Curative Chemoradiotherapy Research Articles

Prognostic value of C-reactive protein-to-albumin ratio and inflammatory markers in esophageal cancer patients treated with chemoradiotherapy

Background: This retrospective research, it was aimed to evaluate disease-free survival (DFS) using inflammatory markers in esophageal cancer patients who received chemoradiotherapy (CRT). Methods: A total of 67 patients who received standard curative chemoradiotherapy for esophageal cancer were included in the study between 2011-2018. The patient, treatment characteristics, and pretreatment inflammatory markers were obtained from the patient's file. Results : Median follow up time was 18 months (6-72 months). ROC curve analyses showed the C-Reactive Protein-to-Albumin (CAR) cut-off value 0.9 for DFS (AUC:78.8%; sensitivity: 85%; specificity; 67.5%). 2-year disease free survival for CAR ≥0.9 and CAR <0.9 were 45.7% and 78%, respectively ( P=0.035). The radiation doses >50Gy (versus <50Gy, p=0.027) and CAR ratio < 0.9 (versus ≥ 0.9, p=0.005) appeared significant associates of better DFS in univariate analyses, but the age, gender, stage, localization, neutrophil-to-lympocyte ratio (NLR) and platelet-to-lymhocyte ratio (PLR) were no statistically significant (p>0.005).On the multivariate logistic analysis, our results showed that CAR < 0.9 [hazard ratio (HR) 1.29; 95% confidence interval [CI], 1.336-2.946; P = 0.014]; and radiation dose >50 Gy (HR 0.91; 95% CI, 1.229-4.997; P = 0.027) independent prognostic indictors. Conclusion: Our study found that the C-Reactive Protein/Albumin ratio is easy to apply and maybe a promising marker to predict disease-free survival in esophageal cancer patients who received chemoradiotherapy.

00003 Volumetric assessment of cervical cancer tumor volume during definitive chemoradiation and the risk of early distant metastasis

ABSTRACT IMPACT: This study assesses patient and volumetric risk factors for distant recurrence within 6 months of completion of curative chemoradiation with brachytherapy in locally advanced cervical cancer. OBJECTIVES/GOALS: Initial tumor volume and tumor shrinkage velocity are prognostic of cure and survival after curative chemoradiation (CRT) for cervical cancer. We explored whether local tumor volumetric changes influence time to distant recurrences outside the radiation field. METHODS/STUDY POPULATION: We performed a retrospective cohort study of patients with FIGO Stage IB-IVA cervical cancer treated with curative CRT and brachytherapy at a tertiary academic center with minimum 3 months follow up and standard post-treatment FDG-PET. Patients received 6 weekly fractions of brachytherapy interdigitated with external beam radiation and cisplatin. Tumor volumes were assessed by MRI at brachytherapy planning. Patients who developed distant metastasis were classified as earliest (3-6 months), early (6-24 months) or late (&gt;24 months) following completion of CRT. Absolute and percent decrease in tumor volume for each fraction were calculated with respect to first brachytherapy volume. Fisher’s exact and Mann Whitney-U tests were used for comparison of categorical and continuous variables. RESULTS/ANTICIPATED RESULTS: 143 of 574 (25%) patients developed distant metastasis. Distribution of age, histology, FIGO 2018 stage, primary tumor SUVmax, treatment length, and pre/post treatment squamous cell carcinoma antigen levels were not associated in each group. Para-aortic lymph metastases were more common in patients with earliest distant recurrence (33% earliest, 26% early, 12% late, p=0.03). Median initial tumor volume in the earliest (n=24), early (n =29) and late (n=9) groups was 57, 28 and 40 mL, respectively (p=0.08); 57 (earliest) vs 30mL (early+late groups), p=0.04. Average mid treatment (fraction 4) and end of treatment (fraction 6) percent shrinkage was 80 (earliest) vs 73 (early+late), p=0.84 and 94 vs 92, p=0.95, respectively. Neither absolute nor percent tumor shrinkage differed between early vs. late groups. DISCUSSION/SIGNIFICANCE OF FINDINGS: Tumor volumetric changes during definitive chemoradiation were not associated with the timing of developing distant metastasis, which is linked to presence of lymph node metastasis and tumor volume at diagnosis.

