Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

BACKGROUND: Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. MATERIAL AND METHODS: A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. RESULTS: On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. CONCLUSION: Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

Impact of Total Lymph Node Count on Staging and Survival After Neoadjuvant Chemoradiation Therapy for Rectal Cancer.

PURPOSE: Current guidelines recommend that a minimum of 12 lymph nodes (LNs) be dissected to accurately stage rectal cancer patients. Neoadjuvant chemoradiation therapy (CRT) decreases the number of LNs retrieved at surgery. The purpose of this study was to assess the impact of the number of LNs dissected on overall survival (OS) for localized rectal cancer patients treated with neoadjuvant CRT. METHODS: Treatment data were obtained on all patients treated for rectal cancer (2000-2013) in the National Oncology Data Alliance™, a proprietary database of merged tumor registries. Eligible patients were treated with neoadjuvant CRT followed by surgery and had complete data on number of positive LNs, number of LNs examined, and treatment dates (n = 4565). RESULTS: Hazard ratios for OS decreased sequentially with increasing number of LNs examined until a maximum benefit was achieved with examination of eight LNs. On multivariate analysis, age, sex, race, marital status, grade, ypT stage, ypN stage, type of surgery, margin status, presence of pathologically confirmed metastasis at surgery, and number of LNs examined were significant predictors of OS. CONCLUSIONS: Examination of eight or more LNs in rectal cancer patients treated with neoadjuvant CRT resulted in accurate staging and assignment into prognostic groups with an ensuing improvement in OS by stage. This study suggests that eight LNs is the threshold for an adequate lymph node dissection after neoadjuvant CRT.

Clinical outcomes of patients treated with a second course of stereotactic radiosurgery for locally or regionally recurrent brain metastases after prior stereotactic radiosurgery.

Patients with metastatic disease are living longer and may be confronted with locally or regionally recurrent brain metastases (BM) after prior stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT). This study analyzes outcomes in patients without prior whole brain radiotherapy (WBRT) who were treated with a second course of SRS/FSRT for locally or regionally recurrent BM. We identified 32 patients at our institution who were treated with a second course of SRS/FSRT after initial SRS/FSRT for newly diagnosed BM. We report clinical outcomes including local control, survival, and toxicities. Control rates and survival were calculated using Kaplan-Meier analysis and the multivariate proportional hazards model. The Kaplan-Meier estimate of local control at 6 months was 77 % for targets treated by a second course of SRS/FSRT with 11/71 (15 %) targets experiencing local failure. Multivariate analysis shows that upon re-treatment, local recurrences were more likely to fail than regional recurrences (OR 8.8, p = 0.02). Median survival for all patients from first SRS/FSRT was 14.6 months (5.3-72.2 months) and 7.9 months (0.7-61.1 months) from second SRS/FSRT. Thirty-eight percent of patients ultimately received WBRT as salvage therapy after the second SRS/FSRT. Seventy-one percent of patients died without active neurologic symptoms. The present study demonstrates that the majority of patients who progress after SRS/FSRT for newly diagnosed BM are candidates for salvage SRS/FSRT. By reserving WBRT for later salvage, we believe that a significant proportion of patients can avoid WBRT all together, thus putting fewer patients at risk for neurocognitive toxicity.

Repair of radiation damage and radiation injury to the spinal cord.

Radiation myelopathy is a rare but devastating injury to the spinal cord that usually results from an excessive radiation dose. In this chapter, we discuss the traditional and current understandings of the pathogenesis of this injury. A distinction is made between radiation damage, which occurs at the subcellular level, and radiation injury, which occurs at the tissue and organ level in response to radiation damage. Recent findings regarding the amelioration and treatment of both radiation damage and radiation injury are explored. These studies are promising developments but, as always, there are attendant caveats.

Radiotherapy and extent of surgical resection in retroperitoneal soft-tissue sarcoma: multi-institutional analysis of 261 patients.

