Concurrent Chemotherapy And Radiotherapy Research Articles

High-Grade Pneumonitis Events in Patients With Unresectable, Locally Advanced NSCLC Treated With Definitive Chemoradiation Followed By Adjuvant Durvalumab

BackgroundThe standard of care for unresectable locally advanced NSCLC is concurrent chemotherapy and radiation (CRT) followed by adjuvant durvalumab, established by the PACIFIC trial, which revealed acceptable although higher rates of pneumonitis with durvaluamb than placebo. We retrospectively reviewed patients with locally advanced NSCLC from 2018 to 2022 treated with definitive CRT (≥60 Gy) followed by at least one dose of adjuvant durvalumab. ObjectiveTo review the incidence of pneumonitis and contributing factors, and also to review grade 5 pneumonitis (G5) events. MethodsWe identified 78 cases with a median age of 70.0 years and a median follow-up of 36 months. All patients received CRT of at least 60 Gy at 2 Gy per fraction. A total of 22 patients (28.2%) completed 12 months of durvalumab. The cumulative incidence of any-grade pneumonitis was 28.2%. Pneumonitis rate in grades 1, 2, 3, 4, and 5 was 1.3%, 10.3%, 7.7%, 0.0%, and 9.0%, respectively. ResultsMultivariate analysis did not reveal significant factors associated with G5 pneumonitis. There were 8 patients who received radiation therapy doses above standard limits and, of these, only two developed G5 pneumonitis. All patients with G5 pneumonitis had multiple comorbidities and/or previous malignancy treated with systemic therapy. The median overall survival was 31.1 months and the median progression-free survival was 12.7 months. ConclusionsWe report comparable overall rates of pneumonitis relative to published data with higher rates of G5 pneumonitis. Patients with high-dose radiation therapy (≥60 Gy) and Eastern Cooperative Oncology Group performance status greater than or equal to 2 may tolerate adjuvant durvalumab, though providers should exercise caution in patients with extensive comorbidities.

Improved survival in cervical cancer patients receiving care at NCI-designated cancer centers (457)

<b>Objectives:</b> Locally advanced cervical cancer (CC) remains a lethal disease in the United States, with the standard of care being concurrent chemotherapy and radiation (CRT) with brachytherapy. We investigated the effect of receiving care at an NCI-designated comprehensive cancer center on survival. <b>Methods:</b> Specific study variables from the California Cancer Registry (CCR) were extracted for women diagnosed with locally advanced CC from January 1, 2004, through December 31, 2016, and who had received radiation treatment. Kaplan-Meier was used to compare CC-specific survival by care (diagnosis and/or treatment) at an NCI- designated cancer center using a log-rank test. Cox proportional hazards regression models were used to assess whether <i>')</i> care at an NCI-designated cancer center was associated with risk of CC-specific death, <i>2)</i> whether this association remained after adjusting for hypothesized confounders, and <i>3)</i> whether the association could be explained by the receipt of a guideline-concordant standard of care, CRT and brachytherapy, treatment. <b>Results:</b> The median age of the patients (<i>n</i>=4,250) was 50 years (interquartile range [IQR]: 41-61 years), with a median follow-up time of 2.7 years (IQR: 1.3-6.0 years). Of the 4,250 patients in the sample, 33% were cared for at an NCI-designated cancer center, and 29% died of CC. The Kaplan-Meier plot showed a distinct survival advantage for those who received care at an NCI-designated cancer center (p=0.0001). The hazard of death due to CC was reduced by 21% for those cared for at NCI-designated cancer centers (HR: 0.79, 95% CI: 0.70-0.89). Adjusting for guideline-concordant treatment as well as other covariates minimally attenuated the hazard ratio to 0.83 (95% CI: 0.74-0.95), suggesting that the CC-specific survival advantage associated with care at NCI-designated cancer centers may not be due to receipt of guideline-concordant treatment alone. <b>Conclusions:</b> In the era of personalized medicine for locally advanced cervical cancer, we continue to seek out treatment options that will benefit survival. Our study shows a statistically significant cervical cancer survival benefit among patients receiving care at NCI- designated cancer centers versus those who are cared for elsewhere. This difference does not appear to be explained by receipt of guidelineconcordant care alone and may instead be due to structural, organizational, provider, or otherwise unknown patient characteristics within and outside of an NCI designation. Further understanding of these potential factors will promote equality across institutions and oncology care facilities as well as survival equity for cervical cancer patients.

