Post Chemoradiotherapy Research Articles

Spindle Cell Sarcoma of the Maxilla: A Rare Entity, Case Report, and Review of the Literature.

Spindle cell sarcoma (SCS) is a malignancy, with the most recent Surveillance, Epidemiology, and End Results (SEER) data citing a total of 250 reported cases occurring in the head and neck. Of these cases, none originated in the maxillofacial hard tissue. The diagnosis of SCS requires its differentiation from other sarcomas and spindle cell neoplasms. Therefore, a comprehensive review to reinforce its inclusion in oral and maxillofacial surgeons' differential diagnosis for osseous neoplastic pathology is desired. In the present case report, we have described a recurrent case of Maxillary Undifferentiated Spindle cell sarcoma in a 11 year old male child post chemoradiotherapy which was excised intoto successfully .

Role of dynamic ctDNA monitoring in cervical and anal epidermoid carcinomas under curative chemoradiation.

3141 Background: Cervical and anal canal squamous cell carcinoma (SSC) are a significant health problem in underdevelopment countries. Definitive chemoradiation (CRT) is the standard-of-care (SOC) approach for curative treatment in locally advanced disease. Due to the common substantial local inflammation during CRT, the conventional clinical image cannot identify non-responders early. In this scenario, the evaluation of circulating tumor DNA (ctDNA) is a promising tool for real-time tumor response monitoring. Methods: We performed a prospective multicentric cohort study of patients treated between 2020 and 2023 in tertiary oncologic centers in Brazil to evaluate the role of ctDNA dynamic monitoring in epidermoid cervical (CC) and anal cancer (AC) T1-4, N0-1, M0 by AJCC 8th edition and candidates to complete curative CRT. The cDNA was assessed by Signatera test at D1, D29, immediately post-treatment, 8 weeks (w) post-CRT, 24w post-CRT, every 6 months (m) in the first 1-2 years(y), and yearly at 3-5y of follow-up (FUP). The primary endpoint was to estimate the correlation of ctDNA with a tumoral response assessed by conventional routine image and clinical evaluation at 8w. Secondary endpoints included a correlation between ctDNA results at different time points with progression-free survival (PFS) and overall survival (OS). The predictive potential of the biomarker was evaluated using receiving operating characteristic (ROC) curve analysis. Results: We included 33 patients, and 27 were evaluable with ctDNA, with a median FUP of 10m. The majority were female (n=23, 85.1%), and 3 (11%) were HIV-positive(+). Most patients presented with positive nodes and stage III disease (n=18, 66.6%). In the AC group (n=15), the majority received CRT with capecitabine and cisplatin (n=12, 55.5%); in the CC group (n=12), all pts received cisplatin. All pts tested expressed ctDNA+ before treatment. At 8w, images had a sensitivity of 42.8% and specificity of 100% for disease progression (area under the curve [AUC] 0.714), while ctDNA yielded a sensitivity of 85.7% and specificity of 89.4% (AUC 0.875). The ctDNA+ immediately after CRT ended (32%) was consistent with ctDNA+ at 8w (30.7%) and 24w (30%). Pts with ctDNA+ immediately post CRT have a higher risk of disease progression with PFS of 8.2m in ctDNA+ and not reached in ctDNA- group (HR:17.5; IC95%:1.9-157.3; p=0.01). Data are immature for OS analysis. Conclusions: CtDNA immediately post-CRT has a high predictive value in patients with anal and cervical tumors in early access CRT non-responders, who are at a high risk of disease progression. This biomarker should be considered for tailoring strategies of treatment escalation in this population.

Durvalumab and consolidation SBRT following chemoradiation for stage III non-small cell lung cancer: A single institution pilot study.