Systemic inflammation is associated with inferior disease control and survival in stage III non-small cell lung cancer

BackgroundThe systemic immune-inflammation index (SII) correlates with patient survival in various types of solid malignancies, including non-small cell lung cancer (NSCLC). However, limited information is available on the prognostic implication and disease-specific survival of SII in patients undergoing definitive chemoradiation therapy (CRT) for stage III NSCLC.MethodsWe retrospectively reviewed 125 patients who underwent curative intent CRT for stage III NSCLC with sufficient laboratory assessment from 2010–2019. SII was calculated at the time of diagnosis as platelet count × neutrophil count/lymphocyte count. Chi-squared analysis was used to compare categorical variables. A Kaplan-Meier analysis was performed to estimate progression-free survival (PFS), disease specific survival (DSS), and overall survival (OS) rates, with Cox regression used to determine absolute hazards.ResultsAt a median follow-up of 19.7 months, 5-year OS, DSS, and PFS rates were 22.6%, 30.9%, and 13.4%, respectively. A low SII (<1,266) at diagnosis was independently associated with an improved OS (HR: 0.399, 95%, CI: 0.247–0.644, P<0.001), DSS (HR: 0.383, 95%, CI: 0.228–0.645, P<0.001), and PFS (HR: 0.616, 95%, CI: 0.407–0.932, P=0.022). We did not detect an association between SII and freedom from recurrence (FFR), freedom from locoregional recurrence (FFLRR), or freedom from distant recurrence (FFDR). NSAID (1,483.4 vs. 2,302.9, P=0.038) and statin usage (1,443.9 vs. 2,201.7, P=0.046) were associated with a lower SII while COPD exacerbations (2,699.7 vs. 1,573.7, P=0.032) and antibiotic prescriptions (2,384.6 vs. 1,347.9, P=0.009) were associated with an elevated SII. These factors were not independently associated with improved survival outcomes.ConclusionsLow SII scores were independently associated with improved OS, DSS, and PFS rates in patients with stage III NSCLC undergoing definitive CRT. NSAIDs and statin usage may be associated with lower SII at diagnosis of NSCLC. This study suggests that SII may be an effective prognostic indicator of patient mortality. Further investigation of the therapeutic potential of these agents in patients with an elevated SII in this setting may be warranted.

CS1001-304: A phase III study of fluorouracil and cisplatin (FP) with CS1001, an anti-PD-L1 antibody, or placebo in unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC).

TPS255 Background: ESCC is the predominant histological subtype of esophageal cancer, particularly in Asian countries. Platinum-based chemotherapy is the first-line standard therapy for patients with unresectable, locally advanced, recurrent or metastatic ESCC. The FP regimen is recommended as the preferred treatment by guidelines. However, the survival benefit conferred by this therapy leaves considerable space for improvement, with median OS being less than 1 year. Blockade of the immune checkpoint receptors has shown clinical benefits in multiple tumor types. Recent studies combining standard treatments with checkpoint inhibitors have shown encouraging efficacy and favorable safety profile in patients with unresectable, locally advanced, recurrent or metastatic ESCC. CS1001 (sugemalimab) is the first full-length, fully human immunoglobin G4 (IgG4, s228p) anti-programmed death-ligand 1 (PD-L1) monoclonal antibody developed by the OMT transgenic rat platform. In an ongoing Phase Ib trial, CS1001 in combination with FP regimen demonstrated an ORR of 67.6% (25/37) and an mPFS of 9.0 months with a manageable safety profile in unresectable, locally advanced or distantly metastatic ESCC (19 Feb 2020 data cutoff; Shen, L., et al, ESMO 2020). Methods: CS1001-304 is a randomized, double-blind Phase III study to compare the efficacy and safety of FP regimen with CS1001 or placebo as first-line treatment in ESCC. The study enrolls patients with histologically or cytologically confirmed unresectable locally advanced, recurrent or metastatic ESCC who have ECOG PS of 0-1, patients are not eligible for curative therapy (curative surgery or definitive chemoradiotherapy), and have not received any prior systemic anti-tumor therapy for locally advanced or metastatic disease. Approximately 540 patients will be randomized at 2:1 into CS1001 + FP and placebo + FP arms respectively, stratified by PD-L1 expression status (PD-L1 expression &lt; 1% vs ≥ 1% and &lt; 10% vs ≥10%), ECOG PS (0 vs 1) and distant metastasis (no vs yes). Patients randomized to either arm will receive FP regimen (fluorouracil: 800 mg/m2/day, continuous intravenous infusion [IV], D1-4 of each cycle; cisplatin: 80 mg/m2, IV, D1 of each cycle), Q3W for up to 6 cycles in combination with CS1001 1200 mg or placebo (IV, D1 of each cycle), Q3W for up to 24 months. AEs will be monitored throughout the study and graded per NCI CTCAE v5.0. Tumor response will be assessed by RECIST v1.1 every 6 weeks in the first 12 months, and every 12 weeks thereafter. The primary endpoints are blinded independent central review (BICR)-assessed PFS and OS. Secondary endpoints include investigator-assessed PFS, BICR and investigator-assessed ORR and DoR, safety, PK profile, and immunogenicity. The study is actively enrolling patients in over 60 sites in China. Clinical trial information: NCT04187352.

