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Christopher G Willett,
Jennifer Moughan,
Elizabeth O'Meara,
James M Galvin,
Christopher H Crane,
Kathryn Winter,
Denise Manfredi,
Tyvin A Rich, Rachel Rabinovitch,
Robert Lustig,
Mitchell Machtay,
Walter J Curran
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ABSTRACT: BACKGROUND: This report analyzes the adherence to radiation therapy protocol guidelines in contemporary Radiation Therapy Oncology Group (RTOG) gastrointestinal trials. We aim to provide insight into current standards and compliance of radiation therapy field design and administration. METHODS: From 1994 to 2006, the Gastrointestinal Cancer Committee of the RTOG initiated and completed 15 phase I-III clinical trials utilizing radiation therapy in the multimodality treatment of gastrointestinal cancers. In each protocol, details for planning and executing radiation therapy were outlined and each protocol contained scoring criteria for these components of radiation therapy, characterized according to per-protocol, variation acceptable and deviation unacceptable. Review of treatment planning and implementation was performed in all studies following therapy completion. RESULTS: Radiation therapy planning and implementation was reviewed in 2309 of 2312 (99.9%) patients. The mean rate of compliance over all for the 15 protocols was 65% (total of the 2309 analyzed patients). The mean variation acceptable rate was 21% whereas the mean deviation unacceptable rate was 5%. The mean "other" rate (no RT given or incomplete RT due to death, progression or refusal) was 8%. Two of the 15 trials (13%) had deviation unacceptable rates >10%. In four studies incorporating pre-treatment review of radiation therapy planning and treatment, compliance with protocol therapy was enhanced. CONCLUSIONS: The fidelity of radiation planning and execution detailed in protocol to actual therapy is heterogeneous, with a mean per-protocol rate of 65%. As clinical trials evolve, available technology should permit efficient pre-treatment review processes, thus facilitating compliance to protocol therapy. These analyses should also permit prospective analysis of outcome measures by compliance to therapy.
Radiotherapy and Oncology 10/2012; · 5.58 Impact Factor
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International journal of radiation oncology, biology, physics 07/2012; 83(4):1075-7. · 4.59 Impact Factor
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ABSTRACT: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy.
An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m(2), 1.3 mg/m(2), and 1.6 mg/m(2)/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, defined as any grade 4 hematologic toxicity, any grade ≥3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for ≥2 weeks.
A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m(2). One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients).
The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m(2) is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m(2).
International journal of radiation oncology, biology, physics 10/2010; 78(2):521-6. · 4.59 Impact Factor
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ABSTRACT: To examine the respiratory motion for target and normal structures during whole breast and nodal irradiation and the resulting dosimetric impact.
Four-dimensional CT data sets of 18 patients with early-stage breast cancer were analyzed retrospectively. A three-dimensional conformal dosimetric plan designed to irradiate the breast was generated on the basis of CT images at 20% respiratory phase (reference phase). The reference plans were copied to other respiratory phases at 0% (end of inspiration) and 50% (end of expiration) to simulate the effects of breathing motion on whole breast irradiation. Dose-volume histograms, equivalent uniform dose, and normal tissue complication probability were evaluated and compared.
Organ motion of up to 8.8mm was observed during free breathing. A large lung centroid movement was typically associated with a large shift of other organs. The variation of planning target volume coverage during a free breathing cycle is generally within 1%-5% (17 of 18 patients) compared with the reference plan. However, up to 28% of V(45) variation for the internal mammary nodes was observed. Interphase mean dose variations of 2.2%, 1.2%, and 1.4% were observed for planning target volume, ipsilateral lung, and heart, respectively. Dose variations for the axillary nodes and brachial plexus were minimal.
The doses delivered to the target and normal structures are different from the planned dose based on the reference phase. During normal breathing, the dosimetric impact of respiratory motion is clinically insignificant with the exception of internal mammary nodes. However, noticeable degradation in dosimetric plan quality may be expected for the patients with large respiratory motion.