e20085 Background: Definitive chemoradiation (CRT) followed by consolidative immunotherapy with durvalumab (IO) demonstrated survival benefit and is now standard of care for Stage III Non-small Cell Lung Cancer (NSCLC). However, local-regional control (LRC) remains a concern with intrathoracic progression representing the most common site of failure. Adding stereotactic body radiotherapy (SBRT) boost may enhance the immunogenicity and antigenicity of tumor cells by regulating cell surface receptors and augmenting T-lymphocyte infiltration into tumor. SBRT boost also allows escalated dose to the primary tumor while minimizing dose to critical structures. Methods: Patients with Stage III NSCLC planned for definitive concurrent CRT with 1 year of consolidative IO were prospectively enrolled on a single institutional pilot trial. IO started 6-8 weeks after completion of CRT. SBRT was delivered between cycle 1 and 2 of IO to the residual, primary tumor (20 Gy in 2 fractions for peripheral, 19.5 Gy in 3 fractions for central tumors). Residual tumors needed to be < 120 cc. Lymph nodes were not boosted. Primary endpoints were grade (gr) ≥3 toxicities (CTCAE V4.03) and progression free survival (PFS). Secondary endpoints were Overall Survival (OS), LRC, and distant metastasis (DM). A sample size of 25 patients was proposed to determine safety and efficacy. Results: Accrual was slower than anticipated, and the study closed with 11 patients enrolled over 54 months. Slow accrual was due to a low rate of eligibility based on post CRT clinical status and SBRT target limitations. 1 patient withdrew consent before receiving treatment leaving 10 evaluable patients. Median age was 73 years and median CRT dose was 60 Gy (range 60-66 Gy). 6/10 of patient were adenocarcinoma. 5/10 pts had central tumor location. Median follow-up for evaluable patients is 2.2 years. OS was 90%, 70%, and 70% at 1-year, 2-years, and 3 years, respectively. PFS was 90%, 47%, and 47% at 1 year, 2 years, and 3 years, respectively. LRC was 100%, 83%, and 63% at 1 year, 2 years, and 3 years, respectively. Rates of DM were 0%, 12%, and 34% at 1 year, 2 years, and 3 years, respectively. 1 patient developed gr 3 pneumonitis requiring discontinuation of IO. 1 additional patient developed gr 2 pneumonitis requiring a brief pause in IO therapy and resumed IO without any further complications. One patient developed gr 5 myocarditis 29 days after the first dose of IO and 18 days after SBRT, on investigation deemed to be myocarditis secondary to IO. There was no other gr 3 toxicity attributable to IO or SBRT. Conclusions: The addition of SBRT to consolidative IO in stage III NSCLC patients treated with CRT was feasible. The single gr 5 toxicity was attributed to IO. SBRT boost demonstrated encouraging efficacy and manageable toxicity and merits further study. Our data adds to the growing evidence of harnessing tumor immunogenicity in enhancing IO responses. Clinical trial information: NCT03589547 .

76 Adjuvant Durvalumab post chemoradiotherapy in stage III unresectable non-small cell lung cancer: A retrospective review from the University Hospitals Bristol and Weston NHS Foundation Trusts

76 Adjuvant Durvalumab post chemoradiotherapy in stage III unresectable non-small cell lung cancer: A retrospective review from the University Hospitals Bristol and Weston NHS Foundation Trusts

Our Experience of Distal and Total Urethrectomies in Post Irradiated Vulvar Malignancies in Low Resource Settings: A Single Centre Study.

At diagnosis, women with vulvar cancer often present in locally advanced stage especially in developing countries, owing to the associated ignorance and social stigma. Generally tumour is seen involving adjacent organs, like the vagina, anus, and urethra. Damage to the sphincter system leads to urinary incontinence. Available evidence regarding urethral resections, subsequent lower urinary tract dysfunction and neo-meatus reconstruction in radical vulvar surgeries is scarce and conflicting. Considering, the lack of literature on outcomes of partial and total urethrectomies post chemoradiation in advanced vulvar malignancies from India, in the current study, we analysed our experience of such cases that have been operated post chemoradiation over a span of 2years (from January 2019 to January 2021). DFS ( disease free survival) of more than 6months was seen in 5 of our patients, however in view of local wound complications after primary closure, we recommend reconstruction with myocutaneous flaps. Also in view of incontinence observed in two of our patients who had undergone more than 1⁄2 of urethral resection, as a result of failed suprapubic catheterisation, further plan of urethral reconstruction should be considered especially in patients who have received prior radiation. Our small group of patients represents a unique cohort of patients in whom surgery was attempted after radiation therapy. We have seen that surgery is a feasible option after radiotherapy in patients with advanced disease.

Cardiac radiation dose is associated with inferior survival but not cardiac events in patients with locally advanced non-small cell lung cancer in the era of immune checkpoint inhibitor consolidation

PurposeWe assessed the association of cardiac radiation dose with cardiac events and survival post-chemoradiation therapy (CRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) after adoption of modern radiation therapy (RT) techniques, stricter cardiac dose constraints, and immune checkpoint inhibitor (ICI) consolidation. Methods and MaterialsThis single-institution, multi-site retrospective study included 335 patients with LA-NSCLC treated with definitive, concurrent CRT between October 2017 and December 2021. All patients were evaluated for ICI consolidation. Planning dose constraints included heart mean dose < 20 Gy (<10 Gy if feasible) and heart volume receiving ≥ 50 Gy (V50Gy) < 25 %. Twenty-one dosimetric parameters for three different cardiac structures (heart, left anterior descending coronary artery [LAD], and left ventricle) were extracted. Primary endpoint was any major adverse cardiac event (MACE) post-CRT, defined as acute coronary syndrome, heart failure, coronary revascularization, or cardiac-related death. Secondary endpoints were: grade ≥ 3 cardiac events (per CTCAE v5.0), overall survival (OS), lung cancer-specific mortality (LCSM), and other-cause mortality (OCM). ResultsMedian age was 68 years, 139 (41 %) had baseline coronary heart disease, and 225 (67 %) received ICI consolidation. Proton therapy was used in 117 (35 %) and intensity-modulated RT in 199 (59 %). Median LAD V15Gy was 1.4 % (IQR 0–22) and median heart mean dose was 8.7 Gy (IQR 4.6–14.4). Median follow-up was 3.3 years. Two-year cumulative incidence of MACE was 9.5 % for all patients and 14.3 % for those with baseline coronary heart disease. Two-year cumulative incidence of grade ≥ 3 cardiac events was 20.4 %. No cardiac dosimetric parameter was associated with an increased risk of MACE or grade ≥ 3 cardiac events. On multivariable analysis, cardiac dose (LAD V15Gy and heart mean dose) was associated with worse OS, driven by an association with LCSM but not OCM. ConclusionsWith modern RT techniques, stricter cardiac dose constraints, and ICI consolidation, cardiac dose was associated with LCSM but not OCM or cardiac events in patients with LA-NSCLC.

