Initiation Of Chemoradiotherapy Research Articles

The Glasgow Prognostic Score as a Predictor of Survival After Chemoradiotherapy for Limited-Disease Small Cell Lung Cancer.

Established biomarkers for predicting chemoradiotherapy efficacy for limited-disease small cell lung cancer (LD-SCLC) are lacking. The inflammation-based Glasgow Prognostic Score (GPS), comprising serum C-reactive protein (CRP) and albumin levels, can predict survival in advanced cancer. This study investigated whether metabolic and inflammatory markers, including the GPS, can predict the efficacy of chemoradiotherapy in patients with LD-SCLC. We retrospectively analyzed 124 patients who underwent chemoradiotherapy for LD-SCLC at two institutions between April 2007 and June 2021, and assessed the prognostic significance of various metabolic and inflammatory markers. The GPS was calculated using the CRP and albumin concentrations, and categorized as follows: 0, CRP<1.0 mg/dL and albumin≥3.5 mg/dL; 1, elevated CRP or decreased albumin; and 2, CRP≥1.0 mg/dL and albumin<3.5 mg/dL. Differences in progression-free survival (PFS) and overall survival (OS) were examined using Kaplan-Meier curves and Cox proportional-hazard models. The overall response rate was 95.1% (95% confidence interval [CI]: 89.6-97.9%). The median PFS and OS from chemoradiotherapy initiation were 12.6 (95% CI: 9.9-15.4) and 29.0 (95% CI: 24.8-45.5) months, respectively. The GPS demonstrated independent predictive ability for the effectiveness of chemoradiotherapy, wherein favorable scores (GPS 0-1) were significantly correlated with superior PFS and OS compared to unfavorable scores (GPS 2: PFS: 14.8 vs. 6.7 months, p=0.0001; OS: 35.4 vs. 11.0 months, p<0.0001). This preliminary examination revealed that the GPS was significantly associated with PFS and OS in patients undergoing chemoradiotherapy for LD-SCLC, indicating its potential utility in assessing the therapeutic outcomes in LD-SCLC.

Use of high-dimensional and spatial immune profiling to explore sotigalimab (CD40 agonist) activation of antigen presenting cells and T cells in the tumor microenvironment in patients with esophageal/gastroesophageal junction cancer.

450 Background: Neoadjuvant chemoradiation (CRT) followed by surgical resection is standard of care for patients with locally advanced esophageal/gastroesophageal junction (E/GEJ) cancer. A pathologic complete response (pCR) at surgery is associated with improved survival outcomes. Sotigalimab (sotiga) is a potent CD40 agonist mAb capable of inducing and expanding anti-tumor immune responses. A recently reported non-randomized phase II clinical trial of sotiga combined with CRT in E/GEJ cancer patients showed promising pCR rates that compared favorably to historical data1. Here, deep immune profiling was performed on a subset of patients to gain insight into the mechanism of sotiga. Methods: In the initial safety cohort (n=6) of this phase II E/GEJ clinical trial, tumor and blood samples were obtained pre-treatment and again following a single lead-in dose of sotiga, prior to initiation of CRT. Immune modulation in the tumor microenvironment and blood of patients was examined using high dimensional techniques, including mass cytometry, multiplexed ion beam imaging, and single cell RNA sequencing. Results: Sotiga administration dramatically re-models the tumor microenvironment, inducing immune infiltration and shifting the immune composition predominantly toward an inflammatory phenotype. At baseline, E/GEJ tumors were infiltrated with myeloid cells and T cells, the majority of which were Tregs. Sotiga increased antigen-presenting cell (APC) infiltration in tumors and activated dendritic cells as demonstrated by expression of MHCII and CD86. Sotiga treatment also induced infiltration of activated cytotoxic T cells and decreased the proportion of Tregs. There was also evidence of T cell activation in peripheral blood with increased expression of 4-1BB, CTLA-4, ICOS and PD-L1. Therapeutic responses to sotiga were associated with distinct T cell signatures both at baseline and on-treatment. At baseline, pCR patients (representing 4 of the 6 pts (67%) in this cohort) had a higher ratio of memory CD4+ T cells to Tregs which further increased following sotiga treatment, whereas patients who did not have a pCR had a higher proportion of myeloid cells at baseline and did not show a decrease in Treg cells after sotiga treatment. Conclusions: Sotiga induced dramatic changes in the tumor microenvironment including increased frequency of activated T cells and APCs, and decreased frequency of Tregs. A distinct signature of T cell infiltration in baseline tumor biopsies was observed in patients who achieved a pCR versus those who did not, potentially identifying patients that may benefit from this novel treatment strategy.

