Completion Of Chemoradiation Therapy Research Articles

Differentiating tumour progression from pseudoprogression in glioblastoma patients: a monoexponential, biexponential, and stretched-exponential model-based DWI study

BackgroundTo investigate the diagnostic performance of parameters derived from monoexponential, biexponential, and stretched-exponential diffusion-weighted imaging models in differentiating tumour progression from pseudoprogression in glioblastoma patients.MethodsForty patients with pathologically confirmed glioblastoma exhibiting enhancing lesions after completion of chemoradiation therapy were enrolled in the study, which were then classified as tumour progression and pseudoprogression. All patients underwent conventional and multi-b diffusion-weighted MRI. The apparent diffusion coefficient (ADC) from a monoexponential model, the true diffusion coefficient (D), pseudodiffusion coefficient (D*) and perfusion fraction (f) from a biexponential model, and the distributed diffusion coefficient (DDC) and intravoxel heterogeneity index (α) from a stretched-exponential model were compared between tumour progression and pseudoprogression groups. Receiver operating characteristic curves (ROC) analysis was used to investigate the diagnostic performance of different DWI parameters. Interclass correlation coefficient (ICC) was used to evaluate the consistency of measurements.ResultsThe values of ADC, D, DDC, and α values were lower in tumour progression patients than that in pseudoprogression patients (p < 0.05). The values of D* and f were higher in tumour progression patients than that in pseudoprogression patients (p < 0.05). Diagnostic accuracy for differentiating tumour progression from pseudoprogression was highest for α(AUC = 0.94) than that for ADC (AUC = 0.91), D (AUC = 0.92), D* (AUC = 0.81), f (AUC = 0.75), and DDC (AUC = 0.88).ConclusionsMulti-b DWI is a promising method for differentiating tumour progression from pseudoprogression with high diagnostic accuracy. In addition, the α derived from stretched-exponential model is the most promising DWI parameter for the prediction of tumour progression in glioblastoma patients.

466. ESOPHAGECTOMY AFTER NEOADJUVANT CHEMORADIATION THERAPY: DOES THE TIMING OF SURGERY INFLUENCE THE OUTCOME?

Abstract Background Multimodality treatment, either neoadjuvant chemoradiotherapy (nCRT) or perioperative chemotherapy (e.g., FLOT), and surgery, represents the standard of care for locally advanced, resectable cancer of the esophagus and esophago-gastric junction. The recommended interval between the ending of nCRT and surgery is between 6 and 8 weeks. A prolonged time to surgery (TTS) is associated with an increase in pathologic complete response (pCR) and survival in different malignancies, with a possible increase in surgical difficulty and postoperative complications. Materials and methods: A retrospective analysis was conducted on 154 patients with cT2-4aN0-(+), cT1bN+, M0 squamous cell (SCC) and adenocarcinoma (AC) cancer of the esophagus and esophagogastric junction (Siewert type 1) treated with nCRT and surgery between August 2017 and January 2022. Three groups were identified: patients operated within 10 (n = 37), between 10 and 12 (n = 48) and beyond 12 weeks (n = 69). Minimum follow-up period was six months. Results Demographic and clinical characteristics were comparable. Mean length of stay was 13.1, 15.6 and 16.5 days (p = 0.06) respectively. Incidence of postoperative complications and their severity were not different between groups. No postoperative deaths were observed. No difference in pCR was found. When analyzed by histology, a slight increase was evident in patients with SCC (33.3%, 43.5%, 39.4%; vs ADC 16%, 16%, 16.7%), though not statistically significant. Similar results were obtained for tumor regression grade, with an increase in major responses for SCC over time (Mandard 1–2: SCC 50%, 61%, 62%; ADC 60%, 64%, 58%). No difference in overall survival was observed. Conclusions Esophagectomy performed more than 10 weeks after the end of chemoradiation therapy was not associated with an increase in postoperative morbidity. We observed, though, a trend towards longer hospital stays. The rate of major pathological response seems to increase over time after completion of chemoradiation therapy, but only for squamous histotype. Larger studies are required to corroborate these findings.

NIMG-54. LOW FRACTIONAL TUMOR BURDEN VOLUME OBTAINED FROM PERFUSION MRI REVEALS SIGNIFICANT SURVIVAL BENEFIT IN MGMT UNMETHYLATED GLIOBLASTOMA

