Median Tumor Dose Research Articles

Impact of setup and geometric uncertainties on the robustness of free-breathing photon radiotherapy of small lung tumors

Purpose:Respiratory motion and patient setup error both contribute to the dosimetric uncertainty in radiotherapy of lung tumors. Managing these uncertainties for free-breathing treatments is usually done by margin-based approaches or robust optimization. However, breathing motion can be irregular and concerns have been raised for the robustness of the treatment plans. We have previously reported the dosimetric effects of the respiratory motion, without setup uncertainties, in lung tumor photon radiotherapy using free-breathing images. In this study, we include setup uncertainty. Methods:Tumor positions from cine-CT images acquired in free-breathing were combined with per-fraction patient shifts to simulate treatment scenarios. A total of 14 patients with 300 tumor positions were used to evaluate treatment plans based on 4DCT. Four planning methods aiming at delivering 54 Gy as median tumor dose in three fractions were compared. The planning methods were denoted robust 4D (RB4), isodose to the PTV with a central higher dose (ISD), the ISD method normalized to the intended median tumor dose (IRN) and homogeneous fluence to the PTV (FLU). Results:For all planning methods 95% of the intended dose was achieved with at least 90% probability with RB4 and FLU having equal CTV D50% values at this probability. FLU gave the most consistent results in terms of CTV D50% spread and dose homogeneity. Conclusions:Despite the simulated patient shifts and tumor motions being larger than observed in the 4DCTs the dosimetric impact was suggested to be small. RB4 or FLU are recommended for the planning of free-breathing treatments.

Machine Learning Based Prediction of Distant Metastasis in Rectal Cancer Patients with Complete Response following Neoadjuvant Chemoradiotherapy

Distant metastasis (DM) is the leading cause of disease recurrence in rectal cancer patients with clinical or pathological complete response (CR) following neoadjuvant chemoradiotherapy (nCRT). Identifying these patients may help to tailor the treatment approach. The aim of this study was to predict the rectal cancer patients with high risk of DM following CR with nCRT, using machine learning (ML), based on patient, disease and treatment related clinical factors. Data of the rectal cancer patients treated with nCRT at three academic centers between 2010-2022 were collected. Patients with secondary malignancies were excluded. 157 patients with CR were included in the analysis. Median age was 63 (31-85). Female/male ratio was 59/98. Tumor location was proximal-, mid- and distal-rectum in 9, 65 and 83 patients, respectively. cT stage was T2, T3 and T4 in 14, 120 and 23 patients, respectively. 122 patients had cN (+). Median tumor and regional lymph nodes doses were 50.4 (45-56) Gy and 45 (45-50.4) Gy, respectively, in 25-28 fractions, concurrently with capecitabine. 63 patients had clinical CR and were followed up without surgery, and 94 had pathological CR. Median RT-surgery interval was 11 (3.4-59) weeks. 41 patients were managed with total neoadjuvant treatment and 52 received adjuvant systemic treatment. Median follow up time was 37 (3-143) months. DM was detected in 18 patients at median 14 (2-87) months and local tumor recurrence/progression was seen in 9. A ML model was used to predict DM based on patient, disease and treatment related 37 clinical factors. Statistical analysis was conducted using Python (v.3.7). P<0.05 was accepted as statistically significant. Multiple Linear Regression was used to analyze the relationship between DM and independent continuous variables. Chi-square test was used to analyze the difference between the observed frequency distribution of a categorical variable and the expected frequency distribution. Confusion matrix algorithm was used to evaluate the performance of the model. Logistic regression algorithm (LRA) was selected as the best performing algorithm for the ML model that used 37 variables from 157 patients. The model was trained using 75% of the data and the remaining 25% was used for testing. CEA, ratio of post- to pre-RT tumor SUVmax, tumor dose, RT-surgery interval, pre-RT weight loss, smoking history, cN status, and gender were significant parameters to predict DM, based on the LRA of the ML model. Accuracy score of the model was 92% and AUC of the ROC was 74%. Precision (positive predictive value) and recall (sensitivity) of the model were 67% and 50%, respectively. Machine learning has a high rate of correctly classifying patients and good performance in predicting those with DM. Further studies with larger patient numbers are needed.

Long-Term Outcome of Unilateral Acoustic Neuromas With or Without Hearing Loss: Over 10 Years and Beyond After Gamma Knife Radiosurgery.

