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At least 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Cancer Incidence Trends in Successive Social Generations in the US

Importance: The incidence of some cancers in the US is increasing in younger age groups, but underlying trends in cancer patterns by birth year remain unclear. Objective: To estimate cancer incidence trends in successive social generations. Design, Setting, and Participants: In this cohort study, incident invasive cancers were ascertained from the Surveillance, Epidemiology, and End Results (SEER) program’s 13-registry database (November 2020 submission, accessed August 14, 2023). Invasive cancers diagnosed at ages 35 to 84 years during 1992 to 2018 within 152 strata were defined by cancer site, sex, and race and ethnicity. Exposure: Invasive cancer. Main Outcome and Measures: Stratum-specific semiparametric age-period-cohort (SAGE) models were fitted and incidence per 100 000 person-years at the reference age of 60 years was calculated for single-year birth cohorts from 1908 through 1983 (fitted cohort patterns [FCPs]). The FCPs and FCP incidence rate ratios (IRRs) were compared by site for Generation X (born between 1965 and 1980) and Baby Boomers (born between 1946 and 1964). Results: A total of 3.8 million individuals with invasive cancer (51.0% male; 8.6% Asian or Pacific Islander, 9.5% Hispanic, 10.4% non-Hispanic Black, and 71.5% non-Hispanic White) were included in the analysis. In Generation X vs Baby Boomers, FCP IRRs among women increased significantly for thyroid (2.76; 95% CI, 2.41-3.15), kidney (1.99; 95% CI, 1.70-2.32), rectal (1.84; 95% CI, 1.52-2.22), corpus uterine (1.75; 95% CI, 1.40-2.18), colon (1.56; 95% CI, 1.27-1.92), and pancreatic (1.39; 95% CI, 1.07-1.80) cancers; non-Hodgkins lymphoma (1.40; 95% CI, 1.08-1.82); and leukemia (1.27; 95% CI, 1.03-1.58). Among men, IRRs increased for thyroid (2.16; 95% CI, 1.87-2.50), kidney (2.14; 95% CI, 1.86-2.46), rectal (1.80; 95% CI, 1.52-2.12), colon (1.60; 95% CI, 1.32-1.94), and prostate (1.25; 95% CI, 1.03-1.52) cancers and leukemia (1.34; 95% CI, 1.08-1.66). Lung (IRR, 0.60; 95% CI, 0.50-0.72) and cervical (IRR, 0.71; 95% CI, 0.57-0.89) cancer incidence decreased among women, and lung (IRR, 0.51; 95% CI, 0.43-0.60), liver (IRR, 0.76; 95% CI, 0.63-0.91), and gallbladder (IRR, 0.85; 95% CI, 0.72-1.00) cancer and non-Hodgkins lymphoma (IRR, 0.75; 95% CI, 0.61-0.93) incidence decreased among men. For all cancers combined, FCPs were higher in Generation X than for Baby Boomers because gaining cancers numerically overtook falling cancers in all groups except Asian or Pacific Islander men. Conclusions and Relevance: In this model-based cohort analysis of incident invasive cancer in the general population, decreases in lung and cervical cancers in Generation X may be offset by gains at other sites. Generation X may be experiencing larger per-capita increases in the incidence of leading cancers than any prior generation born in 1908 through 1964. On current trajectories, cancer incidence could remain high for decades.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

Are Carotid Stent Fractures Clinically Significant?