Abstract INTRODUCTION Standard imaging remains inadequate for the determination of GBM response within the first 3 months following upfront chemoradiation therapy (CRT). Since advanced diffusion and DSC perfusion (pMRI) MRI are currently not included in RANO criteria, greater reliance is placed on MGMT methylation status, with methylated tumors demonstrating survival benefit. While pMRI has demonstrated usefulness following CRT, a newer pMRI biomarker termed Fractional Tumor Burden (FTB) provides both spatial and quantifiable information. The purpose of this study was to evaluate whether advanced MRI including FTB informs a survival benefit beyond MGMT promoter methylation status in newly diagnosed GBM (nGBM). METHODS Consented subjects with nGBM, and known MGMT status who completed standard upfront therapy and had MRI within 6 weeks of CRT completion, were included. Known IDH-mutant tumors were excluded. DSC was collected with the consensus protocol and leakage-corrected relative cerebral blood volume (rCBV) generated. Apparent diffusion coefficient (ADC) was calculated from diffusion MRI (b-value: 0,1000 s/mm2). FTB-defined tumor volumes were calculated from rCBV and delta T1w enhancement. Kaplan-Meier 24-month overall survival (OS) was evaluated for MGMT status and stratified by cohort mean for rCBV (1.3 a.u.) and ADC (1300 x10-6mm2/s), and empirically for FTB (5 ml) (significance: P &amp;gt;.05). RESULTS A total of 43 subjects were included (male/female=21/22; age=57(23-74)). MRI was acquired an average of 29 (12-42) days following CRT. Significant OS differences were confirmed for MGMT methylation (OS=19.08 vs. 10.18 mo; P=.0129). No significant survival differences were found (P &amp;gt;.05) when stratified by rCBV or ADC. While FTB did not provide further OS distinctions in methylated GBM, those with unmethylated MGMT had significant OS benefit when FTB volume was &amp;lt; 5 ml (OS=16.15 vs 8.39 mo; P=.0054). CONCLUSION FTB further informs OS in MGMT promoter unmethylated GBM, where those with lower volume had survival approaching that of methylated subjects.

Web-Based Symptom Monitoring With Patient-Reported Outcomes During Definitive Radiation Therapy With Chemotherapy (SYMPATHY): A Prospective Single-Center Phase 1 Study

We evaluated the feasibility of patient symptom self-reporting using a web-based interface (WBI), with automated message alerts for severe and/or worsening symptoms, in patients undergoing definitive chemoradiation therapy (CRT). Patients receiving definitive CRT for gastrointestinal, lung, and head and neck cancers with access to a computer and/or mobile device were eligible. Symptom self-reporting was conducted via a WBI through surveys adapted from the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events: 2 per week during CRT and 1 per week for 3 months after CRT. Nurses were alerted whenever a patient's symptom worsened by ≥2 points or reached a score of ≥3. Patient-Reported Outcomes Measurement Information System (PROMIS) surveys were conducted at baseline, end of CRT, and 3 months after CRT. Patients also completed exit surveys 3 months after CRT. Nineteen patients were enrolled with a median of 30 fractions (range, 28-33). The median survey completion rate was 26% (range, 0%-100%) during CRT and 33% (range, 0%-100%) during the first 3 months after CRT. Five (26%) had acute hospital encounters during CRT or within 3 months of CRT completion. Two patients (11%) experienced CRT treatment interruptions. During CRT, 70 of 81 surveys (86%) were flagged and 61 of 70 (87%) were acted upon by a nurse or physician within 4 days; during the first 3 months after CRT, 47 of 85 (55%) were flagged and 28 of 47 (60%) were acted upon within 7 days. Ninety-two percent of patients found it always easy to access the survey while 58% found the surveys too long or too frequent. None of the PROMIS domains had statistically significant changes during any time points. Symptom self-reporting via a WBI is feasible during definitive chemoradiation with high patient satisfaction. Survey fatigue is common and may be mitigated by improving the WBI to make it more patient-centered and allowing patients to choose which symptoms to report.

Web-Based Symptom Monitoring with Patient-Reported Outcomes during Definitive Radiation Therapy with Chemotherapy (SYMPATHY): A Prospective Single-Center Phase I Study

<h3>Purpose/Objective(s)</h3> We evaluated the feasibility of patient symptom self-reporting using a web-based interface (WBI), with automated message alerts for severe or worsening symptoms, in patients undergoing definitive chemoradiation therapy (CRT). <h3>Materials/Methods</h3> Patients receiving definitive CRT for gastrointestinal, lung, and head and neck cancer with access to a computer/mobile device were eligible. Symptom self-reporting was conducted via a WBI through surveys adapted from the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE), 2/week during CRT and 1/week for 3 months post-CRT. Nurses were alerted whenever a patient's symptom worsened by ≥ 2 points or reached a score of ≥3. Patient-Reported Outcomes Measurement Information System (PROMIS) surveys were conducted at baseline, end of RT and 3 months post-RT. Patients also completed exit surveys 3 months post-CRT. <h3>Results</h3> Nineteen patients were enrolled with a median of 30 fractions (range 28-33). Median survey completion rate was 26% (range 0-100%) during CRT and 33% (range 0-100%) during the first 3 months post-CRT. Five (26%) patients had acute hospital encounters during CRT or within 3 months of CRT completion. Two patients (11%) experienced CRT treatment interruptions. During CRT, 70/81 (86%) of surveys were flagged and 61/70 (87%) were acted upon by a nurse or physician within 4 days of the survey; during the first 3 months post-CRT, 47/85 (55%) were flagged and 28/47 (60%) were acted upon within 7 days. 92% of patients found it always easy to access the survey while 58% found the surveys too long or too frequent. None of the PROMIS domains had statistically significant changes during any time points. <h3>Conclusion</h3> Symptom self-reporting via a WBI is feasible during definitive chemoradiation with high patient satisfaction. Survey fatigue is common and may be mitigated by improving the WBI to make it more patient-centered and allowing patients to choose which symptoms to report.

Feasibility of a novel non-invasive swab technique for serial whole-exome sequencing of cervical tumors during chemoradiation therapy.

