Retrospective analysis of outcome and toxicity after postoperative radiotherapy in patients with squamous cell carcinoma of the lip.

BACKGROUND: Carcinomas of the lips are a relatively common malignancy of the head and neck region, accounting for roughly one quarter of all oral cavity cancers. Compared to other oral cancer sites, this location has a favorable prognosis, with 5-year survival rates between 85% and 95%. This study summarizes our institutional experience in utilizing postoperative radiation for patients with squamous cell carcinoma of the upper and/or lower lip following incomplete surgical resection or positive lymph node involvement with extracapsular extension. METHODS: We retrospectively reviewed the medical records of all patients at the University Hospital of Heidelberg between 2005 and 2018 treated with postoperative radiotherapy of the upper and lower lip. Nineteen patients were identified with a median age at diagnosis of 67 years (range, 41-95 years), with 58% male and 42% female patients. Fourteen patients (73.7%) underwent neck dissection, with 5 (35.7%) found to have extracapsular extension (ECE) and positive resection margin (R1/2), 2 (14.3%) only ECE, and 7 (50.0%) with only R1/2. All patients received a median cumulative dose of 66.0 Gy (range, 60.0-70.0 Gy) in a median of 2.0 Gy per fraction (range, 1.8-2.2 Gy). RESULTS: Median follow-up was 5.2 years. The median progression-free survival (PFS) was 3.9 years (range, 0.2-12.4 years), local disease-free survival (LDFS) was 4 years (range, 1-12 years) and overall survival (OS) was 5.2 years (range, 0.2-12.4 years). The 5-year Kaplan-Meier estimates for OS, PFS, and LDFS were 61.4%, 85.7%, and 100.0%, respectively. At last follow-up, 13 patients (68.4%) were still alive. Although no patient developed locoregional relapse, two patients developed distant relapse at a median of 15 months after radiotherapy. There was a statistically significant improvement in OS in patients treated with higher radiotherapy doses (>60.0 Gy, p = 0.044) compared to lower radiotherapy doses. PFS was significantly improved among patients who had N0 disease, with a negative resection margin, without ECE, and who were treated with intensity-modulated radiotherapy to doses >60.0 Gy. No grade 3/4 toxicity was detected; the most common grade 1/2 toxicities included dermatitis (n = 11, 57.9%), oral mucositis (n = 8, 42.1%), and dysphagia (n = 8, 42.1%). CONCLUSION: Our results demonstrate excellent local control and OS with acceptable toxicity when utilizing postoperative radiotherapy in patients with squamous cell carcinoma of the upper and lower lip, despite unfavorable characteristics (advanced T or N stage and/or ECE).

Neurocognitive Outcomes in Pediatric Patients Following Brain Irradiation.

Advanced radiation techniques can reduce the severity of neurocognitive sequelae in young brain tumor patients. In the present analysis, we sought to compare neurocognitive outcomes after proton irradiation with patients who underwent photon radiotherapy (RT) and surgery. Neurocognitive outcomes were evaluated in 103 pediatric brain tumor patients (proton RT n = 26, photon RT n = 30, surgery n = 47) before and after treatment. Comparison of neurocognitive outcomes following different treatment modalities were analyzed over four years after treatment completion. Longitudinal analyses included 42 months of follow-up after proton RT and 55 months after photon RT and surgery. Neurocognitive assessment included standardized tests examining seven domains. A comparison of neurocognitive outcomes after RT (proton and photon with >90% additional surgery) and surgery showed no significant differences in any neurocognitive domain. Neurocognitive functioning tests after proton RT failed to identify alterations compared to baseline testing. Long-term follow up over four years after photon RT showed a decrease in non-verbal intelligence (-9.6%; p = 0.01) and visuospatial construction (-14.9%; p = 0.02). After surgery, there was a decline in non-verbal intelligence (-10.7%; p = 0.01) and processing speed (14.9%; p = 0.002). Differences in neurocognitive outcomes between RT and surgical cohorts in direct intermodal comparison at long-term follow-up were not identified in our study, suggesting that modern radiation therapy does not affect cognition as much as in the past. There were no alterations in long-term neurocognitive abilities after proton RT, whereas decline of processing speed, non-verbal intelligence, and visuospatial abilities were observed after both photon RT and surgery. Domains dependent on intact white matter structures appear particularly vulnerable to brain tumor treatment irrespective of treatment approach.

