Radiation Dose-volume Parameters Research Articles

The Influence of Pelvic Bone Dose-volume Parameters on Bone Marrow Suppression During Radiation Therapy in Patients With Stage I to III Rectal Cancer Based on Real-world Data

BackgroundThe aim of this study was to evaluate the impact of pelvic bone dose-volume parameters on bone marrow suppression during radiotherapy (RT) in rectal cancer patients with stage I-III disease receiving either neoadjuvant radiotherapy (neo-RT) or curative-intent radiotherapy (cur-RT). Materials and methodsThis was a retrospective study with data mined from an electronic medical record review at a single institution. Between January 2016 and September 2022, rectal cancer patients who consecutively received neo-RT or cur-RT in our department were included. The data collected included complete baseline peripheral blood counts and hematological toxicity (HT) data collected during RT. The radiation dose-volume parameters of three pelvic bone marrow (PBM) subsites [iliac bone marrow (IBM), lumbosacral bone marrow (LSBM), and lower pelvis bone marrow (LPBM)] were collected. The primary endpoint was grade ≥ 2 HT (HT2+), including leukopenia, neutropenia, anemia, thrombocytopenia and total HTs. Logistic regression was employed to analyze the associations of HT2+ with dosimetric parameters and clinicopathologic characteristics. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were generated to verify the prediction efficacy of the pelvic bone dose-volume parameters combined with clinicopathologic indices. ResultsA total of 130 patients with stage I-III rectal cancer with complete clinical data were included. During neo-RT and cur-RT, 57 (43.8%) of these patients experienced HT2+. Multivariate analysis revealed that gender, the IBM-Dmean, the IBM-V15 and the IBM-V40 were significantly associated with Grade 2+ leukopenia (P < 0.05), and the AUC of gender combined with the IBM-Dmean, the IBM-V15 and the IBM-V40 in predicting Grade 2+ leukopenia was 0.834. The optimal cutoff values were an IBM-Dmean = 2692.75 cGy, an IBM-V15 = 86.65%, and an IBM-V40 = 20.75%. Patients who received oxaliplatin-containing concurrent chemotherapy (ChT) regimens were more likely to experience Grade 2+ thrombocytopenia (P=0.054). The AUC of concurrent ChT regimens in predicting Grade 2+ thrombocytopenia was 0.678. Female gender was significantly associated with Grade 2+ anemia and total HT2+ status. ConclusionAmong rectal cancer patients with stage I-III disease who received neo-RT or cur-RT, female patients with higher IBM-Dmean, IBM-V15 and IBM-V40 were more likely to experience Grade 2+ leukopenia, and oxaliplatin-containing concurrent ChT regimens were identified as a potential factor for increasing the incidence of Grade 2+ thrombocytopenia.

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study

PurposeThe aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. Materials and MethodsBlood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. ResultsHS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. ConclusionSignificant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints.

Risk Factors Causing Hypothyroidism in Patients With Head and Neck Cancer After Radiotherapy Using SIB-VMAT.

We evaluated the incidence of radiation-induced hypothyroidism and its risk factors in patients with head and neck cancer who underwent radiotherapy using simultaneous integrated boost-volumetric-modulated arc therapy (SIB-VMAT). This retrospective study included 86 patients who received definitive radiotherapy using SIB-VMAT for head and neck cancer. The incidence of ≥ grade 2 hypothyroidism was evaluated. We also evaluated the relationships between hypothyroidism development and clinical factors and thyroid dose-volume parameters. During a median follow-up period of 17 months (range=3-65 months), 31 patients (36.0%, 31/86) developed grade 2 hypothyroidism requiring hormone replacement therapy. No patients experienced ≥ grade 3 hypothyroidism. The cumulative incidences of hypothyroidism at 1 and 2 years after radiation therapy were 24.5% and 38.7%, respectively, with a median onset time of 10.0 months (range=3.0-35.0 months). Thyroid volume (p=0.003), volume of the thyroid spared at 60 Gy (VS60; cut-off value, 5.16 ml; p=0.009), VS70 (cut-off value, 8.0 ml; p=0.007), VS60 equivalent dose in 2 Gy fraction (EQD2; cut-off value, 7.78 ml; p=0.001), and VS70EQD2 (cut-off value, 10.59 ml; p=0.008) were significantly associated with the development of radiation-induced hypothyroidism. Radiation-induced hypothyroidism is not rare in patients with head and neck cancer undergoing radiotherapy using SIB-VMAT. Radiation dose-volume parameters detected in this study may be useful indicators to prevent this complication.