The Association of Chemoradiation Induced Lymphopenia with Racial Disparity and Its Prognostic Impact on Survival for Anal Cancer

While the association between chemoradiation induced lymphopenia (CIL) and poor overall survival (OS) is established in multiple solid malignancies, it has not been studied in anal cancer. Racial and socioeconomic disparities as potential predictors of lymphopenia have not been reported. We hypothesize that race and socioeconomic status is associated with increased incidence of severe CIL, which can predict worse overall survival for patients with anal cancer. A cohort of 75 patients treated with definitive chemoradiation (CRT) for squamous cell anal cancer from January 2014 to December 2020 was reviewed. Total lymphocyte counts (TLC) at baseline and TLC nadir at 1 month post-CRT were analyzed. Logistic regression was used to identify associations between race, gender, ethnicity, median household income by zip code, marital status, baseline hematopoietic cell counts, and post-CRT Grade 3+ lymphopenia (TLC <0.5k/μL). Kaplan-Meier method and Cox regression model were used to perform survival analysis. Of the 75 patients identified, mean age was 66.9 years and median follow-up time was 37.1 months. There were 63 females, 53 non-Hispanic whites, 22 minorities (12 Blacks, 9 Hispanics, 1 Asians) Radiation dose ranged from 41.4 Gray to 56 Gray. At 1 month post CRT, 85.3% developed lymphopenia (G1 9.3%, G2 26.7%, G3 37.3%, G4 12.0%). On multivariate logistic regression, non-white race demonstrated a trend to have more Grade 3+ lymphopenia (OR = 3.5, p = 0.07). On univariate Cox regression, poorer overall survival was associated with race (HR 3.7, p = 0.04), baseline white blood count (HR 1.3, p = 0.04), baseline hemoglobin (HR 0.6, p = 0.04), and post-CRT Grade 3+ lymphopenia (HR 5.8, p = 0.03). On multivariate Cox regression, only post-CRT Grade 3+ lymphopenia was associated with worse OS (HR 7.5, p = 0.049). 5-year OS significantly differed between patients with and without post-CRT Grade 3+ lymphopenia (62.3% vs 94.7%, P = 0.01). Lymphopenia is commonly observed after chemoradiation for anal cancer. Racial disparity is associated with severe lymphopenia induced by chemoradiation, which is a robust predictor of poor survival in anal cancer. More attention to lymphopenia induced by chemoradiation for anal cancer is needed, particularly in racial minorities.

A Phase 1 Trial of the Safety, Tolerability, and Biological Effects of Intravenous Enadenotucirev (EnAd), a Novel Oncolytic Virus, in Combination with Chemoradiotherapy in Locally Advanced Rectal Cancer (CEDAR)

Novel treatment combinations are required to increase response rates in rectal cancer. EnAd is an intravenous, tumor selective, oncolytic adenovirus with high affinity for malignant colorectal epithelial cells. Pre-clinical evidence of synergy with radiation warranted further clinical evaluation and assessment of safety in combination with chemoradiation (CRT), 25 × 2Gy and concurrent capecitabine. EnAd was escalated using 2 dose levels of viral particles (1 × 1012, 3 × 1012), given Monday, Wednesday, Friday over 3 schedules (pre-CRT, pre & post CRT). Toxicity and efficacy were used as dual end points in escalation decisions. A 2-parameter and 3-parameter logistic Time to Event Continual Reassessment Method (TiTE-CRM) were used estimate the dose-toxicity and dose-efficacy relationship, respectively. Results are shown as probability and 95% credible interval (Cr.I). The dose limiting toxicity (DLT) window was 13 weeks. Patients who had not completed their DLT window at the time of a dose decision were included in the safety analysis but down-weighted according to their follow-up time and amount of IMP received. Efficacy was assessed at 13 weeks using MRI Tumor Regression Grade (mrTRG), where mrTRG 1-2 equals response. The trial (NCT03916510) was conducted in 4 UK centers. A total of 13 patients were enrolled, 12 of whom were evaluable. Median age was 57 (range 31-84), and 10/13 were male. One patient had two G3 adverse events (AE); diarrhea, acute kidney injury. All other adverse events (AEs) were G1 or 2, with no G4/5 events. The most common AE by organ system was gastrointestinal (20.8%, G1). There were two observed DLTs on Dose schedule 3; leg swelling and acute kidney injury. Responses and toxicities increased with escalating schedules of EnAd (Table 1). CEDAR is the first trial to successfully combine an intravenous oncolytic adenovirus with radiation, demonstrating the feasibility and acceptability of this approach, and a new paradigm in radiosensitization in rectal cancer. Within this small Phase I study, EnAd demonstrated an acceptable safety profile with evidence of a higher-than-expected rate of response by mrTRG. Translation analysis of tissue, blood and microbiome for biological correlates of radiation synergy is underway. PsiOxus, CRUK (A24474). University of Oxford.