Impact of antibiotic use before definitive concurrent chemoradiation in patients with locally advanced non-small cell lung cancer.

This study evaluated whether antibiotic treatment before chemoradiotherapy influenced outcomes in patients with locally advanced non-small cell lung cancer (LA-NSCLC). The records of LA-NSCLC patients treated with chemoradiotherapy between 2010 and 2017 at West China Hospital of Sichuan University were retrospectively examined together with their antibiotic use (antibiotic type, duration of treatment, and time between discontinuation and chemoradiotherapy). The influence of antibiotics on progression-free survival (PFS) and overall survival (OS) was evaluated with Kaplan-Meier curves and univariate and multivariate Cox regression. Of 522patients, 176 had received intravenous broad-spectrum antibiotics in the month before chemoradiotherapy. Antibiotic use was linked to both reduced PFS (7.9 vs. 13.4months, p < 0.001) and OS (20.4 vs. 25.3months, p = 0.049). Multivariate regression demonstrated that antibiotic treatment was an unfavorable independent prognostic factor for LA-NSCLC patients who received chemoradiotherapy (HR 1.234; 95% CI 1.019-1.494; p = 0.031). Prognosis was also influenced by antibiotic type, length of treatment, and interval between discontinuation and chemoradiotherapy initiation. β‑lactamase inhibitors were found to be the most harmful (median OS for β‑lactamase inhibitors/fluoroquinolones/cephalosporins: 16.5/19.9/25.9months, p = 0.045). Cutoff values for interval and duration calculated by the X‑tile procedure showed that intervals of 7-16days or durations ≤ 6days did not significantly affect OS relative to untreated patients (intervals: p = 0.9; duration: p = 0.93). Antibiotic treatment for longer than 6days, especially with β‑lactamase inhibitors, was associated with poor prognosis. Furthermore, delaying chemoradiotherapy for 7-16days after antibiotic discontinuation may reduce these negative effects.

NCOG-21. EFFECT OF PNEUMOCYSTIS JIROVECII PNEUMONIA PROPHYLAXIS ON HEMATOLOGIC TOXICITY IN PATIENTS RECEIVING CHEMORADIATION FOR PRIMARY BRAIN TUMORS

Abstract INTRODUCTION Management of diffuse gliomas often includes radiation plus concomitant and adjuvant temozolomide. Hematologic toxicities are common from this therapy. Patients frequently receive prophylaxis against pneumocystis jirovecii pneumonia (PJP) during chemoradiation; however, some PJP prophylaxis drugs have the potential to independently cause myelosuppression which could exacerbate the hematologic toxicities from chemoradiation requiring chemotherapy dose reduction or cessation. We seek to understand differences in the frequency of hematologic toxicities during chemoradiation when either trimethoprim/sulfamethoxazole (TMP/SMX) or pentamidine are used for PJP prophylaxis. METHODS This was a retrospective chart review of patients with primary brain tumors who were treated with first-time radiation and concurrent temozolomide between April 2014-August 2021 at the Huntsman Cancer Institute. Chi squared analysis was used to evaluate effect of choice of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia within one month of finishing chemoradiation. Logistic regression was performed to evaluate the effect of PJP prophylaxis on the Common Terminology Criteria for Adverse Events (CTCAE) score for the lowest neutrophil, lymphocyte, and platelet count. RESULTS 217 patients were included in analysis. 144 patients received TMP/SMX, 69 received pentamidine, 1 received dapsone, and 3 received no prophylaxis at initiation of chemoradiation. Of patients who received TMP/SMX, 15.4% developed an absolute neutrophil count &amp;lt; 1,500 cells/µL while this occurred in 7.2% of patients receiving pentamidine (p=0.10). Platelet count &amp;lt; 100,000 occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p=0.70). Worst CTCAE scores for hematologic toxicities were similar between PJP prophylaxis groups. CONCLUSION Our study provides preliminary evidence that the type of PJP prophylaxis does not appear to significantly impact risk for hematologic toxicity in patients receiving radiation and concurrent temozolomide; however, there was a trend toward higher rates of neutropenia with TMP/SMX and larger analyses are needed to further evaluate these findings.