International journal of radiation oncology, biology, physics 10/2010; 78(2):609-17. · 4.59 Impact Factor
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ABSTRACT: External beam radiation therapy (RT) is the standard treatment for stage I-II, grade 1-2 follicular lymphoma. Because of an indolent natural history, some advocate alternative management strategies, including watchful waiting for this disease. The relative improvement in outcomes for patients treated with and without RT has never been tested in randomized trials.
The Surveillance, Epidemiology, and End Results database was queried for adult patients with stage I-II, grade 1-2 follicular lymphoma diagnosed from 1973 to 2004. Retrievable patient data included age, sex, race, stage, extranodal disease, and treatment with RT within the first year after diagnosis. Actuarial overall survival (OS) and disease-specific survival (DSS) were analyzed.
A total of 6568 patients were identified. DSS at 5, 10, 15, and 20 years in the RT group was 90%, 79%, 68%, and 63% versus 81%, 66%, 57%, and 51% in the no RT group (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.55-0.68; P<.0001). OS at 5, 10, 15, and 20 years in the RT group was 81%, 62%, 45%, and 35% versus 71%, 48%, 34%, and 23% in patients not receiving RT (HR, 0.68; 95% CI, 0.63-0.73; P<.0001). On multivariate analysis, upfront RT remained independently associated with improved DSS (P<.0001, Cox HR, 0.65; 95% CI, 0.57-0.72) and OS (P<.0001; Cox HR, 0.73; 95% CI, 0.67-0.79). Lymphoma was the most common cause of death (52%). Only 34% of patients received upfront RT.
Upfront RT was associated with improved DSS and OS compared with alternate management approaches, a benefit that persisted over time. This benefit suggests that watchful waiting with administration of salvage therapies on progression/relapse do not compensate for inadequate initial definitive treatment. Although it is the standard of care for this disease, RT for early stage low-grade follicular lymphoma is greatly underused in the US population; increased use of upfront RT could prevent thousands of deaths from lymphoma in these patients.
Cancer 08/2010; 116(16):3843-51. · 4.77 Impact Factor
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International journal of radiation oncology, biology, physics 05/2010; 77(1):317; author reply 318. · 4.59 Impact Factor
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Journal of Clinical Oncology 12/2009; · 18.37 Impact Factor
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ABSTRACT: This prospective study (Radiation Therapy Oncology Group 0319) examines the use of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Initial data on efficacy and toxicity are presented.
Patients with Stage I or II breast cancer with lesions < or =3 cm, negative margins and with < or =3 positive nodes were eligible. The 3D-CRT was 38.5 Gy in 3.85 Gy/fraction delivered 2x/day. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Mastectomy-free, disease-free, and overall survival (MFS, DFS, OS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3, was used to grade acute and late toxicity.
Fifty-eight patients were entered and 52 patients are eligible and evaluable for efficacy. The median age of patients was 61 years with the following characteristics: 46% tumor size <1 cm; 87% invasive ductal histology; 94% American Joint Committee on Cancer Stage I; 65% postmenopausal; 83% no chemotherapy; and 71% with no hormone therapy. Median follow-up is 4.5 years (1.7-4.8). Four-year estimates (95% CI) of efficacy are: IBF 6% (0-12%) [4% within field (0-9%)]; INF 2% (0-6%); CBF 0%; DF 8% (0-15%); MFS 90% (78-96%); DFS 84% (71-92%); and OS 96% (85-99%). Only two (4%) Grade 3 toxicities were observed.
Initial efficacy and toxicity using 3D-CRT to deliver APBI appears comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate the extent of application, limitations, and value of this particular form of APBI.
International journal of radiation oncology, biology, physics 11/2009; 77(4):1120-7. · 4.59 Impact Factor
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ABSTRACT: This patient was found to have a BRCA2 gene mutation. She underwent lumpectomy and axillary lymph node dissection without any evidence of lymph node metastasis. Systemic chemotherapy with doxorubicin and cyclophosphamide for four cycles was administered beginning in the second trimester. She was treated with prophylactic LMWH until delivery and then for 6 weeks postpartum. She delivered a healthy baby boy and, after a period of breast-feeding, underwent bilateral mastectomy with immediate reconstruction. She remains well and is expecting her second child. Prophylactic oophorectomy is planned after completion of this pregnancy.