BACKGROUND AND OBJECTIVE: To examine the impact of adjuvant radiotherapy (RT) and surgical technique on survival in retroperitoneal soft-tissue sarcoma. METHODS: A retrospective analysis was conducted using the National Oncology Database, a proprietary database of aggregated tumor registries owned by IMPAC(R) Medical Systems (Sunnyvale, CA). Patients who received definitive surgery with negative or microscopic-positive margins were included. Multivariate analysis was performed using the Cox proportional hazards model. Survival curves were estimated by the Kaplan-Meier method and were compared for statistical significance (P < 0.05) using the log-rank test. RESULTS: Two hundred sixty-one patients met inclusion criteria. The median follow-up was 59 months (range 0.2-186 months). The 5-year cause-specific survival (CSS) and local failure-free survival (LFFS) were 73% and 66%, respectively. Grade, margin status, and histology were independent predictors for CSS (P < 0.05). Adjuvant RT was associated with a significant improvement in LFFS over surgery alone (hazard ratio = 0.42, 95% confidence interval 0.21-0.86, P < 0.05). Patients receiving simple excision and RT had a 5-year LFFS of 88%, significantly higher than wide resection with or without RT (log-rank, P < 0.05). CONCLUSION: Adjuvant RT is associated with a lower risk of local relapse compared to surgery alone. The impact of surgical technique on adjuvant RT efficacy warrants further study.

Impact of the number of resected and involved lymph nodes on esophageal cancer survival.

BACKGROUND: Using a large data set, we investigated the impact of the number of resected and involved lymph nodes on overall survival for patients with esophageal cancer. METHODS: From the National Oncology Database, esophageal cancer cases with data available on the total number of resected and involved nodes as well as other variables were evaluated as it relates to overall survival by multivariate analysis using Cox proportional hazards method. Patients with 0, exactly 1 or 1-3 positive nodes were separately studied to determine the association between the number of lymph nodes resected and overall survival. RESULTS: From 1969 to 2002, 3,144 (17%) of 18,390 esophageal cancer cases with complete data were identified. Increasing number of involved nodes predicted poorer outcome (P < 10(-6)). Results from studying patients with 0, exactly 1 or 1-3 positive nodes showed that survival improved with increasing number of nodes analyzed up to 12. Three-tier nodal grouping with increasing risk of death were identified, 0, 1-3, and >or=4 positive nodes (P < 10(-5)). CONCLUSIONS: The pathological assessment of minimal 12 lymph nodes provides sufficient prognostic information. Three-tier nodal grouping is suggested for the next version of AJCC staging system for esophageal cancer.

Statistical validation of a new helical tomotherapy patient transfer station.

The purpose of this work is to evaluate statistically the accuracy of a patient transfer station (PTS, TomoTherapy Inc., Madison, WI) that automatically converts one planning-station-generated treatment plan to another one with a different beam model. In our department we have installed 2 HI*ART tomotherapy systems, and patients often need to be transferred from one tomotherapy unit to the other. Thirty patients who underwent patient transfer between the two systems were evaluated. For each patient, dose differences between his/her original plan and PTS-transferred plan were evaluated by comparing doses at 10 randomly selected positions in his/her CT images. The Pearson indexes were calculated to analyze the relationship of the deviations to other parameters, which include absolute dose levels, sites (targets or normal tissues), dose accuracy of original plans and that of transferred plans. The dose accuracy of a treatment plan was determined by comparing delivered doses at the center of a 30 cm x 30 cm x 12 cm solid water phantom to planned doses at the same position. The calculated dose difference between original and transferred plans was, on average, 0.8% +/- 0.5%; the maximum deviation in absolute values was 1.9% in target volumes and 2.5% in normal organs. The errors generated during PTS-based transferring process were random and did not show correlation with other parameters. The PTS took less than 10 minutes to generate a backup plan that is much less than 2 hours that is approximately needed to create a duplicate plan manually. The results show that a PTS-transferred plan is an acceptable match to the original plan. With a physician's approval, a transferred plan is acceptable for treatment without the necessity of being revalidated in phantom. Thus far, all of our PTS plans have been approved by the treating physician without further optimization.