PO40 Presentation Time: 4:45 PM: Definitive Management of Cervical Cancer Patients at an Urban Institution During the COVID-19 Pandemic - Brachytherapy Treatment During the Surge

<h3>Purpose</h3> Locally advanced cervical cancer was defined by an international consensus panel as a high priority malignancy during the COVID-19 pandemic, recommending prompt initiation of definitive treatment and completion of treatment (PMID 32563593). The objective of this study was to study the clinical outcomes of patients (pts) with cervical cancer treated with definitive chemoradiation (CRT) and brachytherapy (BT) at our institution in 2019 (pre-COVID) and in 2020 (peri-COVID). <h3>Materials and Methods</h3> This was a retrospective cohort study of pts with FIGO Stage IB2-IVA cervical cancer at our institutions from 1/1/2019 to 12/31/2020. Pts received CRT followed by intracavitary brachytherapy (IC) with two operative insertions one week apart, or interstitial (IS) BT with one operative insertion. BT treatment was planned using image-guided CT or MR delineation. Pre-COVID was defined by initiation of CRT in 1/2019-12/2019, and peri-COVID was defined by initiation in 1/2020-10/2020. Process changes peri-COVID included limited on-site staff (e.g., minimal OR staff, no trainees, remote physics team), universal implementation of COVID-19 testing prior to surgery, and CT instead of MR-delineation based treatment. Outcomes of interest were time to treatment initiation and completion and differences in treatment planning modality or dosimetry. Fisher's exact and Mann Whitney U tests were used with significance p<0.05. <h3>Results</h3> Thirty-one pts were included, with 18 patients undergoing treatment pre-COVID and 13 peri-COVID. The median age at diagnosis pre-COVID was 57.7 (range 23-77) and for peri-COVID, 45.5 (range 28-62, p=0.06). There were no differences in non-English speaking pts (44% vs 59%, p=0.71) or uninsured pts (11% vs 33%, p=0.184) between the two cohorts. Median time to initiation of treatment from biopsy diagnosis was 52 days (range 13-209) in 2019 and for peri-COVID, 55.5 (range 20-173, p=0.71). During COVID, four pts had delayed initiation to treatment >100 days: two related to fertility, and one due to fear of COVID-19. For this pt, tumor size progressed from 2.3 cm to 4.2 cm maximal dimension. One pt treated in 2020 tested positive following treatment and did not require hospital admission. All pts except one completed CRT with RT: 25 pts pelvic RT (45 Gy), 3 pelvic and para-aortic RT (45 Gy with 57.5 Gy concomitant boost to nodes), 8 pts pelvic RT (45Gy) with sequential parametrial boost (50.4-59.4 Gy) using IMRT with no dose differences between pre and peri-COVID (Table 1). No pts required treatment breaks and the median overall treatment time was 50 days (range 31-85) in 2019 vs 50 days (range 43-63) in 2020 (p=0.710). <h3>Conclusions</h3> Despite the significant burden of the COVID-19 pandemic on our health care system, all cervical cancer pts receiving CRT met standard of care including CRT and BT within the recommended time frame with no significant differences in dosimetric treatment parameters pre- and peri-COVID. Delays in treatment initiation of treatment initiation were seen in 30% of pts in the peri-COVID period, suggesting that patients may have had increased barriers to access care. More follow-up is needed to determine how the Covid pandemic impacted cervical cancer outcome measures.

Neutrophil-to-lymphocyte ratio as a predictor of survival in head and neck squamous cell carcinoma patients treated with cisplatin.

e18004 Background: Neutrophil-to-lymphocyte ratio (NLR) is an easily attainable biomarker that is correlated with systemic inflammation and identifies increased risk of treatment complications and decreased survival in patients with cancer. Our objective was to investigate the use of NLR as an independent prognostic predictor of survival in patients with head and neck squamous cell carcinoma (HNSCC) treated with cisplatin chemotherapy. Methods: We conducted a retrospective study of 2,084 patients in the Veterans Health Affairs system with stages III–IVB head and neck squamous cell carcinoma diagnosed between 2000–2014 and treated with cisplatin-based chemoradiotherapy for curative intent. We calculated NLR values from laboratory values collected in the 30 days prior to initiation of chemoradiotherapy and dichotomized NLR using the Youden J-statistic (NLR = 3.64). We then compared outcomes using Cox proportional hazards methods, adjusting for sociodemographic characteristics (age, race, and sex), date of cancer diagnosis, smoking status, alcohol use, primary site of tumor, tumor characteristics (overall stage, T stage, and N stage), comorbidity score, eGFR, baseline neuropathy and hearing loss, BMI, and oncologic surgical procedures. Results: The cohort had a median age of 61. 99% of cases were male, 82% were white, 13% were black, and 4% were Hispanic. 36% of cases had an NLR &gt; 3.64 prior to treatment initiation. Median overall survival was 32.6 months for the low-NLR group and 24.9 months for the high-NLR group. In unadjusted analyses, a high NLR was associated with an increased risk of all-cause death (hazard ratio [HR]: 1.21; 95% CI 1.08–1.34). In adjusted analyses, high NLR retained significance and predicted overall survival (HR: 1.15; 95% CI 1.02–1.30). We also performed a secondary analysis for death within six months of cancer diagnosis; high NLR was associated with &gt; 50% increased risk of death after adjustment (HR: 1.56; 95% CI 1.04–2.33). Conclusions: In this large cohort of Veterans with advanced HNSCC undergoing chemoradiotherapy, NLR was an independent prognostic predictor of survival. NLR may be a useful clinical risk stratification tool prior to chemoradiotherapy initiation.