Since the long-term outcomes of 162 patients who underwent gamma knife radiosurgery (GKS) as an initial or adjuvant treatment for acoustic neuromas (ANs) with unilateral hearing loss were first reported in 1998, there has been no report of a comprehensive analysis of what has changed in GKS practice. We performed a retrospective study of the long-term outcomes of 106 patients with unilateral sporadic ANs who underwent GKS as an initial treatment. The mean patient age was 50 years, and the mean initial tumor volume was 3.68 cm3 (range, 0.10-23.30 cm3). The median marginal tumor dose was 12.5 Gy (range, 8.0-15.0 Gy) and the median follow-up duration was 153 months (range, 120-216 months). The tumor volume increased in 11 patients (10.4%), remained stationary in 27 (25.5%), and decreased in 68 patients (64.2%). The actuarial 3, 5, 10, and 15-year tumor control rates were 95.3 ± 2.1%, 94.3 ± 2.2%, 87.7 ± 3.2%, and 86.6 ± 3.3%, respectively. The 10-year actuarial tumor control rate was significantly lower in the patients with tumor volumes of ≥ 8 cm3 (P = 0.010). The rate of maintaining the same Gardner-Robertson scale grade was 28.6%, and that of serviceable hearing was 46.4%. The rates of newly developed facial and trigeminal neuropathy were 2.8% and 4.7%, respectively. The patients who received marginal doses of less than 12 Gy revealed higher tumor control failure rates (P = 0.129) and newly occurred facial or trigeminal neuropathy rates (P = 0.040 and 0.313, respectively). GKS as an initial treatment for ANs could be helpful in terms of tumor control, the preservation of serviceable hearing, and the prevention of cranial neuropathy. It is recommended to perform GKS as soon as possible not only for tumor control in unilateral ANs with hearing loss but also for hearing preservation in those without hearing loss.

Definitive High-Dose Radiotherapy for Primary Vulvar Cancer: The DRIVE Multicenter Cohort Study

<h3>Purpose/Objective(s)</h3> There is limited published data on definitive chemoradiation therapy for vulvar cancer. A retrospective multi-institutional cohort study was conducted to determine the efficacy, patterns of failure and long-term toxicity of high-dose radiation therapy (RT) for the primary treatment of vulvar carcinoma. <h3>Materials/Methods</h3> DRIVE (definitive radiation therapy for primary vulvar cancer) is a multicenter cohort study evaluating outcome for definitive high-dose conformal RT (dRT) for first line treatment of vulvar cancer. Treatment compliance, toxicity and patterns of failure were investigated. Actuarial locoregional control (LRC) and survival (OS) were estimated using Kaplan-Meier method and compared using log rank test. Herein, we present our preliminary results. <h3>Results</h3> In total, 48 patients [median (interquartile range) age, 57 (46-67) years] who received dRT between 2010 and 2020 were analyzed. Median follow-up was 28 (2–113) months. Cohort included 15 (31%) with stage I-II, and 33 (69%) patients with stage III-IV disease. Inguinal nodes alone were involved in 13 patients (27%); 19 (40%) had inguinal and/or pelvic node metastases. Elective surgical staging of groins was performed in 16 (33%) patients, of whom 7 had involved nodes. Intensity-modulated RT (IMRT) was used in 45 (94%) patients, and 3 (6%) received 3D-conformal RT. Median tumor dose was 64Gy (52-74.8Gy). Concurrent platinum-based chemotherapy was administered in 40 (83%) patients (1-8 cycles). Clinical complete response (CR) was achieved in 81.3% (39/48) patients at the primary site, and 84% (27/32) at involved nodes. Eight (16.7%) patients had persistent/recurrent disease following treatment, all within treatment volume; 5 (10%) patients developed distant metastasis. Actuarial 2 and 5-year LRC was 77.7% and 73%, respectively. Two and 5-year overall survival were 71% and 55%, respectively. On univariate analysis, determinants of inferior LRC were stage III/IV (p=0.04), non-IMRT technique (p=0.05) and <2 cycles of chemo (p=0.03). Treatment compliance included 90% (43 patients) completing planned treatment, 11/48 (23%) hospitalization, 6/48 (12.5%) blood transfusion, 12/48 (25%) with >5 days interruptions and median weight loss of 2.6Kg during RT. Of 40 evaluable patients, 25 (63%) developed significant vaginal stenosis. Vulvar necrosis was observed in 5 (10%) patients, all received ≥64Gy [2 treated with hyperbaric oxygen, 1 had musculocutaneous flap-reconstruction]. No acute/chronic grade 3 GI or GU toxicity, or any grade 5 toxicities were seen. <h3>Conclusion</h3> Definitive high-dose RT for vulvar cancer achieves high rates of local control, good compliance with acceptable dose dependent long-term toxicity. Use of IMRT does not result in increased geographic miss and was associated with improved locoregional control over existing prospective data from GOG 205 study.