Oncology (Williston Park, N.Y.) 08/2009; 23(9):784-91. · 1.03 Impact Factor
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ABSTRACT: Standard therapy for stage I and II diffuse large B-cell lymphoma consists of combined modality therapy with anthracycline-based chemotherapy, anti-CD20 antibody, and radiation therapy (RT). Curative approaches without RT typically utilize more intensive and/or protracted chemotherapy schedules. Anthracycline-based chemotherapy regimens are associated with a dose-dependent risk of left ventricular systolic dysfunction. We hypothesize that patients treated without RT, i.e., those who are treated with greater total chemotherapy cycles and hence cumulative anthracycline exposure, are at increased risk of cardiac mortality.
The rate of cardiac-specific mortality (CSM) was analyzed in patients with stage I and II diffuse large B-cell lymphoma diagnosed between 1988 and 2004 by querying the National Cancer Institute Surveillance, Epidemiology, and End-Results database. Analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration.
A total of 15,454 patients met selection criteria; 6,021 (39%) patients received RT. The median follow-up was 36 months (range, 6-180 months). The median age was 64 years. The actuarial incidence rates of CSM at 5, 10, and 15 years were 4.3%, 9.0%, and 13.8%, respectively, in patients treated with RT vs. 5.9%, 10.8% and 16.1%, respectively, in patients treated without RT (p < 0.0001; hazard ratio, 1.35; 95% confidence interval [CI]: 1.16-1.56). The increase in cardiac deaths for patients treated without RT persisted throughout the follow-up period. On multivariate analysis, treatment without RT remained independently associated with an increased risk of CSM (Cox hazard ratio, 1.32; 95% CI: 1.13-1.54; p = 0.0005).
Increased anthracycline exposure in patients treated only with chemotherapy regimens may result in an increase in cardiac deaths, detectable only through analysis of large sample sizes. Confirmatory evaluation through meta-analysis of randomized data and design of large prospective trials is warranted.
International journal of radiation oncology, biology, physics 06/2009; 76(3):845-9. · 4.59 Impact Factor
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Journal of Clinical Oncology 05/2009; 27(15):2422-3. · 18.37 Impact Factor
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X Allen Li,
An Tai,
Douglas W Arthur,
Thomas A Buchholz,
Shannon Macdonald,
Lawrence B Marks,
Jean M Moran,
Lori J Pierce, Rachel Rabinovitch,
Alphonse Taghian,
Frank Vicini,
Wendy Woodward,
Julia R White
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ABSTRACT: To quantify the multi-institutional and multiobserver variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT) and its dosimetric impact as the first step of a Radiation Therapy Oncology Group effort to establish a breast cancer atlas.
Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative breast cancer patients. Interobserver differences in structure delineation were quantified regarding volume, distance between centers of mass, percent overlap, and average surface distance. Mean, median, and standard deviation for these quantities were calculated for all possible combinations. To assess the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated.
Variability in contouring the targets and OARs between the institutions and observers was substantial. Structure overlaps were as low as 10%, and volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries and approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These interobserver differences result in substantial variations in dosimetric planning for breast RT.
Differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of intensity-modulated and image-guided RT.
International journal of radiation oncology, biology, physics 04/2009; 73(3):944-51. · 4.59 Impact Factor
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ABSTRACT: This summary focuses on the role of postoperative radiation therapy in patients treated with modified radical mastectomy for invasive breast cancer, particularly in patients receiving systemic therapy.
International journal of radiation oncology, biology, physics 04/2009; 73(4):997-1002. · 4.59 Impact Factor
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ABSTRACT: This summary focuses on the role of postoperative radiation therapy in patients treated with modified radical mastectomy for invasive breast cancer, particularly in patients receiving systemic therapy.