Screening and Psycho-Oncological Support for Patients With Head and Neck Cancer and Brain Malignancies Before Radiotherapy With Mask Fixation: Results of a Feasibility Study.

This single-center, single-arm trial investigates the feasibility of a psycho-oncological care program, which aims to reduce psychological distress and improve compliance with radiotherapy with mask fixation in patients with head and neck cancer or brain malignancies. The care program comprised (1) a screening/needs assessment and (2) the provision of a psycho-oncological intervention using imaginative stabilization techniques for distressed patients (distress due to anxiety ≥5) or in a case of subjective interest in the psycho-oncological intervention. Another allocation path to the intervention was directly through the radiation oncologist in charge who classified the patient as: in need of support to tolerate the immobilization device. Of a total of 1,020 screened patients, 257 (25.2%) patients indicated a distress ≥5 and 141 (13.8%) patients reported panic attacks. 25% of the patients reported a subjective interest in psycho-oncological support. A total of 35 patients received the psycho-oncological intervention, of which 74% were assigned by radiation oncologists. In this small patient cohort, no significant pre-post effects in terms of depression, anxiety, distress, and quality of life (mental and physical component scores) could be detected. Our results indicate a good feasibility (interdisciplinary workflow and cooperation, allocation by physicians in charge) of the psycho-oncological care program for this cohort of patients before radiotherapy with mask fixation. The screening results underline the high psychological distress and demand for psycho-oncological support. However, since the utilization of our intervention was low, future studies should reduce the barriers and improve compliance to psycho-oncological services by these patients.Clinical Trial Registration: https://www.drks.de/drks_web/setLocale_EN.do #DRKS00013493.

Postoperative Radiotherapy for Locally Advanced NSCLC: Implications for Shifting to Conformal, High-Risk Fields.

BACKGROUND: To examine the effect of radiotherapy field size on survival outcomes and patterns of recurrence in patients treated with postoperative radiotherapy (PORT) for non-small-cell lung cancer (NSCLC). METHODS: We retrospectively reviewed the records of 216 patients with T1-4 N1-2 NSCLC following surgery and PORT using whole mediastinum (WM) or high-risk (HR) nodal fields from 1998 to 2015. Survival rates were calculated using the Kaplan-Meier method. Univariate and multivariable analyses were conducted using Cox proportional hazards modeling for outcomes and logistic regression analysis for treatment toxicities. RESULTS: Median follow-up was 28 months (interquartile range [IQR] 13-75 months) and 38 months (IQR 19-73 months) for WM (n = 131) and HR (n = 84) groups, respectively. Overall survival (OS) was not significantly different between groups (median OS: HR 49 vs. WM 32 months; P = .08). There was no difference in progression-free survival (PFS), freedom from locoregional recurrence (LRR), or freedom from distant metastasis (P > .2 for all). Field size was not associated with OS, PFS, or LRR (P > .40 for all). LRR rates were 20% for HR and 26% for WM groups (P = .30). There was no significant difference in patterns of initial site of LRR between groups (P > .1). WM fields (OR 3.73, P = .001) and concurrent chemotherapy (odds ratio 3.62, P = .001) were associated with grade ≥2 toxicity. CONCLUSIONS: Locoregional control and survival rates were similar between PORT groups; an improved toxicity profile was observed in the HR group. Results from an ongoing prospective randomized clinical trial will provide further insight into the consequences of HR PORT fields.

Feasibility of Optical Surface-Guidance for Position Verification and Monitoring of Stereotactic Body Radiotherapy in Deep-Inspiration Breath-Hold.