P03.09.A Proton beam therapy for adults medullobastoma

Abstract Background Although Medulloblastoma (MB) is the most common primary malignant intracranial tumor in childhood, in adults it is extremely rare. Therefore, available data is scarce and experience with radiation and proton beam therapy (PBT) is very limited. The treatment typically includes tumour resection, irradiation of the craniospinal axis (CSI) followed by a boost, +/- concomitant chemotherapy, and maintenance therapy. Herein, we present our preliminary analysis of outcome and toxicity after PBT. Material and Methods Patients ≥ 18 years with primary MB treated with PBT between January 2017 and March 2020 enrolled in the prospective registry study (DRKS00004384) were evaluated in this analysis. Within the registry, adverse events were documented according to CTCAE v4.0 before, during, and after PT. The overall survival (OS), local control (LC) and higher-grade toxicity (≥ grade 3) were analyzed. Results A total of 19 patients (13 males, 6 females) with a median age of 23 years (range, 18.5- 39 years) were included in this study. Histopathology type were classic, desmoplastic /extensive nodularity or anaplastic MB in 52.6%, 26.3% and 21.1 % of patients, respectively. Complete tumor resection was performed in 57.8 % of patients. 68.4 % of patients had local disease without any metastases. Median total CSI dose was 35.2 Gy(RBE) (range, 23.4-40 Gy) with a median single dose of 1.6 Gy(RBE) (range, 1-1.8 Gy). All patients received either boost to the posterior fossa (57.9%) or to the tumor bed only (42.1%). The median total tumor dose was 18.8 Gy(RBE) (range, 54-68 Gy). Concomitant chemotherapy was given to 63.1% of patients. The median follow-up time after first diagnosis was 28.2 months (range, 8-56 months). No higher-grade acute or late adverse event was documented so far. One patient developed local disease progression. Another patient deceased due to an acute pulmonary embolism during maintenance chemotherapy without evidence of disease. The 3-year LC and OS rate were 89 % and 94 %, respectively. Conclusion Early results display good feasibility and high tumor control of PT in adult patient with MB. Results will need to be confirmed in larger cohort with longer follow-up time.&amp;lt;Bookmark(28)&amp;gt;

Realized tumor to normal ratios in hepatocellular carcinoma patients undergoing transarterial radioembolization: a retrospective evaluation.

To determine the realized tumor to normal ratios (TNRs) in patients undergoing radiation segmentectomies (RS); determine the relationship between TNRs and particle load in transarterial radioembolization (TARE). In total, 148 patients who underwent 184 TARE procedures for hepatocellular carcinoma were evaluated. Post treatment SPECT CT bremsstrahlung imaging was analyzed utilizing Simplicit90y™ to determine realized TNR. A model which normalized activity across all RS treatments to a level that would achieve 400Gy by unicompartmental dosing was created to determine the affect realized TNR would have on tumor absorbed dose. The mean TNR in the setting of RS was 2.88 ± 1.60 and was higher for glass as compared to resin microspheres (3.07 ± 1.68 vs 2.24 ± 1.21, p = 0.01). The TNR was significantly greater in the RS as compared to the lobar deliveries (2.88 ± 1.60 vs 2.16 ± 1.12, p < 0.01). When normalizing the activity of RS treatments to the level required to achieve 400Gy by unicompartmental calculations, there was found to be significant differences in the predicted tumor absorbed dose when separated by the median tumor dose (601.2 ± 133.3 vs 1146.9 ± 297.5, p < 0.01) or median realized TNR (1119.2 ± 341Gy vs 635.7 ± 160.2Gy, p < 0.01). Particle load was found to be associated with TNR on univariate (p < 0.01) and multivariate (p < 0.01) analysis. Significant TNRs are seen in RS and perhaps argue for the use of multi-compartmental dosimetry techniques in this setting and particle load may affect TNR. •Tumor to normal ratios were significantly higher in radiation segmentectomies than lobar deliveries. •Tumor to normal ratios were significantly higher when utilizing glass, as compared to resin microspheres. •When creating a model that prescribed the activity required to reach 400Gy by MIRD, realized tumor dose varied significantly in radiation segmentectomies.

Gamma Knife Radiosurgery for Large Vestibular Schwannoma More Than 10 cm 3 : A Single-Center Indian Study.

