COX inhibitor use during definitive radiotherapy is associated with worse hearing preservation in patients with vestibular schwannoma.

PURPOSE: Patients with vestibular schwannoma undergoing definitive radiotherapy commonly experience hearing loss due to tumor and treatment effects; however, there is limited data evaluating concurrent medication use and other clinicopathologic factors associated with hearing preservation during and after radiotherapy. We performed a retrospective cohort study reviewing consecutive patients from 2004 to 2019 treated with radiotherapy for vestibular schwannoma at our institution. METHODS: Ninety four patients with concurrent medications, baseline audiograms, and post-radiotherapy audiograms available were evaluable. We performed chi-squared analyses of the frequency of various clinicopathologic factors and t-tests evaluating the degree of hearing loss based on audiograms. RESULTS: At a median follow-up of 35.7 months (mean: 46.5 months), the baseline pure-tone average (PTA) of the ipsilateral ear worsened from 38.4 to 59.5 dB following completion of radiotherapy (difference: 21.1, 95% CI 17.8-24.4 dB, p < 0.001). 36 patients (38.3%) reported regular use of cyclooxygenase (COX) inhibitors (including acetaminophen and NSAIDs) during radiotherapy. The mean increase in PTA was significantly higher for patients taking COX inhibitors (25.8 dB vs 18.1 dB, p = 0.024) in the ipsilateral ear but not for the contralateral side. COX inhibitor use remained independently associated with worse PTA in the multivariate analysis. CONCLUSION: COX inhibitor use during definitive radiotherapy is associated with worse hearing loss in the affected ear but not for the contralateral side. This suggests the ototoxic effects of COX inhibitors may influence the effects of radiotherapy. These results could have clinical implications and warrant further investigation.

Systemic Immune-Inflammatory Index Association with Survival in Patients Undergoing Trimodality Therapy for Lung Cancer.

PURPOSE: The systemic immune-inflammation index (SII) is correlated with patient survival in various solid malignancies including non-small-cell lung cancer (NSCLC). However, limited information is available on the prognostic implication of the SII in patients undergoing trimodality therapy for stage III NSCLC. METHODS: At our institution, 81 patients underwent curative intent trimodality therapy (neoadjuvant chemoradiotherapy followed by surgical resection) for stage III NSCLC from 2004 to 2019. The SII was calculated at the time of diagnosis as platelet count × neutrophil count/lymphocyte count. χ2 analysis was used to compare categorical variables. A Kaplan-Meier analysis was performed to estimate disease-free survival (DFS), overall survival (OS), and freedom from recurrence (FFR) rates, with Cox regression used to determine absolute hazards. RESULTS: Patients underwent neoadjuvant radiation therapy to a median dose of 4,500 cGy concurrent with a median of 3 cycles of chemotherapy (most commonly carboplatin and paclitaxel) followed by surgical resection (86.4% lobectomy and 13.6% pneumonectomy) with mediastinal lymph node dissection. At a median follow-up of 68.4 months, a low SII (<1,260) at diagnosis was independently associated with an improved OS (hazard ratio [HR]: 0.448, p = 0.004), DFS (HR: 0.366, p < 0.001), and FFR (HR: 0.325, p = 0.002). CONCLUSIONS: We identified that a low SII was associated with improved OS, DFS, and FFR in patients undergoing trimodality therapy for stage III NSCLC. The interplay of the immune system and lung cancer outcomes remains an active area of investigation for which further study is warranted.

Stereotactic body radiation therapy (SBRT) in recurrent, persistent or oligometastatic gynecological cancers.