Exploring the Feasibility of Utilizing Limited Gene Panel Circulating Tumor DNA Clearance as a Biomarker in Patients With Locally Advanced Non-Small Cell Lung Cancer.

IntroductionCirculating tumor DNA (ctDNA) testing may identify patients at high risk for recurrence following chemoradiation (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). We evaluated the feasibility of ctDNA testing on a readily available commercial fixed-gene panel to predict outcomes in patients with LA-NSCLC.MethodsPlasma of 43 patients was collected at CRT initiation (pre-CRT), completion (post-CRT1), quarterly follow up for 12 months (post-CRT2, 3, 4, 5 respectively) after CRT, and at disease progression. ctDNA analysis was performed using InVisionFirst®-Lung to detect mutations in 36 cancer-related genes. ctDNA clearance was defined as absence of pre-CRT variants at post-CRT1. Patients without detectable pre-CRT variants or no post-CRT1 samples were excluded.ResultsTwenty eight of 43 patients (65%) had detectable variants pre-CRT. Nineteen of 43 patients (44%) had detectable pre-CRT variants and post-CRT1 samples and were included in analysis. Median age at diagnosis was 65 years (43-82), and most patients had stage IIIB disease (10/19, 53%). Two patients died from non-cancer related causes before post-CRT2 and were excluded from further analysis. All three patients who did not clear ctDNA had tumor relapse with a median time to relapse of 74 days (30-238), while 50% (7/14) of those who cleared ctDNA have remained disease free. Progression free survival was longer in patients who cleared ctDNA compared to those who did not (median 567 vs 74 d, p = 0.01).ConclusionsAlthough it is feasible to use ctDNA testing on a limited gene panel to identify patients with LA-NSCLC who are at high risk for disease recurrence following CRT, further studies will be necessary to optimize these assays before they can be used to inform clinical care in patients with lung cancer.

A phase II study of S-1 and cisplatin with concurrent thoracic radiotherapy followed by durvalumab for unresectable, locally advanced non-small-cell lung cancer in Japan (SAMURAI study): primary analysis.

The standard of care for unresectable, locally advanced non-small-cell lung cancer (LA-NSCLC) is chemoradiotherapy (CRT) followed by durvalumab, based on the PACIFIC study. Although multiple Japanese phase II studies have shown high efficacy and tolerability of CRT with cisplatin plus S-1 (SP), no prospective study using durvalumab after SP-based CRT has been reported. We conducted a multicenter phase II study of this approach, the interim analysis of which showed a high transition rate to durvalumab consolidation therapy. Here, we report the primary analysis results. In treatment-naïve LA-NSCLC, cisplatin (60 mg/m2, day 1) and S-1 (80-120 mg/body, days 1-14) were administered with two 4-week cycles with concurrent thoracic radiotherapy (60 Gy) followed by durvalumab (10 mg/kg) every 2 weeks for up to 1 year. The primary endpoint was 1-year progression-free survival (PFS). The expected 1-year PFS and its lower limit of the 80% confidence interval (CI) were set as 63% and 47%, respectively, based on the results of TORG1018 study. In all, 59 patients were enrolled, with 51 (86.4%) proceeding to durvalumab. The objective response rate throughout the study was 72.9% (95% CI: 59.7-83.6%). After median follow-up of 21.9 months, neither median PFS nor OS was reached. The 1-year PFS was 72.5% (80% CI: 64.2-79.2%, 95% CI: 59.1-82.2%), while the 1-year overall survival was 91.5% (95% CI: 80.8-96.4%). No grade 5 adverse events were observed throughout the study. The most common adverse event during the consolidation phase was pneumonitis (any grade, 78.4%; grade ⩾3, 2.0%). Eventually, 52.5% of patients completed 1-year durvalumab consolidation therapy from CRT initiation. This study of durvalumab after SP-based CRT met its primary endpoint and found a 1-year PFS of 73% from CRT initiation. This study provides the first prospective data on the prognosis and tolerability of durvalumab consolidation from the initiation of CRT. Japan Registry of Clinical Trials, jRCTs031190127, registered 1 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs031190127.

