Definitive Intensity-modulated Radiotherapy Research Articles

Origin of Locoregional Recurrences After Definitive Intensity-modulated Radiation Therapy (IMRT) for Laryngeal Cancer Determined Based on Follow-up PET/CT Imaging.

Purpose: The aim of our study was to report on patterns of failure using detailed information from follow-up positron emission tomography-computed tomography (PET/CT) scans for patients with laryngeal squamous cell carcinoma (SCCA) treated with definitive radiation therapy using intensity-modulated radiation therapy (IMRT).Methods: One hundred and sixty-eight patients with laryngeal SCCA treated with definitive IMRT using a simultaneous integrated boost were included. The point of recurrence origin on follow-up PET/CT was determined using two separate data-driven methods. The first method, the mathematical epicenter point of origin (POEpi), calculated the mathematical focal epicenter point for which the maximum distance to the surface of the surrounding volume was smaller than for any other point. The second method, maximum standardized uptake value point of origin (POMax), calculated the voxel with maximum standardized uptake value (SUV) uptake within the recurrence volume. The failure pattern was then determined by whether the point of recurrence origin fell within the low, intermediate, or high-risk target volumes in the original treatment planning CT.Results: Thirty-five primary/nodal recurrences in 33 patients were included in the analysis. In the POEpi method, 94% (33/35) of all recurrences originated either within the high-risk gross tumor volume (GTVHigh-risk) or within an average of 0.9 ± 1.3 mm from it. In the POMax method, 91% (32/35) of all recurrences originated either within the GTVHigh-risk or within an average of 1.8 ± 1.7 mm from it. There were no recurrences outside the low-risk planning target volume (PTVLow-risk) for the POEpi method but there was one for the POMax method, which was 19.8 mm away from the edge of the gross tumor volume receiving 70 Gy (GTV70). Increasing distance between the two different origin points was strongly correlated with the size of the recurrence volume.Conclusion: The majority of recurrences for laryngeal cancer patients treated with definitive IMRT originated from within the high-dose treatment region. This can have implications for reducing clinical target volumes while using a risk-adaptive treatment approach to both constrain dose to critical areas and further escalate the dose to the gross tumor to improve locoregional control rates.

MicroRNA-15b-5p Predicts Locoregional Relapse in Head and Neck Carcinoma Patients Treated With Intensity-modulated Radiotherapy.

Head and neck cancers are a heterogenous group of epithelial tumors represented mainly by squamous cell carcinomas (HNSCC), which are the sixth most common type of cancer worldwide. Surgery together with radiotherapy (RT) is among the basic treatment modalities for most HNSCC patients. Various biomarkers aiming to predict patients' response to RT are currently investigated. The reason behind this effort is, on one hand, to distinguish radioresistant patients that show weak benefit from RT and, on the other hand, reduce the ionizing radiation dose in less aggressive radiosensitive HNSCC with possibly less acute or late toxicity. A total of 94 HNSCC patients treated by definitive intensity-modulated radiotherapy were included in our retrospective study. We used a global expression analysis of microRNAs (miRNAs) in 43 tumor samples and validated a series of selected miRNAs in an independent set of 51 tumors. We identified miR-15b-5p to be differentially expressed between patients with short and long time of locoregional control (LRC). Kaplan-Meier analysis confirmed that HNSCC patients with higher expression of miR-15b-5p reach a significantly longer locoregional relapse-free survival compared to patients expressing low levels. Finally, multivariable Cox regression analysis revealed that miR-15b-5p is an independent predictive biomarker of LRC in HNSCC patients (HR=0.25; 95% CI=0.05-0.78; p<0.016). miR-15b-5p represents a potentially helpful biomarker for individualized treatment decisions concerning the management of HNSCC patients.