Purpose: Late stent fatigue is a known complication after carotid artery stenting (CAS) for cervical carotid occlusive disease. The purpose of this study was to determine the prevalence and clinical significance of carotid stent fractures. Materials and Methods: A single-center retrospective review of 253 carotid bifurcation lesions treated with CAS and mechanical embolic protection from April 2001 to December 2009 was performed. Stent integrity was analyzed by two independent observers using multiplanar cervical plain radiographs with fractures classified into the following types: type I = single strut fracture; type II = multiple strut fractures; type III = transverse fracture; and type IV = transverse fracture with dislocation. Mean follow-up was 32 months. Results: Follow-up imaging was completed on 106 self-expanding nitinol stents (26 closed-cell and 80 open-cell stents). Eight fractures (7.5%) were detected (type I n = 1, type II n = 6, and type III n = 1). Seven fractures were found in open-cell stents (Precise n = 3, ViVEXX n = 2, and Acculink n = 2), and 1 fracture was found in a closed-cell stent (Xact n = 1) (p = 0.67). Only a previous history of external beam neck irradiation was associated with fractures (p = 0.048). No associated clinical sequelae were observed among the patients with fractures, and only 1 patient had an associated significant restenosis ({>=}80%) requiring reintervention. Conclusions: Late stent fatigue after CAS is an uncommon event and rarely clinically relevant. Although cell design does not appear to influence the occurrence of fractures, lesion characteristics may be associated risk factors.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Acute Stroke and Obstruction of the Extracranial Carotid Artery Combined with Intracranial Tandem Occlusion: Results of Interventional Revascularization

PurposeDue to high thrombus load, acute stroke patients with tandem obstructions of the extra- and intracranial carotid arteries or the middle cerebral artery show a very limited response to systemic thrombolysis. Interventional treatment with mechanical thrombectomy—often in combination with acute stenting of underlying atherosclerotic stenosis or dissection—is increasingly used. It has been shown that such complex interventions are technically feasible. The lack of optimal management strategies and clinical data encouraged us to review our acute stroke interventions in patient with anterior circulation tandem lesions to determine lesion patterns, interventional approaches, and angiographic or clinical outcomes.Patients and MethodsWe retrospectively analyzed a series of 39 consecutive patients with intracranial vessel occlusion of the anterior circulation simultaneously presenting with high-grade cervical internal carotid artery (ICA) stenosis or occlusion.ResultsEmergency ICA stent implantation was technically feasible in all patients, and intracranial recanalization with TICI ≥ 2b was reached in a large number of patients (64 %). Good clinical outcomes (mRS ≤ 2 at 3 months) were achieved in one third of the patients (36 %). Symptomatic hemorrhages occurred in four patients (10 %). Mortality was 10 %.ConclusionEndovascular recanalization of acute cervical carotid artery occlusion was technically feasible in all patients, and resulted in high extra- and intracranial revascularization rates. A trend for favorable clinical outcome was seen in a higher TICI score, younger age, good collateral status, and combined IV rTPA and endovascular therapy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Treatment of Metastatic Lymph Nodes in the Neck from Papillary Thyroid Carcinoma with Percutaneous Laser Ablation

PurposeTo assess the effectiveness of percutaneous laser ablation (PLA) of cervical lymph node metastases from papillary thyroid carcinoma.Materials and Methods24 patients (62.3 ± 13.2 year; range 32–80) previously treated with thyroidectomy, neck dissection, and radioiodine ablation underwent ultrasound-guided PLA of 46 {sup 18}FDG-PET/CT—positive metachronous nodal metastases. All patients were at high surgical risk or refused surgery and were unsuitable for additional radioiodine ablation. A 300 µm quartz fiber and a continuous-wave Nd-YAG laser operating at 1.064 mm were used. Technical success, rate of complications, rate of serological conversion, and local control at follow-up were derived. Fisher’s exact test and Mann–Whitney U test were used and Kaplan–Meier curve calculated.ResultsTechnical success was obtained in all 46 lymph nodes (100 %). There were no major complications. Thyroglobulin levels decreased from 8.40 ± 9.25 ng/ml before treatment to 2.73 ± 4.0 ng/ml after treatment (p = 0.011), with serological conversion in 11/24 (45.8 %) patients. Overall, local control was obtained in 40/46 (86.9 %) lymph nodes over 30 ± 11 month follow-up, with no residual disease seen at imaging in 19/24 (79.1 %) patients. Local control was achieved in 40/46 (86.9 %) lymph nodes at 1 year and in all of the 25 nodes (100 %) followed for 3 years. Estimated mean time to progression was 38.6 ± 2.7 m.ConclusionUltrasound-guided PLA is a feasible, safe, and effective therapy for the treatment of cervical lymph node metastases from papillary thyroid carcinoma.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