OBJECTIVE: SBRT is a well-tolerated technique and provides local-regional control in a variety of metastatic and recurrent tumor types. The role of SBRT in extracranial recurrent, persistent, or oligometastatic gynecological tumors is not well-studied. We therefore retrospectively analyzed a sizeable number of patients in this setting. METHODS: We performed a retrospective review of 86 patients with 209 tumors treated at our institution with SBRT for recurrent, persistent, or oligometastatic extracranial gynecological tumors. The median follow-up was 20 months (range 1-91). The median SBRT dose was 24 Gy (range 10-50) delivered in a median of 4 fractions (range 1-6). The Kaplan-Meier curves and log rank tests were used to assess local control (LC) and overall survival (OS). Cox proportional hazards model was used to evaluate for covariates associated with LC and OS. RESULTS: The 1- and 3-year LC were 80% and 68% respectively. The 1- and 3-year OS were 70% and 39%. 32% of the lesions demonstrated complete response, 23% partial response and 20% stable disease. SBRT achieved better local control in smaller tumors. Toxicity was typically mild with grade 1 gastrointestinal toxicity and fatigue being the most common. Only 4.3% of treatments resulted in grade 2 or greater toxicity. There was only one case of grade 3 and no grade 4 or 5 toxicities. CONCLUSIONS: SBRT offers a high rate of local control with low incidence of toxicity, mainly grade 1 GI toxicity and fatigue, and provides effective salvage therapy for oligometastatic extracranial pelvic and extra-pelvic gynecological tumors.

Using flattening filter free beams in electronic tissue compensation whole breast irradiation with deep inspiration breath hold.

PURPOSE: In order to reduce heart dose, DIBH has become a common practice in left-sided whole breast irradiation. This technique involves a significant strain on patients due to the breath-hold requirements. We hereby investigate the dosimetric and delivery feasibility of using flattening filter free (FFF) energies with electronic tissue compensation (ECOMP) planning technique to reduce the required breath-hold lengths and increase patient compatibility. METHODS: Fifteen left-sided, postlumpectomy patients previously receiving DIBH whole-breast radiotherapy (266cGy x 16fx) were retrospectively planned using ECOMP for both 6X and 6X-FFF. A dosimetric comparison was made between the two plans for each patient using various dosimetric constraints. Delivery feasibility was analyzed by recalculating the 6X ECOMP plan with 6X-FFF without replanning (6X-FFF QA) and delivering both plans for a one-to-one comparison using Gamma analysis. Beam-on times for the 6X and 6X-FFF plans were measured. For all tests, Wilcoxon signed-rank test was used with P < 0.05 as significant. RESULTS: No statistical difference was observed between 6X and 6X-FFF plans for most dosimetric endpoints except contralateral breast Dmax (P = 0.0008) and skin Dmax (p = 0.03) and Dmin (P = 0.01) for which 6X-FFF showed favorable results when compared with 6X. 6X-FFF significantly reduced beam-on times for all patients by 22%-42% (average 32%). All plan QAs passed departmental gamma criteria (10% low-dose threshold, 3%/3mm, >95% passing). CONCLUSION: ECOMP planning with FFF was found feasible for left-sided breast patients with DIBH. Plan quality is comparable, if not better, than plans using flattened beams. FFF ECOMP could significantly reduce beam-on time and required breath-hold lengths thereby increasing patient compatibility for this treatment while offering satisfactory plan quality and delivery accuracy.

Metachronous medulloblastoma and glioblastoma: Implications for clinical and technical aspects of re-irradiation.

A seven-year-old male underwent surgical resection and chemoradiation for average risk medulloblastoma; twelve years later, the presence of a necrotic and infiltrative mass in the same area and invading the brainstem prompted a subtotal resection. Pathology was indicative of glioblastoma. He was then treated with concurrent temozolomide and using biologically effective dose calculations for gross residual tumor tissue in the brainstem as well as brainstem tolerance, a radiotherapy dose of 3750 cGy was chosen, fractionated in twice-daily fractions of 125 cGy each. The gross tumor volume was expanded with a 5 mm margin to the planning target volume, which was also judiciously subtracted from the normal brainstem. He completed his radiotherapy course with subsequent imaging free of residual tumor and continued adjuvant temozolomide and remains under follow-up surveillance. This case underscores the rarity of metachronous medulloblastoma and glioblastoma, of which only five known cases heretofore have been described. We discuss the technicalities of radiotherapy planning in this patient, including common hurdles for radiation oncologists in similar patients.

Atypical teratoid rhabdoid tumor: long-term survival after chemoradiotherapy.