Five-year outcomes of sparing level IB in node-positive, human papillomavirus–associated oropharyngeal carcinoma: A safety and efficacy analysis

IntroductionThe conformality of modern intensity modulated radiation therapy (IMRT) allows avoidance of the submandibular glands (SMG) in select patients, potentially improving late xerostomia. This study explores the safety and efficacy of this approach in select oropharyngeal carcinoma (OPC) patients. MethodsPatients with T1-2N+ human papillomavirus (HPV)-associated OPC treated with definitive IMRT at one institution from 2009 to 2014 were identified. Patients were divided into 3 groups: bilateral level IB targeted (A, n = 16), a single level IB targeted (B, n = 61), and bilateral IB spared (C, n = 9). Outcomes were reviewed to identify the rate of level IB regional recurrence. Odds ratios were calculated for xerostomia between groups. ResultsLevel Ib was targeted in 93 instances (54.1%) and avoided in 79 instances (45.9%). Mean SMG doses were significantly lower when level IB was spared compared to when targeted (37.5 Gy vs 67.5 Gy; P < 0.0001). Median doses to oral cavity decreased with increasing level Ib sparing (40.7 Gy [A] vs 35.4 Gy [B] vs 30.7 [C]; P = 0.002). The rate of late grade ≥2 xerostomia was significantly lower in patients with bilateral 1b sparing (53% in A vs 0% in C; P = 0.007). Sparing 1b unilaterally resulted in a non-significant decrease in late grade ≥2 xerostomia (P = 0.181). No regional failures were identified in levels IB (median follow up = 59.3 months). ConclusionSparing level IB is safe in T1-2N+ HPV+ OPC. Avoiding level Ib translates into significantly lower SMG and oral cavity doses. Larger studies are needed to validate these findings and the impact of this technique.

Local definitive intensity-modulated radiation therapy recommended for patients initially diagnosed with nasopharyngeal carcinoma with distant metastasis after an effective systemic chemotherapy*

Abstract Objective The aim of the study was to propose a hypothesis that local definitive intensity-modulated radiation therapy (IMRT) should be recommended for initially diagnosed metastatic nasopharyngeal carcinoma (NPC) and demonstrate its feasibility. Methods Recently published papers on local definitive radiotherapy for initially diagnosed metastatic NPC were reviewed to propose a hypothesis. Results Several studies revealed the survival benefits of adding local definitive radiotherapy to the systemic chemotherapy in patients initially diagnosed with metastatic NPC. Conclusion We suggested that local definitive IMRT should be recommended in patients initially diagnosed with NPC with distant metastasis after an effective systemic chemotherapy, which may possibly prolong their survival time and potentially treat the disease.

Radiographic Number of Positive Pelvic Lymph Nodes as a Prognostic Factor in Cervical Cancer Treated With Definitive Concurrent Chemoradiotherapy or Intensity-Modulated Radiotherapy.

Background: This study aims to assess the prognostic significance of radiographic numbers of positive pelvic lymph nodes (PLNs) in patients with cervical cancer treated with definitive concurrent chemoradiotherapy (CCRT) or intensity-modulated radiotherapy (IMRT).Methods: We conducted a retrospective study that included 164 eligible adult patients with cervical cancer who were treated with definitive CCRT or IMRT at our institution from 2009 to 2016. After exclusion of 50 patients, a total of 114 patients whose clinicopathological data and follow-up were finally analyzed. The radiographic numbers of positive PLNs were assessed by pretreatment magnetic resonance imaging (MRI) or computed tomography (CT). The criterion for a positive lymph node was defined as a short-axis diameter >1 cm. Using the Kaplan–Meier method and the Cox proportional hazards regression model, we assessed the overall survival (OS), cancer-specific survival (CSS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRFS).Results: The median follow-up duration was 40 (range: 2–100) months. For patients with 0, 1–2, and ≥3 positive PLNs, the estimated 3-year OS were 85.4% vs. 82.4% vs. 59.7% (p = 0.035), CSS were 90.1% vs. 86.1% vs. 62.9% (p = 0.010), DMFS were 89.4% vs. 91.3% vs. 49.6% (p < 0.001), and LRFS were 77.8% vs. 73.4% vs. 70% (p = 0.690). Per the multivariate Cox regression, positive PLNs ≥3 (HR, 2.51; 95% CI: 1.09–5.80; p = 0.031) and non-squamous cell carcinoma type (HR, 2.82; 95% CI: 1.19–6.69; p = 0.018) were unfavorable factors for the OS. Besides, positive PLNs ≥3 was the independent factor for the CSS (HR, 3.38; 95% CI: 1.32–8.67; p = 0.011) and DMFS (HR, 6.83; 95% CI: 2.62–17.83; p < 0.001). The patients that were treated without intracavitary brachytherapy exhibited inferior LRFS (HR, 13.15; 95% CI: 2.66–65.10; p = 0.002).Conclusions: The radiographic number of positive PLNs (≥ 3) is an independent prognostic factor for OS, CSS, and DMFS in patients treated with definitive CCRT or IMRT.