BACKGROUND: Reductions in tumor movement allow for more precise and accurate radiotherapy with decreased dose delivery to adjacent normal tissue that is crucial in stereotactic body radiotherapy (SBRT). Deep inspiration breath-hold (DIBH) is an established approach to mitigate respiratory motion during radiotherapy. We assessed the feasibility of combining modern optical surface-guided radiotherapy (SGRT) and image-guided radiotherapy (IGRT) to ensure and monitor reproducibility of DIBH and to ensure accurate tumor localization for SBRT as an imaging-guided precision medicine. METHODS: We defined a new workflow for delivering SBRT in DIBH for lung and liver tumors incorporating SGRT and IGRT with cone beam computed tomography (CBCT) twice per treatment fraction. Daily position corrections were analyzed and for every patient two points retrospectively characterized: an anatomically stable landmark (predominately Schmorl's nodes or spinal enostosis) and a respiratory-dependent landmark (predominately surgical clips or branching vessel). The spatial distance of these points was compared for each CBCT and used as surrogate for intra- and interfractional variability. Differences between the lung and liver targets were assessed using the Welch t-test. Finally, the planning target volumes were compared to those of free-breathing plans, prepared as a precautionary measure in case of technical or patient-related problems with DIBH. RESULTS: Ten patients were treated with SBRT according this workflow (7 liver, 3 lung). Planning target volumes could be reduced significantly from an average of 148 ml in free breathing to 110 ml utilizing DIBH (p < 0.001, paired t-test). After SGRT-based patient set-up, subsequent IGRT in DIBH yielded significantly higher mean corrections for liver targets compared to lung targets (9 mm vs. 5 mm, p = 0.017). Analysis of spatial distance between the fixed and moveable landmarks confirmed higher interfractional variability (interquartile range (IQR) 6.8 mm) than intrafractional variability (IQR 2.8 mm). In contrast, lung target variability was low, indicating a better correlation of patients' surface to lung targets (intrafractional IQR 2.5 mm and interfractional IQR 1.7 mm). CONCLUSION: SBRT in DIBH utilizing SGRT and IGRT is feasible and results in significantly lower irradiated volumes. Nevertheless, IGRT is of paramount importance given that interfractional variability was high, particularly for liver tumors.

Radiographic Response of Vessel Involvement and Resectability After Neoadjuvant Chemoradiation in Patients With Locally Advanced Pancreatic Cancer.

OBJECTIVES: Survival of patients with locally advanced pancreatic cancer (LAPC) is improved when neoadjuvant chemoradiation enables subsequent surgical resection. Here, the authors assess changes in vessel involvement as a possible indicator of resectability. METHODS: Pancreatic gross tumor and all major abdominal vessels were contoured for 49 patients with unresectable LAPC before and after neoadjuvant chemoradiation. Changes were compared by paired t tests. Tumor-vessel relationships were automatically quantified using Medical Imaging Interaction Toolkit and examined for correlation with resectability and outcome. RESULTS: Tumor volumes were significantly reduced by chemoradiation (41 to 33 mL, P<0.0001). Maximum circumferential vessel involvement decreased for most patients and was statistically significant for the superior mesenteric (P<0.003) and splenic veins (P<0.038). Resection was possible in some patients and correlated positively with survival (28 vs. 15 mo, r=0.40), a decrease in CA 19.9 levels (r=0.48), and reduced involvement of most vessels. Nevertheless, surgical resection with a successful detachment of tumor tissue from major vessels was also achieved in some patients who did not show improvement in radiographic vessel involvement, but rather a reduction in tumor volume and CA 19.9 levels. CONCLUSIONS: The present analysis demonstrates that neoadjuvant chemoradiation can enable subsequent surgical resection in patients with LAPC. Complete resection substantially prolongs survival. Therefore, surgical exploration should be offered if vessel involvement is improved by chemoradiation and considered in radiographic unchanged vessel involvement if size and CA 19.9 levels decrease, as these factors may indicate resectable disease, too.

Rare entities in head-and-neck cancer: salvage re-irradiation with carbon ions.

BACKGROUND: The objective of this investigation is to evaluate the outcomes and toxicity of carbon-ion re-irradiation (CIR) in patients with rare head and neck cancers (HNC). There is a paucity of data regarding treatment approaches in this patient cohort, which we aim to address in this work. METHODS: Thirty-two (n = 32) consecutive patients with uncommon HNC treated between 2010 and 2017 were retrospectively analyzed in terms of clinical outcomes, patterns of failure, and toxicity. RESULTS: Mucoepidermoid carcinoma (MEC) was the most common histology (22%). Patients received a median cumulative dose equivalent in 2 Gy fractions (EQD2) after CIR of 128.6 Gy (range, 105.8-146.5 Gy). The local and distant control rates 1 year after CIR were 66 and 72%. No serious acute or late toxicity (≥ grade 3) after CIR was observed. CONCLUSIONS: CIR may represent an effective and safe treatment alternative to palliative systemic therapies in these rare indications.