PURPOSE: Atypical teratoid rhabdoid tumors (ATRTs) arise from the central nervous system largely in the pediatric population. They portend a very poor prognosis with few long-term survivors. We describe a series of five cases at our institution. METHODS: We conducted a retrospective chart review and clinical follow-up. RESULTS: Three patients underwent chemoradiation after surgical resection; the two patients whose caretakers declined this therapy passed away soon after diagnosis. Chemoradiation included intravenous and intrathecal chemotherapy as well as intensity-modulated radiotherapy after resection. Of the patients receiving chemoradiation, two patients had infratentorial tumors, two had gross residual tumor after resection, and two were under the age of 3 years. The three patients receiving trimodality therapy remain clinically and symptomatically disease-free with follow-up times of 44, 46, and 55 months. Two of the patients have mild neuropsychiatric sequelae after therapy. CONCLUSIONS: Long-term, high-volume trials of ATRT are currently not published. We offer experience in successful long-term survival of this tumor treated with chemoradiotherapy.

Effects of interobserver and interdisciplinary segmentation variabilities on CT-based radiomics for pancreatic cancer.

Radiomics is a method to mine large numbers of quantitative imaging features and develop predictive models. It has shown exciting promise for improved cancer decision support from early detection to personalized precision treatment, and therefore offers a desirable new direction for pancreatic cancer where the mortality remains high despite the current care and intense research. For radiomics, interobserver segmentation variability and its effect on radiomic feature stability is a crucial consideration. While investigations have been reported for high-contrast cancer sites such as lung cancer, no studies to date have investigated it on CT-based radiomics for pancreatic cancer. With three radiation oncology observers and three radiology observers independently contouring on the contrast CT of 21 pancreatic cancer patients, we conducted the first interobserver segmentation variability study on CT-based radiomics for pancreatic cancer. Moreover, our novel investigation assessed whether there exists an interdisciplinary difference between the two disciplines. For each patient, a consensus tumor volume was generated using the simultaneous truth and performance level expectation algorithm, using the dice similarity coefficient (DSC) to assess each observer's delineation against the consensus volume. Radiation oncology observers showed a higher average DSC of 0.81 ± 0.06 than the radiology observers at 0.69 ± 0.16 (p = 0.002). On a panel of 1277 radiomic features, the intraclass correlation coefficients (ICC) was calculated for all observers and those of each discipline. Large variations of ICCs were observed for different radiomic features, but ICCs were generally higher for the radiation oncology group than for the radiology group. Applying a threshold of ICC > 0.75 for considering a feature as stable, 448 features (35%) were found stable for the radiation oncology group and 214 features (16%) were stable from the radiology group. Among them, 205 features were found stable for both groups. Our results provide information for interobserver segmentation variability and its effect on CT-based radiomics for pancreatic cancer. An interesting interdisciplinary variability found in this study also introduces new considerations for the deployment of radiomics models.

Systemic inflammation is associated with inferior disease control and survival in stage III non-small cell lung cancer.

BACKGROUND: The systemic immune-inflammation index (SII) correlates with patient survival in various types of solid malignancies, including non-small cell lung cancer (NSCLC). However, limited information is available on the prognostic implication and disease-specific survival of SII in patients undergoing definitive chemoradiation therapy (CRT) for stage III NSCLC. METHODS: We retrospectively reviewed 125 patients who underwent curative intent CRT for stage III NSCLC with sufficient laboratory assessment from 2010-2019. SII was calculated at the time of diagnosis as platelet count × neutrophil count/lymphocyte count. Chi-squared analysis was used to compare categorical variables. A Kaplan-Meier analysis was performed to estimate progression-free survival (PFS), disease specific survival (DSS), and overall survival (OS) rates, with Cox regression used to determine absolute hazards. RESULTS: At a median follow-up of 19.7 months, 5-year OS, DSS, and PFS rates were 22.6%, 30.9%, and 13.4%, respectively. A low SII (<1,266) at diagnosis was independently associated with an improved OS (HR: 0.399, 95%, CI: 0.247-0.644, P<0.001), DSS (HR: 0.383, 95%, CI: 0.228-0.645, P<0.001), and PFS (HR: 0.616, 95%, CI: 0.407-0.932, P=0.022). We did not detect an association between SII and freedom from recurrence (FFR), freedom from locoregional recurrence (FFLRR), or freedom from distant recurrence (FFDR). NSAID (1,483.4 vs. 2,302.9, P=0.038) and statin usage (1,443.9 vs. 2,201.7, P=0.046) were associated with a lower SII while COPD exacerbations (2,699.7 vs. 1,573.7, P=0.032) and antibiotic prescriptions (2,384.6 vs. 1,347.9, P=0.009) were associated with an elevated SII. These factors were not independently associated with improved survival outcomes. CONCLUSIONS: Low SII scores were independently associated with improved OS, DSS, and PFS rates in patients with stage III NSCLC undergoing definitive CRT. NSAIDs and statin usage may be associated with lower SII at diagnosis of NSCLC. This study suggests that SII may be an effective prognostic indicator of patient mortality. Further investigation of the therapeutic potential of these agents in patients with an elevated SII in this setting may be warranted.