PD-0054: Baseline symptom burden predicts patient reported well-being following curative (chemo)radiotherapy

PD-0054: Baseline symptom burden predicts patient reported well-being following curative (chemo)radiotherapy

Dose-Toxicity Relationship Algorithm for Reirradiation: A Novel Tool for ‘How to Treat in a ‘No-Treatment’ Zone’

Reirradiation is an increasing problem. Due to longer-life expectancies with better anti-cancer therapies, larger numbers of patients are candidates for reirradiation because of delayed recurrence. Patients are also more commonly undergoing multiple treatment courses within the same body site as part of subsequent metastatic local consolidation (LCT). However, little is known about the safety of reirradiation throughout the body. Given the wide-range of dose/fractionation schedules, and lack of a common conversion format for dose-toxicity relationship assessment, a void has existed for physicians wishing to pursue reirradiation. This is most commonly observed at the time of planning directive placement and knowledge of toxicity thresholds for organs at risk (OARs) in the reirradiation setting. To address this, we created a novel algorithm to convert nominal dose (Gy) from prior treatment plans to corresponding BED and EQD2 values, at voxel size of 2.5mm. Using this algorithm, and an alpha/beta of 3 for normal tissues, a proof of principle analysis was performed on 4 reirradiation NSCLC patients receiving 1) 50Gy in 4 fraction therapy followed by 70Gy in 10, 2) 50Gy in 4 followed by 50Gy in 4, 3) 70Gy in 10 followed by 70Gy in 10, and 4) 50Gy in 4 followed by 60Gy in 30. All cases were in the lung and same lobe. Following the conversion of each plan to its corresponding BED and EQD2 map, deformable registration was used to create a summed composite reirradiation BED/EQD2 plan for each patient. This allowed for composite – and anatomically accurate -- dosimetric EQD2 and BED assessment for each OAR. Evaluation of the algorithm-generated maps revealed accurate conversion of Gy to BED/EQD2 at each voxel. This enabled evaluation of dose summation received by organs at risk in the reirradiation setting (e.g. mean heart BED dose, max BED dose to major vessels, mean esophageal and lung BED). These dose characteristics were then compared to the toxicities experienced by patients following reirradiation to understand what dose thresholds might exist for OARs, regardless of fractionation scheme(s) chosen by physicians. To this end, the novel BED/EQD2 algorithm was successfully used to assess toxicity relationships in OARs for 15 patients receiving re-SABR after initial SABR, and 26 patients receiving curative chemoradiation (CRT) after initial SABR. This relatively simple, but highly clinically relevant, algorithm allows for assessment of dose-toxicity relationships using a common format in the reirradiation setting. Using this algorithm, multiple cohorts of reirradiation patients are being analyzed at our center to characterize dose-thresholds for reirradiation. Using BED/EQD2 reirradiation thresholds, physicians everywhere can calculate dose received to OARs during the first radiation course and, after selecting fractionation for the second, be able to generate evidence-based planning directives for organs at risk in the reirradiation setting.