Assessment of Rate of Laryngeal Preservation in Patients undergoing Radiotherapy with Concurrent Chemotherapy for Advanced Squamous Cell Carcinoma of Larynx: A Prospective Interventional Study

Introduction: Advanced laryngeal cancer carries significant morbidity with deterioration sinquality of life. The Radiation Therapy Oncology Group (RTOG) 91-11 study found that in the management of advanced laryngeal cancers, Concurrent Chemotherapy and Radiation (CCRT) produced significant organ preservation compared with other treatment modalities without compromising locoregional control and survival outcomes. These studies lead to the employment of CCRT for advanced laryngeal cancer with the aim of organ preservation. Aim: To assess the rate of laryngeal preservation in patients undergoing CCRT in a tertiary care centre. Materials and Methods: The present prospective, interventional study was conducted in the Department of Radiotherapy, Government Medical college, Thrissur, Kerala, India comprising the newly diagnosed patients with locally advanced laryngeal cancers from July 2019 to August 2020. Conventional radiotherapy with a dose of 66 Gray in 33 fractions over 6.5 weeks was given concurrently with injection cisplatin 100 mg/m2 intravenously every three weeks and periodically followed-up for one year. Results: Out of 50 study participants, 40% of the target population were between 51-60 years of age and 90% of the cases were males. The rates of laryngeal preservation were found to be 88% according to this study. The study proved that laryngeal preservation was significantly lower in cases with age 61-70 years, with those with Eastern Cooperative Oncology Group (ECOG) performance score of 2, nodal stage N3 and stage IV disease and in those with fewer chemo cycles. There was no relationship between laryngeal preservation sex, tumour stage, composite stage. Conclusion: These results show that the rates of laryngeal preservation were found to be higher in advanced laryngeal cancers undergoing radiotherapy with concurrent chemotherapy. Locoregional control was higher without causing severe toxicities. This study shows that higher rates of laryngeal preservation could be achieved with good locoregional control thereby leading to organ preservation and avoidance of severe morbid surgical procedures.

A Comparison of Different Schemes of Neoadjuvant Chemotherapy Followed by Concurrent Chemotherapy and Radiotherapy for Locally Advanced Cervical Cancer: A Retrospective Study.

PurposeTo examine the clinical significance of unoperated cervical cancer patients treated with different neoadjuvant chemotherapy (NACT) schemes followed by concurrent chemotherapy and radiotherapy (CCRT).MethodsThis retrospective analysis included women with locally advanced cervical cancer treated with NACT-CCRT between September 2011 and September 2014. Neoadjuvant chemotherapy included paclitaxel plus cisplatin (TP group; 62 patients) or paclitaxel plus loplatin (TL group; 58 patients), which were administered three weekly, and cisplatin or loplatin, which were administered weekly for synchronous chemotherapy. External beam radiation therapy (50.4–56.35 Gy/28 f, 180–215 cGy/f, 5 f/w) was followed by intracavitary brachytherapy (5 Gy per fraction, mostly 5 fractions, Ir192 based).ResultsOne hundred twenty women were included in the analysis. The complete/partial response rate was 99.2% after treatment. The one-year, three-year, and five-year survival rates were 99.2%, 82.5%, and 70.8%, respectively. In the TP and TL groups, the three-year and five-year survival rates were 85.5% vs 77.6% and 75.8% vs 65.5%, respectively, with no significant difference. The 5-year overall survival (OS) rates between patients with stage IIB and stage IIIB disease were not significantly different (69.2% vs 64.7%). In the TP group, grade 3 or 4 digestive reactions were more frequent than those in the TL group. Leukopenia, neutropenia, and thrombocytopenia were more common in the TL group. No significant difference was found in anemia, radiation enteritis, radiation proctitis, or radiation cystitis between the groups.ConclusionLobaplatin may be used as an alternative drug for patients with severe digestive system reactions or contraindications to cisplatin, but hematological toxicity must be considered, particularly in dose-intensive schemes. Neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy (NACT-CCRT) warrants further prospective study in cervical cancer patients with a wide range of tumor invasion (eg, mass size ≥5 cm or stage IIIB).