The impact of stereotactic body radiation therapy on the overall survival of patients diagnosed with early-stage non-small cell lung cancer.

BACKGROUND AND PURPOSE: Stereotactic Body Radiotherapy (SBRT) has emerged as a standard treatment for inoperable early-stage non-small cell lung cancer (NSCLC) with remarkable local control. However, it is not clear if this local control translates to overall survival (OS). The objective of this study is to investigate the impact of SBRT on the OS of early-stage NSCLC patients and examine if the extent of this impact changes with the era of diagnosis, T stage, age, and comorbidity status. MATERIALS AND METHODS: Using the National Cancer Database, we compared the OS of cT1-3 cN0 cM0 NSCLC patients with SBRT or observation. Multivariable analyses were adjusted for age, race, sex, income, education, place of living, hospital type, insurance status, comorbidity score, histology types, and diagnosis year. RESULTS: Among 50,819 patients, 27,027 (53.18%) received SBRT and 23,792 (46.82%) were observed. Multivariable Cox Proportional-Hazards analysis demonstrated SBRT was associated with an improved OS compared to observation (HR:0.56, p < 0.001). Subset multivariable Cox Proportional-Hazards analyses stratified by T stage, year of diagnosis, age, or Charlson Score revealed that HRs of SBRT vs. observation decrease from cT1 to cT3 (0.73-0.68), from 2004 to 2015 (0.65-0.51), from <50 to ≥80 years old (1.04-0.58) and from a Charlson Score 0 to 2 (0.69-0.58). CONCLUSION: SBRT was associated with improved OS compared to no treatment in early-stage NSCLC. The magnitude of the impact of SBRT on OS increases in patients with advanced age, higher T stages, higher comorbidity scores and more recent treatment eras.

Percentage of Hormone Receptor Positivity in Breast Cancer Provides Prognostic Value: A Single-Institute Study.

BACKGROUND: A majority of breast cancer tumors express estrogen receptor (ER) and/or progesterone receptor (PR); however, the percentage of cancer cells expressing these receptors can range from 0-100%. The prognostic and therapeutic impact of the percentage of cells expressing hormone receptors in breast cancer is not fully understood. METHODS: A retrospective analysis of 411 breast cancer patients who were treated at the University of Nebraska Medical Center between 2010 and 2017 was performed. Patient tumors were evaluated for percentage of cells expressing ER and PR in conjunction with clinical outcomes. RESULTS: Patient tumors demonstrated a highly bimodal pattern of ER and PR staining with a majority of tumors demonstrating either a high percentage (> 80% of cells) or lack of cells (0%) staining for ER or PR. An increase in the percentage of ER positivity correlated with decreased local recurrence and improved overall survival. An increase in the percentage of PR positivity demonstrated a trend towards decreased local recurrence and improved overall survival, but was not statistically significant. CONCLUSIONS: Results based on both continuous and categorical evaluation of ER expression revealed that increasing expression correlated with improved patient outcomes. Similar evaluation of PR expression demonstrated a trend towards improved patient outcomes though not statistically significant. These findings suggest that the degree of hormone receptor positivity and not a Boolean representation of positivity could provide additional prognostic value in the treatment and management of breast cancer.

Accelerated partial breast radiotherapy: a review of the literature and future directions.