A Novel Prediction Model to Identify Patients with Early-Stage Esophageal Cancer

Esophageal cancer has an insidious presentation with more than half of patients presenting with late-stage disease not amenable to potentially curative chemoradiotherapy or surgery. While screening high risk individuals with endoscopy can provide a survival benefit, screening the general unselected population is not currently recommended. This project used a machine learning approach to create an early prediction model drawing on the content of patients’ electronic health records (EHRs). We identified Medicare beneficiaries diagnosed with esophageal cancer between 2004 and 2013, and classified patients into early-stage esophageal cancer (n = 3,062) and late-stage esophageal cancer (n = 2,359) groups. Early-stage esophageal cancer cases were matched to a cohort of non-esophageal cancer controls in a 16:1 ratio, and this cohort was divided into a training (70%) and test (30%) dataset. From this training cohort we constructed a prediction model to identify individuals with early-stage disease using an eXtreme Gradient Boosting machine learning algorithm that incorporated features including patient demographics, procedure and clinical diagnosis codes, outpatient and PCP visit counts, and an inpatient visit indicator. Model discrimination was assessed with sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) with a score of 1.0 indicating perfect prediction. The final predictive model to identify patients with early-stage esophageal cancer included 202 features of which 127 (62.9%) were procedure codes, 67 (33.2%) were diagnosis codes, 6 (3.0%) were demographic features, and 2 (1%) were provider visit counts. The final predictive model had an AUC of 0.776. We evaluated model performance at varying classification thresholds and among different patient populations. When applied to patients over 65, a threshold with a sensitivity of 20.7% produced a specificity of 96.7% and a PPV of 0.068%. Late-stage esophageal cancer patients identified by the model would have been detected a median of 24 months before their actual diagnosis, with three quarters of these patients identified at least 9 months earlier than their recorded diagnosis date. Using EHR data to identify early-stage esophageal cancer patients shows promise, with potential for significantly earlier detection. While widespread use of this approach on an unselected population would produce high rates of false positives, this technique could be employed among high risk patients, or paired with other screening tools.

282 CERVICAL ESOPHAGECTOMY USING “LARYNX ROTATION METHOD” CAN OBTAIN GOOD CLINICAL OUTCOMES.

Abstract In the treatment of cervical esophageal carcinoma (CEC), preservation of laryngeal function is required as well as curability. Therefore, chemoradiotherapy (CRT) is often selected for larynx-preservation. In our department, larynx-preserving surgery using “larynx-rotation method” is aggressively carried out even when the oral side of the tumor margin extends beyond the esophageal orifice. In this study, we analyzed the clinical outcomes of the resectable CEC and examined ``Which therapeutic modality should be selected, surgery or CRT?'' Methods In the present study, 40 patients whose primary tumor was resectable Stage II/III CEC treated in our department since 2008, whose advanced primary tumor lesion was limited within cervical esophagus, and who undergo surgery or curative CRT were enrolled. The clinical outcomes were retrospectively analyzed. Results The Op group included 25 patients. All of the Op group patients could preserve the larynx. In the CRT group, 2 patients were performed pharyngo-laryngo-cervical esophagectomy as the salvage surgery. 1- and 3-year progression-free survival rate was 80.1 and 69.3% in the Op group, and 63.0 and 31.5% in the CRT group. 1-, 3- and 5-year overall survival rate was 95.8, 80.9 and 67.4% in the Op group and 78.6, 64.3 and 46.9% in the CRT group, respectively. Although there was no significant difference, the Op group showed relatively better clinical outcomes. Conclusion Cervical esophagectomy using “larynx-rotation method” could obtain good therapeutic outcomes while preserving the larynx. Especially in case cervical esophagectomy is sufficient as the curative resection, because the surgical invasion is little and the postoperative quality of life is good while preserving the larynx and the whole stomach, surgery is considered useful treatment modality.