The radiation dose-response of the human spinal cord.

PURPOSE: To characterize the radiation dose-response of the human spinal cord. METHODS AND MATERIALS: Because no single institution has sufficient data to establish a dose-response function for the human spinal cord, published reports were combined. Requisite data were dose and fractionation, number of patients at risk, number of myelopathy cases, and survival experience of the population. Eight data points for cervical myelopathy were obtained from five reports. Using maximum likelihood estimation correcting for the survival experience of the population, estimates were obtained for the median tolerance dose, slope parameter, and alpha/beta ratio in a logistic dose-response function. An adequate fit to thoracic data was not possible. Hyperbaric oxygen treatments involving the cervical cord were also analyzed. RESULTS: The estimate of the median tolerance dose (cervical cord) was 69.4 Gy (95% confidence interval, 66.4-72.6). The alpha/beta = 0.87 Gy. At 45 Gy, the (extrapolated) probability of myelopathy is 0.03%; and at 50 Gy, 0.2%. The dose for a 5% myelopathy rate is 59.3 Gy. Graphical analysis indicates that the sensitivity of the thoracic cord is less than that of the cervical cord. There appears to be a sensitizing effect from hyperbaric oxygen treatment. CONCLUSIONS: The estimate of alpha/beta is smaller than usually quoted, but values this small were found in some studies. Using alpha/beta = 0.87 Gy, one would expect a considerable advantage by decreasing the dose/fraction to less than 2 Gy. These results were obtained from only single fractions/day and should not be applied uncritically to hyperfractionation.

Malignant phyllodes tumor of the breast: local control rates with surgery alone.

PURPOSE: Patients with malignant phyllodes tumors of the breast (MPTB) are routinely treated with surgery alone. We performed a retrospective study to determine local control rates based on tumor size and type of surgery performed. METHODS AND MATERIALS: We reviewed records of 478 patients with MPTB treated between March 1964, and August 2005. The data were extracted from the IMPAC National Oncology Database consisting of merged tumor registries from 130 hospitals. RESULTS: Median follow-up was 64 months (range, 0-410 months). Actuarial 5-year local control rates were 79.4% for 169 lumpectomy patients and 91.2% for 207 mastectomy patients treated by surgery alone. Five-year local control rates for lumpectomy based on tumor size were 91% for 0-2 cm tumors, 85% for 2-5 cm tumors, and 59% for 5-10 cm tumors. For mastectomy patients, 5-year local control rates were 100% for 0-2 cm tumors, 95% for 2-5 cm tumors, 88% for 5-10 cm tumors, and 85% for 10-20 cm tumors. Multivariate analysis of overall survival found several factors to be significant including advancing age with each decade after 50 years of age, appearance of distant metastases, larger primary tumor size, and local control vs. local recurrence (Hazard Ratio [HR] 2.5, p < 0.05). CONCLUSIONS: Malignant phyllodes tumors of the breast local recurrence rates are 15% or greater for patients with tumors >2 cm treated by lumpectomy alone and tumors >10 cm treated by mastectomy alone. Adjuvant radiation therapy should be evaluated for these patients. This may be especially important because our study showed that local recurrence impacted on survival rates.

Impact of drug therapy, radiation dose, and dose rate on renal toxicity following bone marrow transplantation.