External Validation of 8 Normal Tissue Complication Probability Models for Radiation-Associated Primary Hypothyroidism Using Long-Term Thyroid Function Outcomes

Primary hypothyroidism is a common late complication following neck irradiation. The reported incidences were as high as 20-50% among head and neck cancer survivors. Several normal tissue complication probability models for radiation-associated primary hypothyroidism have been proposed, but none has been externally validated using long-term thyroid function outcome. We undertook a systematic review of the literature and identified 8 distinct normal tissue complication probability (NTCP) models for radiation-associated primary hypothyroidism (6 logistic regression models and 2 nomograms). We retrospectively contoured and reviewed the thyroid gland dosimetry of all consecutive head and neck cancer patients who underwent definitive radiotherapy between January 2013 and December 2015 in two tertiary oncology centers. Patients with abnormal pre-radiotherapy thyroid function were excluded. Thyroid function was monitored at least yearly after radiotherapy. Primary hypothyroidism was defined as serum thyroid-stimulating hormone levels above the upper limit of normal. Euthyroid controls were defined as patients who had normal thyroid function at least 5 years beyond the completion of radiotherapy. Diagnostic properties (sensitivity, specificity and accuracy) of the 8 NTCP models were determined. Discrimination and calibration of the models were assessed using c-statistics, discrimination slopes, calibration curves and Brier score. With a median follow-up of 7.0 years, we identified 216 cases of post-radiation primary hypothyroidism and 120 euthyroid controls within the study period. All four logistic regression models (Boomsma 2012, Rønjom 2013, Shen 2021 and Huang 2021) which were based on mean thyroid dose and thyroid volume demonstrated satisfactory diagnostic performances. The accuracy, c-statistic, discrimination slope and Brier score of these four models were > 0.70 (0.711 - 0.732), > 0.75 (0.763 - 0.765), > 0.20 (0.203 - 0.295) and < 0.20 (0.187 - 0.198), respectively. Calibrations of prediction were excellent at ranges of high predicted probabilities. At ranges of low predicted probabilities, these models underestimated the risk of primary hypothyroidism by 10-20%. Other models or nomograms which utilized alternative radiation dose-volume parameters (e.g., V30, V35 or V50), or without factoring in the variation in thyroid volume, had significantly worse performance in terms of both discrimination and calibration. This large external validation study showed that NTCP models that included thyroid volume and mean thyroid dose had satisfactory performances in predicting long-term thyroid function outcomes following neck irradiation. Refinement is required to optimize calibration in patients deemed at low risk of post-radiation primary hypothyroidism.

Normal Tissue Complication Probability (NTCP) Prediction Model for Osteoradionecrosis of the Mandible in Patients With Head and Neck Cancer After Radiation Therapy: Large-Scale Observational Cohort.