Predictors of early progression after curative resection followed by platinum-based adjuvant chemoradiotherapy in oral cavity squamous cell carcinoma

ABSTRACT Objectives Early progression, defined as a disease-free interval (DFI) of less than 6 months after completion of adjuvant platinum-based chemoradiotherapy (CRT), leads to poor outcomes in locally advanced oral cavity squamous cell carcinoma (OCSCC). However, appropriate biomarkers for predicting early progression remain unknown. Methods In this study, 346 patients with OCSCC, who underwent curative surgical resection and platinum-based adjuvant CRT at the Taipei Veterans General Hospital (202 patients, training cohort) and Chung Shan Medical University Hospital (144 patients, validation cohort) were enrolled. The clinical–pathological variables were compared using the χ2 test. Cox proportional-hazards analyses were performed for DFIs. Survival was estimated using the Kaplan–Meier method and log-rank tests, and a scoring system for predicting early progression was established. Results One-fifth (20.5%, 71/346) of all patients experienced progression within 6 months. Each of the independent factors for the DFI in the training cohort, including pT3-4, extracapsular spread, and perineural invasion, were assigned a score of one point to establish a scoring system. The 6-month DFIs of the low-risk (score 0–1), intermediate-risk (score 2), and high-risk (score 3) groups were 97.8%, 78.7%, and 35.7% and 88.2%, 77.6%, and 42.1% in the training and validation cohorts, respectively. If the cutoff level was ≥2 or <2, the sensitivity/specificity/area under the curve for the training and validation cohorts were 94.4%/56.1%/0.837, and 73.3%/56.6%/0.703, respectively. Conclusions The established scoring system effectively predicted early progression after adjuvant CRT for locally advanced OCSCC.

400MO Curative chemoradiation for low rectal cancer: Early clinical outcomes from a multicentre phase II trial

400MO Curative chemoradiation for low rectal cancer: Early clinical outcomes from a multicentre phase II trial

Multiparametric functional MRI and 18F-FDG-PET for survival prediction in patients with head and neck squamous cell carcinoma treated with (chemo)radiation

ObjectivesTo assess (I) correlations between diffusion-weighted (DWI), intravoxel incoherent motion (IVIM), dynamic contrast-enhanced (DCE) MRI, and 18F-FDG-PET/CT imaging parameters capturing tumor characteristics and (II) their predictive value of locoregional recurrence-free survival (LRFS) and overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy.MethodsBetween 2014 and 2018, patients with histopathologically proven HNSCC, planned for curative (chemo) radiotherapy, were prospectively included. Pretreatment clinical, anatomical, and functional imaging parameters (obtained by DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT) were extracted for primary tumors (PT) and lymph node metastases. Correlations and differences between parameters were assessed. The predictive value of LRFS and OS was assessed, performing univariable, multivariable Cox and CoxBoost regression analyses.ResultsIn total, 70 patients were included. Significant correlations between 18F-FDG-PET parameters and DWI-/DCE volume parameters were found (r > 0.442, p < 0.002). The combination of HPV (HR = 0.903), intoxications (HR = 1.065), PT ADCGTV (HR = 1.252), Ktrans (HR = 1.223), and Ve (HR = 1.215) was predictive for LRFS (C-index = 0.546; p = 0.023). N-stage (HR = 1.058), HPV positivity (HR = 0.886), hypopharyngeal tumor location (HR = 1.111), ADCGTV (HR = 1.102), ADCmean (HR = 1.137), D* (HR = 0.862), Ktrans (HR = 1.106), Ve (HR = 1.195), SUVmax (HR = 1.094), and TLG (HR = 1.433) were predictive for OS (C-index = 0.664; p = 0.046).ConclusionsFunctional imaging parameters, performing DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT, yielded complementary value in capturing tumor characteristics. More specific, intoxications, HPV-negative status, large tumor volume-related parameters, high permeability (Ktrans), and high extravascular extracellular space (Ve) parameters were predictive for adverse locoregional recurrence-free survival and adverse overall survival. Low cellularity (high ADC) and high metabolism (high SUV) were additionally predictive for decreased overall survival. These different predictive factors added to estimated locoregional and overall survival.Key Points• Parameters of DWI/IVIM, DCE-MRI, and 18F-FDG-PET/CT were able to capture complementary tumor characteristics.• Multivariable analysis revealed that intoxications, HPV negativity, large tumor volume and high vascular permeability (Ktrans), and extravascular extracellular space (Ve) were complementary predictive for locoregional recurrence.• In addition to predictive parameters for locoregional recurrence, also high cellularity (low ADC) and high metabolism (high SUV) were complementary predictive for overall survival.

Haematotoxicity in IMRT/VMAT curatively treated anal cancer.