General Anesthesia Versus Conscious Sedation in Acute Stroke Treatment: The Importance of Head Immobilization

PurposeWhile today mechanical thrombectomy is an established treatment option for main branch occlusions in anterior circulation stroke, there is still an ongoing debate on the kind of anesthesia to be preferred. Introducing a simple method for head stabilization, we analyzed safety and duration of endovascular recanalization procedures under general anesthesia (GA) and conscious sedation (CS).MethodsWe retrospectively identified 84 consecutive patients who underwent mechanical thrombectomy owing to acute anterior circulation stroke. Fifty-three were treated under GA and 31 under CS equipped with a standard cervical collar to reduce head movement. We evaluated recanalization results, in-house time to start recanalization, procedure times, technical and clinical complication rates, and conversion rates from CS to GA.ResultsRecanalization of mTICI ≥2b was achieved in 80 % under CS and in 81 % under GA. Median in-house time to start recanalization for CS was 60 min (IQR 28; 44–72) and 77 min (IQR 23; 68–91) for GA (P = 0.001). Median procedure time under CS was 35 min (IQR 43; 69–25) and 41 min (IQR 43; 66–23) for GA (P = 0.9). No major complications such as ICH occurred in either group, and no conversions from CS to GA were necessary.ConclusionMechanical thrombectomy can be performed faster and safely under CS in combination with simple head immobilization using a standard cervical collar.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Neck management in head and neck squamous cell carcinomas: where do we stand?

Head and neck squamous-cell carcinomas (HNSCCs) have a significant lymph node tropism. This varies considerably depending on the primary tumor site and the Human Papillomavirus (HPV) status of the disease. The best therapeutic option, between up-front lymph node dissection and chemoradiotherapy (CRT) +/− followed by lymph node dissection in case of persistent lymphadenopathy or regional relapse, remains unclear. The purpose of this review is to discuss the pros and cons related to the different approaches of the neck management in HNSCC. A narrative review of the management of the cervical lymph nodes was undertaken. Searches of PubMed database were performed using the terms ‘neck management’ OR ‘cervical lymphadenopathies’ AND ‘head and neck neoplasms’. Recent advances in imaging, pathological analysis, surgery and radiotherapy let to personalize the type of lymph node dissection and, the volumes of radiation therapy. Excluding inoperable patients and unresectable diseases, N3 lymphadenopathies, as well as bulky N2 stages, specifically HPV− or necrotic nodes, would be in favor of an up-front surgical approach, while HPV+ diseases, and lymphadenopathies of unknown primary would support CRT first. However, efficacy of such strategies is challenged by a significant morbidity in the medium and long terms. In the absence of higher level of evidence, the decision-making tools for the neck dissection before or after the CRT are based on the Mehanna’s trial and retrospective studies with significant biases. Consequently, the approaches and the ensuing outcomes remain not homogenous depending on the centers’ experience, in the context of limited data, especially for N2–3 HPV− HNSCC.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Beam Attenuators and the Risk of Unrecognized Large-Fraction Irradiation of Critical Tissues

The use of radiation beam attenuators led to radiation injury of the spinal cord in one patient and of the peripheral nerve in another due to unsuspected large-fraction irradiation. The anatomic distribution of radiation dose was reconstructed in the sagittal plane for the patient who developed radiation myelopathy and in the axial plane for the patient who developed peripheral neuropathy. The actual dose delivered to the injured structure in each patient was taken from the dose distribution and recorded along with the time, number of fractions, and dose per fraction. The patient who developed radiation myelopathy received a total of 46.5 Gy in twenty-three 2.1 Gy fractions in 31 days to the upper cervical spinal cord where the thickness of the neck was less than the central axis thickness due to cervical lordosis and absence of a posterior compensating filter. The patient who developed peripheral neuropathy received 55 Gy in twenty-five 2.2 Gy fractions in 50 days to the femoral nerve using bolus over the groins and an anterior one-half value layer Cerrobend pelvic block to bias the dose anteriorly. Compensating filters and other beam attenuators should be used with caution because they may result in unsuspected large-fraction irradiation and total doses of radiation that exceed the tolerance of critical structures.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2016