Breast conservation therapy exemplifies the tailoring of medicine in the care of patients with cancer. Akin to improvements in surgical approaches, accelerated partial breast irradiation (APBI) tailors the treatment volume and duration to the needs of well selected patients. Here, we examine the evidence supporting APBI as well as the lessons in patient selection, dose and delivery techniques. Examination of historical techniques and their associated outcomes will support more correct patient selection and treatment delivery in an era where we await the reports of several large prospective trials.

Osteosarcoma of the Larynx: Treatment Outcomes and Patterns of Failure Analysis.

The incidence of laryngeal sarcoma is exceedingly low with osteosarcomas of the larynx being rarer still, comprising less than 1% of all associated malignancies. To date, only 32 cases have been reported since this pathologic entity was first described in 1942. In this article, we discuss the most recent case of laryngeal osteosarcoma in a patient presenting with respiratory distress found to be due to a tumor mass arising from her cricoid cartilage. We further summarize current knowledge regarding the epidemiology, presentation, and diagnosis of this uncommon disease. Lastly, we synthesize all available information regarding treatment and outcomes of the 32 previously described cases of osteosarcoma of the larynx as well as the presently described case in an attempt to offer some insight regarding optimal treatment in future cases.

Chemoradiotherapy for locally advanced squamous cell carcinoma of the oropharynx: Does completion of systemic therapy affect outcomes?

INTRODUCTION: Current standard of care for locally advanced squamous cell carcinoma of the oropharynx (LA-OPC) consists of concurrent chemoradiotherapy. Due to toxicities associated with this treatment, a significant portion of patients are unable to complete the systemic therapy portion of their treatment course. The impact of incomplete systemic therapy on patient outcomes remains unclear. METHODS: Demographic, treatment, and outcome data were retrospectively collected for patients with LA-OPC treated definitively with concurrent chemoradiotherapy between 2007 and 2014. Overall and disease-free survivals were estimated via the Kaplan Meier method. Log rank test was used to compare distributions of survival amongst groups. Cox regression was utilized for all multivariate analyses. P values of <0.05 were considered statistically significant. RESULTS: In total, 73 patients with LA-OPC were identified with a median follow-up of 3.4years. Concurrent systemic therapy regimens consisted of bolus cisplatin every 3weeks (76.7%), weekly cetuximab (20.5%) and weekly cisplatin (2.7%). Forty-three patients (58.9%) were able to complete the prescribed concurrent systemic regimens. Upon multivariate analyses, patients who did not complete systemic therapy were noted to have a non-significant trend towards increased distant failure (20.0% vs 7.0%, p=0.12). Additionally, patients who did not complete systemic therapy were noted to have a near significant trend towards increased risk of death (36.7% vs 17.9%, p=0.053). CONCLUSIONS: These results suggest that completing systemic therapy may affect survival in patients undergoing definitive radiotherapy with concurrent systemic therapy for LA-OPC. Further, this data demonstrates that though local recurrences are not affected when planned systemic therapy cycles are omitted, the risk of distant failure may increase. These associations require further study to clarify the effect Incomplete systemic therapy has on outcomes for LA-OPC.

Quantification of renal function following stereotactic body radiotherapy for pancreatic cancer: secondary dosimetric analysis of a prospective clinical trial.