Introduction Gamma Knife radiosurgery (GKRS) is an effective treatment for benign vestibular schwannomas (VSs). The established cutoffs have recently been challenged, as recent literature expanded the horizon of GKRS to larger tumors. Even though microsurgery remains the primary option for large VS, GKRS can provide reasonable tumor control and is more likely to avoid cranial neuropathies associated with open surgery. Methods We analyzed patients with VS with volume exceeding 10 cm 3 who underwent GKRS at our center from January 2006 to December 2016. Clinicoradiological and radiosurgical data were collected from medical records for statistical analysis. Follow-up was performed every 6 months with a clinical assessment along with magnetic resonance imaging (MRI) of the brain and audiometric evaluation in patients with serviceable hearing. Results The study included 34 patients (18 males and 16 females) with an average age of 45.5 years. The mean tumor volume was 10.9 cm 3 (standard deviation [SD], ± 0.83), with a median tumor dose of 12 Gy (interquartile range, 11.5-12) and a mean follow-up of 34.7 months (SD, ± 23.8). Tumor response was graded as regression in 50%, stable in 44.1%, and increase or GKRS failure in 2 cases (5.8%). Treatment failure was noted in five cases (14.7%), requiring microsurgical excision and a ventriculoperitoneal shunt post-GKRS. The tumor control rate for the cohort is 85.3%, with a facial preservation rate of 96% (24/25) and hearing loss in all (5/5), while three patients developed new-onset hypoesthesia. We noted that gait ataxia and involvement of cranial nerve V or VII at initial presentation were associated with GKRS failure in univariate analysis. Conclusion Microsurgery should remain the first-choice treatment option for large VSs. GKRS is a viable alternative with good tumor control and improved or stabilized cranial neuropathies with a low complication rate.

3D image-guided treatment planning for Ruthenium-106 brachytherapy of choroidal melanomas.

Current standard treatment procedures for Ruthenium-106 (Ru-106) brachytherapy for choroidal melanomas do not use 3D image-guided treatment planning. We evaluated the potential impact of introducing 3D treatment planning and quantified the theoretical clinical benefits in terms of tumour control probability (TCP) and normal tissue complication probability (NTCP). Treatment plans for thirty-two patients were optimized using 3D image-guided treatment planning and compared to the original 2D clinical plans. Optimization of plans was done in an image-based treatment planning system by optimizing the plaque position and treatment time such that the entire tumour received the prescribed dose of 100Gy. TCP and NTCP for 2D clinical plans and optimized 3D image-guided plans were estimated from published outcome prediction models and compared within patients using Wilcoxon signed-rank test. The median minimum tumour dose (D99% ) for 2D clinical plans was 93Gy (range: 23-158Gy), corresponding to 5-year TCP of 75% (IQR 61-86%), while median tumour D99% for optimized 3D image-guided plans was 115Gy (range 103-141Gy), corresponding to TCP of 82% (IQR 80-84%). This was a statistically significant increase in estimated TCP (median increase in TCP 8% (IQR: -5-23, p = 0.006). While the dose to normal tissue increased somewhat, there was no significant change in NTCP. 3D treatment planning theoretically allows for improved tumour dose delivery for Ru-106 brachytherapy of choroidal melanomas, resulting in a significant increase in expected tumour control compared to traditional approaches using 2D calculations. The deliverability of optimized plans, and potential increased risk of late complications, will have to be confirmed in future clinical studies.

RADT-06. VOLUME KINETICS FOLLOWING TWO-SESSION GAMMA KNIFE RADIOSURGERY FOR LARGE BRAIN METASTASES (BM)

Abstract INTRODUCTION Resection is a well-established treatment for BM ≥ 2 cm, albeit with potential for perioperative complications and delays in systemic treatment. Staged stereotactic radiosurgery (S-SRS) may improve outcomes versus traditional SRS, representing an alternative to surgery in responders. We reviewed institutional outcomes using 2-session S-SRS, focusing on lesion volume kinetics. METHODS 25 patients with 27 lesions underwent S-SRS at our institution between 2014 and 2020. Tumor volumes (TV) were measured at both S-SRS sessions and on follow-up MRI studies. RESULTS Median age at S-SRS was 61 years (range (r:) 31–84). Nine patients (10 BM) were lost to follow-up. Two patients failed to receive their second S-SRS due to local progression. The median margin tumor doses at first and second S-SRS were 15 Gy (r: 12–18 Gy) and 15 Gy (r: 12–16 Gy). The median interval between stages was 32 days (r: 8–63), and median TV at the first and second stages were 9.3 cm3 (r: 1.5–34.7 cm3) and 3.3 cm3 (r: 0.76–26.1 cm3), respectively. The median absolute and relative decrement between S-SRS sessions was 3.7 cm3 (r: 2.8-16.5 cm3) and 49.5% (r: 17.1-87.1%), respectively. [1-2]-month, [3-5]-month, and [6-12]-month MRI scans were available for 17, 10, and 15 lesions. The median decrease in TV compared to baseline was 50.2%, 78.2%, 74.9%. Two of 17 lesions (12%) had initial control but subsequently experienced volumetric progression and required resection. There were no G3+ adverse events (AE). Crude tumor control was achieved in 14 of 17 individual lesions (82%). CONCLUSION Two-session S-SRS is an effective treatment modality for treating patients with large BM, which is feasible in over 80% of patients with sustained tumor control and early volumetric regression.