Cachectic Body Composition and Inflammatory Markers Portend a Poor Prognosis in Patients with Locally Advanced Pancreatic Cancer Treated with Chemoradiation.

BACKGROUND: Patients with pancreatic cancer often develop cancer cachexia, a complex multifactorial syndrome with weight loss, muscle wasting and adipose tissue depletion with systemic inflammation causing physical impairment. In patients with locally advanced pancreatic cancer (LAPC) neoadjuvant treatment is routinely performed to allow a subsequent resection. Herein, we assess body composition and laboratory markers for cancer cachexia both before and after neoadjuvant chemoradiation (CRT). METHODS: Subcutaneous fat (SCF), visceral fat (VF), skeletal muscle (SM), weight and laboratory parameters were determined longitudinally in 141 LAPC patients treated with neoadjuvant CRT. Changes during CRT were statistically analyzed and correlated with outcome and Kaplan-Meier curves were plotted. Different prognostic factors linked to cachexia were assessed by uni- and multivariable cox proportional hazards models. RESULTS: There was a significant decrease in weight as well as SCF, VF and SM during CRT. The laboratory parameter C-reactive protein (CRP) increased significantly, whereas there was a significant decrease in leukocyte count, hemoglobin, albumin and cholinesterase as well as in the tumor marker CA 19.9. Cachectic weight loss, sarcopenia, reductions in body compartments SCF, VF and SM, and changes in laboratory markers as well as resection affected survival in univariable analysis. In multivariable analysis, weight loss >5% (HR 2.8), reduction in SM >5% (HR 5.5), an increase in CRP (HR 2.2) or CA 19.9 (HR 1.9), and resection (HR 0.4) remained independently associated with survival, whereas classical cachexia and sarcopenia did not. Interestingly, the subgroup of patients with cachectic weight loss >5% or SM reduction >5% during CRT did not benefit from resection (median survival 12 vs. 27 months). CONCLUSIONS: Persistent weight loss and muscle depletion during CRT as well as systemic inflammation after CRT impacted survival more than cachexia or sarcopenia according classical definitions.

Continued Weight Loss and Sarcopenia Predict Poor Outcomes in Locally Advanced Pancreatic Cancer Treated with Chemoradiation.

Background: Surgical resection offers the best chance of survival in patients with pancreatic cancer, but those with locally advanced disease (LAPC) are usually not surgical candidates. This cohort often receives either neoadjuvant chemotherapy or chemoradiation (CRT), but unintended weight loss coupled with muscle wasting (sarcopenia) can often be observed. Here, we report on the predictive value of changes in weight and muscle mass in 147 consecutive patients with LAPC treated with neoadjuvant CRT. Methods: Clinicopathologic data were obtained via a retrospective chart review. The abdominal skeletal muscle area (SMA) at the third lumbar vertebral body was determined via computer tomographic (CT) scans as a surrogate for the muscle mass and skeletal muscle index (SMI) calculated. Uni- and multi-variable statistical tests were performed to assess for impact on survival. Results: Weight loss (14.5 vs. 20.3 months; p = 0.04) and loss of muscle mass (15.1 vs. 22.2 months; p = 0.007) were associated with poor outcomes. The highest survival was observed in patients who had neither cachectic weight loss nor sarcopenia (27 months), with improved survival seen in those who ultimately received a resection (23 vs. 10 months; p < 0.001). Cox regression revealed that either continued weight loss or continued muscle wasting (SMA reduction) was predictive of poor outcomes, whereas a sarcopenic SMI was not. Conclusions: Loss of weight and lean muscle in patients with LAPC is prognostic when persistent. Therefore, both should be assessed longitudinally and considered before surgery.

Impact of Performance Status and Comorbidity on Palliative Radiation Treatment Tolerance and End-Of-Life Decision-Making.