Purpose:Osteoradionecrosis (ORN) of the mandible represents a severe, debilitating complication of radiation therapy (RT) for head and neck cancer (HNC). At present, no normal tissue complication probability (NTCP) models for risk of ORN exist. The aim of this study was to develop a multivariable clinical/dose-based NTCP model for the prediction of ORN any grade (ORNI-IV) and grade IV (ORNIV) after RT (±chemotherapy) in patients with HNC.Methods and Materials:Included patients with HNC were treated with (chemo-)RT between 2005 and 2015. Mandible bone radiation dose-volume parameters and clinical variables (ie, age, sex, tumor site, pre-RT dental extractions, chemotherapy history, postoperative RT, and smoking status) were considered as potential predictors. The patient cohort was randomly divided into a training (70%) and independent test (30%) cohort. Bootstrapped forward variable selection was performed in the training cohort to select the predictors for the NTCP models. Final NTCP model(s) were validated on the holdback test subset.Results:Of 1259 included patients with HNC, 13.7% (n = 173 patients) developed any grade ORN (ORNI-IV primary endpoint) and 5% (n = 65) ORNIV (secondary endpoint). All dose and volume parameters of the mandible bone were significantly associated with the development of ORN in univariable models. Multivariable analyses identified D30% and pre-RT dental extraction as independent predictors for both ORNI-IV and ORNIV best-performing NTCP models with an area under the curve (AUC) of 0.78 (AUCvalidation = 0.75 [0.69–0.82]) and 0.81 (AUCvalidation = 0.82 [0.74–0.89]), respectively.Conclusions:This study presented NTCP models based on mandible bone D30% and pre-RT dental extraction that predict ORNI-IV and ORNIV (ie, needing invasive surgical intervention) after HNC RT. Our results suggest that less than 30% of the mandible should receive a dose of 35 Gy or more for an ORNI-IV risk lower than 5%. These NTCP models can improve ORN prevention and management by identifying patients at risk of ORN.

Multi-institutional Analysis of Prognostic Factors and Outcomes After Hypofractionated Stereotactic Radiotherapy to the Resection Cavity in Patients With Brain Metastases

For brain metastases, the combination of neurosurgical resection and postoperative hypofractionated stereotactic radiotherapy (HSRT) is an emerging therapeutic approach preferred to the prior practice of postoperative whole-brain radiotherapy. However, mature large-scale outcome data are lacking. To evaluate outcomes and prognostic factors after HSRT to the resection cavity in patients with brain metastases. An international, multi-institutional cohort study was performed in 558 patients with resected brain metastases and postoperative HSRT treated between December 1, 2003, and October 31, 2019, in 1 of 6 participating centers. Exclusion criteria were prior cranial radiotherapy (including whole-brain radiotherapy) and early termination of treatment. A median total dose of 30 Gy (range, 18-35 Gy) and a dose per fraction of 6 Gy (range, 5-10.7 Gy) were applied. The primary end points were overall survival, local control (LC), and the analysis of prognostic factors associated with overall survival and LC. Secondary end points included distant intracranial failure, distant progression, and the incidence of neurologic toxicity. A total of 558 patients (mean [SD] age, 61 [0.50] years; 301 [53.9%] female) with 581 resected cavities were analyzed. The median follow-up was 12.3 months (interquartile range, 5.0-25.3 months). Overall survival was 65% at 1 year, 46% at 2 years, and 33% at 3 years, whereas LC was 84% at 1 year, 75% at 2 years, and 71% at 3 years. Radiation necrosis was present in 48 patients (8.6%) and leptomeningeal disease in 73 patients (13.1%). Neurologic toxic events according to the Common Terminology Criteria for Adverse Events grade 3 or higher occurred in 16 patients (2.8%) less than 6 months and 24 patients (4.1%) greater than 6 months after treatment. Multivariate analysis identified a Karnofsky Performance Status score of 80% or greater (hazard ratio [HR], 0.61; 95% CI, 0.46-0.82; P < .001), 22 to 33 days between resection and radiotherapy (HR, 1.50; 95% CI, 1.07-2.10; P = .02), and a controlled primary tumor (HR, 0.69; 95% CI, 0.52-0.90; P = .007) as prognostic factors associated with overall survival. For LC, a single brain metastasis (HR, 0.57; 95% CI, 0.35-0.93; P = .03) and a controlled primary tumor (HR, 0.59; 95% CI, 0.39-0.92; P = .02) were significant in the multivariate analysis. To date, this cohort study includes one of the largest series of patients with brain metastases and postoperative HSRT and appears to confirm an excellent risk-benefit profile of local HSRT to the resection cavity. Additional studies will help determine radiation dose-volume parameters and provide a better understanding of synergistic effects with systemic and immunotherapies.

Clinical significance of radiation dose-volume parameters and functional status on the patient-reported quality of life changes after thoracic radiotherapy for lung cancer: a prospective study.