Dosimetric Analysis and Normal-Tissue Complication Probability Modeling of Child-Pugh Score and Albumin-Bilirubin Grade Increase After Hepatic Irradiation

This study aimed to develop robust normal-tissue complication probability (NTCP) models for patients with hepatocellular carcinoma treated with radiation therapy (RT) using Child-Pugh (CP) score and albumin-bilirubin (ALBI) grade increase as endpoints for hepatic toxicity. Data from 108 patients with hepatocellular carcinoma treated with RT between 2008 and 2017 were evaluated, of which 47 patients (44%) were treated with proton RT. Of these patients, 29 received stereotactic body RT and 79 moderately hypofractionated RT to median physical tumor doses of 43 Gy in 5 fractions and 59 Gy in 15 fractions, respectively. A generalized Lyman-Kutcher-Berman (LKB) model was used to model the NTCP using 2 clinical endpoints, both evaluated at 3 months after RT: CP score increase of ≥2 and ALBI grade increase of ≥1 from the pre-RT baseline. Confidence intervals on LKB fit parameters were determined using bootstrap resampling. Compared with previous NTCP models, this study found a stronger correlation between normal liver volume receiving low doses of radiation (5-10 Gy) and a CP score or ALBI grade increase. A CP score increase exhibited a stronger correlation to normal liver volumes irradiated than an ALBI grade increase. LKB models for CP increase found values for the volume-effect parameter of a = 0.06 for all patients, and a = 0.02/0.09 when fit to photon/proton patients separately. Subset analyses for patients with superior initial liver functions showed consistent dose-volume effects (a = 0.1) and consistent dose-response relationships. This study presents an update of liver NTCP models in the era of modern RT techniques using relevant endpoints of hepatic toxicity, CP score and ALBI grade increase. The results show a stronger influence of low-dose bath on hepatic toxicity than those found in previous studies, indicating that RT techniques that minimize the low-dose bath may be beneficial for patients.

High-dose intensity-modulated chemoradiotherapy in vulvar squamous cell carcinoma: Outcome and toxicity

IntroductionTo evaluate clinical outcomes, pattern of failure, and toxicity after high-dose intensity-modulated radiation therapy (IMRT) for advanced vulvar cancer. MethodsIn this IRB approved retrospective study, the charts of women with histologically confirmed, non-metastatic vulvar cancer consecutively treated at our institution from 2012 to 2018 were reviewed to identify patients that received high-dose IMRT with curative intent. The treatment compliance, toxicities, and patterns of failure were investigated. Actuarial local, regional and distant recurrence and survival were estimated using Kaplan-Meier method and compared using log rank test. ResultsTwenty-six patients were identified, 23 were unresectable, and 3 refused surgery. Fifteen patients (58%) had inguinal node metastases; 10(38%) had pelvic node metastases. Elective surgical staging of groins was performed in 9-patients. Median tumor dose was 65.4Gy. Concurrent platinum-based chemotherapy was administered in 22(84.6%) patients. Complete response (CR) was achieved in 21/26 (80.7%) patients. Five patients had persistent disease following treatment and one sustained recurrence 5-months following radiotherapy. All persistent or recurrent disease occurred inside the irradiated volume. Median follow-up was 19 months (3–52 months). Actuarial 1-year local, regional and distant controls were 72.4%, 85.4%, and 86%, respectively. One and 2-year overall survivals were 91% and 62%, respectively. Complete response at 3-months was a strong predictor for overall survival (1-yr OS 73% vs 27%, HR 7.1 (95% CI 1.2–44); p = 0.01). Lymph node metastases adversely affected overall survival (2-yr OS 49% vs. 83%, p = 0.09). Grade 3–4 late urinary and soft-tissue toxicity was seen in 5 patients. Tumor doses >66 Gy (p = 0.03) and prior pelvic radiotherapy (p = 0.002) predicted grade 3–4 toxicity. ConclusionHigh-dose IMRT for vulvar cancer achieves high rates of local control with acceptable dose dependent long-term toxicity.

The efficacy of radiotherapy for muscle invasive bladder cancer and its associated factors analysis