E6D25E, HPV16 Asian variant shows specific proteomic pattern correlating in cells transformation and suppressive innate immune response

HPV16 Asian variant (HPV16As) containing E6D25E oncogene, is commonly associated with cervical cancers of Asian populations. To explore a mechanism of E6D25E oncoprotein in carcinogenesis, we compared protein profiles in human keratinocytes expressing E6D25E with E6 of HPV16 prototype (E6Pro). A human cervical keratinocyte cell line, HCK1T, was transduced with retroviruses containing E6D25E or E6Pro genes. Biological properties of E6D25E or E6Pro transduced HCK1T cells were characterized. Protein profiles of the transduced HCK1T cells were analyzed using 2D-PAGE and characterized by mass spectrometry and western blotting. Reactomes of modulated proteins were analyzed by using the Reactome Knowledgebase. The E6D25E and E6Pro oncoproteins were comparable for their abilities to degrade p53 and suppress the induction of p21, and induce cell proliferation. Interestingly, the protein profiles of the HCK1T cells transduced with E6D25E showed specific proteomic patterns different from those with E6Pro. Among altered proteins, more than 1.5-fold up- or down- regulation was observed in E6D25E-expressing cells for gp96 and keratin7 which involved in activation of TLR signaling and transformation of squamocolumnar junction cells, respectively. This report describes new cellular proteins specifically targeted by E6D25E oncoprotein that may contribute to impair immune response against viral infection and cell transformation associated with oncogenic property of HPV16As variant. - Highlights: • E6D25E HPV16 specifically modulates protein profile of human keratinocytes. • E6D25E HPV16 modulates protein profile which involves in TLR signalling and transformation of squamocolumnar junction cells. • E6D25E oncoprotein may correlate to impair of immune response against viral infection and cells transformation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Inhibition of ERK activity enhances the cytotoxic effect of peroxisome proliferator-activated receptor γ (PPARγ) agonists in HeLa cells

In this study, we examined whether the peroxisome proliferator-activated receptor γ (PPARγ) agonists, ciglitazone (CGZ) and troglitazone (TGZ), induce cell death in human cervical cancer HeLa cells. The cells were treated with a range of CGZ or TGZ doses for 24 or 48 h. Low concentrations of CGZ (≤10 μM) or TGZ (≤20 μM) had no effect on cell viability whereas higher doses induced cell death in a time- and dose-dependent manner as evidenced by the detection of activated caspase-3 and PARP cleavage. Treatment with the PPARγ antagonist GW9662 followed by PPARγ agonists did not increase CGZ- or TGZ-induced cell death, indicating that PPARγ agonists induced HeLa cell death independently of PPARγ. Moreover, ERK1/2 activation was observed at a CGZ concentration of 25 μM and a TGZ concentration of 35 μM, both of which induced cell death. To elucidate the role of ERK1/2 activated by the two PPARγ agonists, the effect of U0126, an inhibitor of ERK1/2, on PPARγ-agonist-induced cell death was examined. Treatment with 10 or 20 μM U0126 followed by CGZ or TGZ induced the down-regulation of ERK1/2 activity and a decrease in Bcl-2 expression accompanied by the collapse of mitochondrial membrane potential, which in turn significantly enhanced CGZ- or TGZ-induced apoptotic cell death. Our results suggest that PPARγ agonists are capable of inducing apoptotic cell death in HeLa cells independently of PPARγ and that inhibition of ERK1/2 activity offers a strategy to enhance the cytotoxicity of PPARγ agonists in the treatment of cervical cancer. - Highlights: • The PPARγ agonists CGZ and TGZ induce apoptotic cell death in HeLa cells. • CGZ or TGZ induces apoptotic cell death independently of PPARγ in HeLa cells. • Inhibition of ERK1/2 enhances CGZ- or TGZ-induced cell death via the collapse of MMP.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MYPT1 is targeted by miR-145 inhibiting viability, migration and invasion in 2D and 3D HeLa cultures