PURPOSE: Previous studies have indicated a relationship between functional status and comorbidity on overall survival when treating patients with bone and brain metastases. However, the degree to which these findings have been integrated into modern-day practice remains unknown. This study examines the impact of performance measures, including Karnofsky Performance Status (KPS) and comorbidity, on palliative radiation therapy treatment tolerance and fractionation schedule. The relationship between a shorter fractionation schedule (SFx) and pending mortality is examined. METHODS AND MATERIALS: This study included patients who were treated with palliative intent to the brain or bone between January 1, 2016 and June 30, 2016. Demographic and medical characteristics collected included KPS score (stratified as good [90-100], fair [70-80], and poor (≤60]), socioeconomic status, comorbidity (binary measure using the Adult Comorbidity Evaluation-27 scale), site of metastatic disease, and treatment facility. Univariable analyses were performed using the Cox proportional hazards regression model to assess the impact of the variables on the prescribed number of fractions (binary measure, ≥10 [long fractionation schedule], and <10 [SFx]), and major treatment interruptions (MTIs; defined as missing ≥3 radiation therapy treatment days or ending treatment prematurely). RESULTS: A total of 145 patients were eligible for study inclusion, including 95 patients who were treated for bony metastatic disease and 50 patients for brain metastases. High comorbidity (P = .029) and both fair (P = .051) and poor (P = .065) functional status were associated with more frequent MTIs. However, high comorbidity and low KPS score were not associated with shorter treatment plans. In addition, patients with an earlier time to death were not more likely to receive an SFx (P = .871). CONCLUSIONS: Low KPS and elevated comorbidity scores predict for a poorer prognosis and more frequent MTIs; however, there was no indication that physicians incorporated this information in the fractionation scheduling.

Disparities in adherence to head and neck cancer follow-up guidelines.

OBJECTIVES: In this study, we aim to determine the frequency of adherence to National Comprehensive Cancer Network follow-up guidelines in a population of head and neck cancer patients who received curative treatment. We will also assess the impact of race, ethnicity, socioeconomic status, and treatment setting on utilization of follow-up care. METHODS: This study included patients with biopsy-proven, nonmetastatic oropharyngeal or laryngeal cancer treated with radiotherapy between January 1, 2014, and June 30, 2016, at a safety-net hospital or adjacent private academic hospital. Components of follow-up care analyzed included an appointment with a surgeon or radiation oncologist within 3 months and posttreatment imaging of the primary site within 6 months. Univariable and multivariable analyses were conducted using a logistic regression model to estimate odds ratios and corresponding 95% confidence intervals. RESULTS: Two hundred and thirty-four patients were included in this study. Of those, 88.8% received posttreatment imaging of the primary site within 6 months; 88.5% attended a follow-up appointment with a radiation oncologist within 3 months; and 71.1% of patients attended a follow-up appointment with a surgeon within 3 months. On multivariable analysis, private academic hospital treatment versus safety-net hospital treatment was associated with increased utilization of both surgical and radiation oncology follow-up. Non-Hispanic black (NHB) patients, Hispanic patients, and those with a low socioeconomic status were also less likely to receive follow-up. CONCLUSION: Safety-net hospital treatment, socioeconomic status, Hispanic ethnicity, and NHB race were associated with decreased follow-up service utilization. Quality improvement initiatives are needed to reduce these disparities. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:2303-2308, 2019.

Dosimetric effects of the Smit sleeve on high-dose-rate brachytherapy tandem and ovoids plans for patients with locally advanced cervical cancer.

PURPOSE: Smit sleeves are used to facilitate insertion of the intrauterine tandem during brachytherapy for cervical cancer. When a tandem and ovoids system is used the base of the Smit sleeve displaces the ovoids distally. The dosimetric impact of this displacement is not known. Herein we performed a dosimetric analysis to quantify this impact on the integral dose and dose delivered to the organs at risk (OARs). MATERIAL AND METHODS: Eleven high-dose-rate brachytherapy plans in which a Smit sleeve was used with a tandem and ovoids were reviewed. A second set of plans was generated modifying the position of the ovoids to simulate absence of the Smit sleeve. The high-risk clinical tumor volume (HR-CTV) dose coverage was maintained the same for both sets of plans by appropriately rescaling the dwell times of the simulated plan. The mean integral dose, D2cc to the OARs (bladder, bowel, sigmoid and rectum) and the ICRU rectum point dose were compared between the original and modified plans using a paired two-sample t-test. RESULTS: Simulating removal of the Smit sleeve was associated with an average reduction in the mean integral dose of 6.1% (p < 0.001) and an average reduction of 10.9% (p = 0.004) to the rectal D2cc. Doses to the remaining OARs decreased to a lesser magnitude with only that of the sigmoid being statistically significant. CONCLUSIONS: The use of a Smit sleeve with a tandem and ovoids system could lead to the delivery of a higher mean integral dose to achieve similar HR-CTV coverage. In addition, it could increase the dose to surrounding OARs, primarily the rectum. The clinical significance of these findings is unknown, but the potential dosimetric impact of using a Smit sleeve should be taken into consideration during the planning when this device is used.