PURPOSE: To demonstrate a radiation dose response and to determine the dosimetric and chemotherapeutic factors that influence the incidence of late renal toxicity following total body irradiation (TBI). METHODS AND MATERIALS: A comprehensive retrospective review was performed of articles reporting late renal toxicity, along with renal dose, fractionation, dose rate, chemotherapy regimens, and potential nephrotoxic agents. In the final analysis, 12 articles (n = 1,108 patients), consisting of 24 distinct TBI/chemotherapy conditioning regimens were included. Regimens were divided into three subgroups: adults (age > or =18 years), children (age <18 years), and mixed population (both adults and children). Multivariate logistic regression was performed to identify dosimetric and chemotherapeutic factors significantly associated with late renal complications. RESULTS: Individual analysis was performed on each population subgroup. For the purely adult population, the only significant variable was total dose. For the mixed population, the significant variables included total dose, dose rate, and the use of fludarabine. For the pediatric population, only the use of cyclosporin or teniposide was significant; no dose response was noted. A logistic model was generated with the exclusion of the pediatric population because of its lack of dose response. This model yielded the following significant variables: total dose, dose rate, and number of fractions. CONCLUSION: A dose response for renal damage after TBI was identified. Fractionation and low dose rates are factors to consider when delivering TBI to patients undergoing bone marrow transplantation. Drug therapy also has a major impact on kidney function and can modify the dose-response function.

Acute toxicity in definitive versus postprostatectomy image-guided radiotherapy for prostate cancer.

PURPOSE: To assess the incidence of acute gastrointestinal (GI) and genitourinary (GU) injury and the dose-volume response in patients with clinically localized prostate cancer treated with image-guided radiotherapy using helical tomotherapy. METHODS AND MATERIALS: Between November 2004 and March 2007, 146 consecutive patients with localized prostate cancer were treated with helical tomotherapy at the City of Hope Medical Center. Of the 146 patients, 70 had undergone prostatectomy. Acute GI and GU toxicities were evaluated using the Radiation Therapy Oncology Group/European Organization for Research and Cancer of Medical scoring system. Events were scored for patients developing Grade 2 or greater morbidity within 90 days after the end of radiotherapy (RT). The dosimetric parameters included the minimal dose received by the highest 10%, 20%, 50%, 80%, and 90% of the target volume, the mean rectal dose, minimal rectal dose, maximal rectal dose, and the volume receiving > or =45, > or =65, and > or =70 Gy. These variables, plus the status of radical prostatectomy, hormonal therapy, RT techniques, and medical conditions, were included in a multivariate logistic regression analysis. A goodness-of-fit evaluation was done using the Hosmer-Lemeshow statistic. RESULTS: A dose-response function for acute GI toxicity was elicited. The acute GI Grade 2 or greater toxicity was lower in the definitive RT group than in the postoperative RT group (25% vs. 41%, p <0.05). Acute GU Grade 2 or greater toxicity was comparable between the two groups. No grade 3 or greater complications were observed. No dosimetric variable was significant for GU toxicity. For acute GI toxicity, the significant dosimetric parameters were the minimal dose received by 10%, 20%, and 50% of the target volume and the mean rectal dose; the most predictive parameter was the minimal dose received by 10% of the target volume. The dose-modifying factor was 1.2 for radical prostatectomy. CONCLUSION: The results of our study have shown that acute rectal symptoms are dose-volume related. Postprostatectomy RT resulted in a greater incidence of acute GI toxicity than did definitive RT. For postoperative RT, it would be prudent to use different dose-volume limits.

Actual dose variation of parotid glands and spinal cord for nasopharyngeal cancer patients during radiotherapy.

PURPOSE: For intensity-modulated radiotherapy of nasopharyngeal cancer, accurate dose delivery is crucial to the success of treatment. This study aimed to evaluate the significance of daily image-guided patient setup corrections and to quantify the parotid gland volume and dose variations for nasopharyngeal cancer patients using helical tomotherapy megavoltage computed tomography (CT). METHODS AND MATERIALS: Five nasopharyngeal cancer patients who underwent helical tomotherapy were selected retrospectively. Each patient had received 70 Gy in 35 fractions. Daily megavoltage CT scans were registered with the planning CT images to correct the patient setup errors. Contours of the spinal cord and parotid glands were drawn on the megavoltage CT images at fixed treatment intervals. The actual doses delivered to the critical structures were calculated using the helical tomotherapy Planned Adaptive application. RESULTS: The maximal dose to the spinal cord showed a significant increase and greater variation without daily setup corrections. The significant decrease in the parotid gland volume led to a greater median dose in the later phase of treatment. The average parotid gland volume had decreased from 20.5 to 13.2 cm3 by the end of treatment. On average, the median dose to the parotid glands was 83 cGy and 145 cGy for the first and the last treatment fractions, respectively. CONCLUSIONS: Daily image-guided setup corrections can eliminate significant dose variations to critical structures. Constant monitoring of patient anatomic changes and selective replanning should be used during radiotherapy to avoid critical structure complications.