BackgroundClinically relevant genetic predictors of radiation response for cervical cancer are understudied due to the morbidity of repeat invasive biopsies required to obtain genetic material. Thus, we aimed to demonstrate the feasibility of a novel noninvasive cervical swab technique to (1) collect tumor DNA with adequate throughput to (2) perform whole-exome sequencing (WES) at serial time points over the course of chemoradiation therapy (CRT).MethodsCervical cancer tumor samples from patients undergoing chemoradiation were collected at baseline, at week 1, week 3, and at the completion of CRT (week 5) using a noninvasive swab-based biopsy technique. Swab samples were analyzed with whole-exome sequencing (WES) with mutation calling using a custom pipeline optimized for shallow whole-exome sequencing with low tumor purity (TP). Tumor mutation changes over the course of treatment were profiled.Results216 samples were collected and successfully sequenced for 70 patients (94% of total number of tumor samples collected). A total of 33 patients had a complete set of samples at all four time points. The mean mapping rate was 98% for all samples, and the mean target coverage was 180. Estimated TP was greater than 5% for all samples. Overall mutation frequency decreased during CRT but mapping rate and mean target coverage remained at >98% and >180 reads at week 5.ConclusionThis study demonstrates the feasibility and application of a noninvasive swab-based technique for WES analysis which may be applied to investigate dynamic tumor mutational changes during treatment to identify novel genes which confer radiation resistance.

Anal fistula metastasis of rectal cancer after neoadjuvant therapy: a case report

BackgroundAnal metastasis of colorectal cancer is very rare and may present synchronously or metachronously, regardless of pre-existing anal diseases. We report a case of anal fistula metastasis after completion of neoadjuvant therapy for rectal cancer, followed by surgical resection of the primary tumor and metastatic lesion.Case presentationA 50-year-old man was diagnosed with rectal cancer located 5 cm from the anal verge, with a clinical stage of cT3N0M0. He denied any medical or surgical history, and physical examination revealed no perianal disease. He underwent preoperative chemoradiation therapy (CRT) consisting of a tegafur/gimeracil/oteracil potassium (S-1)-based regimen with 45 Gy of radiation. After completion of CRT, computed tomography (CT) revealed the primary tumor’s partial response, but a liver mass highly suggestive of metastasis was detected. This mass was later diagnosed as cavernous hemangioma 3 months after CRT initiation. He then underwent and completed six cycles of consolidation chemotherapy with a capecitabine-based regimen. Subsequent colonoscopy revealed the complete response of the primary tumor, but CT showed thickening of the edematous rectal wall. Therefore, we planned to perform low anterior resection as a radical surgery. However, he presented with persistent anal pain after the last chemotherapy, and magnetic resonance imaging revealed a high-intensity mass behind the anus, suggestive of an anal fistula. We considered the differential diagnosis of a benign anal fistula or implantation metastasis into the anal fistula. Fistulectomy was performed, and a pathological diagnosis of tubular adenocarcinoma, suggestive of implantation metastasis, was made. Thereafter, we performed laparoscopic abdominoperineal resection. Histopathological examination revealed well-differentiated adenocarcinoma, ypT2N0, with a grade 2 therapeutic effect. Subsequent immunohistochemistry of the resected anal fistula showed a CDX-2-positive, CK20-positive, CK7-negative, and GCDFP-15 negative tumor, with implantation metastasis. There was no cancer recurrence 21 months after the radical surgery.ConclusionsThis is the first report of anal fistula metastasis after neoadjuvant therapy for rectal cancer in a patient without a previous history of anal disease. If an anal fistula is suspected during or after neoadjuvant therapy, physical and radiological assessment, differential diagnosis, and surgical intervention timing for fistula must be carefully discussed.

NEXT: A single-arm, phase 2, open-label study of adjuvant nivolumab after completion of chemo-radiation therapy in patients with localized muscle-invasive bladder cancer.

506 Background: Nivolumab has known efficacy as adjuvant therapy after radical cystectomy in localized muscle invasive bladder cancer (MIBC). We are evaluating the efficacy of nivolumab adjuvant to definitive chemo-radiation therapy (CRT) in MIBC. Methods: In the NEXT study, we are currently enrolling patients with localized MIBC undergoing standard CRT. Participants are started on nivolumab 480 mg IV every 4 weeks (up to 12 doses) within 90 days of completion of CRT. Cystoscopic and scan-based assessments are done every 3 months for the first two years (yrs). The primary endpoint is failure-free survival (FFS) at 2 yrs from the start of CRT, with failure defined as local or systemic disease recurrence. Secondary endpoints include toxicity and quality of life (QOL) assessments. We have planned correlative studies on peripheral blood and tumor tissue. We performed a protocol-defined interim safety and efficacy analysis to assess the 6-month FFS rate with CRT and adjuvant nivolumab. Results: From 8/03/2017 to 9/28/2021, 20 patients were enrolled at two centers; median age is 76 yrs, clinical stage range is T2-T4b, N0-N+, M0; the median number of nivolumab cycles is 6.5, and the median follow-up is 8.9 months. The estimated 6-month FFS rate is 88.2% (95% CI 74.2% - 100%). Disease has progressed in 9 patients, of which 4 have local bladder recurrence (T1 in 3/4) and 5 have distant metastases. The estimated median FFS is 17.1 months (95% CI 8.71 months - infinity). Grade ≥3 treatment-related adverse events (AEs) are noted in 3/20 patients (15%): elevated transaminases, diarrhea, and polymyalgia rheumatica. Grade 3 radiation therapy oncology group (RTOG) AEs occurred in 2 patients. QOL measures are serially evaluable in 13 patients for the first 3 months of adjuvant nivolumab, and are stable in the domains of disease-related physical symptoms, treatment side effects, and function/well-being, while are significantly improved (p=0.023) in the domain of disease-related emotional symptoms. Conclusions: In this first report of the role of immunotherapy adjuvant to CRT for localized bladder cancer, adjuvant nivolumab is well tolerated and has promising efficacy. Clinical trial information: NCT03171025.