BACKGROUND: This is the first known study examining renal function following stereotactic body radiotherapy (SBRT) for pancreatic head adenocarcinoma. METHODS: Thirty-eight borderline-resectable/unresectable patients, part of an ongoing prospective trial, underwent 3 cycles of gemcitabine/5-fluorouracil followed by SBRT (5 daily fractions of 5/6/7/8 Gy) and concurrent nelfinavir. Thereafter, in resectable cases, surgery was performed within 4-8 weeks. The last available pre-SBRT creatinine was recorded, along with the highest post-SBRT value. Glomerular filtration rate (GFR) was calculated by the commonly-utilized Modification of Diet in Renal Disease formula. GFR decline was defined as the post-SBRT nadir GFR minus the pre-SBRT GFR. Correlations with the V5-V30, and mean/maximum kidney doses was performed. Statistics included Pearson correlation, Mann-Whitney, and Fisher's exact tests. RESULTS: The median total kidney volume was 355 cm3. Median dosimetric values were as follows: V5 (209 cm3), V10 (103 cm3), V15 (9 cm3), V20 (0 cm3), V25 (0 cm3); and mean (6.7 Gy) & maximum kidney dose (18.3 Gy). Median GFR change was -23 (range, -105 to 25) mL/min/1.73 cm2. Of all dosimetric parameters, only V5 was significantly associated with changes in GFR (Pearson r = -0.40, p = 0.012). In patients with V5 < 210 cm3, median GFR change was -11.8 mL/min/1.73 cm2, as compared with -37.1 mL/min/1.73 cm2 change in those with V5 ≥ 210 cm3 (p = 0.02). A GFR change < -23 mL/min/1.73 cm2 was observed in 6/20 (30%) patients with V5 < 210 cm3, versus 15/18 (83%) of those with V5 ≥ 210 cm3. Patients with V5 ≥ 210 cm3 were over ten times as likely to have GFR change < -23 mL/min/1.73 cm2 (p = 0.003). Using linear regression, GFR change ≈ -0.1748 × V5(cm3) + 8.63. CONCLUSIONS: In the first known analysis of renal function after pancreatic SBRT, evaluating patients on a prospective study, V5 ≥ 210 cm3 was associated with a post-SBRT GFR decline of >23 mL/min/1.73 cm2. If V5 is kept <210 cm3, median GFR decline was only 11.8 mL/min/1.73 cm2. Further validation is needed to ascertain definite dose-volume parameters and examine late renal decline.

Weight Loss and Percutaneous Endoscopic Gastrostomy Tube Placement during Chemoradiotherapy for Locally Advanced Cancer of the Oropharynx Do Not Negatively Impact Outcomes.

OBJECTIVES: Concurrent chemoradiotherapy is standard of care in locally advanced oropharyngeal cancer (LA-OPC). This treatment regimen results in significant acute toxicities. This study investigates the effect of treatment-related toxicity on patient outcomes. METHODS: Patient information was retrospectively collected for patients treated for LA-OPC between 2007 and 2014. Factors analyzed included age, gender, pretreatment ECOG performance status, smoking history, patient BMI prior to and following treatment, tumor histology, disease stage, disease recurrence, incidence, and timing of feeding tube placement, radiation dose received, chemotherapy regimen used and if it was completed, and patient survival. All statistical analysis was provided through the University of Nebraska Medical Center Department of Biostatistics. RESULTS: 74 patients were identified with a median follow-up of 3.4 years and a median age of 58.5. Most patients were male (87.8%) and had squamous cell histology (98.7%). Most patients underwent chemoradiotherapy alone (98.6%) and received concurrent cisplatin (78.4%) with approximately half (53.4%) receiving all planned chemotherapy. Upon multivariate analysis, both disease-free (DFS) and overall survival (OS) rates were improved by lower pretreatment BMI, increased weight lost during treatment, and lack of percutaneous endoscopic gastrostomy (PEG) tube placement prior to treatment initiation. Neither DFS nor OS was impacted by placement of a PEG tube during active treatment. CONCLUSION: These data suggest that weight loss and PEG tube placement during chemoradiotherapy for LA-OPC, presumably due to treatment-associated mucositis and xerostomia, are not associated with worse outcomes.

A comprehensive dosimetric study on switching from a Type-B to a Type-C dose algorithm for modern lung SBRT.