Stage I and II Endometrial Adenocarcinoma: Analysis of 2009 FIGO Staging Revision and Impact on Survival by Adjuvant Therapy.

BACKGROUND: In 2009, the International Federation of Gynecology and Obstetrics revised the staging classification for endometrial cancer. Mucosal cervical involvement was eliminated from the criteria and only those with stromal cervical involvement were considered stage II. We examined the implications of the staging changes and the survival impact of adjuvant therapy in stage I to II endometrial adenocarcinoma. MATERIALS AND METHODS: Data were obtained from the National Oncology Data Alliance. Stage I to II endometrial adenocarcinoma patients diagnosed between 1988 and 2008 were identified and grouped according to the 1988 International Federation of Gynecology and Obstetrics staging. Multivariate analysis (MVA) was performed using proportional hazards model; comparison of Kaplan-Meier survival curves was based on the log-rank statistic. RESULTS: A total of 14,158 patients with stage I to II endometrial adenocarcinoma were identified with a median follow-up of 41 months. Adjuvant external-beam radiation therapy (EBRT) and adjuvant vaginal brachytherapy (VB) were positive predictors for overall survival (OS) only in IC, IIA, and IIB. On MVA, stages IA and IB OS did not differ (P=0.17), IIA had worse OS compared with IC (P<0.05), and IIA OS did not differ from IIB (P=0.57). Neither IA nor IB benefited from adjuvant radiotherapy on MVA. However, both IC and IIA had OS improvements with VB±EBRT (P<0.05) with the greatest impact from the VB. CONCLUSIONS: Mucosal cervical involvement represents a risk factor and should be considered when determining adjuvant therapy. Adjuvant therapy provided no survival benefit in 1988 stage IA or IB; however, adjuvant radiotherapy is recommended in the management of IC, IIA, and IIB.

Image-guided total marrow and total lymphatic irradiation using helical tomotherapy.

PURPOSE: To develop a treatment technique to spare normal tissue and allow dose escalation in total body irradiation (TBI). We have developed intensity-modulated radiotherapy techniques for the total marrow irradiation (TMI), total lymphatic irradiation, or total bone marrow plus lymphatic irradiation using helical tomotherapy. METHODS AND MATERIALS: For TBI, we typically use 12 Gy in 10 fractions delivered at an extended source-to-surface distance (SSD). Using helical tomotherapy, it is possible to deliver equally effective doses to the bone marrow and lymphatics while sparing normal organs to a significant degree. In the TMI patients, whole body skeletal bone, including the ribs and sternum, comprise the treatment target. In the total lymphatic irradiation, the target is expanded to include the spleen and major lymph node areas. Sanctuary sites for disease (brain and testes) are included when clinically indicated. Spared organs include the lungs, esophagus, parotid glands, eyes, oral cavity, liver, kidneys, stomach, small and large intestine, bladder, and ovaries. RESULTS: With TBI, all normal organs received the TBI dose; with TMI, total lymphatic irradiation, and total bone marrow plus lymphatic irradiation, the visceral organs are spared. For the first 6 patients treated with TMI, the median dose to organs at risk averaged 51% lower than would be achieved with TBI. By putting greater weight on the avoidance of specific organs, greater sparing was possible. CONCLUSION: Sparing of normal tissues and dose escalation is possible using helical tomotherapy. Late effects such as radiation pneumonitis, veno-occlusive disease, cataracts, neurocognitive effects, and the development of second tumors should be diminished in severity and frequency according to the dose reduction realized for the organs at risk.

Setup variations in radiotherapy of esophageal cancer: evaluation by daily megavoltage computed tomographic localization.