Highlights: • miR-143/145 affect viability, migration and invasion on monolayer and spheroid cultures. • miR-145 produces a stronger inhibitory effect and increases pMLC levels through MYPT1 targeting. • MYPT1 silencing by siRNAs reproduces miR-145 effects. The miR-143/145 cluster is down-regulated in cervical tumor cells suggesting a role in tumorigenesis including cytoskeleton remodeling, a key event for tumor progression. The aim of the present work was to determine the role of miR-143/145 in the modulation of the myosin regulator phospho-myosin light chain (pMLC). HeLa monolayer and tridimensional cultures were transfected with miR-143 or miR-145 mimics inhibiting cell viability, proliferation, migration and invasion, mainly through miR-145. MiR-145 transfection increased pMLC levels by targeting the MYPT1 subunit of the regulatory myosin phosphatase. MYPT1 knockdown by siRNAs reproduced miR-145 effects suggesting miR-145 as a tumor suppressor through MYPT1 targeting, leading to a subsequent increase of pMLC levels with implications for cervical cell viability, migration and invasion.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2012

International Brachytherapy Practice Patterns: A Survey of the Gynecologic Cancer Intergroup (GCIG)

Purpose: To determine current practice patterns with regard to gynecologic high-dose-rate (HDR) brachytherapy among international members of the Gynecologic Cancer Intergroup (GCIG) in Japan/Korea (Asia), Australia/New Zealand (ANZ), Europe (E), and North America (NAm). Methods and Materials: A 32-item survey was developed requesting information on brachytherapy practice patterns and standard management for Stage IB-IVA cervical cancer. The chair of each GCIG member cooperative group selected radiation oncology members to receive the survey. Results: A total of 72 responses were analyzed; 61 respondents (85%) used HDR. The three most common HDR brachytherapy fractionation regimens for Stage IB-IIA patients were 6 Gy for five fractions (18%), 6 Gy for four fractions (15%), and 7 Gy for three fractions (11%); for Stage IIB-IVA patients they were 6 Gy for five fractions (19%), 7 Gy for four fractions (8%), and 7 Gy for three fractions (8%). Overall, the mean combined external-beam and brachytherapy equivalent dose (EQD2) was 81.1 (standard deviation [SD] 10.16). The mean EQD2 recommended for Stage IB-IIA patients was 78.9 Gy (SD 10.7) and for Stage IIB-IVA was 83.3 Gy (SD 11.2) (p = 0.02). By region, the mean combined EQD2 was as follows: Asia, 71.2 Gy (SD 12.65); ANZ, 81.18 (SD 4.96); E, 83.24 (SD 10.75); and NAm, 81.66 (SD, 6.05; p = 0.02 for Asia vs. other regions).The ratio of brachytherapy to total prescribed dose was significantly higher for Japan (p = 0.0002). Conclusion: Although fractionation patterns may vary, the overall mean doses administered for cervical cancer are similar in Australia/New Zealand, Europe, and North America, with practitioners in Japan administering a significantly lower external-beam dose but higher brachytherapy dose to the cervix. Given common goals, standardization should be possible in future clinical trials.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Noninvasive and Curative Radiation Therapy for Sebaceous Carcinoma of the Eyelid

Purpose: Sebaceous carcinoma of the eyelid is a rare malignancy. Surgical excision remains the standard and most reliable curative treatment. However, surgery is sometimes not possible because many patients are elderly, and it frequently causes functional and cosmetic impairment of the eyelid. We therefore carried out a study to determine the role of radiation therapy in relation to sebaceous carcinoma of the eyelid. Methods and Materials: Thirteen patients with sebaceous carcinoma of the eyelid underwent radiation therapy with curative intent. There were 6 men and 7 women, and their ages at irradiation ranged from 60 to 85 years (median, 78 years). Only 1 patient had cervical lymph node metastasis, and none of the patients had distant metastasis. A total dose of 50 to 66.6 Gy (median, 60 Gy) was delivered to tumor sites in 22 to 37 fractions. Results: All irradiated tumors were controlled at a median follow-up period of 55 months. Only 1 patient had recurrence of cervical lymph node metastasis outside the radiation field, at 22 months after irradiation. The 5-year local progression-free and disease-free rates were 100% and 89%, respectively. The overall and disease-free survival rates at 5 years were 100% and 89%, respectively. Although acute and transient therapy-related reactions of Grade 2 or less were observed, there were no severe toxicities of Grade 3 or greater. Conclusions: Radiation therapy is a safe and effective treatment for patients with sebaceous carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Magnitude of Interfractional Vaginal Cuff Movement: Implications for External Irradiation