Objective To analyze the efficacy and its impacting factors of pelvic confined muscle invasive bladder cancer (MIBC) treated with radiotherapy, also including the preservation of functional bladders and the treatment related late toxicity. Methods Forty-five MIBC patients who received radiotherapy from March 1999 to October 2016 in our hospital were analyzed.41 of the patients were transitional cell carcinomas. The radiation volume included the bladder±pelvic lymph node with or without local tumor boost, with a median bladder dose of 45 Gy and median tumor dose of 56 Gy.24 patients received concurrent chemoradiotherapy.14 patients received neoadjuvant chemotherapy, and 29 underwent transurethral resection of bladder tumors before radiotherapy. Results The median follow-up duration was 28 months (range, 4–101 months). The 3-year overall survival were 51%.Concurrent chemoradiotherapy had a better survival than that of radiation alone, with 3-year overall survival of 64% and 30%(P=0.001). The effect of neoadjuvant chemotherapy on 3-year overall survival was not obvious, 59% and 47%(P=0.540) with or without neoadjuvant chemotherapy. The 3-year overall survival were 58% and 43%(P=0.160), respectively for patients with or without the transurethral resection of bladder tumors. The 3-year overall survival were 20% and 79%(P=0.001) for patients with or without relapse. Nine patients recurred locally and fourteen patients developed metastases. The highest bowel toxicity of more than 3 months after radiotherapy was grade 2 in 2 patients. Late grade 2 urinary toxicity occurred in 4 patients, grade 3 in 2 patients. All other patients preserved their functional bladders except 7 patients who had an uncontrolled bladder tumors or radiation induced severe injury of bladder function. Conclusions A better survival could be obtained for localized muscle invasive bladder cancer treated with concurrent chemoradiotherapy. Most of the patients can preserve their functional bladders after radiotherapy, and the late toxicity is acceptable. Key words: Bladder neoplasms/chemoradiotherapy; Treatment outcome

Salvage stereotactic re-irradiation with CyberKnife for locally recurrent head and neck cancer: a single center experience.

We report the toxicity and preliminary clinical outcome in patients affected by locally recurrent head and neck cancer treated with stereotactic re-irradiation. Between February 2012 and August 2013, 17 patients were treated with CyberKnife as stereotactic re-irradiation for locally recurrent head and neck cancer. All patients had previously received a full dose radiation treatment with radical intent, with a median total dose of 66 Gy (range, 50-70) delivered with standard fractionation. The median interval between the primary radiotherapy and re-irradiation was 24 months (range, 10-168). All patients completed the prescribed treatment, which was delivered in 5 fractions. The median tumor dose administered was 30 Gy (range, 25-35) prescribed to the 80% isodose line. Treatment sites were as follows: neck lymph nodes in 5 patients, paranasal sinuses in 5, oropharynx in 2, nasopharynx, and larynx, oral cavity, nasal fossa and parotid gland each in 1 patient. The median target volume treated was 58.7 cm3 (range, 8.5-211.3). Sixteen patients (94%) were evaluated for response. At a median follow-up of 7.5 months (range, 2-17), 4 patients achieved complete response (25%), 5 had partial response (31%) and 7 showed stable disease (44%). No patient showed in-field progression after re-irradiation. Grade 3 acute toxicity was noted in one patient only; no late side effect was observed during the follow-up. Stereotactic re-irradiation with CyberKnife is an appealing non-surgical salvage treatment for selected patients with local-regionally recurrent head and neck cancer.

Prospective Trial Using Internal Pair-Production Positron Emission Tomography to Establish the Yttrium-90 Radioembolization Dose Required for Response of Hepatocellular Carcinoma

Toprospectively assess the threshold dose for objective response of hepatocellular carcinoma (HCC), using 90Y internal pair-production positron emission tomography (PET) to quantify the radiation dose delivered to hepatic tumors after radioembolization. A prospective study was performed under institutional review board approval from 2012 to 2014. Thirty-five patients with primary and secondary liver tumors undergoing 90Y treatment were recruited. Eight patients did not meet inclusion criteria, and 27 patients with HCC were included for analysis. Time-of-flight PET imaging was performed immediately after radioembolization and voxel values converted into 90Y activity. The radioembolization dose was calculated from PET images, and image segmentation was performed with volumetric analysis of dose deposition within tumors. Radiographic response was assessed on follow-up imaging. Treated HCC showed 84% objective response, 11% stable disease, and 5% progressive disease according to modified RECIST 1.1 response criteria. Responders had a higher median 90Y tumor dose than nonresponders (225Gy vs 83Gy, P < .01). Logistic regression models show tumor dose (P=.002) strongly predicted objective response. All nonresponders had tumor dose <200Gy. No statistical difference for patient age, tumor volume, multifocal or extrahepatic disease, portal vein invasion, or injected 90Y activity was found between responders and nonresponders. Hepatocellular carcinoma that resulted in objective response after radioembolization had a greater median tumor dose of 225Gy, compared with 83Gy in nonresponders. Delivered tumor dose can be assessed by PET and significantly impacts treatment response in HCC.

Efficacy, safety and outcome of frameless image-guided robotic radiosurgery for brain metastases after whole brain radiotherapy.

