non-progressive locally advanced pancreatic cancer (LAPC), following four months of gemcitabine-based therapy. The results, consistent with previous data, showed that standard chemoradiation improves local control (LC) but not overall survival. In this brief editorial, we emphasize that LC may still be very important in LAPC, as up to 30% of patients with LAPC may die from locally progressive disease. This is particularly likely to be true as systemic therapies continue to improve in efficacy. We very briefly review the data in support of stereotactic body radiotherapy (SBRT) for LAPC, which has been shown to offer excellent LC with minimal late grade ≥ 2 toxicity rate in a recent multi-institutional phase II study. We underscore that a short course of SBRT offers an expeditious alternative to a long course of chemoradiation, allowing the use of fully-intensive systemic therapy.

Effects of definitive chemoradiation on circulating immunologic angiogenic cytokines in head and neck cancer patients

BackgroundPreclinical studies suggest a synergistic effect between radiation, immunotherapy and anti-angiogenic therapy, although the mechanisms are unclear. Angiogenic cytokines are known to affect the immune system, and their levels may...

SU‐F‐R‐50: Radiation‐Induced Changes in CT Number Histogram During Chemoradiation Therapy for Pancreatic Cancer

Purpose:In an effort of early assessment of treatment response, we investigate radiation induced changes in CT number histogram of GTV during the delivery of chemoradiation therapy (CRT) for pancreatic cancer.Methods:Diagnostic‐quality CT data acquired daily during routine CT‐guided CRT using a CT‐on‐rails for 20 pancreatic head cancer patients were analyzed. All patients were treated with a radiation dose of 50.4 in 28 fractions. On each daily CT set, the contours of the pancreatic head and the spinal cord were delineated. The Hounsfiled Units (HU) histogram in these contourswere extracted and processed using MATLAB. Eight parameters of the histogram including the mean HU over all the voxels, peak position, volume, standard deviation (SD), skewness, kurtosis, energy, and entropy were calculated for each fraction. The significances were inspected using paired two‐tailed t‐test and the correlations were analyzed using Spearman rank correlation tests.Results:In general, HU histogram in pancreatic head (but not in spinal cord) changed during the CRT delivery. Changes from the first to the last fraction in mean HU in pancreatic head ranged from −13.4 to 3.7 HU with an average of −4.4 HU, which was significant (P&lt;0.001). Among other quantities, the volume decreased, the skewness increased (less skewed), and the kurtosis decreased (less sharp) during the CRT delivery. The changes of mean HU, volume, skewness, and kurtosis became significant after two weeks of treatment. Patient pathological response status is associated with the changes of SD (ΔSD), i.e., ΔSD= 1.85 (average of 7 patients) for good reponse, −0.08 (average of 6 patients) for moderate and poor response.Conclusion:Significant changes in HU histogram and the histogram‐based metrics (e.g., meam HU, skewness, and kurtosis) in tumor were observed during the course of chemoradiation therapy for pancreas cancer. These changes may be potentially used for early assessment of treatment response.