Purpose: To quantify the extent of interfractional vaginal cuff movement in patients receiving postoperative irradiation for cervical or endometrial cancer in the absence of bowel/bladder instruction. Methods and Materials: Eleven consecutive patients with cervical or endometrial cancer underwent placement of three gold seed fiducial markers in the vaginal cuff apex as part of standard of care before simulation. Patients subsequently underwent external irradiation and brachytherapy treatment based on institutional guidelines. Daily megavoltage CT imaging was performed during each external radiation treatment fraction. The daily positions of the vaginal apex fiducial markers were subsequently compared with the original position of the fiducial markers on the simulation CT. Composite dose-volume histograms were also created by summing daily target positions. Results: The average ({+-} standard deviation) vaginal cuff movement throughout daily pelvic external radiotherapy when referenced to the simulation position was 16.2 {+-} 8.3 mm. The maximum vaginal cuff movement for any patient during treatment was 34.5 mm. In the axial plane the mean vaginal cuff movement was 12.9 {+-} 6.7 mm. The maximum vaginal cuff axial movement was 30.7 mm. In the craniocaudal axis the mean movement was 10.3 {+-} 7.6 mm, with a maximum movement of 27.0 mm. Probability of cuff excursion outside of the clinical target volume steadily dropped as margin size increased (53%, 26%, 4.2%, and 1.4% for 1.0, 1.5, 2.0, and 2.5 cm, respectively.) However, rectal and bladder doses steadily increased with larger margin sizes. Conclusions: The magnitude of vaginal cuff movement is highly patient specific and can impact target coverage in patients without bowel/bladder instructions at simulation. The use of vaginal cuff fiducials can help identify patients at risk for target volume excursion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Unilateral Radiotherapy for the Treatment of Tonsil Cancer

Purpose: To assess, through a retrospective review, clinical outcomes of patients with squamous cell carcinoma of the tonsil treated at the M. D. Anderson Cancer Center with unilateral radiotherapy techniques that irradiate the involved tonsil region and ipsilateral neck only. Methods and Materials: Of 901 patients with newly diagnosed squamous cell carcinoma of the tonsil treated with radiotherapy at our institution, we identified 102 that were treated using unilateral radiotherapy techniques. All patients had their primary site of disease restricted to the tonsillar fossa or anterior pillar, with <1 cm involvement of the soft palate. Patients had TX (n = 17 patients), T1 (n = 52), or T2 (n = 33) disease, with Nx (n = 3), N0 (n = 33), N1 (n = 23), N2a (n = 21), or N2b (n = 22) neck disease. Results: Sixty-one patients (60%) underwent diagnostic tonsillectomy before radiotherapy. Twenty-seven patients (26%) underwent excision of a cervical lymph node or neck dissection before radiotherapy. Median follow-up for surviving patients was 38 months. Locoregional control at the primary site and ipsilateral neck was 100%. Two patients experienced contralateral nodal recurrence (2%). The 5-year overall survival and disease-free survival rates were 95% and 96%, respectively. The 5-year freedom from contralateral nodal recurrence rate was 96%. Nine patients required feeding tubes during therapy. Of the 2 patients with contralateral recurrence, 1 experienced an isolated neck recurrence and was salvaged with contralateral neck dissection only and remains alive and free of disease. The other patient presented with a contralateral base of tongue tumor and involved cervical lymph node, which may have represented a second primary tumor, and died of disease. Conclusions: Unilateral radiotherapy for patients with TX-T2, N0-N2b primary tonsil carcinoma results in high rates of disease control, with low rates of contralateral nodal failure and a low incidence of acute toxicity requiring gastrostomy.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Treatment Outcome of Medium-Dose-Rate Intracavitary Brachytherapy for Carcinoma of the Uterine Cervix: Comparison With Low-Dose-Rate Intracavitary Brachytherapy