To date, limited data exist about the relationship between radiation dose-volume parameters and patient-reported quality of life (QOL) after thoracic radiotherapy (RT) for lung cancer. We conducted this prospective study to investigate which clinico-dosimetric factors have an impact on functional declines and symptom developments after thoracic RT for lung cancer. The study included 44 patients who had underwent thoracic three-dimensional conformal RT at our institution from 2016 to 2017. The health-related QOL was assessed using the EORTC QLQ-C30 and QLQ-LC13 questionnaires before RT (preRT), at the end of RT (endRT), and 3, 6, and 12months after the completion of RT. RT dose-volume parameters of adjacent normal organs such as the lung, heart, and esophagus were retrieved and used for regression analysis. Thoracic RT induced a temporary deterioration of many of the functional statuses and symptoms, but most of those improved and recovered to baseline levels 3months after RT. However, the role function (RF) decline persisted until 6months after RT (p < 0.05). Dysphagia showed the most noticeable change at the endRT (p < 0.001). In the multiple regression analysis, the absolute volume of body received at least 50Gy (p = 0.021) and a preRT RF score (p = 0.001) was significantly associated with the endRT RF scores. Dysphagia at the endRT was significantly associated with the V40 of the esophagus (p = 0.047), preRT emotional function (p = 0.029), and receipt of concurrent chemotherapy (p = 0.022). Both the dosimetric parameters and preRT functional status have an impact on the weak aspect of patient-reported QOL, which may cause poor treatment compliance during and after thoracic RT. For patients with a low preRT QOL score or those having large tumor which may result in higher dose volumes, careful RT planning could prevent the deterioration of QOL after RT.

Radiation dose response of neurologic symptoms during conformal radiotherapy for diffuse intrinsic pontine glioma.

To estimate the rate and magnitude of neurologic symptom change during radiation therapy (RT) and impact of symptom change on survival outcomes in patients with diffuse intrinsic pontine glioma (DIPG). From 2006 to 2014, 108 patients with newly diagnosed DIPG were treated with conventionally fractionated radiation therapy (RT) to 54 Gy (median) at our institution. The presence and severity of neurologic symptoms related to cranial neuropathy (CN) and cerebellar (CB) and long-tract (LT) signs was reviewed before and weekly during RT for each patient. The rate and magnitude of change for each symptom category was evaluated according to accumulated RT dose. The impact of clinical factors and radiation dose-volume parameters was determined using Cox proportional hazards models. Median dose to first sign of symptomatic improvement was 16.2 Gy (CN), 19.8 Gy (LT) and 21.6 Gy (CB). Most patients showed an improvement by 20 Gy. Larger uninvolved brainstem volume, alone or normalized to total brain (TB) or posterior fossa volume (PF), was associated with shorter time to LT sign improvement (P = 0.044, P = 0.033, and P = 0.05, respectively). Patients with any improvement in CN experienced significantly, yet modestly, prolonged progression-free survival (PFS) and overall survival (OS) (P = 0.002 and P = 0.008, respectively). Tumor volume, with or without normalization to TB or PF, was not significantly associated with PFS or OS. Low cumulative RT doses resulted in neurologic improvement in most patients with DIPG. The volume of brainstem spared by tumor influenced time to symptomatic improvement. Neurologic improvement during RT was associated with superior survival.

New Cardiac Abnormalities After Radiotherapy in Breast Cancer Patients Treated With Trastuzumab