Single Arm Prospective Trial on BOLD fMRI Radiation-Induced Changes in Newly Diagnosed Glioblastoma Patients

<h3>Purpose/Objective(s)</h3> Standard therapy for patients with glioblastoma (GBM) consists of maximal safe surgical resection followed by concurrent chemotherapy and radiation (CRT) to the postoperative cavity and residual disease. After CRT, patients are standardly assessed at regular intervals of approximately 1-4 months with magnetic resonance imaging (MRI) of the brain to monitor for residual or recurrent tumor growth. At present, there are no accepted MRI methods or protocols to predict response either during or after CRT. Notably, GBM is associated with vascular dysregulation, manifesting radiographically as asynchrony on resting state BOLD fMRI. However, the impact of radiation therapy on BOLD asynchrony in glioblastoma remains unknown. In this study, we sought to collect radiographic data on a cohort of patients with recently resected glioblastoma prior to the start of CRT and again during the third week of therapy. The aim of this prospective pilot study was to determine the feasibility of collecting radiographic data to inform patient outcomes and ultimately predict the interval to disease progression of GBM using pre-treatment and mid-treatment MRI acquisitions. <h3>Materials/Methods</h3> Twelve patients with newly-diagnosed histologically proven GBM were enrolled in this institutional IRB approved prospective trial between 2015 and 2017. Patients underwent two resting-state BOLD fMRI scans: one immediately prior to starting standard six weeks of radiation and another during the third week of radiation. BOLD scans were processed and linearly registered to structural images. A BOLD asynchrony map was generated by comparing the time series in each voxel to the time series of the contralesional, radiographically normal brain, such that positive values denote synchrony with the contralateral hemisphere. The 60 Gy radiation dose maps were used for the purposes of determining the total radiation dose at each voxel. <h3>Results</h3> There were 8 males and 4 females included in the analysis with a median age at diagnosis of 63 years. We divided the brain into voxels that received lower total doses of radiation (< 24 Gy) and higher total doses of radiation (> 24 Gy), and determined the mean change in the BOLD asynchrony before and during radiation for each group of voxels for each patient. The absolute change in BOLD asynchrony between the two scanning sessions was significantly higher in the regions that received higher doses of radiation (0.71 vs 0.04, <i>P</i> = 0.0007). <h3>Conclusion</h3> Here we show that radiation doses higher than 24 Gy change vascular regulation in glioblastoma patients, manifesting as altered asynchrony on resting-state BOLD fMRI. Further prospective evaluation is warranted to develop a non-invasive radiographic biomarker to predict and monitor responses to standard interventions for glioblastoma.

Modeling Resistance and Recurrence Patterns of Combined Targeted-Chemoradiotherapy Predicts Benefit of Shorter Induction Period.

Optimal integration of molecularly targeted therapies, such as tyrosine kinase inhibitors (TKI), with concurrent chemotherapy and radiation (CRT) to improve outcomes in genotype-defined cancers remains a current challenge in clinical settings. Important questions regarding optimal scheduling and length of induction period for neoadjuvant use of targeted agents remain unsolved and vary among clinical trial protocols. Here, we develop and validate a biomathematical framework encompassing drug resistance and radiobiology to simulate patterns of local versus distant recurrences in a non-small cell lung cancer (NSCLC) population with mutated EGFR receiving TKIs and CRT. Our model predicted that targeted induction before CRT, an approach currently being tested in clinical trials, may render adjuvant targeted therapy less effective due to proliferation of drug-resistant cancer cells when using very long induction periods. Furthermore, simulations not only demonstrated the competing effects of drug-resistant cell expansion versus overall tumor regression as a function of induction length, but also directly estimated the probability of observing an improvement in progression-free survival at a given cohort size. We thus demonstrate that such stochastic biological simulations have the potential to quantitatively inform the design of multimodality clinical trials in genotype-defined cancers. SIGNIFICANCE: A biomathematical framework based on fundamental principles of evolution and radiobiology for in silico clinical trial design allows clinicians to optimize administration of TKIs before chemoradiotherapy in oncogene-driven NSCLC.

A new perspective of different schemes of neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy for locally advanced cervical cancer.