Clinical Outcome and Late Toxicity following Definitive Intensity Modulated Radiation Therapy for Squamous Cell Carcinoma of the Vulva

Clinical Outcome and Late Toxicity following Definitive Intensity Modulated Radiation Therapy for Squamous Cell Carcinoma of the Vulva

Incidence, Pattern and Predictive Factors for Hypoglossal Nerve Palsy after Definitive Intensity-modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma (NPC)

Incidence, Pattern and Predictive Factors for Hypoglossal Nerve Palsy after Definitive Intensity-modulated Radiation Therapy (IMRT) for Nasopharyngeal Carcinoma (NPC)

Racial Disparity in Androgen Deprivation Therapy Utilization for Men with High-Risk Prostate Cancer Treated with Intensity-Modulated Radiation Therapy in the Modern Era – A SEER-Medicare Linked Database Analysis

Multiple randomized trials have confirmed a survival benefit to utilizing concurrent androgen deprivation therapy (ADT) with definitive radiotherapy for high-risk prostate (PCa). Further investigation into the optimal duration of ADT have suggested a disease-specific survival benefit to longer duration ADT. Previous studies suggest that longer durations of ADT are underutilized in general practice, but it remains unclear whether there are racial disparities in this under-utilization. We extracted PCa patients with Gleason 8-10 with N0M0 PCa from the SEER-Medicare linked database diagnosed from 2004 to 2012 who received intensity modulated radiotherapy (IMRT). ADT was defined as treatment with GnRH agonists (not orchiectomy or other forms of pharmacologic ADT) and the duration was calculated from all available and non-duplicate outpatient or carrier claims. The ADT duration was further categorized as 0, 1-23, and >24 months. Ultimately, 1472 White, 186 African American (AA) and 110 Asian patients were identified. Chi-squared tests was used to compare no ADT, short-term ADT (1-23 months) and long-term ADT (>=24 months) across all three races. AA patients who received IMRT were younger (median age of 72 years) as compared to White and Asian patients (75 years for both). There were no significant differences in the distribution of Gleason score or year of diagnosis. However, there were significant differences in ADT utilization, with 24.2% of AA patients receiving no ADT, compared to 13.8% and 16.4% of White and Asian patients, respectively. Specifically, 20% of White patients received long-term ADT compared to 14.5% and 13.4% for Asian and AA patients, respectively (p < 0.002). An analysis of Medicare claims confirms a widespread under-utilization of long-term ADT amongst high-risk PCa patients treated with definitive IMRT in the modern era. There is also racial disparity in ADT utilization, with AA patients less likely to receive any ADT and long-term ADT. Under-utilization in ADT may contribute to previously reported disparities in oncologic outcomes.