Purpose: To evaluate and compare the efficacy of medium-dose-rate (MDR) and low-dose-rate (LDR) intracavitary brachytherapy (ICBT) for uterine cervical cancer. Methods and Materials: We evaluated 419 patients with squamous cell carcinoma of the cervix who were treated by radical radiotherapy with curative intent at Tokyo Women's Medical University from 1969 to 1999. LDR was used from 1969 to 1986, and MDR has been used since July 1987. When compared with LDR, fraction dose was decreased and fraction size was increased (1 or 2 fractions) for MDR to make the total dose of MDR equal to that of LDR. In general, the patients received a total dose of 60 to 70 Gy at Point A with external beam radiotherapy combined with brachytherapy according to the International Federation of Gynecology and Obstetrics stage. In the LDR group, 32 patients had Stage I disease, 81 had Stage II, 182 had Stage III, and 29 had Stage IVA; in the MDR group, 9 patients had Stage I disease, 19 had Stage II, 55 had Stage III, and 12 had Stage IVA. Results: The 5-year overall survival rates for Stages I, II, III, and IVA in the LDR group were 78%, 72%, 55%, and 34%, respectively. In the MDR group, the 5-year overall survival rates were 100%, 68%, 52%, and 42%, respectively. No significant statistical differences were seen between the two groups. The actuarial rates of late complications Grade 2 or greater at 5 years for the rectum, bladder, and small intestine in the LDR group were 11.1%, 5.8%, and 2.0%, respectively. The rates for the MDR group were 11.7%, 4.2%, and 2.6%, respectively, all of which were without statistical differences. Conclusion: These data suggest that MDR ICBT is effective, useful, and equally as good as LDR ICBT in daytime (about 5 hours) treatments of patients with cervical cancer.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Clinical Behaviors and Outcomes for Adenocarcinoma or Adenosquamous Carcinoma of Cervix Treated by Radical Hysterectomy and Adjuvant Radiotherapy or Chemoradiotherapy

Purpose: To compare clinical behaviors and treatment outcomes between patients with squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC) of the cervix treated with radical hysterectomy (RH) and adjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods and Materials: A total of 318 Stage IB-IIB cervical cancer patients, 202 (63.5%) with SCC and 116 (36.5%) with AC/ASC, treated by RH and adjuvant RT/CCRT, were included. The indications for RT/CCRT were deep stromal invasion, positive resection margin, parametrial invasion, or lymph node (LN) metastasis. Postoperative CCRT was administered in 65 SCC patients (32%) and 80 AC/ASC patients (69%). Patients with presence of parametrial invasion or LN metastasis were stratified into a high-risk group, and the rest into an intermediate-risk group. The patterns of failure and factors influencing survival were evaluated. Results: The treatment failed in 39 SCC patients (19.3%) and 39 AC/ASC patients (33.6%). The 5-year relapse-free survival rates for SCC and AC/ASC patients were 83.4% and 66.5%, respectively (p = 0.000). Distant metastasis was the major failure pattern in both groups. After multivariate analysis, prognostic factors for local recurrence included younger age, parametrial invasion, AC/ASC histology, and positive resection margin; for distant recurrence they included parametrial invasion, LN metastasis, and AC/ASC histology. Compared with SCC patients, those with AC/ASC had higher local relapse rates for the intermediate-risk group but a higher distant metastasis rate for the high-risk group. Postoperative CCRT tended to improve survival for intermediate-risk but not for high-risk AC/ASC patients. Conclusions: Adenocarcinoma/adenosquamous carcinoma is an independent prognostic factor for cervical cancer patients treated by RH and postoperative RT. Concurrent chemoradiotherapy could improve survival for intermediate-risk, but not necessarily high-risk, AC/ASC patients.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2012

Impact of Heterogeneity-Based Dose Calculation Using a Deterministic Grid-Based Boltzmann Equation Solver for Intracavitary Brachytherapy