BACKGROUND: Type-C dose algorithms provide more accurate dosimetry for lung SBRT treatment planning. However, because current dosimetric protocols were developed based on conventional algorithms, its applicability for the new generation algorithms needs to be determined. Previous studies on this issue used small sample sizes and reached discordant conclusions. Our study assessed dose calculation of a Type-C algorithm with current dosimetric protocols in a large patient cohort, in order to demonstrate the dosimetric impacts and necessary treatment planning steps of switching from a Type-B to a Type-C dose algorithm for lung SBRT planning. METHODS: Fifty-two lung SBRT patients were included, each planned using coplanar VMAT arcs, normalized to D95% = prescription dose using a Type-B algorithm. These were compared against three Type-C plans: re-calculated plans (identical plan parameters), re-normalized plans (D95% = prescription dose), and re-optimized plans. Dosimetric endpoints were extracted and compared among the four plans, including RTOG dosimetric criteria: (R100%, R50%, D2cm, V105%, and lung V20), PTV Dmin, Dmax, Dmean, V% and D90%, PTV coverage (V100%), homogeneity index (HI), and Paddick conformity index (PCI). RESULTS: Re-calculated Type-C plans resulted in decreased PTV Dmin with a mean difference of 5.2% and increased Dmax with a mean difference of 3.1%, similar or improved RTOG dose compliance, but compromised PTV coverage (mean D95% and V100% reduction of 2.5 and 8.1%, respectively). Seven plans had >5% D95% reduction (maximum reduction = 16.7%), and 18 plans had >5% V100% reduction (maximum reduction = 60.0%). Re-normalized Type-C plans restored target coverage, but yielded degraded plan conformity (average PCI reduction 4.0%), and RTOG dosimetric criteria deviation worsened in 11 plans, in R50%, D2cm, and R100%. Except for one case, re-optimized Type-C plans restored RTOG compliance achieved by the original Type-B plans, resulting in similar dosimetric values but slightly higher target dose heterogeneity (mean HI increase = 13.2%). CONCLUSIONS: Type-B SBRT lung plans considerably overestimate target coverage for some patients, necessitating Type-C re-normalization or re-optimization. Current RTOG dosimetric criteria appear to remain appropriate.

Automatic planning on hippocampal avoidance whole-brain radiotherapy.

Mounting evidence suggests that radiation-induced damage to the hippocampus plays a role in neurocognitive decline for patients receiving whole-brain radiotherapy (WBRT). Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) has been proposed to reduce the putative neurocognitive deficits by limiting the dose to the hippocampus. However, urgency of palliation for patients as well as the complexities of the treatment planning may be barriers to protocol enrollment to accumulate further clinical evidence. This warrants expedited quality planning of HA-WBRT. Pinnacle3 Automatic treatment planning was designed to increase planning efficiency while maintaining or improving plan quality and consistency. The aim of the present study is to evaluate the performance of the Pinnacle3 Auto-Planning on HA-WBRT treatment planning. Ten patients previously treated for brain metastases were selected. Hippocampal volumes were contoured on T1 magnetic resonance (MR) images, and planning target volumes (PTVs) were generated based on RTOG0933. The following 2 types of plans were generated by Pinnacle3 Auto-Planning: the one with 2 coplanar volumetric modulated arc therapy (VMAT) arcs and the other with 9-field noncoplanar intensity-modulated radiation therapy (IMRT). D2% and D98% of PTV were used to calculate homogeneity index (HI). HI and Paddick Conformity index (CI) of PTV as well as D100% and Dmax of the hippocampus were used to evaluate the plan quality. All the auto-plans met the dose coverage and constraint objectives based on RTOG0933. The auto-plans eliminated the necessity of generating pseudostructures by the planners, and it required little manual intervention which expedited the planning process. IMRT quality assurance (QA) results also suggest that all the auto-plans are practically acceptable on delivery. Pinnacle3 Auto-Planning generates acceptable plans by RTOG0933 criteria without time-consuming planning process. The expedited quality planning achieved by Auto-Planning (AP) may facilitate protocol enrollment of patients to further investigate the hippocampal-sparing effect and be used to ensure timely start of palliative treatment in future clinical practice.

Target migration from re-inflation of adjacent atelectasis during lung stereotactic body radiotherapy.

Stereotactic body radiotherapy (SBRT) is a widely accepted option for the treatment of medically inoperable early-stage non-small cell lung cancer (NSCLC). Herein, we highlight the importance of interfraction image guidance during SBRT. We describe a case of early-stage NSCLC associated with segmental atelectasis that translocated 15 mm anteroinferiorly due to re-expansion of the adjacent segmental atelectasis following the first fraction. The case exemplifies the importance of cross-sectional image-guided radiotherapy that shows the intended target, as opposed to aligning based on rigid anatomy alone, especially in cases associated with potentially "volatile" anatomic areas.

Fractionated stereotactic radiation therapy for vestibular schwannomas: Dosimetric factors predictive of hearing outcomes.

