A 44-year-old male initially presented with a right thalamic brain tumor that was confirmed with stereotactic biopsy to be glioblastoma (GBM). The patient was treated with radiotherapy and temozolomide for 6 weeks. At 1 month after completing chemoradiation therapy, the patient underwent follow-up imaging that revealed the primary lesion had mildly responded to chemoradiation, but a secondary lesion had developed along the biopsy needle tract. This secondary lesion was outside of the field of radiation therapy for the primary tumor and concluded to be intracranial spread of GBM along the biopsy tract. The patient's final imaging 4 months after initial diagnosis revealed the primary and secondary lesions had enlarged. Subsequently, the patient clinically deteriorated and died 7 months after initial diagnosis.
Objectives: The patterns of care for salivary gland adenoid cystic carcinomas (ACC) are unknown. We sought to assess predictors of receiving postoperative radiation and/or chemotherapy for patients with nonmetastatic, definitively resected ACC, as well as report unexpected nodal disease. Methods: The National Cancer Data Base was queried for definitively resected nonmetastatic ACC from 2004 to 2014. Logistic regression, Kaplan-Meier, and Cox proportional-hazard models were utilized. Propensity-score matched analysis was employed to reduce confounding variables. Results: A total of 3,136 patients met entry criteria: 2,252 (71.8%) received postoperative radiation, with 223 (7.4%) also receiving concurrent chemotherapy. Median follow-up was 4.87 years. In clinically lymph node negative (cN0) patients, 7.4% had pathologically positive lymph nodes (pN) + after elective neck dissection. Patients who lived closer to their treatment facility and had positive margins were more likely to receive postoperative radiation. Black patients and uninsured patients were less likely to receive radiation. Older age, male sex, advancing stage, and positive surgical margins were associated with worse overall survival (OS). With limited follow-up, receipt of radiation or chemotherapy was not associated with OS. Conclusion: Postoperative radiation was frequently given for resected ACC, with a minority receiving chemotherapy. Black patients and uninsured patients were less likely to receive radiation. Postoperative radiation and/or chemotherapy had no association with OS but were given in greater frequency in more advanced disease, and our series is limited by short follow-up. The disparity findings for this rare disease need to be addressed in future studies. Level of Evidence: 2c Laryngoscope, 129:377–386, 2019.
In attempt to improve long-term disease control outcomes for high-risk prostate cancer, numerous clinical trials have tested the addition of chemotherapy (CTX)—either adjuvant or neoadjuvant—to definitive local therapy, either radical prostatectomy (RP) or radiation therapy (RT). Neoadjuvant trials generally confirm safety, feasibility, and pre-RP PSA reduction, but rates of pathologic complete response are rare, and no indications for neoadjuvant CTX have been firmly established. Adjuvant regimens have included CTX alone or in combination with androgen deprivation therapy (ADT). Here we provide a review of the relevant literature, and also quantify utilization of CTX in the definitive management of localized high-risk prostate cancer by querying the National Cancer Data Base. Between 2004 and 2013, 177 patients (of 29,659 total) treated with definitive RT, and 995 (of 367,570 total) treated with RP had CTX incorporated into their treatment regimens. Low numbers of RT + CTX patients precluded further analysis of this population, but we investigated the impact of CTX on overall survival (OS) for patients treated with RP +/− CTX. Disease-free survival or biochemical-recurrence-free survival are not available through the National Cancer Data Base. Propensity-score matching was conducted as patients treated with CTX were a higher-risk group. For nonmatched groups, OS at 5-years was 89.6% for the CTX group vs. 95.6%, for the no-CTX group (P < 0.01). The difference in OS between CTX and no-CTX groups did not persist after propensity-score matching, with 5-year OS 89.6% vs. 90.9%, respectively (Hazard ratio 0.99; P = 0.88). In summary, CTX was not shown to improve OS in this retrospective study. Multimodal regimens—such as RP followed by ADT, RT, and CTX; or RT in conjunction with ADT followed by CTX—have shown promise, but long-term follow-up of randomized data is required.
Radiation therapy to treat cancer has evolved significantly since the discovery of x-rays. Yet, radiation therapy still has room for improvement in reducing side effects and improving control of cancer. Safer and more effective delivery of radiation has led us to novel techniques and use of biomaterials. Biomaterials in combination with radiation and chemotherapy have started to appear in pre-clinical explorations and clinical applications, with many more on the horizon. Biomaterials have revolutionized the field of diagnostic imaging, and now are being cultivated into the field of theranostics, combination therapy, and tissue protection. This review summarizes recent development of biomaterials in radiation therapy in several application areas.
Purpose
Radical cystectomy currently remains the standard of care for muscle-invasive bladder cancer (MIBC). However, surgery can be associated with considerable morbidity and mortality, including the removal of the bladder. An alternative strategy is to preserve the bladder through concurrent chemo-radiation following a maximal trans-urethral resection of the tumor. National protocols using a bladder preservation approach have demonstrated disease-specific outcomes comparable to radical cystectomy in selected patients, but these results have not been replicated in previously reported population-based series. Here, we describe an outcomes analysis of patients with MIBC treated with either radical surgery or bladder-preserving chemo-radiation (BPCRT) for those patients meeting BPCRT criterion using the National Cancer Database (NCDB).