Treating through the surge: institutional experience of definitive management of cervical cancer patients at an urban institution during the COVID-19 pandemic

Objectives:An international consensus panel has defined locally advanced cervical cancers as a high priority malignancy during the COVID-19 pandemic and recommends prompt initiation of definitive treatment and completion of treatment (PMID 32563593). The objective of this study was to study the clinical outcomes of patients (pts) with cervical cancer treated with definitive chemoradiation (CRT) and brachytherapy (BT) at our institution in 2019 (pre-COVID) and in 2020 (peri-COVID).Methods:This was a retrospective cohort study of pts with FIGO Stage IB2-IVA cervical cancer at our institutions from 1/2019 to 10/2020. Pts received CRT followed by intracavitary brachytherapy (IC) with two operative insertions one week apart, or interstitial (IS) BT with one operative insertion. BT treatment was planned using image-guided CT or MR delineation. Pre-COVID was defined by initiation of CRT between 1/2019-12/2019, and peri-COVID was defined by initiation between 1/2020-10/2020. Process changes peri-COVID included limited on-site staff (e.g., minimal OR staff, no trainees, remote physics team), universal implementation of COVID-19 testing prior to surgery, and CT instead of MR-delineation based treatment. Outcomes of interest were time to treatment initiation and completion and differences in treatment planning modality or dosimetry. Fisher's exact and Mann Whitney U tests were used with significance p<0.05.Results:Thirty pts were included, with 18 patients undergoing treatment pre-COVID and 12 peri-COVID. The median age at diagnosis pre-COVID was 57.7 (range 23-77) and for peri-COVID, 45.5 (range 28-62, p=0.06). There were no differences in non-English speaking pts (44% vs 59%, p=0.71) or uninsured pts (11% vs 33%, p=0.184) between the two cohorts. Median time to initiation of treatment from biopsy diagnosis was 52 days (range 13-209) in 2019 and for peri-COVID, 55.5 (range 20-173, p=0.71). During COVID, three pts had delayed initiation to treatment >100 days: two related to fertility and one due to fear of COVID-19. For this pt, tumor size progressed from 2.3cm to 4.2 cm maximal dimension. One pt treated in 2020 tested positive following treatment and did not require hospital admission. All pts completed CRT with RT: 24 pts pelvic RT (45 Gy), 3 pelvic and para-aortic RT (45 Gy with 57.5 Gy concomitant boost to nodes), 8 pts pelvic RT (45Gy) with sequential parametrial boost (50.4-59.4 Gy) using IMRT with no dose differences between pre and peri-COVID (Table 1). No pts required treatment breaks and the median overall treatment time was 50 days (range 31-85) in 2019 vs 50 days (range 43-63) in 2020 (p=0.710).Conclusions:Despite the significant burden of the COVID-19 pandemic on our health care system, all cervical cancer pts receiving CRT met standard of care including CRT and BT within the recommended time frame with no significant differences in treatment parameters pre- and peri-COVID.

STMO-07 Adverse events related to the glioblastoma surgery and their perioperative management in our hospital

Background: The standard treatment for glioblastoma is surgical resection following chemoradiation therapy. The rate of removal or the amount of residual tumor has some impact on the prognosis of patients with glioblastoma, but the highly invasive nature of this tumor makes complete removal limited to the contrast-enhanced lesions difficult due to its localization. Furthermore, when postoperative seizures and venous thrombosis are included in surgery-related complications, these perioperative adverse events can cause delays in the initiation of chemoradiotherapy and delay the return to work and home, such as prolonged hospitalization and rehabilitation time.Methods: We retrospectively reviewed the perioperative status of the recent 50 consecutive cases with histologically confirmed as glioblastoma at our hospital, the patient background, tumor localization, and perioperative treatment, and so on. Results: The major perioperative complications were ischemic or hemorrhagic complications, epileptic seizures, venous thrombosis, and pneumonia; CTCAE grade 2 or higher, grade 3 or higher, and grade 4 occurred in about 40%, 20%, and 10%, respectively, with some patients having multiple complications. Discussion: Although there was a tendency for ischemic changes around the cavity of the resection as the resection rate increased, most cases were asymptomatic and it seemed to be acceptable if residual brain function could be preserved. Residual tumors tended to show hemorrhagic changes and epileptic seizures because this is thought to be that the tumor was deliberately left in place to preserve function, based on the localization of the tumor. Postoperative FDP levels were useful in predicting the development of deep vein thrombosis and pulmonary artery thromboembolism. Conclusion: Because glioblastoma has short survival time and patient PS before and after surgery varies greatly depending on tumor localization, it is important to consider risk-benefit strategies for each case and to establish a scheme for a seamless transition from perioperative management to the introduction of postoperative therapy and maintenance therapy.