Curative chemoradiotherapy of squamous cell carcinoma achieves long-term complete remissions in most patients and minimizing treatment toxicity becomes crucial issue. The aim of the retrospective analysis was to determine an acceptable dose to the bone marrow for radiotherapy planning not leading to increased haematological toxicity. In the period 2013-2019, 40 patients with squamous cell carcinoma were curatively treated at the Department of Oncology of the University Hospital Motol using intensity modulated radiotherapy (IMRT) /volumetric modulated arc radiotherapy (VMAT) technique. Women make up 90% of the group, the average age at the time of dia-gnosis was 65 years (47-81). Chemotherapy mitomycin C and 5-fluorouracil was given to 68% of patients. The bone marrow was contoured in the Varian Eclipse planning system, version 15.6. Acute hematotoxicity (G3, 4, 5 according to Common Terminology Criteria for Adverse Events - CTCAE) was significantly associated with the concomitant chemoradiotherapy (P = 0.002) and the average dose to the bone marrow 27 Gy (P = 0.011). Late haematological toxicity was mild (maximum grade 1), asymptomatic, and no dependence of late haematotoxicity on any risk factor (age, gender, WHO performance status, bone marrow dose, CHT, BMI, smoking, stage) was proved. The overall survival at 5 years was 100% in stage I, 83% in stage II, 61% in stage III and 0% in stage IV. Local control at 5 years is 100% in stage I, 92% in stage II, 87% in stage III and 0% in stage IV. Local recurrence developed in 5% of radically treated patients. Distant metastases occurred in 8% of radically treated patients. Local recurrences or metastases occurred only during the first 2 years after the treatment. Radical chemoradiotherapy in the treatment of squamous cell anal carcinoma is highly effective. IMRT/VMAT enabled to apply a sufficiently effective dose to the tumor and elective areas and reduced not only acute skin, GI and GU toxicity, but also acute haematological toxicity in cases with the dose Dmean to bone marrow lower than 27 Gy. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical, papers.

A Bio-Imaging Signature as a Predictor of Clinical Outcomes in Locally Advanced Pancreatic Cancer.

Purpose: To evaluate the predictive value of 18F-FDG PET/CT semiquantitative parameters of the primary tumour and CA 19-9 levels assessed before treatment in patients with locally advanced pancreatic cancer (LAPC). Methods: Among one-hundred twenty patients with LAPC treated at our institution with initial chemotherapy followed by curative chemoradiotherapy (CRT) from July 2013 to January 2019, a secondary analysis with baseline 18F-FDG PET/CT was conducted in fifty-eight patients. Pre-treatment CA 19-9 level and the maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of primary tumour were measured. The receiving operating characteristics (ROC) analysis was performed to define the cut-off point of SUVmax, MTV, TLG and CA 19-9 values to use in prediction of early progression (EP), local progression (LP) and overall survival (OS). Areas under the curve (AUCs) were assessed for all variables. Post-test probability was calculated to evaluate the advantage for parameters combination. Results: For EP, CA 19-9 level > 698 U/mL resulted the best marker to identify patient at higher risk with OR of 5.96 (95% CI, 1.66–19.47; p = 0.005) and a Positive Predictive Value (PPV) of 61%. For LP, the most significant parameter was TLG (OR 9.75, 95% CI, 1.64–57.87, p = 0.012), with PPV of 83%. For OS, the most significant parameter was MTV (OR 3.12, 95% CI, 0.9–10.83, p = 0.07) with PPV of 88%. Adding consecutively each of the other parameters, PPV to identify patients at risk resulted further increased (>90%). Conclusions: Pre-treatment CA 19-9 level, as well as MTV and TLG values of primary tumour at baseline 18F-FDG PET/CT and their combination, may represent significant predictors of EP, LP and OS in LAPC patients.

Management of Muscle-Invasive Bladder Cancer During a Pandemic: Impact of Treatment Delay on Survival Outcomes for Patients Treated With Definitive Concurrent Chemoradiotherapy.