e18011 Background: To observe the clinical effect, survival time and toxicity and side effects in unoperated cervical cancer patients treated with different schemes of neoadjuvant chemotherapy (NACT) followed by concurrent chemotherapy and radiotherapy (CCRT). Methods: A retrospective analysis was performed in 120 patients who were followed up until they died or being followed up at least 5 years. The treatment schedules consisted of 2 cycles of intravenous paclitaxel 135-175 mg/m2 plus cisplatin 60-80mg/m2 (TP group, 62 patients) or lobaplatin 30mg/m2 (TL group, 58 patients) every 21 days. Patients were then submitted to CCRT. Chemotherapy regimen of CCRT was cisplatin 40 mg/m2 (TP group) or lobaplatin 30mg/m2 (TL group) weekly. External beam radiation therapy (total 50.4-56.35Gy, 28 fractions, 180-215cGy per fraction daily) was administered using the3D-CRT or IMRT followed by intracavitary brachytherapy (5Gy per fractions, mostly 5 fractions, Ir192 based). Results: The proportion who had a complete/partial response was 81.7% after NACT, and 99.2% after all treatment. In all patients, the one-year, three-year and five-year survival rates were 99.2%, 81.7% and 69.2% respectively. In TP group vs. TL group, the 3-yr and 5-yr survival rates were 85.5% vs.77.6% (χ2= 1.248, p = 0.264) and 75.8% vs. 63.8% (χ2= 2.059, p = 0.151) with no significant difference. In mass size ≥ 5cm group vs. &lt;5cm group, 3-yr survival rates were 88.0% vs.77.1% with no significant difference (χ2= 2.296, p = 0.130), but 5-yr survival rates were 82.0% vs.61.4% (χ2= 5.878, p = 0.015) with significant difference. The 3-yr and 5-yr OS rates between stage IIB and stage IIIB were not significantly different, respectively 83.1% vs. 70.6% (χ2= 2.083, p = 0.149) and 67.7% vs. 64.7% (χ2= 0.090, p = 0.765) . In TP group, grade 3 or 4 digestive reaction was obviously more frequent than TL group, respectively 54.3% vs. 1.8%(p = 0.000). Neutropenia and thrombocytopenia are more common in TL group than TP group, respectively 48.3% vs. 30.6%(p = 0.0.048) and 44.8% vs. 1.6%(p = 0.000). Conclusions: For patients with severe digestive system reaction or contraindications of cisplatin, lobaplatin was might be used as an alternative drug. A prospective research is undergoing in our hospital. NACT may improve the prognosis of patients with large-scale mass. A undergoing prospective study protocol was approved by the Ethics Committee of hospital number 2017-02 and was registered in ClinicalTrial.gov as ChiCTR-IIR-17011559.

Immune Checkpoint Inhibitors for the Treatment of Unresectable Stage III Non-Small Cell Lung Cancer: Emerging Mechanisms and Perspectives.

There has been no improvement in outcome for patients with unresectable locally advanced (stage III) non–small cell lung cancer (NSCLC) for more than 10 years. The standard treatment for these patients is definitive concurrent chemotherapy and radiation (CCRT). Although the goal of treatment in this setting is to achieve a cure, most patients progress and their prognosis is poor, with a 5-year survival rate of 15–30%. There is thus an urgent need for the development of novel anticancer treatments in this patient population. Recent advances in cancer immunotherapy have led to a marked improvement in clinical outcome for advanced NSCLC. Such immunotherapy mainly consists of the administration of immune checkpoint inhibitors (ICIs) such as antibodies to cytotoxic T lymphocyte–associated protein–4 (CTLA-4) or to either programmed cell death–1 (PD-1) or its ligand PD-L1. Durvalumab (MEDI4736) is a high-affinity human immunoglobulin G1 monoclonal antibody that blocks the binding of PD-L1 on tumor cells or antigen-presenting cells to PD-1 on T cells. The PACIFIC study recently evaluated consolidation immunotherapy with durvalumab versus placebo administered after concurrent chemoradiotherapy (CCRT) in patients with unresectable stage III NSCLC. It revealed a significant improvement in both progression-free and overall survival with durvalumab, and this improvement was associated with a favorable safety profile. This achievement has made durvalumab a standard of care for consolidation after CCRT in patients with unresectable stage III NSCLC, and it has now been approved in this setting by regulatory agencies in the United States, Canada, Japan, Australia, Switzerland, Malaysia, Singapore, India, and the United Arab Emirates. In this review, we briefly summarize the results of the PACIFIC trial, including those of post hoc analysis, and we address possible molecular mechanisms, perspectives, and remaining questions related to combined treatment with CCRT and ICIs in this patient population.

Integrative Molecular Characterization of Resistance to Neoadjuvant Chemoradiation in Rectal Cancer.

Molecular properties associated with complete response or acquired resistance to concurrent chemotherapy and radiotherapy (CRT) are incompletely characterized.Experimental Design: We performed integrated whole-exome/transcriptome sequencing and immune infiltrate analysis on rectal adenocarcinoma tumors prior to neoadjuvant CRT (pre-CRT) and at time of resection (post-CRT) in 17 patients [8 complete/partial responders, 9 nonresponders (NR)]. CRT was not associated with increased tumor mutational burden or neoantigen load and did not alter the distribution of established somatic tumor mutations in rectal cancer. Concurrent KRAS/TP53 mutations (KP) associated with NR tumors and were enriched for an epithelial-mesenchymal transition transcriptional program. Furthermore, NR was associated with reduced CD4/CD8 T-cell infiltrates and a post-CRT M2 macrophage phenotype. Absence of any local tumor recurrences, KP/NR status predicted worse progression-free survival, suggesting that local immune escape during or after CRT with specific genomic features contributes to distant progression. Overall, while CRT did not impact genomic profiles, CRT impacted the tumor immune microenvironment, particularly in resistant cases.