Prognostic Value and Staging Classification of Lymph Nodal Necrosis in Nasopharyngeal Carcinoma after Intensity-modulated Radiation Therapy

To evaluate the prognostic value of magnetic resonance imaging (MRI)-determined lymph nodal necrosis (LNN) in patients with nasopharyngeal carcinoma (NPC) and further explored the feasibility of an N-classification system based on the 8th edition of the American Joint Committee on Cancer (AJCC) system. The MRI scans of 616 patients with newly diagnosed stage T1, 4N1, 3M0 NPC treated with definitive intensity-modulated radiotherapy (IMRT) were reviewed retrospectively. The incidence of LNN was 38.1% (235 of 616). Multivariate analysis showed that LNN was an independent prognostic predictor of distant metastasis free survival and overall survival. The survival outcomes for patients with classification N2 disease and LNN were similar to patients with classification N3 disease. Patients with classification N1 disease and LNN had similar survival outcomes as those with stage N2 disease without LNN. Patients of classification N1 disease with LNN were reclassified as classification N2, and classification N2 disease with LNN as classification N3 in the proposed N-classification system. Correlation with death and distant failure was significant, and the total difference between N1 and N3 was wider with the proposed system. The overall distribution pattern of the proposed N-classification was more equitable than that of the 8th AJCC N-classification. MRI-determined LNN is an independent prognostic factor for NPC treated by IMRT. The proposed N classification system with MRI-determined LNN based on the 8th AJCC system is powerfully predictive.

Long-Term Therapeutic Outcome and Prognostic Factors for Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiation Therapy: An Analysis of 608 Patients from Low-Endemic Regions of China

This study aimed at evaluating the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) from low-endemic regions of China who received definitive intensity-modulated radiotherapy (IMRT). Clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January, 2008 to December, 2013 were retrospectively reviewed. All patients received definitive IMRT, and 87.7% received platinum-based chemotherapy. Survival data were analyzed by Kaplan-Meier method, and Log-rank test and Cox regression analyses were performed to determine the prognostic factors. The median follow-up duration was 51 months (follow-up rate, 98.5%; range, 10-106 months) for the entire cohort. The 5-year overall survival (OS) rate was 79.6%. The 5-year local relapse-free survival rate (LRFS), region relapse-free survival rate (RRFS), distant metastasis-free survival rate (DMFS) and progression-free survival rate (PFS) were 92.4%, 93.4%, 79.2% and 74.2%, respectively. A total of 153 patients have experienced treatment failure, with distant metastasis as the primary cause in 77.1% (118/153). Patients with T4 or N3 diseases had much poorer prognosis than other subcategories. The 5-year OS rates for patients with T1-T4 diseases were 87.9%, 82.1%, 83.3% and 69.2%, respectively. The 5-year OS rates for patients with N1-N3 were Stage T4 and N3 were closely associated with distant metastasis, with metastatic rate of 29.2% and 45.5%, respectively. Multivariate analysis revealed that prognosis was primarily influenced by T stage, N stage and clinical stage, with N stage and T stage acting as the independent prognostic factor for OS, PFS, RRFS and DMFS, and clinical stage for OS, PFS, LRFS and DMFS. IMRT provides patients with non-metastatic NPC with satisfactory long-term survival. T stage, N stage and clinical stage are important prognostic factors for NPC patients. Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival.

Risk Assessment of Secondary Primary Malignancies in Nasopharyngeal Carcinoma: A Big-Data Intelligence Platform-Based Analysis of 6,377 Long-term Survivors from an Endemic Area Treated with Intensity-Modulated Radiation Therapy during 2003-2013.

PurposeThe incidence, risk factors and survival impact of secondary primary malignancies (SPMs) among survivors of nasopharyngeal carcinoma (NPC) treated with definitive intensity-modulated radiation therapy (IMRT) with or without chemotherapy are poorly characterized.Methods and MaterialsConsecutive patients (n=6,377) from the big-data intelligence platform at Sun Yat-sen University Cancer Center, China (in a high-incidence area) with newly diagnosed non-metastatic pathologically proven non-keratinizing undifferentiated NPC treated with IMRT±chemotherapy between January 2003 and June 2013 were retrospectively analyzed. Cumulative incidence of SPMs was calculated using the Kaplan-Meier method. Cox proportional hazards model was used to identify potential risk factors for SPMs and assess whether SPMs affect overall survival.ResultsOf the 6,377 patients, 189 (3.0%) suffered SPMs (median follow-up, 62 months). One-, 2-, 3-, 4-, and 5-cumulative risks of SPMs were 0.4%, 0.9%, 1.6%, 2.2%, and 2.6%, respectively. Latency from start of IMRT to SPMs diagnosis was 37 months (range, 6 to 102 months). In patients with SPMs, 14.3% suffered SPMs within 1 year post-IMRT: 1-3 years, 38.1%; 3-5 years, 33.9%; and >5 years, 13.7%. Lung cancer was the most common SPM (50/6,377, 0.78%). Multivariate analysis demonstrated sex (male, 64% increase), age (≥50 years, 68% increase), and smoking history (41% increase) were significant risk factors for SPMs, and SPMs were associated with poorer overall survival.ConclusionThis large cohort study confirms SPMs a dreadful complication for long-term survivors of NPC treated with IMRT. SPMs negatively impact overall survival in NPC. Close follow-up is recommended for older male survivors with a smoking history.