PurposeTo evaluate cardiac imaging abnormalities after modern radiotherapy and trastuzumab in breast cancer patients. Patients and MethodsAll patients treated with trastuzumab and radiotherapy for breast cancer between 2006 and 2014 with available cardiac imaging (echocardiogram or multigated acquisition scan) were retrospectively analyzed. Cardiac abnormalities included myocardial abnormalities (atrial or ventricular dilation, hypertrophy, hypokinesis, and impaired relaxation), decreased ejection fraction > 10%, and valvular abnormalities (thickening or stenosis of the valve leaflets). Breast laterality (left vs. right) and heart radiation dose volume parameters were analyzed for association with cardiac imaging abnormalities. ResultsA total of 110 patients with 57 left- and 53 right-sided breast cancers were evaluated. Overall, 37 patients (33.6%) developed a new cardiac abnormality. Left-sided radiotherapy was associated with an increase in new cardiac abnormalities (relative risk [RR] = 2.51; 95% confidence interval [CI], 1.34-4.67; P = .002). Both myocardial and valvular abnormalities were associated with left-sided radiotherapy (myocardial: RR = 2.21; 95% CI, 1.06-4.60; P = .029; valvular: RR = 3.30; 95% CI, 0.98-10.9; P = .044). There was no significant difference in decreased ejection fraction between left- and right-sided radiotherapy (9.6% vs. 2.1%; P = .207). A mean heart dose > 2 Gy as well as volume of the heart receiving 20 Gy (V20), V30, and V40 correlated with cardiac abnormalities (mean heart dose > 2 Gy: RR = 2.00; P = .040). ConclusionNew cardiac abnormalities, including myocardial and valvular dysfunction, are common after trastuzumab and radiotherapy. The incidence of new abnormalities correlates with tumor laterality and cardiac radiation dose exposure. Long-term follow-up is needed to understand the clinical significance of these early imaging abnormalities.

Association between dose-volume parameters and acute bone marrow suppression in rectal cancer patients treated with concurrent chemoradiotherapy.

Concurrent chemoradiotherapy is one of the main treatments for rectal cancer. Bone marrow suppression is one of the critical factors that affect the progress of radiotherapy. We aimed to explore the association of incidence of acute bone marrow suppression with dose-volume parameters of pelvic bone marrow among rectal cancer patients with concurrent chemoradiotherapy. We retrospectively analyzed 50 rectal cancer patients for multivariate logistic regression analyses. Three subdomains of pelvic bone marrow (PBM), bilateral ilium (IBM), lower pelvis (LPBM), and lumbosacral spine (LSBM) were assigned. The radiation dose-volume parameters from the three subdomains and the whole pelvis were evaluated. Compared to Grade 0-1 leukopenia patients, ≥Grade 2 leukopenia patients exhibited significantly higher levels of IBM V20, V25, V35, mean dose (Dmean), LPBM V20, V25, V30, LSBM V15, PBM V15, V20, and PTV. The PBM V20 of ≥Grade 2 neutropenia patients was significantly higher than that of Grade 0-1 neutropenia patients. Multivariate analysis have demonstrated that IBM V20 and LSBM V15 were the independent factors affecting ≥ Grade 2 leukopenia. There is a correlation between low dose-volume parameters with acute bone marrow suppression. IBM V20, LSBM V15 and PBM V20 can be employed as the predictors of acute bone marrow suppression.

Neurocognitive Outcomes and Dosimetric Correlates in Central Nervous System Germ Cell Tumors