Metformin Induces Pro-Tumorigenic Cytokines And Natural Killer Cells In Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma

Concurrent chemotherapy and radiation (CRT) continues to be standard of care for unresectable locally advanced head and neck squamous cell carcinoma (LAHNSCC). In the HPV (human papillomavirus) positive non-smoker population the cure rate approaches greater than 90%. However, the cure rate can be as low as 50% in HPV negative smokers necessitating newer and more effective treatments. Interestingly, diabetic HNSCC patients taking the biguanide, metformin, have been shown to have superior survival outcomes. However, the mechanism by which metformin results in superior outcomes for these patients is unclear. In vivo, metformin was shown to prevent HNSCC tumor formation in mouse models via activation of AMPK and inhibition of the mTOR pathway. Metformin has also been shown to activate CD8+ T cells and activation of AMPK has been shown to activate NKT cells. Therefore, we hypothesized that the addition of metformin to CRT would be safe and would result in enhanced tumor responses through activation of AMPK and activation of the innate immune system. Here we report our findings on the effect of metformin on the immune system utilizing our phase 1 open label clinical trial (NCT02325401) entitled “Dose-finding Study of Metformin With Chemoradiation in Locally Advanced Head and Neck Squamous Cell Carcinoma”. Trial eligibility criteria included newly diagnosed, non-diabetic, LAHNSCC patients eligible for definitive CRT. Patients received a 14-day lead-in of metformin in escalating dose cohorts (1000, 2550, or 3000 mg daily in divided doses) followed by a combination of metformin and standard of care CRT (cisplatin 100mg/m2 days 1, 22, and 43, 70 Gy radiation in 35 fractions) using a modified toxicity probability interval design. Blood was collected before and after metformin treatment and was processed for serum and separation of peripheral blood mononuclear cells (PBMCs). PBMCs were analyzed by flow cytometry to determine immune cell subsets and serum was analyzed by Luminex (Human 10-plex) for cytokine release. Eighteen patients have been enrolled out of 18 planned patients for dose escalation. Median time to follow-up is 21 months (range 3-29 months). Patient serum ELISA examination revealed overall increases in the pro-tumor immune cytokines TNF-a, IL-2, and decrease in the anti-tumor immune cytokine IL-4 in response to metformin. Metformin treatment also resulted in increased populations of cytotoxic T cells, NK and NKT cells and overall activation of innate immunity. Clinically, median overall survival has not been reached, and in fact, no patients on study have relapsed. Metformin administration in LAHNSCC results in activation of pro-tumorigenic immunity which may result in enhanced tumor responses and decreased tumor relapse.

Radiation dose to the thoracic vertebral bodies and impact on hematologic toxicity in patients receiving concurrent chemoradiation for esophageal cancer.

105 Background: Concurrent chemotherapy and radiation (CRT) for the treatment of esophageal cancer (EC) is associated with acute hematologic toxicity (HT). There are few data evaluating the relationship between radiation dose (RT) to the thoracic vertebral bodies (TVB) and the development of HT in EC patients receiving CRT. We hypothesized that increasing RT to the TVB contributes to the development of HT in EC patients receiving CRT. Methods: We identified cases of EC treated with curative intent CRT from 2007-2016. We retrospectively contoured the thoracic vertebral bodies (TVB). The TVB-mean dose and the TVB V5-V50 were calculated from the dose volume histogram. HT was graded according to the Common Terminology Criteria for Adverse Events, v4 based on leukocyte, neutrophil, and platelet nadirs during CRT. Grade≥3 HT (HT3+) was the primary endpoint. Logistic regression was used to test associations between HT3+ and dosimetric/clinical parameters. Results: We included 137 cases: 115 males (84%); median age 61 years (Interquartile range [IQR], 55-67); predominantly stage III (54%). Most patients received concurrent carboplatin/paclitaxel (N = 83). Median RT dose was 50.4 (IQR = 50.4-50.4) Gy, and the majority underwent surgery (60.6%). The rate of HT3+ was 39.4% (N = 54) at a median of 28 (IQR = 21-32) days after CRT start. On univariate analysis, a 5% increase in TVB-V40 was associated with increased odds of HT3+ (OR = 1.13, 95% CI 1.04-1.23, p = 0.0004). TVB-mean and TVB V30-V50, age (OR = 1.04, p = 0.03), males (OR = 0.38, p = 0.04), and carboplatin/paclitaxel vs. other regimen (OR = 2.66, p = 0.01) were significantly associated with HT3+, while BMI was not (OR = 1.00, p = 0.94). On multivariate analysis, TVB-V40 (OR = 1.20, p = 0.0004), carboplatin/paclitaxel (OR = 4.84, p = 0.0007), and age (OR = 1.04, p = 0.03) were independently associated with HT3+ while male gender (OR = 0.48, p = 0.16) was not. The results were similar for TVB-mean and TVB V30-V50. Conclusions: We found that increasing TVB dose was associated with HT3+ in EC patients treated with CRT. This suggests that efforts to spare RT to the TVB may reduce rates of HT3+ and prospective evaluation of these results is needed.