IntroductionDuring the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making to ensure that the benefit of early intervention for muscle-invasive bladder cancer exceeds the risk of contracting COVID-19 in the clinical setting. It is unknown whether treatment delays for patients eligible for curative chemoradiation (CRT) compromise long-term outcomes.Patients and MethodsWe used the National Cancer Data Base to investigate whether there is an association between a ≥ 90-day delay from transurethral resection of bladder tumor (TURBT) in initiating CRT and overall survival. We included patients with cT2-4N0M0 muscle-invasive bladder cancer from 2004 to 2015 who underwent TURBT and curative-intent concurrent CRT. Patients were grouped on the basis of timing of CRT: ≤ 89 days after TURBT (earlier) vs. ≥ 90 and < 180 days after TURBT (delayed).ResultsA total of 1387 (87.5%) received earlier CRT (median, 45 days after TURBT; interquartile range, 34-59 days), and 197 (12.5%) received delayed CRT (median, 111 days after TURBT; interquartile range, 98-130 days). Median overall survival was 29.0 months (95% CI, 26.0-32.0) versus 27.0 months (95% CI, 19.75-34.24) for earlier and delayed CRT (P = .94). On multivariable analysis, delayed CRT was not associated with an overall survival difference (hazard ratio, 1.05; 95% CI, 0.87-1.27; P = .60).ConclusionAlthough these results are limited and require validation, short, strategic treatment delays during a pandemic can be considered on the basis of clinician judgment.

Association between nutritional risk index and outcomes for head and neck cancer patients receiving concurrent chemo-radiotherapy.

Patients receiving chemoradiotherapy for head and neck cancer (HNC) are often malnourished. We assessed the utility of nutritional risk index (NRI) in HNC patients undergoing chemoradiotherapy. A population-based retrospective review of HNC patients treated with curative chemoradiation was performed. Demographics, anthropometrics, overall survival (OS), and the composite treatment complication rate (G-tube dependence, radiation incompletion, 90-day mortality, and unplanned hospitalization) were collected. Two hundred ninety-two patients were identified. Average pretreatment and posttreatment NRI were 110 (SD 3) and 99 (SD 12), respectively (P < .01). Pretreatment NRI risk category, age, ECOG status, and tumor subsites were associated with OS on multivariate analysis. Pretreatment NRI risk category was associated with risk of treatment related complications. There was a significant decrease between pretreatment and posttreatment NRI in HNC patients receiving chemoradiation. Pretreatment NRI risk category may predict OS and composite treatment complications. Investigation of NRI as a prognostic factor is warranted.

Gastrostomy dependency trends over 15 years of patients at a large tertiary referral center following the insertion of a prophylactic gastrostomy for chemoradiation for mucosal head and neck cancer.

The routine use of prophylactic percutaneous endoscopic gastrostomy (PEG) tubes for nutrition support during radical chemoradiation for head and neck cancer has been suggested to result in PEG dependency. This research aimed to determine the rates of gastrostomy dependency at the Calvary Mater Newcastle (CMN) where PEGs are routinely used and to identify potentially modifiable risk factors. All patients with head and neck cancer planned for curative chemoradiation with a prophylactic PEG inserted were included in this review. Medical records of 250 patients treated between 2000 and 2015 were examined. Overall, eight patients (3%) were unable to wean. At 12 months following treatment, 16 patients (6%) still required PEG tubes for feeding. A greater T extent (T4 or synchronous head and neck tumors) and number of days Nil By Mouth (NBM) remained as significant independent risk factors for PEG dependency at 12 months (Textent OR 6.96 P<.001; NBM OR 1.01 P=.004) and overall (Textent OR8.04 P=.02; NBM OR1.01 P=.001). Associations with NBM were investigated, which demonstrated that patients had less NBM days with intensity-modulated radiation therapy (IMRT) (β-13.3, P=.007) and seeing a speech pathologist during treatment (β-11.9, P=.026). More NBM days were associated with tumors with greater T extent (β+22; P<.001). The routine use of prophylactic PEGs has not resulted in significant rates of PEG dependency at the CMN. Seeing a speech pathologist during treatment and IMRT may decrease time NBM, which was identified as a potentially modifiable risk factor for PEG dependency.

Can we safely reduce the radiation dose to the heart while compromising the dose to the lungs in oesophageal cancer patients?

