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At least 1,135 records · Page 63
All sourcesNASA NTRSDOE OSTI
DOE OSTI2016

Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

Purpose: In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy. Methods and Materials: Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined using follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival. Results: A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence. Conclusions: Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Patterns of Recurrence in Electively Irradiated Lymph Node Regions After Definitive Accelerated Intensity Modulated Radiation Therapy for Head and Neck Squamous Cell Carcinoma

Purpose: To provide a comprehensive risk assessment on the patterns of recurrence in electively irradiated lymph node regions after definitive radiation therapy for head and neck cancer. Methods and Materials: Two hundred sixty-four patients with stage cT2-4N0-2M0 squamous cell carcinoma of the oropharynx, larynx, or hypopharynx treated with accelerated intensity modulated radiation therapy between 2008 and 2012 were included. On the radiation therapy planning computed tomography (CT) scans from all patients, 1166 lymph nodes (short-axis diameter ≥5 mm) localized in the elective volume were identified and delineated. The exact sites of regional recurrences were reconstructed and projected on the initial radiation therapy planning CT scan by performing coregistration with diagnostic imaging of the recurrence. Results: The actuarial rate of recurrence in electively irradiated lymph node regions at 2 years was 5.1% (95% confidence interval 2.4%-7.8%). Volumetric analysis showed an increased risk of recurrence with increasing nodal volume. Receiver operating characteristic analysis demonstrated that the summed long- and short-axis diameter is a good alternative for laborious volume calculations, using ≥17 mm as cut-off (hazard ratio 17.8; 95% confidence interval 5.7-55.1; P<.001). Conclusions: An important risk factor was identified that can help clinicians in the pretreatment risk assessment of borderline-sized lymph nodes. Not overtly pathologic nodes with a summed diameter ≥17 mm may require a higher than elective radiation therapy dose. For low-risk elective regions (all nodes <17 mm), the safety of dose de-escalation below the traditional 45 to 50 Gy should be investigated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Elective Nodal Irradiation and Patterns of Failure in Head and Neck Cancer After Primary Radiation Therapy

Purpose: The delineation of elective clinical target volumes in head and neck cancer (HNC) is important; however, the extent of lymph node levels necessary to include is debated. A comprehensive analysis of recurrence patterns in a large cohort of patients with HNC was performed, with an emphasis on recurrence in the retropharyngeal region and level IB. Methods and Materials: From 2005 to 2012, 942 patients with oropharyngeal, hypopharyngeal, laryngeal or oral cavity carcinomas were curatively treated with primary radiation therapy. The median follow-up period was 34 months, and 77% of the patients underwent intensity modulated radiation therapy. The retropharyngeal region was only routinely included in cases of involvement of the posterior pharynx wall and level IB only in cases of involvement of the oral cavity. In patients with regional recurrence, the anatomic site of the recurrence was assessed from the surgical descriptions or computed tomography scans and compared with the original radiation treatment plan (available from 2007 onward). The p16 status was available for 282 oropharynx carcinoma cases, with 65% p16-positive. Results: Of the 942 patients, 376 (40%) developed recurrences: 228 (24.2%) local, 123 (13.1%) regional, and 109 (11.6%) distant. In 700 patients with available treatment plans, retropharyngeal and level IB recurrence was observed in 2 and 7 patients, respectively. Eight patients (1.1%) had recurrence in a lymph node level not included in their primary treatment plan. For oropharynx carcinoma, the locoregional control rate (90% vs 70%) but not distant control rate (92% vs 87%), was significantly better in the p16-positive than in the p16-negative patients. Although fewer recurrences developed in the p16-positive group, patients with recurrence of p16-positive tumors were more likely to develop recurrence in distant sites. Conclusions: Retropharyngeal or level IB recurrence after primary HNC radiation therapy is rare. Thus, inclusion of these regions in the elective treatment volumes should be limited to patients with involvement of the posterior pharyngeal wall or oral cavity.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Clinical Outcomes and Patterns of Disease Recurrence After Intensity Modulated Proton Therapy for Oropharyngeal Squamous Carcinoma