Next-Generation Sequencing Analysis of Mutations in Circulating Tumor DNA from the Plasma of Patients with Head-Neck Cancer Undergoing Chemo-Radiotherapy Using a Pan-Cancer Cell-Free Assay.

Using next-generation sequencing (NGS), we investigated DNA mutations in the plasma tumor cell-free circulating DNA (ctDNA) of 38 patients with inoperable squamous cell head neck cancer (SCHNC) before and after the completion of chemoradiotherapy (CRT). Baseline mutations of the TP53 were recorded in 10/38 (26.3%) and persisted in 4/10 patients after CRT. ΤP53 mutations were further detected post CRT in 7/38 additional patients with undetectable mutations at baseline (overall rate 44.7%). Furthermore, 4/38 patients exhibited baseline mutations of the EGFR, AR, FGFR3, and FBXW3, and four new gene mutations were detected after CRT (MTOR, EGFR3, ALK, and SF3B1). Τ4 stage was related with a significantly higher rate of mutations (TP53 and overall). Mutations were observed in 8/30 (26.6%) responders (complete/partial response) vs. in 6/8 (75%) of the rest of the patients (p = 0.03). Significant poorer LRFS was noted for patients with mutations detected before and after CRT (p = 0.02). Patients who had detectable mutations either before or after CRT had significantly worse DMFS (p = 0.04 overall, and p = 0.02 for TP53 mutations). It was concluded that assessment of mutations before and after the end of CRT is essential to characterize patients with a high risk of locoregional recurrence or metastatic progression.

SDPS-29 SERUM-DERIVED CD47 AS A MARKER OF TUMOR BURDENAND OUTCOME IN GBM PATIENTS – CORRELATIVE ANALYSISOF TUMOR LOCATION, RADIATION THERAPY VOLUMES,AND SURVIVAL

Abstract Glioblastomas (GBM) are the most aggressive central nervous system tumors exhibiting near universal recurrence following resection and chemoradiation (CRT). CD47 is an integrin-associated transmembrane protein associated with immunomodulation, invasion, and stemness that is highly expressed in GBM. We tested the hypothesis patient serum-derived CD47 measured pre vs. post-CRT may be related to tumor burden by exploring its association with tumor dissemination in the brain, RT volumes, and outcomes. CD47 was analyzed using an aptamer-based SOMAscan proteomic assay on serum collected pre and post CRT for 82 individuals with a pathologic diagnosis of GBM. Clinical features (tumor location (cortical/periventricular), gross tumor volumes (GTVT1, GTVT2), and outcome (overall survival (OS), progression-free survival (PFS)) were analyzed in conjunction with alteration in CD47 levels. Alteration in CD47 level was associated with OS (HR = 32.34 CI: 3.520 - 288.3, p = 0.0004053) and PFS (HR =8.5, p = .0008 CI: 0.2291-4.011). Expression of CD47 increased after CRT (p = .022). Patients with periventricular tumors had higher expression of CD47 pre vs. post CRT (p = 0.0188) and worse OS (median 13 vs. 25 months) and PFS (median 5 vs. 10 months) as compared to patients with strictly cortical tumor presence. A positive correlation was identified between GTVT1 and GTVT2 and CD47 expression levels (p = .0006). Lower CD47 expression values were associated with higher survival probability (p = .013). The stratification of CD47 expression levels yielded increasingly significant results with the separation of discrete survival groups (p = .00013), indicating clinically distinct subtypes of GBM. Tumor location (cortical vs. periventricular) and GTVT1 correlated with OS and PFS (p&amp;lt;0.05), unlike GTVT2 in this cohort in the absence of CD47 expression level. CD47 expression levels correlate with tumor location, RT volumes, OS, and PFS with distinct GBM subtypes potentially stratified via serum CD47 expression levels.