Image-guided, intensity-modulated radiation therapy in definitive radiotherapy for 1433 patients with cervical cancer

ObjectiveImage guidance should be used for patients with cervical cancer treated with definitive intensity-modulated radiation therapy (IMRT). In this study, we provided a pattern of image guidance and verified it in a large population. MethodsWe retrospectively analyzed patients with stages IB1–IVA cervical cancer treated with IMRT combined with high-dose brachytherapy and concurrent chemotherapy in our institute from January 2005 to December 2015. A dose of 50.4 Gy in 28 fractions was prescribed to the planning target volume with fixed-field IMRT, volumetric modulated arc therapy, or helical tomotherapy. Daily megavoltage computed tomography (CT) or weekly cone-beam CT (CBCT)/CT-on-rail were used for image guidance. Considering tumor regression during treatment, a second CT simulation and IMRT planning after 20 fractions of IMRT was performed. ResultsA total of 1433 patients were included in this study. Four hundred thirteen patients (28.8%) had regional lymph node metastases. A total of 1261 patients (88.0%) received concurrent chemotherapy. The median follow-up was 32.2 months (range, 1.9–124.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and local control (LC) rates were 83.0%, 75.0%, and 87.4%, respectively. The 3-year DFS rates for patients with stages IB1, IB2, IIA, IIB, IIIA, IIIB, and IVA disease were 90.2%, 87.6%, 84.0%, 76.7%, 61.6%, 59.8%, and 25.9%. The incidence rates of grade 3 or greater chronic gastrointestinal and genitourinary toxicities were 2.3% and 1.3%. ConclusionThis pattern of image guidance was rational for patients with cervical cancer treated with IMRT. The survival rates were high, and the toxicities were acceptable.

The Effect of Body Mass Index and Weight Change on Late Gastrointestinal Toxicity in Locally Advanced Cervical Cancer Treated With Intensity-modulated Radiotherapy.

To evaluate the effects of body mass index (BMI) and weight change during radiotherapy on the development of toxicity in patients with locally advanced cervical cancer (LACC) treated with intensity-modulated radiotherapy (IMRT). A total of 245 patients were analyzed after undergoing definitive IMRT treatment between 2004 and 2015 for stage IB2 to stage IVA LACC. The patients were divided into 3 groups: underweight (BMI <18.5 kg/m), normal weight (BMI 18.5-24.9 kg/m), and overweight (BMI ≥25.0 kg/m). The relationships between toxicity, clinical factors, and the bowel dose-volume histogram were analyzed. V45 indicated the bowel volume that received a radiation dose of 45 Gy. The median follow-up period was 63 months. The V45 was similar among the 3 groups. The 5-year rates of grade 3 or higher late gastrointestinal toxicities were 18.6%, 4.0%, and 4.2% for the underweight, normal weight, and overweight groups, respectively (P = 0.002). In the multivariable analysis, underweight (hazard ratio, 13.99; 95% confidence interval, 3.22-60.82; P < 0.001) and weight loss (> -5%) (hazard ratio, 5.91; 95% confidence interval, 1.75-19.98; P = 0.004) were significant predictors of grade 3 or higher-grade late gastrointestinal toxicities. A BMI of less than 18.5 kg/m and weight loss (> -5%) were associated with a higher risk of grade ≥3 or higher late gastrointestinal toxicity in patients with LACC treated with definitive IMRT. Future research on the development of a standardized and structured approach to improve the therapeutic ratio for the supportive care of patients with LACC is needed.