Real-World Safety and Efficacy of Consolidation Durvalumab After Chemoradiation Therapy for Stage III Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis

Consolidation durvalumab after chemoradiation therapy (CRT) has improved patient outcomes in stage III non-small cell lung cancer (NSCLC) since the practice-changing results of the PACIFIC trial, whereas real-world evidence regarding the PACIFIC regimen has not been systematically reviewed. This meta-analysis comprehensively investigated the real-world toxicity and efficacy of this regimen and identified differences between the real world and clinical trials. Real-world studies (RWSs) on patients with stage III NSCLC treated with durvalumab after CRT were identified in MEDLINE, EMBASE, PubMed, and Cochrane Library databases. We summarized the differences in demographic and therapeutic characteristics between RWSs and the PACIFIC trial. A meta-analysis of short-term efficacy and adverse event rates was performed. Subgroup analyses were conducted to identify potential influencing factors. Thirteen studies involving 1885 patients were included. More elderly and poor-performance-status patients, prolonged interval from CRT completion to durvalumab exceeding 42 days, median infusions of durvalumab <20 cycles, and sequential CRT were observed in the real world. The pooled 12-month overall survival (OS) and progression-free survival (PFS) rates were 90% (95% confidence interval [CI], 83%-98%) and 62% (95% CI, 56%-68%), respectively. Subgroup analysis determined that delay in durvalumab initiation beyond 42 days did not affect 12-month OS (P=.068) or PFS (P=.989). Pooled incidences of all-grade and grade ≥3 pneumonitis were 35% (95% CI, 22%-48%) and 6% (95% CI, 3%-8%), respectively. Higher all-grade pneumonitis rates were observed in the studies of patients with a median age of >65 years (P=.008) and from Asian regions (P=.017), whereas expanded access program-related studies reported significantly lower rates (P=.024). The safety and short-term efficacy of consolidation durvalumab in real-life use aligns with the PACIFIC trial. RWSs can be helpful for understanding the true efficacy and toxicity of consolidation durvalumab given the less-restrictive eligibility criteria.

The efficiency of 18F-FDG-PET/CT in the assessment of tumor response to preoperative chemoradiation therapy for locally recurrent rectal cancer

BackgroundLocally recurrent rectal cancer (LRRC) remains a major problem after curative resection of primary rectal cancer. A noninvasive, prognostic biomarker with which to accurately evaluate disease status and assess the treatment response is critically needed to optimize treatment plans. This study assesses the effectiveness of PET/CT evaluation of preoperative chemoradiation therapy (CRT) in patients with LRRC.MethodsSince 2004, we have been performing preoperative CRT to improve local tumor control and survival. Between 2004 and 2013, 40 patients with LRRC underwent preoperative CRT (radiation: 50 Gy/25 fractions; chemotherapy: irinotecan plus UFT [tegafur and uracil]/leucovorin) and radical surgery, and underwent 18F-FDG-PET/CT before and 3 weeks after the completion of CRT. The maximum standardized uptake values (SUVmax) of the pre-CRT scan (Pre-SUV) and the post-CRT scan (Post-SUV) were measured. The predictive value of the 18F-FDG-PET and CT/MRI response assessments was evaluated.ResultsThe mean Pre-SUV was significantly higher than the Post-SUV (8.2 ± 6.1, vs. 3.8 ± 4.0; P < 0.0001). Following CRT, 17/40 patients (42.5%) were classified as responders according to the Mandard tumor regression grade (TRG1–2). The mean Post-SUV was significantly lower in responders than in nonresponders (2.0 ± 1.7 vs. 5.1 ± 3.9; P = 0.0038). Pathological response was not correlated with the response as evaluated by CT (P > 0.9999) or MRI (P > 0.9999). Multivariate regression analysis identified Post-SUV as an independent predictor of local re-recurrence-free survival (P = 0.0383) and for overall survival (P = 0.0195).ConclusionsPET/CT is useful in assessing tumor response to preoperative CRT for LRRC and predicting prognosis after surgery.

