Schild, Steven E.

Estimating post-treatment ambulatory status can improve treatment personalization of patients irradiated for malignant spinal cord compression (MSCC). A new clinical score was developed from data of 283 patients treated with radiotherapy alone in prospective trials. Radiotherapy regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, other bone metastases, visceral metastases, time developing motor deficits, ambulatory status, performance score, sensory deficits, and sphincter dysfunction were evaluated. For factors with prognostic relevance in the multivariable logistic regression model after backward stepwise variable selection, scoring points were calculated (post-radiotherapy ambulatory rate in % divided by 10) and added for each patient. Four factors (primary tumor type, sensory deficits, sphincter dysfunction, ambulatory status) were used for the instrument that includes three prognostic groups (17–21, 22–31, and 32–37 points). Post-radiotherapy ambulatory rates were 10%, 65%, and 97%, respectively, and 2-year local control rates were 100%, 75%, and 88%, respectively. Positive predictive values to predict ambulatory and non-ambulatory status were 97% and 90% using the new score, and 98% and 79% using the previous instrument. The new score appeared more precise in predicting non-ambulatory status. Since patients with 32–37 points had high post-radiotherapy ambulatory and local control rates, they may not require surgery.

AbstractBackgroundBoth dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil‐beam‐scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important.PurposeTo perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis.MethodsA total of 113 head‐and‐neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 control patients were used to derive the feature‐based volume constraint of mandible osteoradionecrosis. The AE regions were contoured and the corresponding dose–LET volume histograms of AE regions were generated for all patients in the AE group. We selected high LET voxels (the highest 5% of each dose bin) with a range of moderate‐to‐high dose (≥∼40‐Gy relative biological effectiveness) as critical voxels. Critical voxels that were contiguous with each other were grouped into clusters. Each cluster was considered a potential independent seed spot for AE initialization. Seed spots were displayed in a 2D dose–LET plane based on their mean dose and LET to derive the descriptive features of AE initialization. A volume constraint of mandible osteoradionecrosis was then established based on the extracted features using a receiver operating characteristic curve.ResultsThe product of dose and LET (xBD) was found to be a descriptive feature of seed spots leading to AE initialization in this preliminary study. The derived xBD volume constraint for mandible osteoradionecrosis showed good performance with an area under curve of 0.87 (sensitivity of 0.714 and specificity of 0.807 in the leave‐one‐out cross‐validation) for the very limited patient data included in this study.ConclusionOur exploratory study showed that both dose and LET were observed to be important in AE initializations. The derived xBD volume constraint could predict mandible osteoradionecrosis reasonably well in the very limited H&N cancer patient data treated with PBS included in this study.

AbstractPurpose/ObjectivesHolmium laser enucleation of the prostate (HoLEP) is commonly performed in patients with significant bladder outlet obstruction. However, there are few reports on the toxicity of external beam irradiation (RT) for prostate cancer in patients after prior HoLEP. In this study, we evaluate the side effects and treatment outcomes of RT after HoLEP.Materials/MethodsEighteen patients who had HoLEP and subsequently received RT for prostate cancer were included. Data collected included patient and disease characteristics, urinary function, and radiation dose. Acute and late urinary (GU) and gastrointestinal (GI) side effects were evaluated. Disease control and survival rates were calculated using Kaplan–Meier method.ResultsMedian follow‐up was 18 months (range: 4–46 months). Median prostate volume was 107 ml before HoLEP and 24 ml after HoLEP. Median International Prostate Symptom Score (IPSS) was 17 (range: 5–32) before HoLEP. Median decline in IPSS score after HoLEP was 7 (range: −2–21). On uroflow study, peak flow rate, and post‐void residual were significantly improved after HoLEP. After radiation, peak flow rate and average flow rate showed a decline but remained significantly improved compared to pre‐HoLEP measurements. Maximum acute Common Terminology Criteria for Adverse Events (CTCAE) adverse events were 12 grade 1 and 3 grade 2 for GU, and 3 grade 1 for GI, respectively. Maximum late adverse events were 13 grade 1 and 2 grade 2 for GU, and all grade 0 for GI, respectively. At last follow‐up, there were 8 grade 1 and 1 grade 2 late GU, and 3 grade 1 late GI adverse events, respectively. There was no significant increase in urinary incontinence after RT compared to before RT. The 18‐month biochemical control, local control, distant control rates were 78%, 94%, and 80%, respectively.ConclusionsPatients who received RT as definitive treatment for prostate cancer after prior HoLEP had low risk of serious acute and late side effects. HoLEP can be safely performed and should be considered in patients with significant bladder outlet obstruction and large prostate volume before RT.