PURPOSE: To use pretreatment megavoltage computed tomography (MVCT) scans to evaluate setup variations in anterior-posterior (AP), lateral, and superior-inferior (SI) directions and rotational variations, including pitch, roll, and yaw, for esophageal cancer patients treated with helical tomotherapy. METHODS AND MATERIALS: Ten patients with locally advanced esophageal cancer treated by combined chemoradiation using helical tomotherapy were selected. After patients were positioned using their skin tattoos/marks, MVCT scans were performed before every treatment and automatically registered to planning kilovoltage CT scans according to bony landmarks. Image registration data were used to adjust patient setups before treatment. A total of 250 MVCT scans were analyzed. Correlations between setup variations and body habitus, including height, weight, relative weight change, body surface area, and patient age, were evaluated. RESULTS: The standard deviations for systematic setup corrections in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 1.5, 3.7, and 4.8 mm and 0.5 degrees, 1.2 degrees, and 0.8 degrees, respectively. The appropriate averages of random setup variations in AP, lateral, and SI directions and pitch, roll, and yaw rotations were 2.9, 5.2, and 4.4 mm, and 1.0 degrees, 1.2 degrees, and 1.1 degrees, respectively. Setup variations were stable throughout the entire course of radiotherapy in all three translational and three rotational displacements, with little change in magnitude. No significant correlations were found between setup variations and body habitus variables. CONCLUSIONS: Daily MVCT scans before each treatment can effectively detect setup errors and thereby reduce planning target volume (PTV) margins. This will reduce radiation dose to critical organs and may translate into lower treatment-related toxicities.

Dosimetric study and in-vivo dose verification for conformal avoidance treatment of anal adenocarcinoma using helical tomotherapy.

This study evaluated the efficacy of using helical tomotherapy for conformal avoidance treatment of anal adenocarcinoma. We retrospectively generated step-and-shoot intensity-modulated radiotherapy (sIMRT) plans and helical tomotherapy plans for two anal cancer patients, one male and one female, who were treated by the sIMRT technique. Dose parameters for the planning target volume (PTV) and the organs-at-risk (OARs) were compared between the sIMRT and the helical tomotherapy plans. The helical tomotherapy plans showed better dose homogeneity in the PTV, better dose conformity around the PTV, and, therefore, better sparing of nearby OARs compared with the sIMRT plans. In-vivo skin dose measurements were performed during conformal avoidance helical tomotherapy treatment of an anal cancer patient to verify adequate delivery of skin dose and sparing of OARs.

Helical tomotherapy for radiotherapy in esophageal cancer: a preferred plan with better conformal target coverage and more homogeneous dose distribution.

We compare different radiotherapy techniques-helical tomotherapy (tomotherapy), step-and-shoot IMRT (IMRT), and 3-dimensional conformal radiotherapy (3DCRT)-for patients with mid-distal esophageal carcinoma on the basis of dosimetric analysis. Six patients with locally advanced mid-distal esophageal carcinoma were treated with neoadjuvant chemoradiation followed by surgery. Radiotherapy included 50 Gy to gross planning target volume (PTV) and 45 Gy to elective PTV in 25 fractions. Tomotherapy, IMRT, and 3DCRT plans were generated. Dose-volume histograms (DVHs), homogeneity index (HI), volumes of lung receiving more than 10, 15, or 20 Gy (V(10), V(15), V(20)), and volumes of heart receiving more than 30 or 45 Gy (V(30), V(45)) were determined. Statistical analysis was performed by paired t-tests. By isodose distributions and DVHs, tomotherapy plans showed sharper dose gradients, more conformal coverage, and better HI for both gross and elective PTVs compared with IMRT or 3DCRT plans. Mean V(20) of lung was significantly reduced in tomotherapy plans. However, tomotherapy and IMRT plans resulted in larger V(10) of lung compared to 3DCRT plans. The heart was significantly spared in tomotherapy and IMRT plans compared to 3DCRT plans in terms of V(30) and V(45). We conclude that tomotherapy plans are superior in terms of target conformity, dose homogeneity, and V(20) of lung.