To evaluate clinical outcomes of patients with central nervous system germ cell tumor (CNS GCT) who received radiation therapy (RT) as a component of definitive treatment, with a focus on longitudinal neurocognitive outcomes in relation to radiation dose-volume parameters and clinical and pathologic variables. Sixty consecutively treated pediatric and young adult patients with CNS GCT who received definitive RT at our institution from 1995 to 2015 were reviewed. Forty-three patients underwent age appropriate neuropsychologic assessment with at least three measures of interest after diagnosis. Variance of neuropsychometric evaluations from normative means was evaluated by t-test. Differential dose-volume histograms for 14 brain volumes were obtained in 35 patients. Dose-volume parameters were modelled with time and clinical variables using neurocognitive test scores as the response variable. Median age at diagnosis of the overall cohort was 12 years (range, 2 – 28 years). Pure germinoma was diagnosed in 65% patients and nongerminomatous germ cell tumor (NGGCT) in 35%. Eighty six percent of patients were treated with craniospinal irradiation (CSI), 12% with whole ventricle irradiation, and 2% with focal RT. With a median follow-up of all patients of 6.2 years (range, 0.36 – 18.4 years), 5 patients developed recurrent disease, with all but one failing outside the high dose region. The 5 year event-free survival (EFS) and overall survival (OS) estimates for patients with pure germinoma were 91% and 100%, respectively, while 5 year EFS and OS estimates for patients with NGGCT were and 79.6% and 90.0%, respectively. The median time from start of RT to neurocognitive assessment was 4.1 years (range, 0.41 – 11.1 years). Domains significantly worse than normative expectations included intelligence, attention, memory, executive function, adaptive, psychosocial, visuomotor, and academic measures. Using the Conners’ Continuous Performance Test-II (CPT-II), there was an association between time after irradiation and mean dose to the mammillary bodies and Response Style Indicator (β) Scores were lower (less concern about mistakes) at a rate of -0.00167 points/Gy/day (p=0.007). Statistically significant (p≤0.05) associations were found between time and mean dose to several supratentorial brain regions (hippocampi, bilateral subventricular zones, left temporal lobe) and CPT Detectability (d') Scores were higher (lower discriminating power) at a rate ranging from 0.000345 to 0.00433 points/Gy/day. This study confirms excellent disease control rates achieved with RT as a component of CNS GCT management. However, patients do experience cognitive late effects of disease and treatment with deficits in attentional regulation associated with extent and location of irradiation. Ultimately, we aim to use identified dosimetric factors to inform proton-based treatment planning to limit these long term complications.

Pulmonary function and quality of life after VMAT-based stereotactic ablative radiotherapy for early stage inoperable NSCLC: a prospective study.

To analyze changes in pulmonary function and quality of life (QoL) at different time points after Stereotactic Ablative Radiotherapy (SABR) for early stage inoperable lung cancer, and potential correlations between radiation dose-volume parameters and pulmonary toxicity or changes in pulmonary function tests (PFT) and QoL. From July 2012 to October 2013, 30 patients were enrolled in this prospective observational study. Complete PFT were performed and Lung Cancer Symptoms Scale (LCSS) questionnaire administered prior to SABR; all patients then underwent Computed Tomography (CT) scan and PFT at 45, 135, 225 and 315 days after SABR, together with LCSS questionnaire. Clinical lung toxicity and radiological toxicity (acute and late) were prospectively recorded by using the Radiation Therapy Oncology Group (RTOG) scoring system. A decline in Slow Vital Capacity (SVC), Forced Expiratory Volume in 1s (FEV1), Single-breath lung diffusing capacity (DLCO) and blood partial pressure of oxygen (PaO2) was seen at 135 days post-SABR. PaO2 values rescued to normal levels at 315 days. None of the baseline PFT parameters resulted to be associated with the occurrence of pulmonary toxicity or with late radiological changes. Mean V5, V10, and V20 and MLD2Gy were higher in patients who developed radiation pneumonitis, even if not significantly associated at Cox regression analysis. LCSS QoL showed a significant worsening of the single item fatigue at 135 days after SABR. A small (mean 10%) but significant decline in lung volumes and DLCO was recorded after SABR, with clinical impact of such change difficult to estimate in individual patients. Global QoL was not significantly impaired. Dose-volume parameters did not emerge as significantly predictive of any clinical, radiological or functional toxicity.

Proton therapy for prostate cancer: An analysis of rectal toxicity outcomes at University of Florida Proton Therapy Institute (UFPTI).