International journal of radiation oncology, biology, physics 03/2009; 73(4). · 4.59 Impact Factor
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Oncology (Williston Park, N.Y.) 11/2008; 22(11):1270-6. · 1.03 Impact Factor
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ABSTRACT: During the past 2 decades, breast conservation therapy (BCT) has become firmly established as a standard therapeutic approach for eligible women with early-stage breast cancer. Breast radiation after conservative surgery is an integral component of BCT, resulting in comparable local control and equivalent survival to mastectomy. Successful breast conservation relies on understanding key elements for patient selection, evaluation, treatment contraindications, radiation therapy methods, and integration with systemic therapy.
The Appropriateness Criteria Committee of the American College of Radiology convened an expert panel to examine BCT for early-stage breast cancer. By using a modified Delphi technique to generate consensus, the expert panel responded to questionnaires on 9 clinical cases that address various key elements of breast conservation. A literature review on BCT led to the generation of an evidence table to support the consensus and overview.
Consensus for appropriateness criteria for BCT was produced for various clinical scenarios commonly encountered in practice. These topics include radiation oncology management issues related to young patient age, sentinel node biopsy, elderly patients, other histology, positive margins, extensive intraductal component, node-positive breast cancer, genetic breast cancer, partial breast irradiation, and systemic therapy. Radiation methods for BCT are reviewed.
The Breast Cancer Panel has generated a consensus of up-to-date guidelines for the appropriate use of radiation for BCT by using a modified Delphi process for the American College of Radiology Appropriateness Criteria.
Journal of the American College of Radiology: JACR 07/2008; 5(6):701-13.
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ABSTRACT: Randomized trials provide evidence for improved outcomes with postmastectomy radiotherapy (PMRT) in high-risk patients. It has been suggested that patients with T3N0 breast cancer represent a favorable subgroup for which PMRT renders little benefit. In the current study, the authors used a United States population database to evaluate PMRT in this subgroup.
The cause-specific survival (CSS) and overall survival (OS) of women with T3N0M0 breast cancer in the Surveillance, Epidemiology, and End Results database after mastectomy and axillary staging from 1988 to 2002 were analyzed. Univariate analysis was performed to relate CSS with PMRT (yes vs no), tumor size (< or =7 cm vs >7 cm), grade (1 vs 2 or 3), patient age (< or =50 years vs >50 years), the number of lymph nodes dissected (< or =13 vs >13), and the era treated (1988-1997 vs 1998-2002). Multivariate analyses for CSS and OS were also performed.
In total, 1865 women met the analysis criteria for OS; CSS data were available for 98.8% of those women. Of the women who were diagnosed during the era from 1988 to 1997, 22% received PMRT, and that rate increased to 41% during the era from 1998 to 2002. The actuarial 10-year CSS for those who received PMRT versus those who did not receive PMRT was 81.6% versus 79.8%, respectively (P = .38). PMRT was not associated with a CSS benefit in any subgroup, a finding that persisted in multivariate analyses. Women who received PMRT had an increased 10-year OS rate (70.7% vs 58.4%; P < .001) that was confined to women aged >50 years in a subgroup analysis.
This retrospective, population-based analysis demonstrated no increase in CSS with PMRT for women with T3N0 breast cancer, lending further support to the hypothesis that T3N0 disease postmastectomy represents a favorable subset of locally advanced breast cancer. The increased OS associated with PMRT in the absence of improved CSS likely reflects patient selection in this nonrandomized dataset. Prospective evaluation of PMRT in this population subset is warranted.
Cancer 06/2008; 113(4):683-9. · 4.77 Impact Factor
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ABSTRACT: To assess disease-specific survival (DSS), overall survival (OS), and the effect of radiotherapy (RT) in patients with localized diffuse large B-cell lymphoma (DLBCL).
The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with Stage I, IE, II, or IIE DLBCL between 1988 and 2004. The analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. Patients who had died or were lost to follow-up within 6 months of diagnosis were excluded.