Methods and Materials
Using the NCDB, patients with AJCC clinical T2-3, N0, M0 urothelial carcinoma diagnosed between 2004–2013 were included for analysis. Only patients treated with definitive intent with either radical cystectomy or concurrent chemotherapy and radiation after a maximal transurethral tumor resection were included. Propensity-score matching was employed.
Results
Among 8,454 eligible patients, 7,276 (86%) underwent radical cystectomy, and 1,178 (14%) underwent BPCRT. Patients undergoing BPCRT were significantly older (median age 77 vs 68, p <0.001) and had higher Charlson-Deyo comorbidity scores (p=0.002). Using propensity-matched analysis, 1,002 patients remained in each cohort, and there was no significant difference in survival found between the two cohorts (median OS: 2.7 vs 3.0 (p=0.20); 4-year OS: 39.1% and 42.6% (p=0.15), for BPCRT and surgery, respectively). Additionally, the hazard ratio (HR) of surgery versus BPCRT decreased over time, with an initial HR of 1.27 favoring BPCRT which decreased by a factor of 0.85 per year.
Conclusions
From 2004–2013, approximately 14% of patients from the NCDB who potentially met bladder preservation criteria underwent the procedure. Our propensity-matched analysis is the only report of its kind to demonstrate similar survival outcomes with bladder preservation when patients are properly selected. This study is also the first to demonstrate a dynamic hazard ratio between radical surgery and BPCRT over time.
Keywords: MIBC, trimodality therapy, bladder preservation therapy, bladder cancer
Allele-specific copy number analysis of tumors (ASCAT) assesses copy number variations (CNV) while accounting for aberrant cell fraction and tumor ploidy. We evaluated if ASCAT-assessed CNV are associated with survival outcomes in 56 patients with WHO grade IV gliomas. Tumor data analyzed by Affymetrix OncoScan FFPE Assay yielded the log ratio (R) and B-allele frequency (BAF). Input into ASCAT quantified CNV using the segmentation function to measure copy number inflection points throughout the genome. Quantified CNV was reported as log R and BAF segment counts. Results were confirmed on The Cancer Genome Atlas (TCGA) glioblastoma dataset.
25 (44.6%) patients had MGMT hyper-methylated tumors, 6 (10.7%) were IDH1 mutated. Median follow-up was 36.4 months. Higher log R segment counts were associate with longer progression-free survival (PFS) [hazard ratio (HR) 0.32, p < 0.001], and overall survival (OS) [HR 0.45, p = 0.01], and was an independent predictor of PFS and OS on multivariable analysis. Higher BAF segment counts were linked to longer PFS (HR 0.49, p = 0.022) and OS (HR 0.49, p = 0.052). In the TCGA confirmation cohort, longer 12-month OS was seen in patients with higher BAF segment counts (62.3% vs. 51.9%, p = 0.0129) and higher log R (63.6% vs. 55.2%, p = 0.0696). Genomic CNV may be a novel prognostic biomarker for WHO grade IV glioma patient outcomes.
by
Hal Scherz;
Caroline Jansen;
Roshan Prabhu;
Meghana Pagadala;
Prasanthi Chappa;
Subir Goyal;
Chengjing Zhou;
Stewart Neill;
Nataliya Prokhnevska;
Maria Cardenas;
Kimberly Hoang;
Jim Zhong;
Mylin Torres;
Suzanna Logan;
Jeffrey Olson;
Edjah Nduom;
Luke Del Balzo;
Kirtesh Patel;
Stuart Burri;
Anthony Asher;
Scott Wilkinson;
Ross Lake;
Krisitin Higgins;
Pretesh Patel;
Vishal Dhere;
Adam Sowalsky;
Mohammad Khan;
Haydn Kissick;
Zachary Buchwald
The CD8 + T-cell response is prognostic for survival outcomes in several tumor types. However, whether this extends to tumors in the brain, an organ with barriers to T cell entry, remains unclear. Here, we analyzed immune infiltration in 67 brain metastasis (BrM) and found high frequencies of PD1 + TCF1 + stem-like CD8 + T-cells and TCF1- effector-like cells. Importantly, the stem-like cells aggregate with antigen presenting cells in immune niches, and niches were prognostic for local disease control. Standard of care for BrM is resection followed by stereotactic radiosurgery (SRS), so to determine SRS’s impact on the BrM immune response, we examined 76 BrM treated with pre-operative SRS (pSRS). pSRS acutely reduced CD8 + T cells at 3 days. However, CD8 + T cells rebounded by day 6, driven by increased frequency of effector-like cells. This suggests that the immune response in BrM can be regenerated rapidly, likely by the local TCF1 + stem-like population.