Magnetic Resonance-guided External Beam Radiation and Brachytherapy for a Patient with Intact Cervical Cancer.

Radiation treatment verification has improved significantly over the past decades. The field has moved from film X-rays and skin marks to fiducial tracking and daily cone beam computed tomography (CBCT) for tumor localization. We now have the ability to perform daily on-board magnetic resonance imaging (MRI), which provides superior soft tissue contrast compared to computed tomography (CT). In the management of cervical cancer, the brachytherapy literature has demonstrated that MRI allows for better delineation of the high-risk clinical target volume (HR-CTV) and the use of MRI-guided brachytherapy has translated into improved treatment outcomes. Consensus contouring guidelines for intensity modulated radiation therapy (IMRT) for cervical cancer advise including the whole uterus in the target volume and adding large planning target volume (PTV) margins to account for inter-fractional uterine motion and target motion resulting from variable rectal and bladder filling. MRI-guided radiation therapy (MRgRT) systems enable the possibility to precisely delineate the target volume on a daily basis and to perform truly adaptive delivery. This advancement in technology provides the opportunity to explore how external beam treatment volumes could be safely reduced for better sparing of pelvic organs for the benefit of our patients with cervical cancer. We describe the MR-guided definitive external beam radiation therapy and brachytherapy for a 32-year-old woman with intact cervical cancer. We contoured the uterus, bladder, rectum, and gross tumor volume (GTV) on each of her 25 set-up MRIs. We demonstrate a steady reduction in the GTV and increased displacement of the uterus and GTV as the GTV decreased in size. The findings presented suggest that cervical cancer could greatly benefit from an adaptive MRgRT approach.

Nutrition and Swallowing Therapy in Head and Neck Cancer: Utilization of Care and Preventative Efficacy.

PURPOSE: To examine the impact of ethnicity, Spanish language preference, socioeconomic status, and treatment setting on utilization of supportive services before radiotherapy (RT) among head and neck cancer patients and to determine whether a lack of these services is associated with an increased rate of adverse events. METHODS AND MATERIALS: Demographic, staging, and treatment details were retrospectively collected for patients treated at a safety-net hospital (n = 56) or adjacent private academic hospital (n = 183) from January 1, 2014, to June 30, 2016. Supportive care services evaluated were limited to speech/swallowing therapy and nutrition therapy. Adverse events and performance measures examined included weight loss during RT, gastric tube placement, emergency department visits, hospital admissions, and missed RT days. RESULTS: On multivariable analysis, patients receiving treatment at the safety-net hospital were less likely to receive speech/swallowing services. Receiving speech/swallowing therapy before treatment was associated with less weight loss during treatment, and in conjunction with nutrition therapy, was associated with fewer missed RT days. CONCLUSION: Safety-net hospital treatment was associated with a lack of utilization of pre-RT speech/swallowing therapy which in turn was associated with increased weight loss. Interventions aimed at improving utilization of these services would improve treatment tolerance and patient outcomes.

Reirradiation of Recurrent Pediatric Brain Tumors after Initial Proton Therapy.