Assessment of Prognostic Value of High-Sensitivity Cardiac Troponin T for Early Prediction of Chemoradiation Therapy-Induced Cardiotoxicity in Patients with Non-Small Cell Lung Cancer: A Secondary Analysis of a Prospective Randomized Trial

Cardiotoxicities induced by cancer therapy can negatively affect quality of life and survival. We investigated whether high-sensitivity cardiac troponin T (hs-cTnT) levels could serve as biomarker for early detection of cardiac adverse events (CAEs) after chemoradiation therapy (CRT) for non-small cell lung cancer (NSCLC). This study included 225 patients who received concurrent platinum and taxane-doublet chemotherapy with thoracic radiation therapy to a total dose of 60 to 74 Gy for NSCLC. All patients were evaluated for CAEs; 190 patients also had serial hs-cTnT measurements. Grade ≥3 CAEs occurred in 24 patients (11%) at a median interval of 9 months after CRT. Pretreatment hs-cTnT levels were higher in men, in patients aged ≥64 years, and in patients with pre-existing heart disease or poor performance status (P < .05). hs-cTnT levels increased at 4 weeks during CRT (P < .05) and decreased after completion of CRT but did not return to pretreatment levels (P = .002). The change (Δ) in hs-cTnT levels during CRT correlated with mean heart dose (P = .0004), the heart volumes receiving 5 to 55 Gy (P < .05), and tumor location (P = .006). Risks of severe CAEs and mortality were significantly increased if the pretreatment hs-cTnT was >10 ng/L or the Δ during CRT was ≥5 ng/L. Elevation of hs-cTnT during CRT was radiation heart dose-dependent, and high hs-cTnT levels during the course of CRT were associated with CAEs and mortality. Routine monitoring of hs-cTnT could identify patients who are at high risk of CRT-induced CAEs early to guide modifications of cancer therapy and possible interventions to mitigate cardiotoxicity.

Sequential monitoring of PD-L1 on circulating stromal cells in blood predicts PFS in NSCLC patients undergoing immunotherapy after definitive chemoradiation.

8534 Background: Cancer Associated Macrophage-Like cells (CAMLs) are circulating stromal cells in the blood of patients (pts) with solid tumors that are phagocytic macrophages that may represent the inflammatory state of the tumor microenvironment. Previously, we demonstrated CAMLs ≥50µm after chemo-radiation therapy (CRT) in NSCLC is associated with worse progression free survival (PFS) and overall survival (OS). We also showed that PDL1 expression in CAMLs is dynamic &amp; can change with CRT, difficult to assess with repeat biopsies, but possible with liquid biopsy. For this study we evaluated whether CAML properties can predict response to CRT with/without immunotherapy (IMT) agents in unresectable NSCLC. Methods: A single blind multi-year prospective study was undertaken to test the relationship of PDL1 expression and ≥50µm CAML size to PFS/OS in NSCLC, pre and post CRT with (n = 96) and without (n = 72) anti-PDL1/PD1 IMT. This included atezolizumab (prospective single arm NCT02525757) n = 39, durvalumab n = 52 or pembrolizumab n = 5 both after 2018 FDA approval. We recruited 168 pts with pathologically confirmed unresectable NSCLC prior to CRT. Blood samples 15 mL were taken at baseline (BL), CRT completion (T1), and ̃1 month after CRT (T2) (with n = 96 or without n = 72 IMT). Blood was filtered by CellSieve filtration and CAMLs quantified for size ( &lt; 49 µm or ≥50 µm) and PDL1 expression to evaluate PFS and OS hazard ratios (HRs) by censored univariate and multivariate analysis at 24 months. Results: CAMLs were found in 90% of all samples, average 5.8 CAMLs/15mL. At BL, ≥50µm CAMLs did not predict PFS in CRT/IMT pts (HR 1.6, p = 0.220) nor CRT alone (HR 1.3, p = 0.593). However, after completion of CRT (T1) ≥50µm CAMLs predicted PFS in CRT/IMT pts (HR 2.7, p = 0.003) and CRT alone (HR 2.5, p = 0.015). In primary tumor biopsies, PDL1 expression &gt; 1% did not predict CRT/IMT response (PFS HR 1.8, p = 0.262 &amp; OS HR 2.3, p = 0.158). At BL, high CAML PDL1 did not predict PFS in CRT/IMT pts (HR 1.4, p = 0.427) nor CRT alone (HR 1.1, p = 0.982). Further, at CRT completion (T1), high CAML PDL1 only trended for better PFS in CRT/IMT pts (HR 1.7, p = 0.137), but not CRT alone (HR 1.1, p = 0.972). At T2, however, pts with continuously high CAML PDL1 had significantly better PFS with IMT (HR 3.2, p = 0.002) vs CRT alone (HR 1.4, p = 0.616). While ≥50µm CAMLs at BL did not predict 24 month progression, ≥50 µm CAMLs after CRT (with or without 1 cycle of anti-PDL1 IMT) was 84% accurate at predicting progression. Further subtyping and analysis is ongoing to evaluate OS and PDL1 in the CAML populations. Conclusions: Our data suggests that in unresectable NSCLC, ≥50 µm CAMLs after completion of CRT is prognostic regardless of IMT use. PDL1 expression in CAMLs also appears to predict for response to consolidated IMT after CRT. Additional studies are needed to validate these findings.