For optimal personalization of treatment for metastatic spinal cord compression (MSCC), the patient’s survival prognosis should be considered. Estimation of survival can be facilitated by prognostic factors. This study investigated the prognostic value of pre-treatment preclinical markers, namely hemoglobin, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lactate dehydrogenase (LDH), and c-reactive protein (CRP), in 190 patients from two prospective trials who had poor or intermediate survival prognoses and were irradiated for MSCC with motor deficits. In addition, clinical factors including radiation regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, visceral metastases, other bone metastases, time developing motor deficits, ambulatory status, sensory function, and sphincter function were evaluated. On univariate analyses, NLR (p = 0.033), LDH (p < 0.001), CRP (p < 0.001), tumor type (p < 0.001), pre-radiotherapy ambulatory status (p < 0.001), and sphincter function (p = 0.011) were significant. In the subsequent Cox regression analysis, LDH (p = 0.007), CRP (p = 0.047), tumor type (p = 0.003), and ambulatory status (p = 0.010) maintained significance. In addition to clinical factors, preclinical markers may help in estimating the survival of patients irradiated for MSCC. Additional prospective trials are warranted.

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non–Small Cell Lung Cancer (NSCLC) provide recommended management for patients with NSCLC, including diagnosis, primary treatment, surveillance for relapse, and subsequent treatment. Patients with metastatic lung cancer who are eligible for targeted therapies or immunotherapies are now surviving longer. This selection from the NCCN Guidelines for NSCLC focuses on targeted therapies for patients with metastatic NSCLC and actionable mutations.

AbstractPurposeTo develop an online graphic processing unit (GPU)‐accelerated Monte Carlo‐based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS.Methods and MaterialsA four‐step workflow was developed using our in‐house developed GPU‐accelerated Monte Carlo‐based treatment planning system to implement online Monte Carlo‐based ART for PBS. The first step conducts diffeomorphic demon‐based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the verification plan in the second step and the reopotimized plan in the third step. The fourth step involves a two‐stage (before and after delivery) patient‐specific quality assurance (PSQA) of the reoptimized plan. The before‐delivery PSQA is to compare the plan dose to the dose calculated using an independent fast open‐source Monte Carlo code, MCsquare. The after‐delivery PSQA is to compare the plan dose to the dose recalculated using the log file (spot MU, spot position, and spot energy) collected during the delivery. Jaccard index (JI), dice similarity coefficients (DSCs), and Hausdorff distance (HD) were used to assess the quality of the propagated contours in the first step. A commercial plan evaluation software, ClearCheck™, was integrated into the workflow to carry out efficient plan evaluation. 3D Gamma analysis was used during the fourth step to ensure the accuracy of the plan dose from reoptimization. Three patients with three different disease sites were chosen to evaluate the feasibility of the online ART workflow for PBS.ResultsFor all three patients, the propagated contours were found to have good volume conformance [JI (lowest‐highest: 0.833–0.983) and DSC (0.909–0.992)] but suboptimal boundary coincidence [HD (2.37–20.76 mm)] for organs‐at‐risk. The verification dose evaluated by ClearCheck™ showed significant degradation of the target coverage due to the interfractional anatomical changes. Reoptimization on the vCT resulted in great improvement of the plan quality to a clinically acceptable level. 3D Gamma analyses of PSQA confirmed the accuracy of the plan dose before delivery (mean Gamma index = 98.74% with a threshold of 2%/2 mm/10%), and after delivery based on the log files (mean Gamma index = 99.05% with a threshold of 2%/2 mm/10%). The average time cost for the complete execution of the workflow was around 858 s, excluding the time for manual intervention.ConclusionThe proposed online ART workflow for PBS was demonstrated to be efficient and effective by generating a reoptimized plan that significantly improved the plan quality.

Abstract Background Pineoblastoma is a rare brain tumor usually diagnosed in children. Given its rarity, no pineoblastoma-specific trials have been conducted. Studies have included pineoblastoma accruing for other embryonal tumors over the past 30 years. These included only occasional children with pineoblastoma, making clinical features difficult to interpret and determinants of outcome difficult to ascertain. Patients and Methods Centrally or independently reviewed series with treatment and survival data from North American and Australian cases were pooled. To investigate associations between variables, Fisher’s exact tests, Wilcoxon-Mann-Whitney tests, and Spearman correlations were used. Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models were used in survival analyses. Results We describe a pooled cohort of 178 pineoblastoma cases from Children’s Oncology Group (n = 82) and institutional series (n = 96) over 30 years. Children &lt;3 years of age have significantly worse survival compared to older children, with 5-year progression-free survival (PFS) and overall survival (OS) estimates of 13.5 ± 5.1% and 16.2 ± 5.3%, respectively, compared with 60.8 ± 5.6% and 67.3 ± 5.0% for ≥3 years old (both P &lt; .0001). Multivariable analysis showed male sex was associated with worse PFS in children &lt;3 years of age (hazard ratio [HR] 3.93, 95% CI 1.80-8.55; P = .0006), suggestive of sex-specific risks needing future validation. For children ≥3 years of age, disseminated disease at diagnosis was significantly associated with an inferior 5-year PFS of 39.2 ± 9.7% (HR 2.88, 95% CI 1.52-5.45; P = .0012) and 5-year OS of 49.8 ± 9.1% (HR 2.87, 95% CI 1.49-5.53; P = .0016). Conclusion Given the rarity of this tumor, prospective, collaborative international studies will be vital to improving the long-term survival of these patients.