PURPOSE: The use of reirradiation for recurrent pediatric brain tumors has been increasing, but the effect of repeat radiation on critical cranial structures is unknown. METHODS AND MATERIALS: Between July 2009 and May 2013, the records of 12 pediatric patients initially treated with proton therapy and then with reirradiation for recurrent brain tumors were retrospectively reviewed for toxicity and outcomes. Initial and repeat radiation dose distributions were deformed and merged to determine the maximum dose to 0.03 cm3 of the optic chiasm, optic nerves, spinal cord, brainstem, cochleae, pituitary, and uninvolved brain, and to 1 cm3 of the brainstem and brain on individual and composite plans. These dosimetric results were compared with auditory, neurocognitive, ophthalmologic, and endocrine outcomes to identify radiation-associated toxicities. RESULTS: Median follow-up was 3.5 years from diagnosis. Median ages at initial and repeat radiation were 4.6 and 6.7 years, respectively. All patients initially received proton radiotherapy to a median tumor dose of 55.8 Gy relative biological effectiveness (RBE) (range, 45 to 60 Gy [RBE]). At progression, patients completed a second course of radiation to local fields (n = 7) or the craniospinal axis (n = 5) with a median tumor dose of 40 Gy (RBE) (range, 20 to 54 Gy [RBE]). Median progression-free survival was 22.7 months from the last day of the second radiation course. No patient developed central nervous system necrosis requiring treatment. Of evaluable patients, none developed radiation-related high-grade hearing loss (n = 11), visual pathway deficit (n = 10), or significant change in pre- and post-reirradiation full-scale intelligence quotient (n = 4). Of 11 evaluable patients, 4 (36.4%) developed secondary hypothyroidism and 1 (9.1%) developed growth hormone deficiency. CONCLUSION: Repeat radiation for recurrent brain tumors after proton therapy may be performed in the pediatric population with acceptable short- and long-term toxicity.

Gamma knife stereotactic radiosurgery in the treatment of brainstem metastases: The MD Anderson experience.

BACKGROUND: Brainstem metastases (BSMs) represent a significant treatment challenge. Stereotactic radiosurgery (SRS) is often used to treat BSM. We report our experience in the treatment of BSM with Gamma Knife SRS (GK_SRS). METHODS: The records of 1962 patients with brain metastases treated with GK_SRS between 2009 and 2013 were retrospectively reviewed. Seventy-four patients with 77 BSMs and follow-up brain imaging were identified. Local control (LC), overall survival (OS), progression-free survival (PFS), and toxicity were assessed. RESULTS: Median follow-up was 5.5 months (range, 0.2-48.5 months). Median tumor volume was 0.13 cm3 (range, 0.003-5.58 cm3). Median treatment dose was 16 Gy (range, 10-20 Gy) prescribed to 50% isodose line (range, 40%-86%). Crude LC was 94% (72/77). Kaplan-Meier estimate of median OS was 8.5 months (95% CI, 5.6-9.4 months). Symptomatic lesions and larger lesions, especially size ≥2 cm3, were associated with worse LC (HR = 8.70, P = .05; HR = 14.55, P = .02; HR = 62.81, P < .001) and worse OS (HR = 2.00, P = .02; HR = 2.14, P = .03; HR = 2.81, P = .008). Thirty-six percent of BSMs were symptomatic, of which 36% (10/28) resolved after SRS and 50% (14/28) had stable or improved symptoms. Actuarial median PFS was 3.9 months (95% CI, 2.7-4.9 months). Midbrain location was significant for worse PFS (HR = 2.29, P = .03). Toxicity was low (8%, 6/74), with size and midbrain location associated with increased toxicity (HR 1.57, P = .05; HR = 5.25, P = .045). CONCLUSIONS: GK_SRS is associated with high LC (94%) and low toxicity (8%) for BSMs. Presence of symptoms or lesion size ≥ 2 cm3 was predictive of worse LC and OS.

Ethical analysis as a tool for addressing treatment controversies: radiotherapy timing in children with orbital rhabdomyosarcoma as a case example.

PURPOSE: The treatment of orbital rhabdomyosarcoma is a topic of debate between North American and European clinicians, with the utility of radiation therapy as part of initial management in question. Despite differences in philosophy, the dominant North American approach of upfront radiation and the dominant European approach of radiation only in the event of recurrence yield a similar rate of overall survival. We sought to identify the ethical arguments for each approach. METHODS: Established moral principles and appeals in contemporary medical ethics were utilized to identify the ethical arguments supporting each treatment approach. The potential for technologic advances to alter the analysis was considered. RESULTS: Emphasizing the principle of beneficence, the North American approach seeks to reduce recurrence rates. In contrast, the European approach seeks to avoid radiation-induced sequelae, emphasizing the principle of nonmaleficence. Both approaches are based on well-established ethical principles, evidence, and clinical experience. Thus, both approaches currently appear to have legitimacy and should be included in the informed consent process. However, if treatment-related toxicity is reduced through improvements in radiation delivery, the North American approach could emerge as ethically superior. CONCLUSIONS: Ethical analysis can aid in addressing challenges that arise when professional practices and perspectives differ in the management of cancer patients.