Genomic Evolution after Chemoradiotherapy in Anal Squamous Cell Carcinoma.

Purpose: Squamous cell carcinoma of the anal canal (ASCC) accounts for 2% to 4% of gastrointestinal malignancies in the United States and is increasing in incidence; however, genomic features of ASCC are incompletely characterized. Primary treatment of ASCC involves concurrent chemotherapy and radiation (CRT), but the mutational landscape of resistance to CRT is unknown. Here, we aim to compare mutational features of ASCC in the pre- and post-CRT setting.Experimental Design: We perform whole-exome sequencing of primary (n = 31) and recurrent (n = 30) ASCCs and correlate findings with clinical data. We compare genomic features of matched pre- and post-CRT tumors to identify genomic features of CRT response. Finally, we investigate the mutational underpinnings of an extraordinary ASCC response to immunotherapy.Results: We find that both primary and recurrent ASCC tumors harbor mutations in genes, such as PIK3CA and FBXW7, that are also mutated in other HPV-associated cancers. Overall mutational burden was not significantly different in pre- versus post-CRT tumors, and several examples of shared clonal driver mutations were identified. In two cases, clonally related pre- and post-CRT tumors harbored distinct oncogenic driver mutations in the same cancer gene (KRAS or FBXW7). A patient with recurrent disease achieved an exceptional response to anti-programmed death (PD-1) therapy, and genomic dissection revealed high mutational burden and predicted neoantigen load.Conclusions: We perform comprehensive mutational analysis of ASCC and characterize mutational features associated with CRT. Although many primary and recurrent tumors share driver events, we identify several unique examples of clonal evolution in response to treatment. Clin Cancer Res; 23(12); 3214-22. ©2016 AACR.

A review of weight loss and sarcopenia in patients with head and neck cancer treated with chemoradiation.

BackgroundConcurrent chemotherapy and radiation (CTRT) improves disease-free survival in locally advanced head and neck cancer but is associated with numerous acute and chronic toxicities resulting in substantial alterations in body mass and composition. We aim to summarize the current evidence on body composition changes experienced by patients undergoing CTRT, examine the impact of these changes on clinical outcomes and address potential interventions aimed at mitigating the loss.Main BodyLoss of 20 % of pre-CTRT weight predicts poorer treatment tolerance and 30-day mortality. While clinical practice focuses on body weight, emerging data indicates that CTRT causes profound adverse changes in lean body mass (sarcopenia). Higher prevalence of sarcopenia predicts poorer disease-free survival as well as overall survival, lower quality of life and functional performance. The magnitude of CTRT-induced sarcopenia is the equivalent to that observed in a decade of aging in a healthy adult. Alterations in body composition are only explained, in part, by decreased caloric intake; other significant predictors include body mass index, stage, and dysphagia. Lifestyle interventions aimed at preventing loss of whole-body and especially lean mass include nutritional counseling, nutritional supplements, dietary supplements and exercise training. Personalized nutritional counseling has been associated with improvement in quality of life, while the benefits of feeding tube placement are inconsistent. There are inconsistently reported benefits of resistance training in this population.ConclusionPatients with head and neck cancer undergoing CTRT therapy experience dramatic shifts in body composition, including sarcopenia, which can negatively impact clinical outcomes. Efforts to understand the magnitude, clinical importance and mechanisms of sarcopenia are needed to inform a more personalized approach to mitigating the body composition changes associated with CTRT.

Maintaining physical activity during (head and neck) cancer treatment (MPACT): Results of a pilot controlled trial.

e20606 Background: Concurrent chemotherapy and radiation (CCRT) to treat head and neck cancer (HNCa) is associated with significant reductions of weight, mobility and quality of life (QoL). Support...