Purpose: A single-institution prospective study was conducted to assess disease control and toxicity of proton therapy for patients with head and neck cancer. Methods and Materials: Disease control, toxicity, functional outcomes, and patterns of failure for the initial cohort of patients with oropharyngeal squamous carcinoma (OPC) treated with intensity modulated proton therapy (IMPT) were prospectively collected in 2 registry studies at a single institution. Locoregional failures were analyzed by using deformable image registration. Results: Fifty patients with OPC treated from March 3, 2011, to July 2014 formed the cohort. Eighty-four percent were male, 50% had never smoked, 98% had stage III/IV disease, 64% received concurrent therapy, and 35% received induction chemotherapy. Forty-four of 45 tumors (98%) tested for p16 were positive. All patients received IMPT (multifield optimization to n=46; single-field optimization to n=4). No Common Terminology Criteria for Adverse Events grade 4 or 5 toxicities were observed. The most common grade 3 toxicities were acute mucositis in 58% of patients and late dysphagia in 12%. Eleven patients had a gastrostomy (feeding) tube placed during therapy, but none had a feeding tube at last follow-up. At a median follow-up time of 29 months, 5 patients had disease recurrence: local in 1, local and regional in 1, regional in 2, and distant in 1. The 2-year actuarial overall and progression-free survival rates were 94.5% and 88.6%. Conclusions: The oncologic, toxicity, and functional outcomes after IMPT for OPC are encouraging and provide the basis for ongoing and future clinical studies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Patterns and Timing of Failure for Diffuse Large B-Cell Lymphoma After Initial Therapy in a Cohort Who Underwent Autologous Bone Marrow Transplantation for Relapse

Purpose: To evaluate the location and timing of initial recurrence in patients with diffuse large B-cell lymphoma (DLBCL) who subsequently underwent high-dose chemotherapy with autologous stem cell transplant (HDC/ASCT), to direct approaches for disease surveillance, elucidate the patterns of failure of contemporary treatment strategies, and guide adjuvant treatment decisions. Methods and Materials: We analyzed consecutive patients with DLBCL who underwent HDC/ASCT between May 1992 and March 2014 at our institution. Of the 187 evaluable patients, 8 had incomplete data, and 79 underwent HDC/ASCT as a component of initial treatment for de novo or refractory DLBCL and were excluded from further analysis. Results: The median age was 50.8 years; the median time to relapse was 1.3 years. Patients were segregated according to the initial stage at diagnosis, with early stage (ES) defined as stage I/II and advanced stage (AS) defined as stage III/IV. In total, 40.4% of the ES and 75.5% of the AS patients relapsed in sites of initial disease; 68.4% of those with ES disease and 75.0% of those with AS disease relapsed in sites of initial disease only. Extranodal relapses were common (44.7% in ES and 35.9% in AS) and occurred in a variety of organs, although gastrointestinal tract/liver (n=12) was most frequent. Conclusions: Most patients with DLBCL who relapse and subsequently undergo HDC/ASCT initially recur in the previously involved disease site(s). Time to recurrence is brief, suggesting that frequency of screening is most justifiably greatest in the early posttherapy years. © 2016 Elsevier Inc.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Analysis of Lung Tumor Motion in a Large Sample: Patterns and Factors Influencing Precise Delineation of Internal Target Volume

Purpose/Objective: To evaluate lung tumor motion during respiration and to describe factors affecting the range and variability of motion in patients treated with stereotactic ablative radiation therapy. Methods and Materials: Log file analysis from online respiratory tumor tracking was performed in 145 patients. Geometric tumor location in the lungs, tumor volume and origin (primary or metastatic), sex, and tumor motion amplitudes in the superior-inferior (SI), latero-lateral (LL), and anterior-posterior (AP) directions were recorded. Tumor motion variability during treatment was described using intrafraction/interfraction amplitude variability and tumor motion baseline changes. Tumor movement dependent on the tumor volume, position and origin, and sex were evaluated using statistical regression and correlation analysis. Results: After analysis of >500 hours of data, the highest rates of motion amplitudes, intrafraction/interfraction variation, and tumor baseline changes were in the SI direction (6.0 ± 2.2 mm, 2.2 ± 1.8 mm, 1.1 ± 0.9 mm, and −0.1 ± 2.6 mm). The mean motion amplitudes in the lower/upper geometric halves of the lungs were significantly different (P<.001). Motion amplitudes >15 mm were observed only in the lower geometric quarter of the lungs. Higher tumor motion amplitudes generated higher intrafraction variations (R=.86, P<.001). Interfraction variations and baseline changes >3 mm indicated tumors contacting mediastinal structures or parietal pleura. On univariate analysis, neither sex nor tumor origin (primary vs metastatic) was an independent predictive factor of different movement patterns. Metastatic lesions in women, but not men, showed significantly higher mean amplitudes (P=.03) and variability (primary, 2.7 mm; metastatic, 4.9 mm; P=.002) than primary tumors. Conclusion: Online tracking showed significant irregularities in lung tumor movement during respiration. Motion amplitude was significantly lower in upper lobe tumors; higher interfraction amplitude variability indicated tumors in contact with mediastinal structures, although adhesion to parietal pleura did not necessarily reduce tumor motion amplitudes. The most variable lung tumors were metastatic lesions in women.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Patterns of Failure in Pediatric Rhabdomyosarcoma After Proton Therapy