Prognostic impact of combined immunoprofiles in oropharyngeal squamous cell carcinoma patients with respect to AJCC 8th edition.

To examine combined immunoprofiles of epidermal growth factor receptor (EGFR), CD44, and p16 in oropharyngeal squamous cell carcinoma (OPSCC) and to correlate them with radiotherapy treatment outcomes and clinicopathological parameters. Prognostic impact of the American Joint Committee on Cancer (AJCC) 8th edition staging system in comparison with 7th edition was analyzed. The study included 77 OPSCC patients treated by definitive intensity-modulated radiotherapy (IMRT). Clinical staging was assessed according to the AJCC, both 7th and 8th edition. Immunohistochemical (IHC) analysis of CD44 and EGFR was performed on primary biopsy tumor tissues. To evaluate the HPV status, IHC detection of p16 was employed. The AJCC 8th edition staging system revealed correlations between overall survival (OS), progression-free survival (PFS), locoregional control (LRC), and clinical stage. EGFR and CD44 positivity (+) and p16 negativity (-) were associated with clinical stage IV of the disease. CD44+ and EGFR+ OPSCC displayed worse OS and LRC, and these cases also showed the worst 3-year OS and LRC. Combined analysis of protein expressions identified an association between p16- and EGFR+, p16- and CD44+, EGFR+, and CD44+. Combined immunoprofiles CD44+/p16-, EGFR+/p16-, and EGFR+/CD44+ were associated with worst OS and LRC. Combined immunoprofiles of p16, EGFR, and CD44 might provide valuable prognostic and predictive information for the individual OPSCC patients, especially in terms of response to IMRT and prediction of treatment outcomes. Application of the AJCC 8th edition staging for HPV+ OPSCC proved to improve hazard discrimination and prognostication of OPSCC.

Risk, pattern and survival impact of second primary tumors in patients with nasopharyngeal carcinoma following definitive intensity‐modulated radiotherapy

Second primary tumor (SPT) is a serious late complication after definitive radiotherapy for nasopharyngeal carcinoma (NPC). We evaluated the incidence, pattern, risk factors and survival impact of SPT in NPC patients following definitive intensity-modulated radiotherapy (IMRT). A retrospective review of 780 consecutive IMRT-treated NPC patients between February 2003 and September 2011 was conducted. Cumulative SPT incidence and overall survival after SPT diagnosis were estimated. Associations between clinical characteristics and SPT risk were analyzed. Standardized incidence ratios (SIR) were calculated using age, gender and calendar-year-specific cancer incidences from the Hong Kong Cancer Registry. At a median follow-up of 7.5 years, 51 SPTs (6.7%) were identified, 22 (43.1%) of which occurred within previous radiotherapy fields. Tongue cancers (31.8%) and sarcomas of the head and neck (31.8%) were the most common in-field SPTs. Age [hazard ratio (HR), 1.051; 95% confidence interval (CI), 1.025-1.078] and smoking status (HR, 1.755; 95% CI, 1.002-3.075) were independent risk factors associated with SPT development. Median overall survival after SPT diagnosis was 2.9 years. There was an 84% increase in cancer risk (SIR, 1.84; 95% CI, 1.37-2.42) compared with the general population. Significant excess risks were observed for sarcoma, tongue, oropharyngeal, prostate and liver cancer. Excess risks were higher beyond 5 years of follow-up. Substantial risk of SPT, especially for in-field sarcoma and tongue cancers, exists after definitive IMRT for NPC. SPT severely negates longevity of NPC survivors. High awareness and careful surveillance is warranted for this late lethal complication.

Pretreatment risk stratification of feeding tube use in patients treated with intensity-modulated radiotherapy for head and neck cancer.