Abstract 4727: Prognostic roles of DDB2 and XPC mRNA expressions in treatment responses and overall survivals of head and neck cancer patients

Abstract Background: DNA repair genes function in the maintenance of genome integrity and prevent tumorigenesis. On another hand, DNA repair genes modulate cancer cell responses to DNA-damaging therapeutics. We hypothesize that altered expression of DNA repair genes are correlated with therapeutic outcomes of head and neck cancer patients. Patients and methods: Messenger RNA (mRNA) expressions of DDB2 and XPC were examined in specimens of 95 head and neck cancer patients using real-time quantitative RT-PCR. Patients were dichotomized by ROC curve analysis based on their DDB2 and XPC mRNA levels. Overall survival (OS) rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. Results: The levels of DDB2 and XPC mRNA expression in tumor tissues were reduced (tumor/normal &amp;lt; 0.9) in 84 and 80 cases, respectively, when compared with those in adjacent normal parts. Lower DDB2 (tumor/normal &amp;lt; 0.24) and XPC (tumor/normal &amp;lt; 0.36) mRNA expressions were correlated with larger tumor, positive lymph node invasion, advanced stage, and poor 5-yr OS rates (26.7% vs. 54.3%, and 28.1% vs. 53.0%, respectively). Multivariate Cox model showed that, in addition to T and N stages, lower XPC mRNA level (&amp;lt; 0.36) was an independent risk factor for patient's survival (HRR = 2.68, 95% CI 1.12-6.40). Concurrent chemotherapy and radiotherapy (CCRT) did not improve OS of patients with lower XPC mRNA (&amp;lt; 0.36) and showed even worse outcomes within 5 years for patients with lower DDB2 expression (&amp;lt; 0.24). However, patients with higher DDB2 (&amp;gt; 0.24) and XPC (&amp;gt; 0.36) mRNA levels had improved 5-yr OS rates if they received CCRT (64.4% vs. 41.8% and 73.3% vs. 39.2%). Conclusion: mRNA expressions of XPC and DDB2 might be useful biomarkers for prognosis and efficacy of CCRT medication in head and neck cancer patients. Citation Format: Chang-Shen Lin, Ka-Wo Lee, Jau-Ling Huang, Yu-Chu Wang, Yi-Shan Tsai. Prognostic roles of DDB2 and XPC mRNA expressions in treatment responses and overall survivals of head and neck cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4727. doi:10.1158/1538-7445.AM2014-4727

Feeding tube use in patients with head and neck cancer

Use of a prophylactic feeding tube before concurrent chemotherapy and radiotherapy (CRT) for patients with head and neck cancer is often debated. A retrospective, exploratory study of 109 veterans with stage III/IV head and neck cancer who completed standard CRT was conducted. Relationships among 3 feeding tube status groups: prophylactic feeding tube (PFT), reactive feeding tube (RFT), and no feeding tube (no-FT) were compared for clinical outcomes. Patients with a PFT had significantly less weight loss during CRT, fewer nutrition-related emergency department visits or hospitalizations, and higher proportions of chemotherapy cycles completed compared to those with an RFT or no-FT. At 12 months post-CRT, there was no relationship between the use of a PFT and 100% feeding tube dependency. Use of a PFT in this veteran population with stage III/IV head and neck cancer produced better outcomes when compared to both an RFT or no feeding tube without higher rates of long-term dysphagia.

Predictors of Radiation Pneumonitis in Patients with Lung Cancer after Chemoradiotherapy

The reported incidence of radiation pneumonitis (RP) has varied widely in clinical studies ranging from 0% to 54%. This wide range is probably the result of differences in its precipitating factors. This study aimed to find out the predictive factors of RP in patients with NSCLC who were treated with concurrent chemotherapy and radiotherapy (CCRT). We prospectively studied 76 lung cancer patients who were treated with CCRT consecutively between January 2011 and May 2013 in the Department of Radiation Oncology at Cancer Institute, Assiut University. Radiographic images, pulmonary function tests and symptom assessment were used for the diagnosis of RP. Of the studied 76 patients, 25 patients developed RP (33%), 15 of them developed grade 2 RP, 8 patients developed grade 3 RP, 1 patient developed grade 4 toxicity, and 1 patient developed grade 5 toxicity. In multivariate analysis, FEV1 value (p = 0.000) and chronic obstructive pulmonary disease (COPD) (p = 0.012) were the most significant factors associated with RP. Pretreatment FEV1 value and COPD are useful indicators for predicting RP in NSCLC patients treated with CCRT. Pretreatment of pulmonary function and base-line pulmonary disease is critical for patients’ well being after chemoradiotherapy.