A total of 13,420 patients met the search criteria. Of these, 5,547 (41%) had received RT and 7,873 (59%) had not. RT was associated with a significant DSS (hazard ratio, 0.82, p <0.0001) and OS benefit that persisted during the 15 years of follow-up. Elderly patients, defined either as those >60 or >70 years old, had significantly improved DSS and OS associated with RT. On multivariate analysis, RT was significantly associated with increased DSS and OS. The 5-year DSS outcomes were highly variable among patient subsets, defined by age, stage, and extranodal disease (range for RT-treated patients, 70% for Stage II, age >60 years to 87% for Stage I, age </=60 years).
This analysis presents the largest detailed data set of Stage I-II DLBCL patients. The results of our study have demonstrated that RT is associated with a survival advantage in patients with localized DLBCL, a benefit that extends to elderly patients. Outcomes for discrete patient subsets varied greatly. The development of tailored therapy according to the relapse risk is warranted, rather than uniform treatment of all early-stage DLBCL.
International journal of radiation oncology, biology, physics 05/2008; 72(5):1465-71. · 4.59 Impact Factor
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ABSTRACT: Biopsy of the breast sentinel lymph node (SLN) is now a standard staging procedure for early-stage invasive breast cancer. The anatomic location of the breast SLN and its relationship to standard radiation fields has not been described.
A retrospective review of radiotherapy treatment planning data sets was performed in patients with breast cancer who had undergone SLN biopsy, and those with a surgical clip at the SLN biopsy site were identified. The location of the clip was evaluated relative to vertebral body level on an anterior-posterior digitally reconstructed radiograph, treated whole-breast tangential radiation fields, and standard axillary fields in 106 data sets meeting these criteria.
The breast SLN varied in vertebral body level position, ranging from T2 to T7 but most commonly opposite T4. The SLN clip was located below the base of the clavicle in 90%, and hence would be excluded from standard axillary radiotherapy fields where the inferior border is placed at this level. The clip was within the irradiated whole-breast tangent fields in 78%, beneath the superior-posterior corner multileaf collimators in 12%, and outside the tangent field borders in 10%.
Standard axillary fields do not encompass the lymph nodes at highest risk of containing tumor in breast cancer patients. Elimination of the superior-posterior corner MLCs from the tangent field design would result in inclusion of the breast SLN in 90% of patients treated with standard whole-breast irradiation.
International Journal of Radiation OncologyBiologyPhysics 05/2008; 70(5):1468-71. · 4.11 Impact Factor
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ABSTRACT: Radiation Therapy Oncology Group 95-17 is a prospective Phase II cooperative group trial of accelerated partial breast irradiation (APBI) alone using multicatheter brachytherapy after lumpectomy in select early-stage breast cancers. Tumor control and survival outcomes are reported.
Eligibility criteria included Stage I/II breast carcinoma confirmed to be <3 cm, unifocal, invasive nonlobular histology with zero to three positive axillary nodes without extracapsular extension. APBI treatment was delivered with either low-dose-rate (LDR) (45 Gy in 3.5-5 days) or high-dose-rate (HDR) brachytherapy (34 Gy in 10 twice-daily fractions over 5 days). End points evaluated included in-breast control, regional control, mastectomy-free rate, mastectomy-free survival, disease-free survival, and overall survival. The study was designed to analyze the HDR and LDR groups separately and without comparison.
Between 1997 and 2000, 100 patients were accrued and 99 were eligible; 66 treated with HDR brachytherapy and 33 treated with LDR brachytherapy. Eighty-seven patients had T1 lesions and 12 had T2 lesions. Seventy-nine were pathologically N0 and 20 were N1. Median follow-up in the HDR group is 6.14 years with the 5-year estimates of in-breast, regional, and contralateral failure rates of 3%, 5%, and 2%, respectively. The LDR group experienced similar results with a median follow-up of 6.22 years. The 5-year estimates of in-breast, regional, and contralateral failure rates of 6%, 0%, and 6%, respectively.
Patients treated with multicatheter partial breast brachytherapy in this trial experienced excellent in-breast control rates and overall outcome that compare with reports from APBI studies with similar extended follow-up.
International Journal of Radiation OncologyBiologyPhysics 03/2008; 72(2):467-73. · 4.11 Impact Factor