Differentiating high-grade glioma recurrence from pseudoprogression: Comparing diffusion kurtosis imaging and diffusion tensor imaging

PurposeTo compare the diagnostic value of DKI and DTI in differentiation of high-grade glioma recurrence and pseudoprogression (PsP). MethodForty patients with high-grade gliomas who exhibited new enhancing lesions (24 high-grade glioma recurrence and 16 PsP) within 6 months after surgery followed by completion of chemoradiation therapy. All patients underwent repeat surgery or biopsy after routine MRI and DKI (including DTI). They were histologically classified into high-grade glioma recurrence and PsP groups. DKI (mean kurtosis [MK], axial kurtosis [Ka], and radial kurtosis [Kr]) and DTI (mean diffusivity [MD] and fractional anisotropy [FA]) parameters in the enhancing lesions and in the perilesional edema were measured. Inter-group differences between high-grade glioma recurrence and PsP were compared using the Mann-Whitney U test The receiver operating characteristic (ROC) curve was used to assess differential diagnostic efficacy of each parameter, and Z-scores were used to compare the value between DKI and DTI. ResultsRelative MK (rMK) was significantly higher and relative MD (rMD) was significantly lower in the enhancing lesions of high-grade glioma recurrence compared to PsP (P < 0.001, P = 0.006, respectively). The AUC was 0.914 for rMK and 0.760 for rMD, and this difference was significant (P = 0.030). In the perilesional edema, rMK values were significantly higher and rMD values were significantly lower in high-grade glioma recurrence compared to PsP (P < 0.001, P = 0.005). ConclusionsDKI had superior performance in differentiating high-grade glioma recurrence from PsP, and rMK appeared to be the best independent predictor.

NIMG-39. UTILITY OF PHYSIOLOGIC MR METRICS IN DISTINGUISHING TRUE-PROGRESSION FROM PSEUDOPROGRESSION IN GLIOBLASTOMAS STRATIFIED BY MGMT PROMOTER METHYLATION

Abstract BACKGROUND Methylation of O6-methyl-guanine-methyl transferase MGMT gene promoter is associated with favorable prognosis in glioblastoma (GBM) patients treated with surgery and chemoradiation therapy (CRT). OBJECTIVE To investigate potential of diffusion and perfusion MR imaging in distinguishing TP from PsP in GBM patients stratified by MGMT status. METHODS A cohort of 92 patients demonstrating new/increasing enhancing lesions within six months of completion of CRT underwent 3T MR imaging. Median values of mean diffusivity (MD), fractional anisotropy (FA), anisotropy coefficients [linear(CL), planar (CP), and spherical (CS)] and maximum relative cerebral blood volume (rCBVmax) were computed from enhancing lesions. Patients were classified as TP (n=65) and PsP (n=27) based on histopathology or follow-up MRI scans. Mann-Whitney, independent-sample T-tests and receiver operating characteristic (ROC) curve analyses were performed to distinguish TP from PsP. Of 92 patients, MGMT status was available from 60 patients [MGMT-methylated (n=23) and MGMT-unmethylated (n=37)]. Statistical analyses were also performed in distinguishing TP (n=15) and PsP (n=8) from MGMT-methylated and MGMT-unmethylated subgroups (TP=28; PsP=9). A p-value of 0.05 was considered significant. RESULTS Significantly higher rCBVmax and FA and a trend towards higher CP were observed in TP compared to PsP. Among these parameters, rCBVmax had the best sensitivity=62%, specificity=68% and accuracy=67% in distinguishing TP from PsP. ROC analysis revealed sensitivity=54%, specificity=78% and accuracy=68% after combination of these parameters. In MGMT methylated patients, only rCBVmax was significantly higher in TP than in PsP with sensitivity=79%, specificity=67% and accuracy=74% at a threshold rCBVmax value of 2.23. In MGMT unmethylated group, a trend towards higher rCBVmax was observed in TP than in PsP with sensitivity=67%, specificity=77%, accuracy=69%, threshold value=2.89. CONCLUSION Physiologic imaging parameters demonstrate variable diagnostic values for detecting PsP in GBM patients stratified by MGMT status. The best parameter in distinguishing TP from PsP was rCBVmax in patients demonstrating MGMT promoter methylation.

Characteristics of Patients Presented With Metastases During or After Completion of Chemoradiation Therapy for Locally Advanced Rectal Cancer: A Case Series.

PurposeLocally advanced rectal cancer (LARC) is managed by chemoradiotherapy (CRT), followed by surgery. Herein we reported patients with metastases during or after CRT.MethodsData of patients with LARC who received CRT from 2008 to 2017 were reviewed. Patients with metastases after CRT were included. Those with metastatic tumors at the initial diagnosis were excluded.ResultsFourteen patients (1.3%) of 1,092 who received CRT presented with metastases. Magnetic resonance circumferential resection margin (mrCRM) and mesorectal lymph nodes (LNs) were positive in 12 patients (85.7%). Meanwhile, magnetic resonance extramural vascular invasion (mrEMVI) was positive in 10 patients (71.4%). Magnetic resonance tumor regression grade (mrTRG) 4 and mrTRG5 was detected in 5 and 1 patient respectively. Ten patients (71.4%) underwent combined surgery and 3 (21.4%) received palliative chemotherapy.ConclusionPatients with metastases after CRT showed a higher rate of positive mrCRM, mrEMVI, mesorectal LNs, and poor tumor response. Further studies with a large number of patients are necessary for better survival outcomes in LARC.

Sequential monitoring of circulating stromal cells from blood is predictive of progression in NSCLC patients undergoing anti-PD-L1 therapy after definitive chemoradiation therapy.