Estimation of radiation-induced secondary cancer risks for early-stage non-small cell lung cancer patients after stereotactic body radiation therapy.

PURPOSE: In this study, we evaluated radiation-induced secondary lung cancer risks for the lung and the breast from stereotactic body radiation therapy treatment of early-stage non-small cell lung cancer with different radiation therapy treatment modalities. METHODS AND MATERIALS: Ten patients (5 men and 5 women) with early-stage non-small cell lung cancer who received definitive stereotactic body radiation therapy treatments were retrospectively selected. For each patient, two 3-dimensional conformal radiation therapy (3D-CRT) plans using 6- and 10-MV photons, respectively; a helical tomotherapy (HT) plan; and 2 volumetric modulated arc therapy (VMAT) plans using 1 and 2 arcs, respectively, were generated. The excess absolute risk (EAR) for secondary cancer occurrence was calculated using 3 organ equivalent dose models: the linear-exponential model, the plateau model, and the linear model for prescription dose range of 30 to 70 Gy. RESULTS: The 3D-CRT plans showed significantly lower monitor units compared with the rotational intensity modulate radiation therapy plans. Based on each of the 3 organ equivalent dose models, HT and VMAT plans showed comparable average EARs to both the lung and the breast compared with the 3D-CRT plans in the prescription dose range of 30 to 70 Gy. At a prescription dose of 50 Gy and using the linear-exponential model, the average lung EAR estimation ranged from 15.7 ± 5.3 to 16.0 ± 6.5 per 10,000 patients per year with the 5 delivery techniques, and the average EAR estimation for the breast ranged from 18.0 ± 14.0 to 21.0 ± 15.0 per 10,000 patients per year. The secondary cancer risk increased approximately linearly with mean organ dose. The 3D-CRT plans showed significantly higher secondary cancer risk for the ipsilateral lung and lower risk for the contralateral lung compared with the HT and VMAT plans. CONCLUSIONS: Rotational intensity modulate radiation therapy techniques including helical tomotherapy and VMAT do not increase secondary cancer risks for the lung or the breast compared with 3D-CRT techniques, despite higher monitor units used.

The use of dose-escalated radiation for locally advanced non-small cell lung cancer in the U.S., 2004-2013.

PURPOSE/OBJECTIVES: The clinical effects of radiation dose-intensification in locally advanced non-small cell lung (NSCLCa) and other cancers are challenging to predict and are ideally studied in randomized trials. The purpose of this study was to assess the use of dose-escalated radiation for locally advanced NSCLCa in the U.S., 2004-2013, a period in which there were no published level 1 studies on dose-escalation. MATERIALS/METHODS: We performed analyses on two cancer registry databases with complementary strengths and weaknesses: the National Oncology Data Alliance (NODA) 2004-2013 and the National Cancer Database (NCDB) 2004-2012. We classified locally advanced patients according to the use of dose-escalation (>70 Gy). We used adjusted logistic regression to assess the association of year of treatment with dose-escalated radiation use in two periods representing time before and after the closure of a cooperative group trial (RTOG 0617) on dose-escalation: 2004-2010 and 2010-2013. To determine the year in which a significant change in dose could have been detected had dose been prospectively monitored within the NODA network, we compared the average annual radiation dose per year with the forecasted dose (average of the prior 3 years) adjusted for patient age and comorbidities. RESULTS: Within both the NODA and NCDB, use of dose-escalation increased from 2004 to 2010 (p < 0.0001) and decreased from 2010 to 2013 (p = 0.0018), even after controlling for potential confounders. Had the NODA network been monitoring radiation dose in this cohort, significant changes in average annual dose would have been detected at the end of 2008 and 2012. CONCLUSIONS: Patterns of radiation dosing in locally advanced NSCLCa changed in the U.S. in the absence of level 1 evidence. Monitoring radiation dose is feasible using an existing national cancer registry data collection infrastructure.