Clinical Swallowing Profile Change in HNC Patients Treated with C/RT.

To demonstrate utility of the Mann Assessment of Swallowing Ability-Cancer (MASA-C) to describe change in swallowing ability in a cohort of HNC patients from pre-C/RT to post-C/RT to follow up at 3 months post-C/RT. An exploratory analysis compared patients treated with radiotherapy (RT) only to patients treated with chemoradiation (CRT). Prospective Cohort. The MASA-C and Functional Oral Intake Scale (FOIS) were completed on 85 HNC patients within the first 5 days of CRT initiation, at the completion of C/RT (6 weeks), and 3 months after completion of C/RT. MASA-C total scores and clinical profiles were used to describe change in swallowing performance at each time point. MASA-C and FOIS scores were significantly lower at 6 weeks and 3 months compared to baseline. Patients treated with CRT demonstrated more frequent and more severe dysphagia. Post C/RT items demonstrating the most deterioration included taste, diet level, oral mucosa, saliva, weight loss, and pharyngeal functions. Significant recovery was observed between 6 weeks and 3 months on both the MASA-C and FOIS. MASA-C items revealing the greatest recovery included taste, diet level, oral mucosa, tongue movement, weight loss, oral transit, voice, and pharyngeal phase. Few significant differences were noted between RT and CRT cases at 3 months. Swallowing functions deteriorate significantly following C/RT with incomplete recovery at 3 months. Few differences were noted between RT and CRT treated patients at 3 months. Clinical profiling with the MASA-C provides a standard, simple method to document swallow function change over time in these patients. 2 Laryngoscope, 131:E1873-E1880, 2021.

NCOG-33. HEMATOLOGIC PREDICTORS OF OUTCOMES IN GLIOBLASTOMA TREATED WITH SURGERY AND CHEMORADIATION

Abstract BACKGROUND There are conflicting reports regarding the prognostic value of platelet and other blood counts in glioblastoma. However, few series have looked at all hematologic parameters simultaneously. METHODS We performed a retrospective chart review of patients diagnosed with supratentorial glioblastoma from 2014-2019 who started conventional chemoradiation following initial surgical biopsy and/or resection. Hematologic parameters were collected at baseline, in the preoperative and postoperative periods and at the initiation and completion of chemoradiation. This included platelet counts, hemoglobin levels, white blood cell counts (WBC), neutrophil and lymphocyte counts with neutrophil:lymphocyte (NLR) and platelet:lymphocyte ratios (PLR) calculated at each time point. Cox regression was performed to assess the association between each hematologic parameter and both overall survival (OS) and progression free survival (PFS). A multivariate Cox proportional hazards model adjusted for all hematologic parameters, age, sex, race and KPS was generated for each time point. All hematologic parameters were modeled as continuous variables. RESULTS A total of 58 patients met inclusion criteria. 18 were female and 40 male. The median age was 59.5 (range 43-82). Median follow up for all patients was 15.3 months. A total of 52 patients completed radiation therapy and 18 completed 6 cycles of adjuvant chemotherapy. Hemoglobin and neutrophil counts at the conclusion of chemoradiation were associated with OS and PFS on univariate and multivariate analyses. The HR for OS were 0.74 (95% CI 0.5807-0.9313) and 1.28 (1.143-1.441) respectively. The HR for PFS were 0.70 (0.5531-0.8881) and 1.16 (1.05-1.271) respectively. Postoperative lymphocyte and platelet counts at initiation of chemoradiation were both associated with OS with unadjusted HR of 3.2 (1.037-9.960) and HR of 0.99 (0.9898-0.9999) respectively, which remained significant on multivariate analysis. However, neither were associated with PFS. CONCLUSION Several hematologic parameters are associated with glioblastoma outcomes in these initial analyses. Further analyses with additional patients are ongoing.

Is EAT-10 Useful to Assess Swallowing during the Chemo-Radiotherapy Phase in Patients with Head and Neck Cancer? A Pilot Study.