Estimating efficacy, safety and outcome of frameless image-guided robotic radiosurgery for the treatment of recurrent brain metastases after whole brain radiotherapy (WBRT). We performed a retrospective single-center analysis including patients with recurrent brain metastases after WBRT, who have been treated with single session radiosurgery, using the CyberKnife® Radiosurgery System (CKRS) (Accuray Inc., CA) between 2011 and 2016. The primary end point was local tumor control, whereas secondary end points were distant tumor control, treatment-related toxicity and overall survival. 36 patients with 140 recurrent brain metastases underwent 46 single session CKRS treatments. Twenty one patients had multiple brain metastases (58%). The mean interval between WBRT and CKRS accounted for 2years (range 0.2-7years). The median number of treated metastases per treatment session was five (range 1-12) with a tumor volume of 1.26ccm (mean) and a median tumor dose of 18Gy prescribed to the 70% isodose line. Two patients experienced local tumor recurrence within the 1st year after treatment and 13 patients (36%) developed novel brain metastases. Nine of these patients underwent additional one to three CKRS treatments. Eight patients (22.2%) showed treatment-related radiation reactions on MRI, three with clinical symptoms. Median overall survival was 19months after CKRS. The actuarial 1-year local control rate was 94.2%. CKRS has proven to be locally effective and safe due to high local tumor control rates and low toxicity. Thus CKRS offers a reliable salvage treatment option for recurrent brain metastases after WBRT.

Modeling of Normal Tissue Complications Using Imaging and Biomarkers After Radiation Therapy for Hepatocellular Carcinoma

To develop normal tissue complications (NTCP) models for hepatocellular cancer (HCC) patients who undergo liver radiation therapy (RT) and to evaluate the potential role of functional imaging and measurement of blood-based circulating biological markers before and during RT to improve the performance of these models. The data from 192 HCC patients who had undergone RT from 2005 to 2014 were evaluated. Of the 192 patients, 146 had received stereotactic body RT (SBRT) and 46 had received conventional RT to a median physical tumor dose of 49.8Gy and 50.4Gy, respectively. The physical doses were converted into 2-Gy equivalents for analysis. Two approaches were investigated for modeling NTCP: (1) a generalized Lyman-Kutcher-Burman model; and (2) a generalization of the parallel architecture model. Three clinical endpoints were considered: the change in albumin-bilirubin (ALBI), change in Child-Pugh (C-P) score, and grade ≥3 liver enzymatic changes. Local dynamic contrast-enhanced magnetic resonance imaging portal venous perfusion information was used as an imaging biomarker for local liver function. Four candidate inflammatory cytokines were considered as biological markers. The imaging findings and cytokine levels were incorporated into NTCP modeling, and their role was evaluated using goodness-of-fit metrics. Using dosimetric information only, the Lyman-Kutcher-Burman model for the ALBI/C-P change had a steeper response curve compared with grade ≥3 enzymatic changes. Incorporating portal venous perfusion imaging information into the parallel architecture model to represent functional reserve resulted in relatively steeper dose-response curves compared with dose-only models. A larger loss of perfusion function was needed for enzymatic changes compared with ALBI/C-P changes. Increased transforming growth factor-β1 and eotaxin expression increased the trend of expected risk in both NTCP modeling approaches but did not reach statistical significance. The incorporation of imaging findings and biological markers into NTCP modeling of liver toxicity improved the estimates of expected NTCP risk compared with using dose-only models. In addition, such generalized NTCP models should contribute to a better understanding of the normal tissue response in HCC SBRT patients and facilitate personalized treatment.

Hearing Outcomes After Stereotactic Radiosurgery for Jugular Paraganglioma.

To describe audiometric outcomes following stereotactic radiosurgery (SRS) for jugular paraganglioma (JP). Retrospective review. Tertiary referral center. Patients with pretreatment serviceable hearing (American Academy of Otolaryngology-Head and Neck Surgery [AAO-HNS] Class A or B) and serial post-SRS audiometric follow-up who underwent Gamma Knife SRS for JP between 1990 and 2017. Gamma Knife SRS. Progression to nonserviceable hearing; correlation between baseline hearing and treatment parameters with audiometric outcomes. Of 85 patients with JP who underwent SRS during the study period, 35 (66% female, median age 53) had pretreatment serviceable hearing and serial post-treatment audiometry available for review. Median tumor volume at the time of treatment was 7,080 mm, median cochlear point dose was 5.8 Gy (interquartile range [IQR] 4.1 to 7.3 Gy), and median marginal and maximum tumor doses were 16 and 32 Gy, respectively. After a median follow-up of 37 months (IQR 16 to 77 mo), the median change in pure-tone average and speech discrimination score in the treated ear was -1.2 dB HL/yr (IQR -4.5 to 0.3) and 0%/yr (IQR 0-3.5%), compared with 0.07 dB HL/yr (IQR -0.03 to 0.12) and 0 %/yr (IQR 0 to 0%) in the contralateral untreated ear. Seven patients developed nonserviceable hearing (AAO-HNS Class C or D) at a median of 13.2 months following SRS (IQR 4.8 to 24 mo). Among those who maintained serviceable hearing, median audiometric follow-up was 42 months (IQR 18 to 77 mo). The Kaplan-Meier estimated rates of serviceable hearing at 1, 3, and 5 years following SRS were 91%, 80%, and 80%, respectively. Sixty percent of patients with pulsatile tinnitus who underwent SRS experienced varying levels of symptomatic improvement following treatment. The short- and intermediate-term risk of progression to nonserviceable hearing following SRS for JP is low. Data regarding the impact of cochlear dose from the vestibular schwannoma literature should not be freely applied to JP, since the impact of SRS parameters on hearing preservation seems to be less significant.

Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer

Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non-small-cell lung cancer (NSCLC). A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45-83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63-86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%-92%) and 62% (95% CI, 43%-77%), respectively. Median overall survival was 25 months (95% CI, 12-32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%-66%) and 30% (95% CI, 16%-45%), respectively. Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. clinicaltrials.gov Identifier: NCT01190527.

ATRT-10. EARLY POST RADIATION CHANGES AND EFFICACY IN CHILDREN WITH ATRT TREATED ON COG ACNS 0333: A COMPARISON OF PROTON VS PHOTON THERAPY

Abstract BACKGROUND/OBJECTIVES: COG ACNS0333 is a prospective study evaluating surgery, intensive chemotherapy and radiation therapy (RT) in the management of ATRT. The therapy sequence was based on patient age, disease location and extent. Both proton RT (PRT) and photon RT (XRT) modalities were permitted. In this study the early post-RT changes and efficacy of PRT and XRT were compared. METHODS: All RT plans were reviewed centrally. Pre-operative, post-operative, pre-RT and first post-RT MRI scans were available and reviewed. Patient characteristics, treatment sequence, RT plan, tumor volume, brain and brainstem dosimetric parameters were evaluated. RESULTS: 41 of 65 evaluable patients on protocol received RT between 5/2009 and 11/2013 (14 PRT, 27 XRT). Median age at RT was 1.7y (range 0.6 – 13.9y). 6/41 patients received craniospinal RT. Median tumor dose was 50.4Gy (range 45-54Gy). All patients had >1 post-RT MRI scans available. At a median post-diagnosis follow up of 9 months, tumor control was equivalent after PRT and XRT (p=0.83). At a median post-RT follow up of 5 months (range 1.4–36.1) 10/42 patients had in-field MRI changes of varying severity (3 PRT, 7 XRT) in the absence of clear tumor progression. These MRI changes were noted between 2–6 months post-RT. Patients with post-RT MRI changes tended to have larger tumors with larger pre-operative tumor volume (median 137 cc vs 57 cc) and larger CTV’s (median 257cc vs 125 cc); however, the difference was not statistically different (p=0.21). CONCLUSION: In this early analysis of COGACNS 0333 there were no detectable differences in tumor control between the patients treated with PRT vs XRT. Reactive changes were seen with both modalities but were not excessive with either.

Image-guided adaptive brachytherapy dose escalation for cervix cancer via fractionation compensation

PurposeIn image-guided adaptive brachytherapy (IGABT), dose distributions are optimized for each fraction. Optimum fractional dose can be constant or adapted to previous fractions and a conjecture about the future ones. We evaluate the efficacy of different fraction size schemes, derived from total IGABT dose constraints, against constant per-fraction constraints. Methods and MaterialsThis retrospective planning study included 20 IGABT patients where four different fractionation schedules were compared based on modern planning recommendations. A total high-risk–clinical target volume D90 (minimum dose in 90% of the volume) dose aim of 90.0 Gy with constant per-fraction organs at risk (OARs) dose constraint planning (CONST) was compared with conservative and aggressive fractionation compensation (COMP) techniques. COMP allows variations in the per-fraction dose constraints. Dose accumulation was performed through dose summation at a given volume and equivalent uniform dose (EUD) worst-case dose estimates. ResultsNo significant differences were identifiable between dose metrics of CONST and COMP in the total patient population. However, a subgroup of patients with alternating dose-limiting OARs had significant benefit from COMP. Median high-risk–clinical target volume dose escalation ranged from 5% to 12%, whereas OAR dose increases were lower and ranged from 3% to 8%. EUD-based planning delivered similar tumor doses, although slightly lower OAR doses. By distributing the treatment aim over an increased number of treatment fractions, median tumor dose could be increased by a further 8% per additional treatment fraction at the same OAR dose levels for both CONST and COMP. ConclusionsCOMP is effective in patients with alternating dose-limiting OARs and is enhanced using more treatment fractions and EUD constraints.