PurposeThe aim of this study was to evaluate which clinical and treatment-related factors are associated with heart and lung toxicity in oesophageal cancer patients treated with chemoradiation (CRT). The secondary objective was to analyse whether these toxicities are associated with overall survival (OS). Materials and methodsThe study population consisted of a retrospective cohort of 216 oesophageal cancer patients treated with curative CRT. Clinical and treatment related factors were analysed for OS and new pulmonary and cardiac events by multivariable regression analyses. The effect of these toxicities on OS was assessed by Kaplan Meyer analyses. ResultsMultivariable analysis revealed that pulmonary toxicity was best predicted by the mean lung dose. Cardiac complications were diverse; the most frequently occurring complication was pericardial effusion. Several cardiac dose parameters correlated with this endpoint. Patients developing radiation pneumonitis had significantly worse OS than patients without radiation pneumonitis, while no difference was observed in OS between patients with and without pericardial effusion. OS was best predicted by the V45 of the lung and tumour stage. None of the cardiac dose parameters predicted OS in multivariable analyses. ConclusionCardiac dose volume parameters predicted the risk of pericardial effusion and pulmonary dose volume parameters predicted the risk of radiation pneumonitis. However, in this patient cohort, pulmonary DVH parameters (V45) were more important for OS than cardiac DVH parameters. These results suggest that reducing the cardiac dose at the expense of the dose to the lungs might not always be a good strategy in oesophageal cancer patients.

Locally Advanced Oral Cavity Cancers: What Is The Optimal Care?

Patients with oral cavity cancers often present late to seek medical care. Surgery is usually the preferred upfront treatment. However, surgical resection cannot be achieved in many cases with advanced disease without major impact on patient’s quality of life. On the other hand, radiotherapy (RT) and chemotherapy (CT) have not been employed routinely to replace surgery as curative treatment or to facilitate surgery as neoadjuvant therapy. The optimal care of these patients is challenging when surgical treatment is not feasible. In this review, we aimed to summarize the best available evidence-based treatment approaches for patients with locally advanced oral cavity cancer. Surgery followed by RT with or without CT is the standard of care for locally advanced oral cavity squamous cell carcinoma. In the case of unresectable disease, induction CT prior to surgery or chemoradiotherapy (CRT) can be attempted with curative intent. For inoperable patients or when surgery is expected to result in poor functional outcome, patients may be candidates for possibly curative CRT or palliative RT with a focus on quality of life.

Can serial evaluation of serum SCC-Ag-level predict tumor recurrence and patient survival in squamous-cell carcinoma of uterine cervix treated with definitive chemoradiotherapy? A multi-institutional analysis.

Tumor marker screening may be useful to evaluate tumor response and detect tumor recurrence. However, usefulness and cut-off value of squamous-cell carcinoma antigen (SCC-Ag) for recurrence and survival has not yet established in cervical cancer. From January 2010 to October 2016, 304 patients with cervical squamous-cell carcinomas with FIGO stage IB-IVA who underwent curative chemoradiotherapy followed by brachytherapy at four institutions were included in this study. Serum SCC-Ag level was measured before treatment, re-measured after completion of treatment, and again at the time of relapse during follow-up. SCC-Ag levels at each measurement point were analyzed using receiver operating characteristic (ROC) curve. Their associations with recurrence-free survival (RFS) and overall survival (OS) were analyzed. During a median follow-up time of 36.5months, there were 66 (21.7%) recurrences and 76 (25.0%) deaths. The ROC curve showed optimal Youden indices were 4, 1.5, and 4ng/mL at pretreatment, treatment, and recurrence, respectively. In patients with SCC-Ag ≥ 4ng/mL, not SCC-Ag < 4ng/mL before treatment, post-treatment SCC-Ag level (≥ 1.5ng/mL vs. < 1.5ng/mL) showed significant differences in 3-year RFS (65.5% vs. 45.0%, p < 0.001) and OS (78.5% vs. 55.4%, p < 0.001). In 66 recurrent patients, patients with SCC-Ag ≥ 4ng/mL at recurrence showed a significantly lower OS rate than others (59.5% vs. 33.0%, p = 0.041). SCC-Ag level after treatment and at recurrence was useful for predicting recurrence and survival only when its pretreatment value was high (≥ 4ng/mL).

Baroreceptor Reflex Failure after Curative Chemoradiation for Oropharyngeal Cancer: A Potential Use of an Established Therapy

Baroreceptor Reflex Failure after Curative Chemoradiation for Oropharyngeal Cancer: A Potential Use of an Established Therapy