Management and treatment of patients with stage III unresected NSCLC at UPMC: A quality initiative by Integra Connect Precision Q.

e20588 Background: The PACIFIC trial led to improved OS in patients (pts) with unresectable stage 3 NSCLC who received durvalumab (durva) post chemoradiation (CRT).1 In 2019, the University of Pittsburgh Medical Center (UPMC) and IC initiated a QI to improve immunotherapy (IO) use post CRT. A baseline analysis was done to assess scanning and treatment patterns post-CRT, and duration of treatment (DOT) with durva. Drawing on this analysis, IC and UPMC conducted a focus group to address gaps in care and initiated improvements. This real-world study aims to assess the change in IO use post-CRT, the time to scan (TTS), time to treatment (TTT), and duration of treatment (DOT) compared to baseline. The DOT of durva was compared between pts initiated &lt;14 days of CRT and those who started ≥14 days. Methods: From the UPMC and IC Precision Q real-world databases, we identified 555 pts with stage 3 unresectable NSCLC for manual chart abstraction. Pts received CRT between 2/16/2018 and 12/31/2021. TTS was calculated from the last day of CRT to the 1st scan and the TTT obtained from the last day of CRT to the 1st durva dose. The baseline period was from 2/16/2018 to 8/31/2020 and the post-intervention stage from 9/1/2020 to 12/31/2021 based on CRT start date. Pts were excluded if they had no scan data, a 1st scan ≥90 days post CRT (TTS analyses), a duration of zero days (DOT analyses) or a TTT &gt;120 days (TTT analyses). At least 1 yr of follow up was required for DOT comparisons. Descriptive analyses were used. A two-tailed 2 sample z-test was used for proportions and the nonparametric Wilcoxon rank sum test was used for TTS, TTT and DOT comparisons. Results: The baseline pts were 46% female with an average age of 67.7 years and the post-intervention were 47% female with an average age of 69.4 years. The rate of durva use post CRT in pts who did not progress increased from 66% (n =128/194) at baseline to 83% (n =96/116) post intervention (p &lt; 0.01). The baseline median TTS decreased from 22.5 days (n=174) to 20 days (n=121) post intervention (p &lt;0.05), and median TTT decreased from 35 days (n=121) to 28 days (n=90) (p &lt; 0.05). The median DOT increased from 6 (n=127) to 8.2 months (n=76) (p &gt;0.05). During the study period, 8% (n =17/223) of pts started durva &lt; 14 days post CRT and 92% started ≥14 days (n =206/223). The median DOT in the &lt; 14 days group was 10.8 months versus 6.2 months in ≥14 days (p &gt;0.05). The median overall survival (OS) was 36.5 months in the &lt; 14 days vs. 27.8 months in the ≥14 days group (p &gt; 0.05). Conclusions: QIs in NSCLC are effective tools that can improve appropriate durva utilization, TTT and DOT in eligible pts. Practices that assess their clinical performance can identify gaps in care and act. In this study, a superior OS, though lacking statistical significance, was seen in the group that started IO &lt;14 days post CRT compared to ≥14 days. Further studies with larger sample size, are needed to validate these findings.

Risk stratification of postoperative cardiopulmonary toxicity after trimodality therapy for esophageal cancer.

Postoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes. Patients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin etal. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used. From 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and proton therapy (19%). 61 patients had major CPTTB (score ≥ 70). Increasing CPTTB was predictive of decreased OS (p<0.001), lengthier post-esophagectomy length of stay (LOS, p<0.001), and death or readmission within 60 days of surgery (DR60, p<0.001). Major CPTTB was also predictive of decreased OS (hazard ratio = 1.70, 95% confidence interval: 1.17-2.47, p=0.005). The RPA-based risk score included: age ≥ 65, grade ≥ 2 nausea or esophagitis attributed to chemoradiation, and grade ≥ 3 hematologic toxicity attributed to chemoradiation. Patients treated with 3D radiotherapy had inferior OS (p=0.010) and increased major CPTTB (18.5% vs. 6.1%, p<0.001). CPTTB predicts for OS, LOS, and DR60. Patients with 3D radiotherapy or age ≥ 65 years and chemoradiation toxicity are at highest risk for major CPTTB, predicting for higher short and long-term morbidity and mortality. Strategies to optimize medical management and reduce toxicity from chemoradiation should be strongly considered.

DNA methylation biomarkers accurately detect esophageal cancer prior and post neoadjuvant chemoradiation.

Esophageal cancer (ECa) is associated with high mortality, mostly due to late diagnosis, precluding curativeintent surgery. Hence, neoadjuvant chemoradiation (ChRT) is recommended in most patients regardless of histological subtype. A proportion of these patients, however, achieve complete disease remission and might be spared of radical surgery. The lack of reliable, minimally invasive biomarkers able to detect post-ChRT disease persistence is, nonetheless, a major drawback. We have previously shown that miRNA promotor methylation enables accurate cancer detection in tissues and liquid biopsies but has been seldom explored in ECa patients. Herein, we sought to unveil and validate novel candidate biomarkers able to detect ECa prior and post ChRT. Promoter methylation of miR129-2, miR124-3 and ZNF569 was assessed, using quantitative methylation-specific PCR (qMSP), in tissue samples from normal esophagus, treatment-naïve and post-ChRT ECa, as well as in liquid biopsies from ECa patients. All genes disclosed significantly different promoter methylation levels between ECa and normal esophagus, accurately detecting post-ChRT disease, especially for adenocarcinoma. Remarkably, miR129-2me /ZNF569me methylation panel identified ECa in liquid samples with 53% sensitivity and 87% specificity. MiR129-2me , miR124-3me and ZNF569me accurately discriminate ECa, either pre- or post-ChRT, from normal tissue, enabling ECa detection. Furthermore, circulalting methylation-based biomarkers are promising minimally invasive tools to detect post-ChRT residual ECa. Overall, our results encourage the use of miRNA methylation biomarkers as accurate ECa detection tools as a novel approach for ChRT response monitoring.