The 10-item Eating-Assessment Tool (EAT-10) is a dysphagia screening test. In HNC patients, screening and diagnosis of dysphagia are not well-established. To determine the metrological properties of the EAT-10 compared with videofluoroscopy in non-surgical HNC-patients and to assess the relationship between EAT-10 scores and patients' self-reported symptoms. Prospective cohort study. Forty-six HNC-patients recently diagnosed and referred to chemoradiotherapy (CRT). Main outcome was evidence of dysphagia according to EAT-10 score, self-perception on a Visual Analog Scale (VAS) of impaired swallowing, severity on the Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale (FOIS). Patients were assessed at baseline, before-CRT, after-CRT, and at 3-month follow-up. A strong baseline correlation between EAT-10, VAS, and FOIS was observed. All 3 values decreased in weeks 6 to 9 after CRT initiation; a poor correlation of EAT-10 with VAS was observed at 3-month follow-up. A receiver operating characteristic curve determined new cut-off points (sensitivity/specificity) for safe swallowing: baseline 3 (86%, 77%); post-CRT, 15 (62.5%, 80%); and 3-month follow-up, 4 (83%, 75%). New safe-swallow EAT-10-points are suggested for this population during screening and the oncological follow-up. A poor correlation between EAT10-score and patient self-reported symptoms was observed at the end-RT and at 3-month follow-up, highlighting the need for an objective evaluation instrument.

Survival impact of delaying postoperative chemoradiotherapy in newly-diagnosed glioblastoma patients.

BackgroundMaximal safe resection followed by adjuvant chemoradiotherapy (CRT) with temozolomide (TMZ) is the standard treatment for newly diagnosed glioblastoma multiforme (GBM) patients. Time of initiation of postoperative adjuvant therapy has been demonstrated to impact on prognosis. For GBM patients, the optimal interval between definitive surgery and CRT is still uncertain. Current study aims to find whether the delayed initiation of CRT after surgery has a negative impact on patients’ outcome.MethodsSixty-six consecutively patients with newly-diagnosed GBM treated with surgery and adjuvant CRT from April 2014 to September 2019 at Ruijin Hospital School of Medicine Shanghai Jiaotong University were retrospectively reviewed. The impact of postoperative time from surgery to adjuvant treatment on patient’s overall survival (OS) and progression-free survival (PFS) were evaluated by univariate Log-rank test and multivariate Cox regression analysis. Factors including age, Karnofsky performance status (KPS), maximum diameter of primary tumor, extent of resection, isocitrate dehydrogenase (IDH) mutation status and O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation status were also analyzed in Cox regression model.ResultsThe median OS for patients who started CRT less than 6 weeks (n=48) and more than 6 weeks (n=18) were 26.6 months (95% CI: 18.3–34.9) and 15.7 months (95% CI: 9.2–22.3) (P=0.001). The median PFS for the short interval group was 16.3 months (95% CI: 14.7–18.0) and for the long interval group was 9.1 months (95% CI: 4.7–13.4) (P=0.006). On multivariate Cox regression analysis, high KPS and initiation of CRT less than 6 weeks were two independent prognostic factors for better OS and PFS (all P<0.05).ConclusionsInitiation of adjuvant CRT beyond 6 weeks contributed to worse survival in GBM patients, therefore CRT should be initiated within 6 weeks after surgery.

The Role of Gut Microbiome Perturbation in Fatigue Induced by Repeated Stress from Chemoradiotherapy: A Proof of Concept Study.

Objectives The objectives of this proof of concept study were to (a) examine the temporal changes in fatigue and diversity of the gut microbiome over the course of chemoradiotherapy (CRT) in adults with rectal cancers; (b) investigate whether there are differences in diversity of the gut microbiome between fatigued and nonfatigued participants at the middle and at the end of CRT; and (c) investigate whether there are differences in the relative abundance of fecal microbiota at the phylum and genus levels between fatigued and nonfatigued participants at the middle and at the end of CRT. Methods Stool samples and symptom ratings were collected prior to the inception of CRT, at the middle (after 12–16 treatments) and at the end (after 24–28 treatments) of the CRT. Descriptive statistics and Mann–Whitney U test were computed for fatigue. Gut microbiome data were analyzed using the QIIME2 software. Results Participants (N = 29) ranged in age from 37 to 80 years. The median fatigue score significantly changed at the end of CRT (median = 23.0) compared with the median score before the initiation of CRT for the total sample (median = 17.0; p ≤ 0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, t(23) = 2.08, p ≤ 0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla for fatigued participants, and Escherichia, Bacteroides, Faecalibacterium, and Oscillospira were the most abundant genera for fatigued participants. Conclusion CRT-associated perturbation of the gut microbiome composition may contribute to fatigue.

Preoperative chemoradiotherapy using gemcitabine for pancreatic ductal adenocarcinoma in patients with impaired renal function.