The purpose of this study was to establish a risk stratification model for feeding tube use in patients who undergo intensity-modulated radiotherapy (IMRT) for head and neck cancers. One hundred thirty-nine patients treated with definitive IMRT (+/- concurrent chemotherapy) for head and neck mucosal cancers were included in this study. Patients were recommended a prophylactic feeding tube and followed up by a dietician for at least 8 weeks postradiotherapy (post-RT). Potential prognostic factors were analyzed for risk and duration of feeding tube use for at least 25% of dietary requirements. Many variables had significant effects on risk and/or duration of feeding tube use in univariate analyses. Subsequent multivariable analysis showed that T classification ≥3 and level 2 lymphadenopathy were the best independent significant predictors of higher risk and duration of feeding tube use, respectively, in oral cavity, pharyngeal, and supraglottic primaries. In patients treated with definitive IMRT, T classification ≥3 and level 2 lymphadenopathy can potentially stratify patients into 4 risk groups for developing severe dysphagia requiring feeding tube use.

Aging-related prognosis analysis of definitive radiotherapy for very elderly esophageal cancer.

Because of the exclusion for the patients more than 75 years (very elderly patients) in many clinical trials of esophageal cancer (EC), there is no consensus on prognosis and treatment for this population. We aim to evaluate the outcomes and aging‐related prognostic factors of definitive radiotherapy (RT) for very elderly EC patients. We retrospectively analyzed 149 very elderly EC patients consecutively treated between January 2015 and June 2016 by definitive intensity‐modulated radiotherapy (IMRT) with or without chemotherapy. The clinical outcome and toxicities were assessed, and the potential prognostic factors, such as nutritional risk index (NRI) and neutrophil–lymphocyte ratio (NLR), were analyzed statistically. The median follow‐up time for survivors was 22.5 months. The 2‐year overall survival (OS), local–regional failure‐free survival (LRFFS), and distant metastasis‐free survival (DMFS) were 51.6%, 54.7%, and 85.2%, respectively. Independent predictors for poorer OS were higher American Joint Committee on Cancer (AJCC) stage, lower NRI, and higher NLR value before RT. Meanwhile, the total dose (cutoff value 60 Gy) of planning gross tumor volume (PGTV) and chemotherapy was also identified as independent prognostic indicator for LRFFS and DMFS, respectively. 72 patients had treatment failure and 58 (80.6%), 6 (8.3%), and 18 (25.0%) patients had experienced local, regional, and distant failure, respectively. Few severe toxicities were observed. The conservative definitive RT with modern technique was effective for very elderly EC patients in short term with low rate and tolerable toxicities. Local residue or recurrence was the most common failure pattern. The aging‐related prognostic factors concerned nutrition and immune, such as NRI and NLR before RT, should be considered for use in future clinical practice.

Cost-Effectiveness Analysis of Routine Magnetic Resonance Imaging in the Follow-Up of Patients With Nasopharyngeal Carcinoma After Intensity Modulated Radiation Therapy

To estimate the clinical benefit and cost-effectiveness of routine head and neck magnetic resonance imaging (MRI) in the follow-up of patients with nasopharyngeal carcinoma after definitive intensity modulated radiation therapy. Two Markov models were developed to compare the cost and effectiveness of 3 strategies: routine clinical surveillance without serial imaging and routine annual and biannual MRI surveillance in the first 5years. Two hypothetical cohorts of patients with primary stage T1-2 or T3-4 nasopharyngeal carcinoma who achieved complete remission after radical treatment and remained asymptomatic were analyzed. Baseline probabilities, transition probabilities, utilities, and costs were derived from published studies. Markov models were used to calculate life-time costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Model robustness was addressed via univariable and probabilistic sensitivity analyses. In T1-2 patients, surveillance strategies utilizing routine MRI provided few QALYs compared with non-MRI clinical follow-up (annual MRI, 0.022 QALYs; biannual MRI, 0.035 QALYs), whereas the costs associated with MRI surveillance were considerable. Compared with clinical follow-up, the ICERs for annual and biannual MRI strategies were $328,389 and $403,857 per QALY. In T3-4 patients, annual and biannual MRI surveillance provided 0.052 and 0.088 incremental QALYs, with ICERs of $156,204 and $169,772 per QALY, respectively. Model conclusions were robust and remained stable in 1-way and probabilistic sensitivity analyses. Routine MRI surveillance was not cost-effective owing to the high cost of MRI coupled with low rates of failure in T1-2 patients, whereas annual MRI surveillance was the dominant and possibly a cost-effective strategy for T3-4 patients, depending on the social willingness to pay.