Purpose: To report on the patterns of failure in children with rhabdomyosarcoma treated with proton therapy. Patients and Methods: Between February 2007 and November 2013, 66 children with a median age of 4.1 years (range, 0.6-15.3 years) diagnosed with nonmetastatic rhabdomyosarcoma were treated with proton therapy. Clinical target volume 1 was defined as the prechemotherapy tumor plus a 1-cm anatomically constrained margin. Clinical target volume 2 was defined as the postchemotherapy tumor (or tumor bed) plus a 0.5-cm anatomically constrained margin, further expanded to encompass potential pathways of spread, including soft tissue infiltrated with tumor at diagnosis. Results: Of the 66 children, 11 developed locally progressive disease at a median of 16 months (range, 14-32 months), for an actuarial 2-year local control rate of 88%. Among the children who progressed, median age and tumor size at diagnosis were 6.7 years (range, 0.6-16 years) and 6 cm (range, 2-8 cm), respectively. Of the recurrences, 64% and 36% were embryonal and alveolar, respectively. Disease progression was observed in 7 (64%) parameningeal, 2 (18%) head and neck (other), and 2 (18%) bladder/prostate subsites. At diagnosis, 8 of 11 patients who developed a recurrence were Intergroup Rhabdomyosarcoma Study stage 3, and all 11 were group III. Of the relapses, 100% (11 of 11) were confirmed as in-field within the composite 95% isodose line. One of the 11 patients (9%) developed a new simultaneous regional nodal recurrence outside of the previously treated radiation field. Conclusion: Early data suggest that the sharp dosimetric gradient associated with proton therapy is not associated with an increased risk of marginal failure. Routine use of a 0.5- to 1-cm clinical target volume 1/2 margin with highly conformal proton therapy does not compromise local control in children diagnosed with rhabdomyosarcoma with unfavorable risk features.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Patterns of Care in Proton Radiation Therapy for Pediatric Central Nervous System Malignancies

Purpose: Proton beam therapy (PBT) potentially allows for improved sparing of normal tissues, hopefully leading to decreased late side effects in children. Using a national registry, we sought to perform a patterns-of-care analysis for children receiving PBT for primary malignancies of the central nervous system (CNS). Methods and Materials: Using the National Cancer Data Base, we identified pediatric patients with primary CNS malignancies that were diagnosed between 2004 and 2012. We used a standard t test for comparison of means and χ{sup 2} testing to identify differences in demographic and clinical characteristics. Univariate and multivariate logistical regression was applied to identify predictors of PBT use. Results: We identified 4637 pediatric patients receiving radiation therapy from 2004 to 2012, including a subset of 267 patients treated with PBT. We found that PBT use increased with time from <1% in 2004 to 15% in 2012. In multivariate logistical regression, we found the following to be predictors of receipt of PBT: private insurance, the highest income bracket, younger age, living in a metropolitan area, and residing >200 miles from a radiation treatment facility (P<.05). Conclusions: We noted the proportion of children receiving PBT to be significantly increasing over time from <1% to 15% from 2004 to 2012. We also observed important disparities in receipt of PBT based on socioeconomic status. Children from higher-income households and with private insurance were more likely to use this expensive technology. As we continue to demonstrate the potential benefits of PBT in children, efforts are needed to expand the accessibility of PBT for children of all socioeconomic backgrounds and regions of the country.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Patterns of Care in Adjuvant Therapy for Resected Oral Cavity Squamous Cell Cancer in Elderly Patients