Optimising management approaches for locally advanced oropharyngeal squamous cell carcinoma (LAOPSCC): A retrospective review of prognostic factors and outcomes in an Asian tertiary institution.

e16022 Background: LAOPSCC is treated with concurrent chemotherapy and radiation (CRT). However, certain subsets of OPSCC may have favourable prognoses, thus raising the question if all patients require similar CRT. This study aims to identify prognostic factors in Asian LAOPSCC and explore patient outcomes according to treatment modality and chemotherapy type. Methods: A retrospective review of resectable LAOPSCC from 2001-2006 were included in this analysis. Patient demographics, risk factors, treatment modalities were collated. Results: Out of the 130 patients, 87 received CRT, 24 received RT alone whilst 19 underwent surgery followed by adjuvant therapy. 74% of the patients were male with median age of 60. 30% were non-smokers. Median OS was 5.2 years. Univariable cox regression analysis showed that older age, male gender, smokers, history of alcohol consumption, higher cancer stage, higher T-stage, base of tongue tumors, higher Charlson Comorbidity Index (CCI) and low albumin were associated with worse overall survival (OS), progression free survival (PFS) and local relapse- free survival (LRFS). After multivariate analysis, smoking status, CCI scores and cancer stage were independently prognostic for OS. Patients who received RT alone, despite being older, predominantly smokers and having higher CCI, had similar OS, PFS and LRFS compared to CRT: Hazard Ratio (HR) 1.7, p=0.2; HR 1.7, p=0.1 and HR 1.6, p=0.2 respectively on multivariable cox regression analysis. In an exploratory analysis, after adjusting for age, CCI, smoking status and cancer stage, patients who received cisplatin-based CRT (n=70) had superior overall survival compared with RT alone (HR=0.4, p=0.01). However, patients who received non-cisplatin-based CRT (n=17) had similar overall survival compared to RT alone, independent of age, CCI, smoking status and cancer stage (HR=1.5,p=0.3). Conclusions: Asian LAOPSCC consists of a significant proportion of non-smokers and females. Amongst Asian LAOPSCC, cisplatin-based CRT remains the standard of care. In patients unfit for cisplatin-based treatment, RT alone should be considered.

Quality-of-Life-Adjusted Survival Analysis of Concurrent Chemo Radiotherapy for Locally Advanced (Nonmetastatic) Nasopharyngeal Cancer

To assess whether the benefits of adding cisplatin (CDDP) concurrent with radiotherapy, followed by adjuvant CDDP and fluorouracil, justifies the toxicity cost for nasopharyngeal cancer (NPC) using the quality-adjusted time without symptoms or toxicity (Q-TWiST) approach. One hundred seven patients treated with radiotherapy (RT) and 111 with concurrent chemotherapy and radiotherapy (CRT) were analyzed. The overall survival was divided into three health states: time on active treatment only, during which any subjective nonhematologic toxic event of grade > = 3 was reported; time without symptoms of disease relapse; or treatment and time following first disease RELapse. The relative advantage of CRT and RT was examined by conducting the analysis cumulatively at restriction times 3, 6, 24, 36, 48 months. At 48 months, the improvement in disease-free survival was 14.4% for CRT, whereas that for overall survival was 18.9%. The differences in Q-TWiST were -0.4, -0.7, 0.1, 1.6, and 3.6 months at 3, 6, 24, 36, and 48 months, respectively, with positive differences favoring CRT. At 24 months, the difference in Q-TWiST began to favor CRT. At 36 months, CRT may be the preferred option from the patient's viewpoint if the time spent in the REL state is valued to be <0.83, with the value of perfect health being 1. Finally, Q-TWiST accumulated within 48 months indicated a significant advantage in quality-adjusted survival time for CRT (p = 0.020). Irrespective of how patients valued periods of toxicity and delayed disease progression, concurrent chemotherapy and radiotherapy offered NPC patients significantly more quality-adjusted survival than radiotherapy alone in the long term.

Is Concurrent Chemotherapy and Radiotherapy in Elderly Head and Neck Patients a Reasonable and Safe Approach? The Notre-Dame Hospital Experience

Ageing is still a frequent limiting factor for aggressive treatments in patients with advanced head and neck squamous cell carcinoma (HNSCC). Some studies reported poor or no benefits from concurrent chemotherapy and radiotherapy (CTRT) in such patients, probably because of increased co-morbidities.