3051 Background: Cancer Associated Macrophage-Like cells (CAMLs) are a recently described circulating stromal cell common in the peripheral blood of patients with solid tumors. In non-small cell lung carcinoma (NSCLC), patients with CAMLs ≥50µm after completion of chemoradiation therapy (CRT) have been shown to have worse progression free survival (PFS). However, with the recent addition of anti-PD-L1 therapies in conjunction with CRT as standard of care, it has never yet to be evaluated whether CAMLs remain predictive for monitoring progression in NSCLC patients post anti-PD-L1 therapy. Methods: A 2 year single blind prospective study was undertaken to test the relationship of ≥50µm CAMLs to PFS based on imaging in lung patients before and after induction of CRT and PD-L1. We recruited 104 patients with pathologically confirmed unresectable NSCLC Stage II (n = 14), Stage III (n = 83), Stage IV (n = 3), and locally recurrent disease (n = 4). Baseline (BL) blood samples were taken prior to start of therapy. A second time point blood sample (T1) was taken at the end of radiotherapy (~40 days). A third time blood sample (T2) was taken after induction of anti-PD-L1 therapy (e.g. Imfinizi, Keytruda, etc.). Blood was filtered by CellSieve filtration and CAMLs were quantified. Analysis by CAML size of &lt; 49 µm or ≥50 µm was used to evaluate PFS hazard ratios (HRs) by censored univariate &amp; multivariate analysis. Results: CAMLs were found in 87% of samples averaging 2.9 CAMLs/7.5mL sample. At BL, CAMLs ≥50 µm had similar PFS to patients with &lt; 50 µm CAMLs (HR = 1.1 95%CI 0.6-1.95 p = 0.8661). However, after CRT (T1), patients with CAML size ≥50 µm had worse PFS (HR = 3.2, 95%CI 1.8-5.8 p = 0.0002). After induction of anti-PD-L1 therapy (T2), patients with ≥50 µm CAMLs also had worse PFS (HR = 2.8 95%CI 1.5-5.4 p = 0.0037). CAML size at BL was not accurate at predicting progression within 24 months; however ≥50 µm CAMLs after CRT or after 1 cycle of anti-PDL1 therapy was 71% accurate at predicting progression of disease. Conclusions: Our data suggests that in NSCLC, ≥50 µm CAMLs after completion of CRT or appearing after induction of anti-PD-L1 therapy appears to predict progressive disease. If validated, additional studies are needed to determine if CAMLs can serve as a significantly prognostic blood based marker for predicting survival in NSCLC patients early in the treatment regime.

Assessing tumor response to neoadjuvant chemoradiation in rectal cancer with rectoscopy and 18F-FDG PET/CT: results from a prospective series.

rectoscopy and 18F-FDG PET/CT as a diagnostic algorithm for the assessment of tumor response in rectal cancer after neoadjuvant chemoradiation therapy (CRT) is very useful. this was a prospective longitudinal study in patients with locally advanced rectal cancer treated with neoadjuvant CRT. Patients were assessed after CRT completion with a digital rectal examination, proctoscopy and 18F-FDG PET/CT. Patients were subdivided as clinical (cCR) or radiologic (rCR) responders and non-responders according to tumor response. Clinical and radiological re-assessment was compared with the surgical specimen. Pathological tumor regression (pCR) grade was determined according to Mandard's classification. Of the 68 patients included, 15 (22 %) presented pCR in the surgical specimen and tumor persistence (non-PCR) was detected in the remaining 53 (78 %). Clinical assessment (DRE+ rectoscopy) identified 15 patients as cCR and 53 as non-cCR, two were false positives and two were false negatives. The overall accuracy was 94 %. 18F-FDG PET/CT identified 18 patients as rCR and 50 as non-rCR, one was a false positive and four were false negatives. The overall accuracy was 92 %. A combination of clinical findings and 18F-FDG PET/CT resulted in an accuracy of 96 %. The combination of clinical findings + 18F-FDG PET/CT was able to correctly identify all cases of pCR, with the exception of one case that presented a tumor regression of 80 %. In this series, 18F-PET-CT and clinical assessment had excellent accuracies in differentiating PCR from non-PCR after CRT completion. PET-CT combined with clinical assessment had a better accuracy than both modalities independently. 18F-FDG PET/CT is a valid tool that complements the clinical assessment of tumor response.

Salvage surgery for a locally persistent or recurrent tumour in maxillary cancer patients who have undergone radiotherapy and concomitant intra-arterial cisplatin: implications for surgical margin assessment

Limited information about salvage surgery is available for locally persistent and recurrent maxillary sinus cancers after the completion of chemoradiation therapy. Seventy-six maxillary sinus cancer patients who had undergone chemoradioselection using initial radiotherapy and concomitant intra-arterial cisplatin were screened retrospectively. Twenty-four of these patients who had a locally persistent or recurrent tumour were investigated. The 2-year overall survival rate of patients with maxillary sinus cancer of all types was 39.0% for those who underwent salvage surgery and 10.0% for those who did not. The 2-year overall survival rate of patients with maxillary sinus squamous cell carcinoma was 45.8% for those who underwent salvage surgery and 11.1% for those who did not. Furthermore, the 2-year local control and overall survival rates of patients with positive and negative surgical margins were 14.3% and 83.3% and 14.3% and 66.7%, respectively. There were significant differences in local control (P=0.004) and overall survival (P=0.005) regarding surgical margin status. Although salvage surgery for a locally persistent or recurrent maxillary sinus cancer is a feasible treatment, patients with positive surgical margins are more prone to local relapse. Therefore, surgical safety margins should be assessed thoroughly.