Prognostic values of hematological biomarkers in nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy

PurposeIn this study, we evaluated the prognostic values of hematological biomarkers in primary nasopharyngeal carcinoma (NPC) patients receiving definitive intensity-modulated radiotherapy (IMRT).MethodsThere were 427 NPC patients enrolled between January 2010 and March 2013 at Fudan University Shanghai Cancer Center. Pre-treatment absolute neutrophil count (ANC), platelet count (APC), lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were collected as prognostic biomarkers. The Kaplan–Meier method and log-rank test were utilized to calculate progression-free survival (PFS) and overall survival (OS). The Cox proportional hazard models were applied to assess variables.ResultsANC, APC and ALC were declined, while NLR and PLR were elevated significantly after therapy (P < 0.001 each). On multivariate analysis, pre-treatment NLR ≥ 2.32 was associated with shortened OS (P = 0.048) and PFS (P = 0.008), whereas PLR ≥ 123.0 was related with inferior OS (P = 0.032), yet it was not correlated with PFS (P = 0.161).ConclusionsHigh pre-treatment NLR and PLR indicated poor survival in NPC patients treated with IMRT-based therapy. As easily accessible and economically feasible biomarkers, NLR and PLR can be applied into clinical practice, in combination with current TNM staging, to design a more personalized treatment in these patients.

Treatment outcomes and HPV characteristics for an institutional cohort of patients with anal cancer receiving concurrent chemotherapy and intensity-modulated radiation therapy.

BackgroundIntensity-modulated radiation therapy (IMRT) has been used to limit treatment-related toxicity for patients with anal squamous cell carcinoma (SCC). The treatment outcomes and HPV characteristics for a cohort of patients receiving definitive concurrent chemotherapy and IMRT are reported.Materials and methods52 patients with anal SCC were treated with IMRT and concurrent chemotherapy. Radiation was delivered sequentially to the pelvis and inguinal lymph nodes (45 Gy) and anal tumor (median dose, 54 Gy). Multiplex real-time PCR for 7 high-risk HPV subtypes (n = 22) and p16 immunohistochemistry (n = 21, rated on a 0, 1, and 2+ scale) were performed on available specimens. Survival was estimated using Kaplan-Meier analysis, and toxicities were recorded.ResultsMedian follow-up was 33 months. Three-year freedom from locoregional failure (FFLRF), freedom from distant metastasis (FFDM), freedom from colostomy (FFC), and overall survival (OS) were 94%, 85%, 91%, and 90%, respectively. Acute grade 2+ skin, GI, and GU toxicities occurred in 83%, 71%, and 19% of evaluable patients, respectively. The rates of late grade 2+ GI and GU toxicities for evaluable patients (n = 32) were 28% and 9%, respectively. Of patients with available pathology, 91% and 71% were positive for HPV and p16 (2+), respectively. HPV genotypes included 16 (n = 17), 33 (n = 2), 18 (n = 1), and 45 (n = 1). HPV and p16 status were associated on Chi-square analysis (p = 0.07). Neither HPV nor p16 status was significantly associated with any clinical outcome. For HPV+ patients, 3-year FFLRF, FFDM, FFC, and OS were 100%, 69%, 100%, and 88%, respectively.ConclusionsIn this patient cohort, disease control was excellent for anal SCC treated with definitive concurrent chemotherapy and IMRT, and treatment was well tolerated. HPV and p16 status were not prognostic for treatment outcomes which may be related to our small sample size.