Speech and swallowing rehabilitation of post-partial mandibulectomy: a case report

&lt;p class="abstract"&gt;Squamous cell carcinomas of the oral cavity require multiple treatment approaches such as chemotherapy, radiotherapy, and surgical treatment. Glossectomy and mandibulectomy are the most common surgical treatment procedures for oral carcinoma with pre-, and post-surgical chemo-radiotherapy depending on the stage of cancer. The patients with glossectomy and mandibulectomy are at risk of developing a wide range of impairments in speech and swallowing functions due to surgical procedures and post chemo-radiation therapy (trismus and xerostomia). The present case report describes a 52-year-old male who had a history of oral squamous cell carcinoma and underwent wide excision of maxillar and mandibular regions who presented with severe speech and swallowing impairments. On examination of speech and swallowing functions, the patient exhibited oral dysphagia of moderate severity and poor speech intelligibility. The patient had undergone 50 speech and swallow therapy sessions over two months duration and post-therapy evaluation showed improvements in speech and swallowing functions. The patient had exhibited improvements in quality of life on various physical and functional domains post-rehabilitation. However, the improvements were limited due to the presence of trismus and hypernasality due to maxillar resection. This case report describes the importance of speech and swallowing rehabilitation to improve the post-surgical impairments in speech and swallowing functions and also the overall quality of life of patients with oral cancers.&lt;/p&gt;

Head and Neck Symptom Severity (HNSS) and Health-Related Quality of Life (HRQL) Trajectories during and after Chemoradiotherapy (CRT) for HPV-Associated Oropharyngeal Cancer (HPVOPC): A TROG 12.01 Secondary Analysis

<h3>Purpose/Objective(s)</h3> This secondary analysis aimed to identify HNSS and HRQL trajectories during and following CRT for HPVOPC. <h3>Materials/Methods</h3> All 182 evaluable TROG 12.01 patients were included. HNSS was assessed with the MDASI-HN (range 0-10) at baseline (BL), weekly during CRT (weeks (w) 1-7) and then 1, 3, 5, 9 and 13w and 6, 12 and 24 months (m) post CRT. HRQL was assessed using the FACT-G (range 0-108) at BL, and 7w, 6m, 12m and 24m post CRT. Latent class growth mixture modelling (LCMM) was performed to identify trajectories. Mean estimates and 95% confidence intervals (CI) were calculated at each time point. <h3>Results</h3> The HNSS model identified 4 trajectory classes (HNSS1-4) distinguished by differences in HNSS at BL, during the peak of treatment symptoms (w7 CRT/1w post CRT) and during early (1w to 9w post CRT) and intermediate recovery (9w to 12m post CRT). The trajectories of all 4 classes were stable beyond 12m. The reference trajectory (HNSS4, n=74) score was 0.1 (CI 0.1-0.2) at BL, peaking at 4.6 (CI 4.2-5.0), with rapid early recovery (1.1, CI 0.8-2.2) and gradual improvement to 12m (0.6, CI 0.5-0.8). HNSS2 ("high BL", n=30) reported higher BL scores (1.4, CI 0.8-2.0) but was otherwise similar, HNSS3 ("low acute", n=53) reported reduced acute symptoms (2.5, CI 2.2-2.9) with stable scores beyond 9w post CRT (1.1, CI 0.9-1.4). HNSS1 ("slow recovery", n=25) had slower recovery from an acute peak of 4.9 (CI 4.3-5.6) to 0.9 (CI 0.6-1.3) at 12m. Compared to HNSS4, the high BL group were younger (mean 53.6 vs 57.4), with fewer ECOG0 (87 vs 99%) or with higher degree (38 vs 69%), and higher baseline anxiety (HADS, mean 6.8 vs 4.4). The low acute group were older (mean 60.1), had fewer ECOG0 patients (87%) and were more likely to have received cetuximab (68% vs 43%). The slow recovery group had fewer with a higher degree (52%). The HRQL model included 2 trajectory classes. The reference trajectory (HRQL2, n=156) scores were 90 (CI 88-92) at BL, similar 7w post CRT (88, CI 85-90) with slow but clinically meaningful improvement to 12m (98, CI 96-100). HRQL1 (n=26) had lower BL mean scores (80, CI 74-86), with a significant decline at 7w post CRT (57, CI 50-63) and a slower recovery to BL scores over 12m (83, CI 72-94). Both trajectories were flat beyond 12m. The slow recovery group were older (mean 61.1 vs 56.8), with worse BL anxiety (mean 6.5 vs 4.4) and depression (mean 4.5 vs 2.1). In addition, LCMM identified 4 trajectories for head and neck symptom interference, 3 for anxiety and 4 for depression, which will be presented. <h3>Conclusion</h3> LCMM identified distinct trajectories of HNSS and HRQL during and after CRT. These and their associations with variations in HPVOPC patients' characteristics and treatment factors provide clinically relevant insights into identifying patients who may require increased support during and after CRT.