Purpose: To investigate the dosimetric impact of the heterogeneity dose calculation Acuros (Transpire Inc., Gig Harbor, WA), a grid-based Boltzmann equation solver (GBBS), for brachytherapy in a cohort of cervical cancer patients. Methods and Materials: The impact of heterogeneities was retrospectively assessed in treatment plans for 26 patients who had previously received {sup 192}Ir intracavitary brachytherapy for cervical cancer with computed tomography (CT)/magnetic resonance-compatible tandems and unshielded colpostats. The GBBS models sources, patient boundaries, applicators, and tissue heterogeneities. Multiple GBBS calculations were performed with and without solid model applicator, with and without overriding the patient contour to 1 g/cm{sup 3} muscle, and with and without overriding contrast materials to muscle or 2.25 g/cm{sup 3} bone. Impact of source and boundary modeling, applicator, tissue heterogeneities, and sensitivity of CT-to-material mapping of contrast were derived from the multiple calculations. American Association of Physicists in Medicine Task Group 43 (TG-43) guidelines and the GBBS were compared for the following clinical dosimetric parameters: Manchester points A and B, International Commission on Radiation Units and Measurements (ICRU) report 38 rectal and bladder points, three and nine o'clock, and {sub D2cm3} to the bladder, rectum, and sigmoid. Results: Points A and B, D{sub 2} cm{sup 3} bladder, ICRU bladder, and three and nine o'clock were within 5% of TG-43 for all GBBS calculations. The source and boundary and applicator account for most of the differences between the GBBS and TG-43 guidelines. The D{sub 2cm3} rectum (n = 3), D{sub 2cm3} sigmoid (n = 1), and ICRU rectum (n = 6) had differences of >5% from TG-43 for the worst case incorrect mapping of contrast to bone. Clinical dosimetric parameters were within 5% of TG-43 when rectal and balloon contrast were mapped to bone and radiopaque packing was not overridden. Conclusions: The GBBS has minimal impact on clinical parameters for this cohort of patients with unshielded applicators. The incorrect mapping of rectal and balloon contrast does not have a significant impact on clinical parameters. Rectal parameters may be sensitive to the mapping of radiopaque packing.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Radiation Dose to the Esophagus From Breast Cancer Radiation Therapy, 1943-1996: An International Population-Based Study of 414 Patients

Purpose: To provide dosimetric data for an epidemiologic study on the risk of second primary esophageal cancer among breast cancer survivors, by reconstructing the radiation dose incidentally delivered to the esophagus of 414 women treated with radiation therapy for breast cancer during 1943-1996 in North America and Europe. Methods and Materials: We abstracted the radiation therapy treatment parameters from each patient’s radiation therapy record. Treatment fields included direct chest wall (37% of patients), medial and lateral tangentials (45%), supraclavicular (SCV, 64%), internal mammary (IM, 44%), SCV and IM together (16%), axillary (52%), and breast/chest wall boosts (7%). The beam types used were {sup 60}Co (45% of fields), orthovoltage (33%), megavoltage photons (11%), and electrons (10%). The population median prescribed dose to the target volume ranged from 21 Gy to 40 Gy. We reconstructed the doses over the length of the esophagus using abstracted patient data, water phantom measurements, and a computational model of the human body. Results: Fields that treated the SCV and/or IM lymph nodes were used for 85% of the patients and delivered the highest doses within 3 regions of the esophagus: cervical (population median 38 Gy), upper thoracic (32 Gy), and middle thoracic (25 Gy). Other fields (direct chest wall, tangential, and axillary) contributed substantially lower doses (approximately 2 Gy). The cervical to middle thoracic esophagus received the highest dose because of its close proximity to the SCV and IM fields and less overlying tissue in that part of the chest. The location of the SCV field border relative to the midline was one of the most important determinants of the dose to the esophagus. Conclusions: Breast cancer patients in this study received relatively high incidental radiation therapy doses to the esophagus when the SCV and/or IM lymph nodes were treated, whereas direct chest wall, tangentials, and axillary fields contributed lower doses.

62 RADIOLOGY AND NUCLEAR MEDICINE↗