In 2005, a randomized trial showed that addition of surgery to radiotherapy improved outcomes in patients with metastatic spinal cord compression (MSCC). Since then, only a few studies compared radiotherapy plus surgery to radiotherapy alone. We performed a retrospective matched-pair study including data from prospective cohorts treated after 2005. Seventy-nine patients receiving radiotherapy alone were matched to 79 patients assigned to surgery plus radiotherapy (propensity score method) for age, gender, performance score, tumor type, affected vertebrae, other bone or visceral metastases, interval tumor diagnosis to MSCC, time developing motor deficits, and ambulatory status. Improvement of motor function by ≥1 Frankel grade occurred more often after surgery plus radiotherapy (39.2% vs. 21.5%, p = 0.015). No significant differences were found for post-treatment ambulatory rates (59.5% vs. 67.1%, p = 0.32), local progression-free survival (p = 0.47), overall survival (p = 0.51), and freedom from in-field recurrence of MSCC (90.1% vs. 76.2% at 12 months, p = 0.58). Ten patients (12.7%) died within 30 days following radiotherapy alone and 12 patients (15.2%) died within 30 days following surgery (p = 0.65); 36.7% of surgically treated patients did not complete radiotherapy as planned. Surgery led to significant early improvement of motor function and non-significantly better long-term control. Patients scheduled for surgery must be carefully selected considering potential benefits and risk of perioperative complications.

AbstractIntroductionPatients with small‐cell lung cancer (SCLC) have a very poor prognosis. However, a subset of SCLC achieves long‐term survival. The objective of this study was to investigate factors and pattern of long‐term survival in patients with limited‐stage small cell lung cancer (LS‐SCLC) who achieved a complete response (CR) after chemoradiotherapy.Patient and MethodsThis was a single‐center retrospective study. The analysis of hazard ratio (HR) and 95% confidence interval (CI) was performed using Cox proportional hazards model. For pattern analysis, the date of recurrence was used as the endpoint. The nominal categorical variables were analyzed by the χ2 test. Survival was estimated using the Kaplan–Meier model, and the results were reported as the median and interquartile range.ResultsWe identified 162 patients, median age was 64.7 (56.2–70.2) years, and 94 (58%) were females. Eighty‐one patients (50%) had recurrence during follow‐up. Gastroesophageal reflux disease (GERD) (HR, 0.65; 95% CI, 0.45–0.93; p = 0.016) and neurological paraneoplastic syndrome (PNS) (HR, 0.46; 95% CI, 0.29–0.72; p < 0.001) were independent factors associated with improved overall survival (OS). Patients with GERD had prolonged recurrence free survival (RFS) compared to patients without GERD (median, 29.1 months vs. 13.9 months, p < 0.001), whereas patients with neurological PNS had a reduced recurrence rate compared to those patients without neurological PNS (No. [%], 8 [20.5] vs. 73 [59.3], p < 0.001).ConclusionsPatients with LS‐SCLC achieving a CR after chemoradiotherapy, GERD, and neurological PNS were associated with improved OS. GERD and neurological PNS were associated with longer RFS and lower recurrence rate, respectively.

Patients with small cell lung cancer (SCLC) are at significant risk of developing brain metastases during their disease course. Prophylactic cranial irradiation (PCI) has been incorporated into SCLC treatment guidelines to diminish the risk of developing brain metastases. In 2007, a randomized trial suggested that PCI decreases the incidence of brain metastases and prolongs overall survival (OS) in patients with extensive-stage SCLC (ES-SCLC) who have responded to initial therapy. However, this study did not include modern central nervous system imaging with CT or MRI prior to randomization. A more recent Japanese trial with MRI staging and surveillance demonstrated that PCI diminished the incidence of brain metastases but did not improve survival. This review examines the largest clinical studies, controversies, and future directions of PCI in patients with ES-SCLC.