Preoperative chemoradiotherapy (CRT) can be a promising treatment for pancreatic ductal adenocarcinoma (PDAC). However, its administration for patients with impaired renal function has not been well investigated, let alone its clinical effect. We previously reported preliminary feasibility of CRT in PDAC patients with renal impairment. Herein, we aimed to investigate the clinical effects of preoperative CRT including safety and long-term prognosis in more PDAC patients with renal impairment as an extension to our previous work. This study enrolled twenty patients harboring resectable PDAC with creatinine clearance level less than 60ml/min. Patients underwent preoperative CRT with gemcitabine, followed by surgery. The clinical effects of the therapy were evaluated in terms of safety and long-term prognosis. Preoperative CRT was completed in all 20 patients. Grade 4 leukopenia/neutropenia was identified as an observed toxicity in four cases (20.0%). Renal function was not worsened after CRT. After CRT, 17 cases were judged resectable and underwent laparotomy. Pancreatic resection was performed in 15 of the 17 patients; it was not performed in two patients because of peritoneal dissemination. The 1-/3-/5-year cumulative survival rate from the initiation of CRT for the 20 patients was 88.8%/45.5%/22.8%. In the 15 patients, renal function was not worsened after surgery. Our findings suggest that the clinical effects of preoperative CRT would be favorable in PDAC patients with renal impairment.

Effect of Diet Counseling on Anthropometric Indices and Dietary Intake of the Head and Neck Cancer Patients Undergoing Chemo-Radiotherapy

Malnutrition is common in patients with head and neck cancer due to cancer cachexia, anti-cancer therapies, impairment in food intake due to the tumor etc. This study aims at studying the effect of diet counseling intervention on dietary intake and anthropometric indices. Experimental design with only one experimental group was conducted on 14 head and neck cancer patients who were admitted for chemo-radiotherapy. Detailed assessment of anthropometry and diet was done in the before, during and after the diet counseling intervention of 7 weeks. There was mean weight improvement of 2 kg (p&lt;0.001) during the intervention period that can be attributed to a significant increase in the dietary intake of energy (p=0.034), protein (p=0.011), calcium (p&lt;0.001), zinc (p=0.041), vitamin C (p=0.046) and vitamin A (p=0.019). However there was no statistically significant improvement in the mid-upper arm circumference (MUAC). This increase may be a sign of improvement of nutritional status as normally cancer patients tend to show a decrease in MUAC. This indicates the success of the diet counseling intervention. An even greater improvement in these parameters can be achieved if intervention is provided before the initiation of chemoradiotherapy and has to be continued even after the therapy is complete.

HIF-1α Levels in patients receiving chemoradiotherapy for locally advanced non-small cell lung carcinoma.

To examine the relationship between treatment response and hypoxia-inducible factor-1 alpha (HIF-1α) levels in patients with locally advanced non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT). Eighty patients with NSCLC were included in the study and treated at Acibadem Mehmet Ali Aydınlar University Medical Faculty. HIF-1 α levels were measured before and after CRT by the enzyme-linked immunosorbent assay (ELISA) method. Patients' stages were as follows; stage IIIA (65%) and stage IIIB (35%). Squamous histology was 45%, adenocarcinoma was 44%, and others were 11%. Chemotherapy and radiotherapy were given concurrently to 80 patients. Forty-five (56%) patients received cisplatin-based chemotherapy, and 35 (44%) received carboplatin-based chemotherapy. Serum HIF-1α levels (42.90 ± 10.55 pg/mL) after CRT were significantly lower than the pretreatment levels (63.10 ± 10.22 pg/mL, p<0.001) in patients with locally advanced NSCLC. The results of this study revealed that serum HIF-1α levels decreased after CRT. Decrease of HIF-1α levels after the initiation of CRT may be useful for predicting the efficacy of CRT.

1458PD - Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer: 10-year follow-up of West Japan thoracic oncology group WJTOG0105

1458PD - Phase III study comparing second- and third-generation regimens with concurrent thoracic radiotherapy in patients with unresectable stage III non-small cell lung cancer: 10-year follow-up of West Japan thoracic oncology group WJTOG0105

Treatment patterns and overall survival among patients with unresectable, stage III non-small-cell lung cancer.

Aim: To analyze treatment patterns and overall survival (OS) across time (2009-2014) among patients with unresected, stage III non-small-cell lung cancer (NSCLC). Patients & methods: Stage III NSCLC patients aged ≥65years who initiated therapy were identified using SEER-Medicare data. Results: Among 4564 patients, 84% received chemotherapy (with or without radiotherapy), and 59% received chemoradiotherapy (CRT). Carboplatin+paclitaxel was the most frequent regimen. Median (interquartile range) OS among chemotherapy patients was 13.2 (6.0-28.9) months, and 14.8 (6.7-33.4) months among CRT patients. Among CRT patients, there was no difference in OS across years of CRT initiation. Conclusion: OS remained static across 2009-2014, indicating stagnancy in clinical outcomes for stage III NSCLC patients and a need for more effective therapeutic options.