PURPOSE: To determine dosimetric factors predictive of hearing loss in vestibular schwannoma (VS) patients treated with definitive fractionated stereotactic radiation therapy (FSRT), and to report tumor control, serviceable hearing preservation, and cranial nerve toxicities. METHODS AND MATERIALS: We identified 45 patients (29 men and 16 women) with unilateral sporadic VS, who underwent definitive FSRT. All patients had serviceable hearing prior to treatment, defined as Gardner-Robertson Class 1 or 2. All patients underwent an audiogram before the start of treatment and serial audiometric assessments after treatment. The median audiometric follow-up time was 35.2 months (range, 5.0-89.7 months). Patients underwent a median of 4.5 (range, 1-9) posttreatment audiograms. The ipsilateral cochlea was contoured retrospectively, and dosimetric data were used to determine factors predictive of losing serviceable hearing. The median clinical follow-up time was 29.9 months (range, 1.5-83.6 months). RESULTS: At the time of the last audiometric follow-up, 62% of patients retained serviceable hearing. The actuarial 1-, 2-, and 3-year serviceable hearing preservation rates were 83%, 75%, and 51%, respectively. The estimated median time to loss of serviceable hearing was 42.2 months. On multivariate analysis, cochlear volume <0.15 mL (hazard ratio, 2.849; 95% confidence interval, 1.116-7.270; P = .029) and mean cochlear dose <4000 cGy (hazard ratio, 3.178; 95% confidence interval, 1.116-9.049; P = .030) were statistically significant variables associated with serviceable hearing preservation. The actuarial tumor control was 100%. Three of 39 patients (8%) developed hemifacial spasm after FSRT (House-Brackmann Grade 3), 2 of which completely resolved. No patients experienced deterioration in trigeminal nerve function after FSRT. CONCLUSIONS: Fractionated stereotactic radiation therapy can provide excellent tumor control with acceptable clinical outcomes. The mean dose to the cochlea is highly predictive of the probability of maintaining serviceable hearing after FSRT.

Effect of Akimbo versus Raised Arm Positioning on Breast and Cardiopulmonary Dosimetry in Pediatric Hodgkin Lymphoma.

PURPOSE: In pediatric Hodgkin lymphoma (HL), radiotherapy (RT)-related late toxicities are a prime concern during treatment planning. This is the first study to examine whether arm positioning (raised versus akimbo) result in differential cardiopulmonary and breast doses in patients undergoing mediastinal RT. METHODS: Two treatment plans were made for each patient (akimbo/arms raised); treatment was per Children's Oncology Group AHOD0031 protocol, including AP/PA fields. The anterior midline T6-T7 disk space was used as an anatomic reference of "midline." Heart/lungs were contoured for each setup. For females, breasts were also contoured and nipple positions identified. Volumetric centers of contoured organs were defined and three-dimensional distances from "midline" were computed. Analyzed dosimetric parameters included V5 (volume receiving ≥5 Gy), V10, V15, V20, and mean dose. Statistics were performed using the Mann-Whitney test. RESULTS: Fifteen (6 females, 9 males) pediatric HL patients treated with mediastinal RT were analyzed. The median lateral distance from the breast center/nipple to "midline" with arms akimbo was larger than that with arms raised (8.6 vs. 7.7 cm left breast, p = 0.04; 10.7 vs. 9.2 cm left nipple, p = 0.04; 8.7 vs. 7.0 cm right breast, p = 0.004; 9.9 vs. 7.9 cm right nipple, p = 0.007). Raised arm position was associated with a median 2.8/3.0 cm decrease in breast/nipple separation, respectively. There were no significant differences in craniocaudal breast/nipple position based on arm positioning (p > 0.05). Increasing breast volume was correlated with larger arm position-related changes in breast/nipple separation (r = 0.74, p = 0.06/r = 0.85, p = 0.02). Akimbo positioning lowered median breast V5, V10, V15, and mean dose (p < 0.05), with no differences observed in patients with both mediastinal and axillary disease for any parameters (p > 0.05). Arm position had no significant effect on cardiopulmonary doses. CONCLUSION: Akimbo arm positioning may be advantageous to decrease breast doses in female pediatric HL patients undergoing mediastinal RT, especially in the absence of axillary disease.