161 Background: We aimed to characterize gastrointestinal effects of proton therapy (PT) in patients treated for prostate cancer, identify factors associated with rectal bleeding (RB), and compare RB between patients on investigational protocols (IP) versus outcome tracking protocols (OTP). Methods: 1,290 patients treated consecutively with PT between August 2006 and June 2010 were studied. Pre-existing potential risk factors for RB (hemorrhoids, diabetes, aspirin, other anticoagulants) were recorded. Common terminology criteria for adverse events (CTCAE version 4.0) were used to grade toxicity. Median follow up was 3.5 years. Results: The majority (94.6%) of Grade 2 or higher gastrointestinal toxicity (GR2+) events after PT were rectal bleeding. GR1 RB occurred in 390 (30.2%) of patients, including those requiring no prescription intervention (82.6%) and those placed on a vitamin A regimen (16.3%). GR2 RB occurred in 14.7% of patients, including patients requiring prescription rectal suppositories (9.5%), cautery (4.9%), or hyperbaric oxygen (0.3%). Grade 3 (GR3) occurred in 0.8% of patients, including those requiring transfusion (0.6%) or colostomy (0.1%). Multivariate analyses showed that pretreatment daily aspirin (p=0.03), other anticoagulation (p=0.001), and the volume of rectum exposed to radiation dose levels (V70) (&lt;.0001) were associated with an increased risk of Gr2+RB. Patients treated on investigational protocols (IP) had similar toxicity rates as those treated on an outcomes tracking protocol (OTP). Reduced rectal toxicity was noted in latter years of the study, which correlated with changes in treatment technique, pretreatment evaluation, and post-treatment supportive care regimens. Conclusions: PT was associated with low rates of GI toxicity, the most common toxicity being transient RB. GR2+RB is strongly associated with patient use of aspirin, other anti-coagulation and radiation dose volume parameters.

Correlation Between Dose-Volume Parameters and Patient-reported Quality of Life (QOL) During Image-guided Intensity Modulated Radiation Therapy (IGRT) for Prostate Cancer

There is increasing recognition of the importance of patient-reported QOL as an outcome in cancer treatment. However, to date, limited research has examined the relationship between radiation dose-volume parameters and patient-reported acute genitourinary (GU) and gastrointestinal (GI) symptom development during IGRT for prostate cancer. We analyzed the relationship between dose-volume parameters of the rectum and bladder with prospectively collected patient-reported QOL. One hundred four men with prostate cancer who received radiation therapy to a median 75 Gy at our institution from 2010 to 2012 were included. Weekly during treatment, patients completed a validated questionnaire assessing severity of GI (diarrhea, urgency, bleeding, pain, cramping, mucus, and tenesmus) and GU (ease of flow, dysuria, nocturia, frequency, urgency, and incontinence) symptoms on a 4 or 5-point Likert scale. The association between dose-volume parameters and maximum GI and GU symptom scores was examined using Spearman's correlation. Median age was 64 years, and 72% of patients had clinical T1c or T2a disease. The percent volume of bladder receiving at least 75 Gy and 80 Gy was significantly associated with overall GU symptom score (V75: correlation coefficient .27, p = 0.005; V80: coefficient .30, p = 0.001). GI symptom score was significantly associated with V60 (coefficient .22, p = 0.03) and V65 (coefficient .26, p = 0.007) of the rectum. The proportions of bladder and rectum receiving higher doses of radiation were significantly associated with patient-reported acute GU and GI symptoms during IGRT for prostate cancer. A better understanding of the relationship between dose-volume parameters to surrounding organs and patient-reported QOL may allow physicians to improve radiation planning to optimize patient outcomes.

Predicting, preventing, treating and understanding radiation nephropathy.

Predicting, preventing, treating and understanding radiation nephropathy.

Association of Technetium(99m) MAG-3 renal scintigraphy with change in creatinine clearance following chemoradiation to the abdomen in patients with gastrointestinal malignancies.

Information on differential renal function following abdominal chemoradiation is limited. This study evaluated the association between renal function as measured by biochemical endpoints and scintigraphy and dose volume parameters in patients with gastrointestinal malignancies. Patients who received abdominal chemoradiation between 2002 and 2009 were identified for this study. Technetium(99m) MAG-3 scintigraphy and laboratory data were obtained prior to and after chemoradiation in 6 month intervals. Factors assessed included age, gender, hypertension, diabetes, and dose volume parameters. Renal function was assessed by biochemical endpoints and renal scintigraphy. Significant reductions in relative renal function of the primarily irradiated kidney and creatinine clearance were seen. Split renal function decreased from 49.75% pre-radiation to 47.74% and 41.28% at 6-12 months and >12 months post-radiation (P=0.0184). Creatinine clearance declined from 90.67ml/min pre-radiation to 82.23ml/min and 74.54ml/min at 6-12 months and >12 months post-radiation (P<0.0001). Univariate analysis of patients who had at least one post-radiation renogram showed the percent volumes of the primarily irradiated kidney receiving ≥ 25 Gy (V(25)) and 40 Gy (V(40)) were significantly associated with ≥5% decrease in relative renal function (P=0.0387 and P=0.0438 respectively). Decline in split renal function using Technetium(99m) MAG-3 scintigraphy correlates with decrease in creatinine clearance and radiation dose-volume parameters following abdominal chemoradiation. Change in split perfusion can be detected as early as 6 months post-radiation. Scintigraphy may provide early determination and quantification of subclinical renal injury prior to clinical evidence of nephropathy.