A Prospective Observational Study of Significance of MRI Assessed Tumor Response for Locally Advanced Rectal Cancer Treated with Longcourse Neoadjuvant Chemoradiation

<h3>Purpose/Objective(s)</h3> Use of MRI in comparing the morphological features of rectal cancer pre and post chemo radiation and to correlate the post treatment MRI appearances with the histological findings in resected tumors. <h3>Materials/Methods</h3> After staging MRI, immobilization and planning CT, target volumes for primary, nodal stations and OARs were drawn as per the RTOG atlas. Majority of the plans were 3DCRT such that 95% of PTV volume covered by at least 90% isodose. Patients were prescribed 50.4Gy in 28 fractions over 5 ½ weeks to the PTV along with oral capecitabine 825mg/m2 twice daily during treatment. 6-8 weeks after the treatment completion patients MRI pelvis was done and the radiologist was asked to grade the tumor response according to the Mandard system. Post-surgery the pathologist who was blinded for the MRI report was asked to grade the tumor regression according to Dworak et al. Both the tumor regression grades are compared and the correlation between two was recorded using statistical software. <h3>Results</h3> Based on the mrTRG, we have 3/37(8%) patients showed complete regression, 13/37(35.1%) showed good regression, 17/37(45.9%) showed moderate regression, 4/37(10.8%) showed slight regression. pTRG, we have 3/37(8.1%) patients showed total regression, majority of the patients 17/37(45.9%) showed pTRG 3, 13/37(35.1%) showed pTRG 2 and 4/37(10.8%) people showed slight regression. Nearly 43% (16/37) of the patients showed good response to the therapy, while remaining 57% (21/37) of the patients showed poor response. Nodal staging has prognostic importance, tumors with less nodal burden has good response to NACTRT. 15 out of 16 patients (93.75%) belonging to the favorable response group, (mrTRG 1–2) were also found to have a good pathological tumor regression (pTRG 3–4), the remaining patients being classified as having a pTRG of 2 (35%) or 0–1 (10.8%). Among 21 patients with predicted poor response due to suboptimal tumor regression on MRI scan (mrTRG 3–5), 4 (19.04%) were confirmed to have minimal pathological tumor regression (pTRG 0–1), while 12 (57.14%) and 5 (23.80%) showed a pTRG of 2 and 3–4, respectively. When a dichotomous classification (i.e., pTRG 0–3 vs pTRG 4 and mrTRG 3–5 vs mrTRG 1–2) was used to assess the ability of MRI to predict complete regression, 3 out of 3 patients (100%) with pathological complete response were correctly identified using mrTRG. Sensitivity, specificity of mrTRG were 94.4% (95% CI: 68.8– 96.5), 82.8% (95% CI: 74.5–90.6) respectively. Using Pearson's correlation, we found a correlation between mrTRG and pTRG significant at the level of 0.01(p value = 0.01). Negative correlation of, r² = -0.830 indicates that increasing trend of TRG in MRI correlates to decreasing trend of TRG on postsurgical pathology specimen. <h3>Conclusion</h3> Correlation and comparisons depicted in our study concluded that there is a significant association between mrTRG and pTRG. mrTRG can be used as surrogate marker for the prediction of pTRG.

Histopathological Spectrum of Urinary Bladder Tumors: One Year Study in a Tertiary Health Care Centre

Introduction: This study was conducted to describe the Histopathological spectrum of various urinary bladder tumors and to classify them according to W.H.O(2004)/ISUP classification of urinary bladder tumors. Methods: This was a cross-sectional, observational study carried out between June 1, 2019 to May 31, 2020 for a period of one year in the Department of Pathology and Urology, Indira Gandhi Medical College, Shimla. One hundred and ninety seven patients (TURBT and radical cystectomy) with primary epithelial urinary bladder cancer were included in the study. However, Patients with inflammatory and metastatic lesions of urinary bladder and post chemoradiotherapy were excluded from the study. Results: The age of patients ranged from 36 to 89 years with mean age of 62 years. Male preponderance was observed with male to female ratio of 6.9:1. Most common histological type found in our study was urothelial carcinoma (98%) followed by other types such as Squamous cell carcinoma (1%), Small cell carcinoma (0.5%) and Adenocarcinoma (0.5%). In urothelial tumors (193), majority, 126(65.3%) cases, were high grade urothelial carcinoma followed by 67(34.7%) cases of low grade urothelial carcinoma. Conclusion: High grade urothelial carcinomas were mostly associated with muscularis propria invasion. Keywords: Urinary Bladder Tumors, Histopathological Spectrum, High grade urothelial carcinomas .