Severe Lymphopenia after Chemoradiation Treatment is Associated with Worse Survival in Patients with Newly Diagnosed GBM

To investigate the rate of lymphopenia after receiving definitive adjuvant chemoradiation therapy (CRT) for glioblastoma (GBM) patients and potential effects on clinical outcomes. We conducted a retrospective review of GBM patients treated with definitive adjuvant CRT at our institution covering a period from 2008 to 2016. We identified 96 patients with sufficient details regarding their treatment course as well as complete blood count with differential at approximately 1 month after completion of adjuvant CRT and subsequent follow-up information. Lymphopenia was determined as lymphocyte count <850 cells/μL (severe lymphophenia defined as lymphocyte count <400 cells/μL, mild-moderate lymphopenia≥400 cells/ μL and <850 cells/μL), while pancytopenia was determined as lymphopenia plus leukopenia (WBC<3.8x103/μL), anemia (RBC<4.2x106/μL), and thrombocytopenia (platelet<140x103). We measured overall survival (OS) as well as progression-free survival (PFS). We performed summary statistics on baseline patient characteristics as well as Kaplan-Meier analysis for outcomes with log-rank test to compare subgroups. Of the 96 patients, 51 (53.5%) were male, and 45 (46.9%) were female. Median age at start of RT was 61 years old (range 33 to 88). Median follow-up was 16.8 months (range 2.3 to 61.1). Seven (7.3%) patients were still alive at time of writing, of which five had evidence of recurrence, leaving only two (2.1%) which remained disease free. Lymphopenia at 1 month post-RT was observed in 55 (57.3%) of patients, of which 13 patients (13.5%) had severe lymphopenia. Four patients (4.2%) had lymphopenia occurring in the setting of pancytopenia. Median OS for all patients was 16.5 months, with 1 year OS at 69.8% and 2 year OS at 29.9%. When comparing subgroups of patients with lymphopenia vs without, there was no significant difference in OS or PFS. The median OS was 16.5 mos vs 18 mos, with 1 year OS at 67.3% vs 73.2%, and 2 year OS at 32.5% vs 26.9%, respectively (p=0.68). Median PFS for all patients was 6.7 months, with 1 year PFS at 25% and 2 year PFS at 7.3%. For patients with lymphopenia vs without, median PFS was 6.2 mos vs 6.9 mos, with 1 year PFS at 30.9% vs 17.1%, and 2 year PFS at 9.1% vs 4.9%, respectively (p=0.34). For patients with severe lymphopenia, overall survival was worse, with median OS of 8.4 mos, 1 year OS was 46.1% and 2 year OS was 15.3%, with significantly worse prognosis when compared to patients without lymphopenia (p=0.041) as well as with those with mild-moderate lymphopenia (p=0.024). Median PFS for severe lymphopenia patients was 5.5 mos, with 1 year PFS of 23.1% and 2 year PFS at 7.7% with no statistically significant difference amongst subgroup comparison (p>0.05). Severe lymphopenia appears to have a negative impact on overall survival for GBM patients and should be considered as a prognostic factor for clinical outcomes.

Initial experience with intensity modulated proton therapy for intact, clinically localized pancreas cancer: Clinical implementation, dosimetric analysis, acute treatment-related adverse events, and patient-reported outcomes

PurposePencil-beam scanning intensity modulated proton therapy (IMPT) may allow for an improvement in the therapeutic ratio compared with conventional techniques of radiation therapy delivery for pancreatic cancer. The purpose of this study was to describe the clinical implementation of IMPT for intact and clinically localized pancreatic cancer, perform a matched dosimetric comparison with volumetric modulated arc therapy (VMAT), and report acute adverse event (AE) rates and patient-reported outcomes (PROs) of health-related quality of life. Methods and materialsBetween July 2016 and March 2017, 13 patients with localized pancreatic cancer underwent concurrent capecitabine or 5-fluorouracil-based chemoradiation therapy (CRT) utilizing IMPT to a dose of 50 Gy (radiobiological effectiveness: 1.1). A VMAT plan was generated for each patient to use for dosimetric comparison. Patients were assessed prospectively for AEs and completed PRO questionnaires utilizing the Functional Assessment of Cancer Therapy-Hepatobiliary at baseline and upon completion of CRT. ResultsThere was no difference in mean target coverage between IMPT and VMAT (P > .05). IMPT offered significant reductions in dose to organs at risk, including the small bowel, duodenum, stomach, large bowel, liver, and kidneys (P < .05). All patients completed treatment without radiation therapy breaks. The median weight loss during treatment was 1.6 kg (range, 0.1-5.7 kg). No patients experienced grade ≥3 treatment-related AEs. The median Functional Assessment of Cancer Therapy-Hepatobiliary scores prior to versus at the end of CRT were 142 (range, 113-163) versus 136 (range, 107-173; P = .18). ConclusionsPencil-beam scanning IMPT was feasible and offered significant reductions in radiation exposure to multiple gastrointestinal organs at risk. IMPT was associated with no grade ≥3 gastrointestinal AEs and no change in baseline PROs, but the conclusions are limited due to the patient sample size. Further clinical studies are warranted to evaluate whether these dosimetric advantages translate into clinically meaningful benefits.