Dosimetric analysis for thyroid disorders after radiotherapy to the neck

e17025 Background: In our study, we aimed to evaluate the possible predictors of thyroid disorders after radiotherapy to the neck, focusing on radiation dose-volume factors. Methods: Thyroid function was measured in 65 patients treated with radiation ports including the thyroid, between 2005 and 2008. All of the radiation-induced thyroid dysfunction was determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4), thyroglobulin antibodies (ATG), thyroid peroxidase antibodies (TPA), thyroid binding globulin (TBG) levels. In 65 patients, radiation dose-volume parameters were calculated; e.g. total volume of the thyroid, mean radiation dose to the thyroid, and percentage of the thyroid volume which received radiation doses of no less than 10–50 Gy (V10-V50). The evaluated risk factors for thyroid dysfunction included these dose-volume parameters, sex, age, treatment modality and primary disease. Results: Most patients (72.3%) had a normal thyroid function, 17 (26.2%) hypothyroidism, 1 (1.5%) hyperthyroidism, and 12 (18.4%) thyroiditis with normal thyroid function. Four of 17 patients with hypothyroidism had overt hypothyroidism. In our analysis, DVHs (dose volume histograms) were calculated and no associations were found between the V10, V20, V40, and V50 percentages and thyroid disorders. V30 and minimum absorbed thyroid dose (Dmin) more than 25 Gy appeared to be correlated with high TSH values (p = 0.01 and p = 0.04, respectively). The patients with hypothyroidism were between 40–60 years. Female gender was associated with a higher incidence of TBG abnormality. Baseline TSH values were available in 16 patients, and hypothyroidism was diagnosed in 4 (25%) of them. No correlation was found between tumor-related variables and incidence of thyroid disorders. Conclusions: Thyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. Further prospective well designed studies on dose-effect relationship for radiotherapy-induced thyroid toxicity are therefore needed, and thyroid should be considered as an organ at risk in all patients treated for head and neck tumors. No significant financial relationships to disclose.

Dose–volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy

Purpose To identify clinical risk factors and dose–volume thresholds for treatment-related pneumonitis (TRP) in patients with non-small cell lung cancer (NSCLC). Methods and materials Data were retrospectively collected from patients with inoperable NSCLC treated with radiotherapy with or without chemotherapy. TRP was graded according to Common Terminology Criteria for Adverse Events, version 3.0, with time to grade ⩾3 TRP calculated from start of radiotherapy. Clinical factors and dose–volume parameters were analyzed for their association with risk of TRP. Results Data from 576 patients (75% with stage III NSCLC) were included in this study. The Kaplan–Meier estimate of the incidence of grade ⩾3 TRP at 12 months was 22%. An analysis of dose–volume parameters identified a threshold dose–volume histogram (DVH) curve defined by V 20 ⩽25%, V 25 ⩽20%, V 35 ⩽15%, and V 50 ⩽10%. Patients with lung DVHs satisfying these constraints had only 2% incidence of grade ⩾3 TRP. Smoking status was the only clinical factor that affected the risk of TRP independent of dosimetric factors. Conclusions The risk of TRP varied significantly, depending on radiation dose–volume parameters and patient smoking status. Further studies are needed to identify biological basis of smoking effect and methods to reduce the incidence of TRP.