Background: Adjuvant radiotherapy (RT) can help achieve local control (LC) and reduce hormonal overexpression for pituitary adenomas (PAs). Prior reports involved Gamma Knife or older linear accelerator (LINAC) techniques. The aim of this study was to report long-term outcomes for modern LINAC RT. Methods: Institutional retrospective review of LINAC RT for PAs with minimum 3 years of magnetic resonance imaging follow-up was performed. Hormonal control was defined as biochemical remission in absence of medications targeting hormone excess. LC defined using Response Evaluation Criteria in Solid Tumors on surveillance magnetic resonance imaging. Progression-free survival defined as time alive with LC without return of or worsening hormonal excess from secretory PA. Kaplan-Meier and Cox proportional hazard models used. Results: From 2003 to 2017, 140 patients with PAs (94 nonsecretory, 46 secretory) were treated with LINAC RT (105 fractionated RT, 35 radiosurgery) with median follow-up of 5.35 years. Techniques included fixed gantry intensity-modulated radiotherapy (51.4%), dynamic conformal arcs (9.3%), and volumetric modulated arc therapy (39.3%). Progression-free survival at 5 years was 95.3% for secretory tumors and 94.8% for nonsecretory tumors. Worse progression-free survival was associated with larger planning target volume on multivariable analysis (hazard ratio 2.87, 95% confidence interval 1.01–8.21, P = 0.049). Hormonal control at 5 years was 50.0% and associated with higher dose to tumor (hazard ratio 1.05, 95% confidence interval 1.02–1.09, P = 0.005) and number of surgeries (hazard ratio 1.74, 95% confidence interval 1.05–2.89, P = 0.032). Patients requiring any pituitary hormone replacement increased from 57.9% to 70.0% after RT. Conclusions: Modern LINAC RT for patients with PAs was safe and effective for hormonal control and LC. No difference in LC was noted for functional versus nonfunctional tumors, possibly owing to higher total dose and daily image guidance.
Purpose:
To introduce a novel, deep-learning method to generate synthetic computed tomography (SCT) scans for proton treatment planning and evaluate its efficacy.
Materials and Methods:
50 Patients with base of skull tumors were divided into 2 nonoverlapping training and study cohorts. Computed tomography and magnetic resonance imaging pairs for patients in the training cohort were used for training our novel 3-dimensional generative adversarial network (cycleGAN) algorithm. Upon completion of the training phase, SCT scans for patients in the study cohort were predicted based on their magnetic resonance images only. The SCT scans obtained were compared against the corresponding original planning computed tomography scans as the ground truth, and mean absolute errors (in Hounsfield units [HU]) and normalized cross-correlations were calculated. Proton plans of 45 Gy in 25 fractions with 2 beams per plan were generated for the patients based on their planning computed tomographies and recalculated on SCT scans. Dose-volume histogram endpoints were compared. A c-index analysis along 3 cardinal planes intercepting at the isocenter was performed. Proton distal range along each beam was calculated.
Results:
Image quality metrics show agreement between the generated SCT scans and the ground truth with mean absolute error values ranging from 38.65 to 65.12 HU and an average of 54.55 6 6.81 HU and a normalized cross-correlation average of 0.96 6 0.01. The dosimetric evaluation showed no statistically significant differences (p. 0.05) within planning target volumes for dose-volume histogram endpoints and other metrics studied, with the exception of the dose covering 95% of the target volume, with a relative difference of 0.47%. The c-index analysis showed an average passing rate of 98% with a 10% threshold and 2% and 2-mm criteria. Proton ranges of 48 of 50 beams (96%) in this study were within clinical tolerance adopted by 4 institutions.
Conclusions:
This study shows our method is capable of generating SCT scans with acceptable image quality, dose distribution agreement, and proton distal range compared with the ground truth. Our results set a promising approach for magnetic resonance imaging-based proton treatment planning.
Background: Glioblastomas (GBMs) are aggressive brain tumors despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Spectroscopic magnetic resonance imaging (sMRI), which measures levels of specific brain metabolites, can delineate regions at high risk for GBM recurrence not visualized on contrast-enhanced (CE) MRI. We conducted a clinical trial to assess the feasibility, safety, and efficacy of sMRI-guided RT dose escalation to 75 Gy for newly diagnosed GBMs. Methods: Our pilot trial (NCT03137888) enrolled patients at 3 institutions (Emory University, University of Miami, Johns Hopkins University) from September 2017 to June 2019. For RT, standard tumor volumes based on T2-FLAIR and T1w-CE MRIs with margins were treated in 30 fractions to 50.1 and 60 Gy, respectively. An additional high-risk volume based on residual CE tumor and Cho/NAA (on sMRI) ≥2× normal was treated to 75 Gy. Survival curves were generated by the Kaplan-Meier method. Toxicities were assessed according to CTCAE v4.0. Results: Thirty patients were treated in the study. The median age was 59 years. 30% were MGMT promoter hypermethylated; 7% harbored IDH1 mutation. With a median follow-up of 21.4 months for censored patients, median overall survival (OS) and progression-free survival were 23.0 and 16.6 months, respectively. This regimen appeared well-tolerated with 70% of grade 3 or greater toxicity ascribed to TMZ and 23% occurring at least 1 year after RT. Conclusion: Dose-escalated RT to 75 Gy guided by sMRI appears feasible and safe for patients with newly diagnosed GBMs. OS outcome is promising and warrants additional testing. Based on these results, a randomized phase II trial is in development.