Stereotactic radiosurgery for intraventricular brain metastases.

OBJECT: The authors' institution previously reported a 69% rate of crude local control for surgical management of lateral ventricle metastases at the University of Texas MD Anderson Cancer Center. For comparison, the authors here report their institutional experience with use of stereotactic radiosurgery (SRS) to treat intraventricular metastases. METHODS: To identify patients with intraventricular metastases for this retrospective review, the authors queried an institutional SRS database containing the medical records of 1962 patients with 5800 brain metastases who consecutively underwent SRS from June 2009 through October 2013. End points assessed were local control (crude and locoregional), distant failure-free survival, progression-free survival, and overall survival. RESULTS: Of the 1962 records examined, those for 25 (1.3%) patients with 30 (0.52%) intraventricular metastases were identified. Median patient age at SRS was 55.8 years. The most common primary malignancy was renal cell carcinoma (n = 13), followed by melanoma (n = 7) and breast adenocarcinoma (n = 5). Median tumor volume was 0.75 cm(3) (range 0.01-5.6 cm(3)). Most lesions were located in the lateral ventricles (n = 25, 83.3%) and were treated to a median dose of 20 Gy (range 14-20 Gy). A total of 12 (48%) patients received whole-brain radiation therapy, most (n = 10) before SRS. With a median follow-up of 11.4 months (range 1.6-39.2 months), the rate of crude local control was 93.3%, and the rates of 6-month and 1-year actuarial locoregional control were 85.2% and 56.2%, respectively. The median overall survival time after SRS was 11.6 months (range 1.3-38.9 months), and the 6-month and 1-year actuarial rates were 87.1% and 46.7%, respectively. Disease dissemination developed in 7 (28%) patients as a second intraventricular metastatic lesion (n = 3, 12%), leptomeningeal disease (n = 3, 12%), or both (n = 1, 4%). Radiographic changes developed in 5 (20%) patients and included necrosis (n = 2, 8%) and hemorrhage (n = 3, 12%). A primary diagnosis of renal cell carcinoma was associated with an improved rate of distant failure-free survival (p = 0.05) and progression-free survival (p = 0.08). CONCLUSIONS: SRS provides excellent local control for intraventricular metastases, with acceptable treatment-related toxicity, thereby supporting nonsurgical treatment for these lesions. The propensity for intraventricular dissemination among intraventricular metastases seems to be histologically dependent.

Clinical outcomes and patterns of failure in pineoblastoma: a 30-year, single-institution retrospective review.

OBJECTIVE: To update outcomes and assess prognostic factors in the modern, multimodality treatment of patients with pineoblastoma. METHODS: The medical records of patients with pineoblastoma evaluated at the M.D. Anderson Cancer Center between 1982 and 2012 were reviewed retrospectively. RESULTS: Thirty-one patients with medical records suitable for review were identified. The majority of patients were female (67.7%) with a median age at diagnosis of 18.2 years (range, 0.3-52.8 years). Twenty-one patients underwent surgical resection, recorded as gross total (n = 9) or subtotal (n = 12) resections. Thirty patients received radiation with photon-based therapy (n = 16), proton-based therapy (n = 13), or radiosurgery (n = 1) to a median craniospinal irradiation dose of 36 Gy (range, 23.4-40 Gy) and a median focal dose of 54 Gy (range, 40-58.4 Gy). Twenty-eight patients received chemotherapy before (n = 10), during (n = 10), and after (n = 22) radiation. Median overall survival was 8.7 years for the entire cohort, with 2-, 5-, and 10- year actuarial rates of 89.5%, 69.4%, and 48.6%, respectively. Median disease-free survival was 10 years with 2-, 5-, and 10- year actuarial rates of 84.3%, 62.6%, and 55.7%, respectively. Univariate analysis failed to correlate age, sex, or extent of surgical resection with disease-free or overall survival. CONCLUSIONS: Modern, multimodality treatment of pineoblastoma yields a high rate of overall survival, with acceptable short- and long-term toxicity. A greater M-stage at presentation and development of disease recurrence correlate with worse overall survival. Patients who received focal radiation initially experienced a greater rate of disease recurrence compared with those treated to the craniospinal axis.