Purpose: To characterize the patterns of care and potential barriers to access to care for elderly patients with oral cavity cancer in the adjuvant setting. Methods and Materials: We performed a retrospective cohort study using the National Cancer Data Base and identified patients with resected oral cavity squamous cell carcinoma diagnosed between 2004 and 2012, who survived for ≥3 months after surgery. We used logistic regression models to assess the association between age (<70, 70-79, and ≥80 years) and the receipt of adjuvant therapy within 3 months of surgery. We additionally assessed the association between patient and tumor characteristics and the receipt of adjuvant therapy among those aged ≥70 years. Results: A total of 25,829 patients were included in the study. Compared with those aged <70 years, older patients were more likely to have no neck dissection or have fewer lymph nodes dissected and were less likely to receive adjuvant therapy than younger patients. Among our cohort, 11,361 patients (44%) had pathologic T3-T4 disease or N2-N3 disease, and 4185 patients (16%) had extracapsular nodal extension or positive surgical margins. In multivariate analyses controlling for comorbidity and demographic characteristics, older age was independently associated with lower odds of receiving adjuvant radiation therapy in the subgroup with T3 or T4 disease or N2 or N3 disease and adjuvant chemoradiation therapy in the positive extracapsular nodal extension or positive surgical margin subgroup. Among elderly patients, both greater patient distance from reporting facility and older age were associated with lower odds of receiving both adjuvant radiation therapy (odds ratio 0.66; 95% confidence interval, 0.55-0.81) and chemoradiation therapy (odds ratio 0.56; 95% confidence interval, 0.40-0.79). Conclusions: In a national hospital-based cohort of patients with oral cavity cancer, elderly patients were less likely to receive adjuvant radiation or chemoradiation therapy. Greater patient distance from reporting facility, in addition to older age, was associated with lower odds of receiving both adjuvant radiation therapy and adjuvant chemoradiation therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Prognostic Factors and Patterns of Locoregional Failure After Surgical Resection in Patients With Cholangiocarcinoma Without Adjuvant Radiation Therapy: Optimal Field Design for Adjuvant Radiation Therapy

Purpose: To identify prognostic factors and patterns of local failure in patients with cholangiocarcinoma (CCA), after surgical resection in the absence of adjuvant radiation, for optimal definition of target volumes encompassing the majority of local recurrences. Methods and Materials: A chart review was performed in patients who underwent resection for primary CCA (intrahepatic, hilar, and distal) between 1999 and 2014. Local failure was defined as recurrence in a theoretical reasonable postoperative radiation volume. This includes the cut surface of liver, biliary anastomosis, hilum, portal nodes, celiac nodes, peri-pancreatic nodes, gastro-hepatic nodes, and retroperitoneal nodes. Patients who received adjuvant radiation were excluded. Results: A total of 189 patients underwent surgical resection for CCA, of whom 145 patients had sufficient follow-up. Median follow-up was 41.6 months (95% confidence interval 35.4-48.7 months). Of the 145 cases, 102 were intrahepatic and 43 were hilar/distal CCA. Adjuvant chemotherapy was given in 38 cases (26%), of which 20 (54%) were gemcitabine-based. Eighty-six patients (59%) had a documented recurrence, of whom 44 (51%) had a locoregional component. Among patients who had a recurrence, 23 (27%) had a recurrence at the biliary anastomosis and/or cut liver surface. Twenty-eight patients (32.6%) had a recurrence in the regional lymph nodes, most prevalent in the portal (16.3%) and retroperitoneal (17.4%) lymph nodes. Univariable analysis identified tumor size, any vascular invasion, presence of satellites, stage/nodal status, and receipt of chemotherapy as significant prognostic factors of overall recurrence among intrahepatic patients. Presence of satellites, and stage 3/Nx status remained statistically significant in multivariable modeling. Conclusions: The areas at highest risk for locoregional recurrence after surgical resection for primary CCA are the biliary anastomosis/cut liver surface, portal lymph nodes, and retroperitoneal lymph nodes. Although these results need to be validated, adjuvant radiation should possibly cover these areas to maximize locoregional control.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Patterns of Failure in Patients With Double Hit or Double Expressor Lymphomas: Implications for Radiation Therapy

Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL).

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Patterns and Predictors of Failure in Recurrent or Refractory Large B-Cell Lymphomas After Chimeric Antigen Receptor T-Cell Therapy

Chimeric antigen receptor T-cell (CAR T) therapy is capable of eliciting durable responses in patients with relapsed/refractory (R/R) lymphomas. However, most treated patients relapse. Patterns of failure after CAR T have not been previously characterized, and may provide insights into the mechanisms of resistance guiding future treatment strategies.

62 RADIOLOGY AND NUCLEAR MEDICINE↗