Phase III randomized control study evaluating adjuvant metronomic chemotherapy in locally advanced head and neck cancers post-radical chemoradiation (MACE-CTRT).

6073 Background: Locally advanced head and neck cancer treated with radical chemoradiation have unsatisfactory outcomes. Oral metronomic chemotherapy improves outcomes in comparison to maximum tolerated dose chemotherapy in the palliative setting. There is also limited evidence that it may do so in an adjuvant setting. Hence this randomised study was conducted. Methods: Patients of HN cancer with primary in oropharynx, larynx or hypopharynx, with PS 0-2 post radical chemoradiation with documented complete response were 1:1 randomised to either observation or oral metronomic adjuvant chemotherapy (MAC) for 18 months. MAC consisted of weekly oral methotrexate (15 mg/m2) and celecoxib (200 mg PO BD). The primary endpoint was OS and the overall sample size was 1038. The study had 3 planned interim analyses for efficacy and futility. Results: 137 patients were recruited and an interim analysis was done. The 3 year PFS in the observation arm was 67.1% (95% CI 53.8-77.3) and the same in the MAC arm was 62.5%(95%CI 49.4-73.1). The corresponding hazard ratio was 1.402 (95% CI 0.7393-2.66, P-value = 0.3). The 3 year OS in the observation arm was 77.3% (95% CI 64.4-86) and the same in the MAC arm was 64.1% (95%CI 51-74.5). The corresponding hazard ratio was 1.588 (95% CI 0.8734-2.886, P-value = 0.1). Any grade mucositis was seen in 30 patients (45.5%) in the MAC arm and 20 patients (28.2%) in the observation arm (P-value = 0.05). The rate of grade 3 or above mucositis was 7.6%(n = 5) in the MAC arm and 1.4%(n = 1) in the observation arm (P-value = 0.106). Conclusions: Both arms had similar OS. Hence observation post complete response post radical chemoradiation remains the standard of care. Clinical trial information: CTRI/2016/09/007315.

FOXO transcriptional activity is associated with response to chemoradiation in EAC

In this study we aimed to investigate signaling pathways that drive therapy resistance in esophageal adenocarcinoma (EAC). Paraffin-embedded material was analyzed in two patient cohorts: (i) 236 EAC patients with a primary tumor biopsy and corresponding post neoadjuvant chemoradiotherapy (nCRT) resection; (ii) 66 EAC patients with resection and corresponding recurrence. Activity of six key cancer-related signaling pathways was inferred using the Bayesian inference method. When assessing pre- and post-nCRT samples, lower FOXO transcriptional activity was observed in poor nCRT responders compared to good nCRT responders (p = 0.0017). This poor responder profile was preserved in recurrences compared to matched resections (p = 0.0007). PI3K pathway activity, inversely linked with FOXO activity, was higher in CRT poor responder cell lines compared to CRT good responders. Poor CRT responder cell lines could be sensitized to CRT using PI3K inhibitors. To conclude, by using a novel method to measure signaling pathway activity on clinically available material, we identified an association of low FOXO transcriptional activity with poor response to nCRT. Targeting this pathway sensitized cells for nCRT, underlining its feasibility to select appropriate targeted therapies.

EGFR EXPRESSION IN PRIMARY EPITHELIAL URINARY BLADDER TUMORS AND ITS CORRELATION WITH CLINICOPATHOLOGICAL PARAMETERS

Introduction: EGFR is over expressed in many epithelial tumors including urothelial carcinomas. Over expression of EGFR is considered as a poor prognostic marker in various studies. Thus, the present study was done to evaluate the EGFR expression in primary urothelial carcinomas and its correlation with clinicopathological parameters. Methods: This was a cross-sectional, observational study carried out between June 1, 2019 to May 31, 2020 in the Department of Pathology and Urology, Indira Gandhi Medical College, Shimla. One hundred and ninety seven patients with primary epithelial urinary bladder cancer were included. Patients with inammatory and metastatic lesions of urinary bladder and post chemoradiotherapy were excluded. The correlation between EGFR expression and the various factors like age (&lt;60 years or ≥60 years), sex (male/female), size of tumor (&lt; 3cm or ≥ 3cm), number of tumors (solitary/multiple) and grade (high/low) were evaluated using EpiInfoV.7 software version and chi-square test. Results: The age of patients ranged from 36 to 89 years. Male preponderance was observed. Most common clinical presentation was painless hematuria. EGFR positivity was observed in majority, 190 cases, irrespective of histological type and grade of tumor. No statistical signicant correlation was found between EGFR expression and age of patient, size of tumor, number of tumor and histological grades of urothelial tumors. Conclusion: Majority of urothelial carcinomas over expressed EGFR irrespective of their histological grade. So, targeted EGFR therapy in urothelial carcinomas can emerge as a novel therapy improving overall survival and prognosis of the patients with urothelial carcinomas.