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Julie Gralow,
Robert F Ozols,
Dean F Bajorin,
Bruce D Cheson,
Howard M Sandler,
Eric P Winer,
James Bonner,
George D Demetri,
Walter Curran,
Patricia A Ganz, [......],
Derek Raghavan,
Scott Ramsey,
Gregory H Reaman,
Raymond Sawaya,
Lynn M Schuchter,
John W Sweetenham,
Linda T Vahdat,
Nancy E Davidson,
Richard L Schilsky, Allen S Lichter
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ABSTRACT: A MESSAGE FROM ASCO'S PRESIDENT: For the third year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO publishes this report to demonstrate the important progress being made on the front lines of clinical cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and organizations, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on the use of magnetic resonance imaging for breast cancer screening, the association between hormone replacement therapy and breast cancer incidence, the link between human papillomavirus and head and neck cancers, and the use of radiation therapy to prevent lung cancer from spreading. They also report on effective new targeted therapies for cancers that have been historically difficult to treat, such as liver cancer and kidney cancer, among many others. A total of 24 advances are featured in this year's report. These advances and many more over the past several years show that the nation's long-term investment in cancer research is paying off. But there are disturbing signs that progress could slow. We are now in the midst of the longest sustained period of flat government funding for cancer research in history. The budgets for the National Institutes of Health and the National Cancer Institute (NCI) have been unchanged for four years. When adjusted for inflation, cancer research funding has actually declined 12% since 2004. These budget constraints limit the NCI's ability to fund promising cancer research. In the past several years the number of grants that the NCI has been able to fund has significantly decreased; this year, in response to just the threat of a 10% budget cut, the nation's Clinical Trials Cooperative Groups reduced the number of patients participating in clinical trials by almost 2,000 and senior researchers report that many of the brightest young minds no longer see the promise of a career in science, choosing other careers instead. It's time to renew the nation's commitment to cancer research. Without additional support, the opportunity to build on the extraordinary progress to date will be lost or delayed. This report demonstrates the essential role that clinical cancer research plays in finding new and better ways to care for the more than 1.4 million people expected to be diagnosed with cancer this year. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report. I hope you find it useful. Sincerely, Nancy E. Davidson, MD President American Society of Clinical Oncology.
Journal of Clinical Oncology 02/2008; 26(2):313-25. · 18.37 Impact Factor
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Merav A. Ben-David MD,
David E. Sturtz MD,
MS Kent A. Griffith MPH,
Kathye R. Douglas CTR,
James A. Hayman MD,
Allen S. Lichter MD,
Lori J. Pierce MD,
Merav A. Ben‐David,
David E. Sturtz,
Kent A. Griffith,
Kathye R. Douglas,
James A. Hayman, Allen S. Lichter,
Lori J. Pierce
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ABSTRACT: The purpose of the study was to review the treatment outcomes of 198 patients treated with breast-conserving surgery (BCS) and whole breast radiation therapy using lung density correction for ductal carcinoma in situ (DCIS). Between April 1985 and December 2002, 198 patients with 200 lesions diagnosed as DCIS (AJCC stage 0) were treated at the University of Michigan. All underwent BCS and whole breast radiotherapy. Median total follow-up was 6.2 years (range: 0.8–18.2). The 5- and 10-year cumulative rates of in-breast only failure were 5.9% (95% CI: 2.6–9.3%) and 9.8% (95% CI: 5.2–14.4%), respectively. Factors that significantly predicted for an increased risk of local failure were family history of breast cancer, positive or close surgical margins and age ≤ 50 years at diagnosis. Cosmetic outcome was scored as “excellent” or “good” in 94% of the assessed patients. On multivariate analysis, only patient separation significantly predicted cosmetic outcome (p = 0.04). BCS and radiotherapy using lung density correction resulted in high rates of local control at 5 and 10 years with excellent cosmetic results. To the best of our knowledge, this is the first study to report outcome in a series of patients with DCIS treated with lung density correction and results compare favorably with other series in which plans were calculated using unit density.
The Breast Journal 06/2007; 13(4):392 - 400. · 1.64 Impact Factor
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ABSTRACT: Advances in radiation oncology have been made on three major fronts: biology, physics, and clinical application. Our biological understanding of how radiation kills cells and how malignant cells avoid damage has identified new targets for therapeutic manipulation. Research in physics has yielded sophisticated methods to direct the deposition of radiation energy in ways that enhance target coverage while minimizing dose to normal structures as much as possible. Intensity-modulated radiation therapy (IMRT) and image-guided radiation therapy represent new paradigms in treatment planning and dose delivery. Clinical management of the cancer patient is multidisciplinary. Increasingly, combinations of radiation and chemotherapy, with or without surgery, are enhancing cure rates, often with preservation of organ function. Taken together, these advances have increased the effectiveness of radiation therapy and promise better treatment results in the future.
Annual Review of Medicine 02/2006; 57:19-31. · 9.94 Impact Factor
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ABSTRACT: Radiotherapy (RT) planning for breast cancer using lung density correction improves dose homogeneity. Its use obviates the need for a medial wedge, thus reducing scatter to the opposite breast. Although lung density correction is used at many centers in planning for early-stage breast cancer, long-term results of local control and survival have not been reported. Since 1984, we have used lung density correction for dose calculations at the University of Michigan. We now present our 10-year and 15-year results.
The records of 867 patients with Stage I/II breast cancer treated with breast-conserving surgery and RT with or without systemic therapy were reviewed. Tangential fields delivering 45-50 Gy to the whole breast calculated using lung density correction were used. A boost was added in 96.8% of patients for a total median dose of 61.8 Gy.
With a median follow-up of 6.6 years (range, 0.2-18.9 years), 5-, 10-, and 15-year actuarial rates of in-breast tumor recurrence as only first failure were 2.2%, 3.6%, and 5.4%, respectively. With surgical salvage, the 15-year cumulative rate of local control was 99.7%. Factors that significantly predicted for increased rate of local recurrence in multivariate analysis were age </= 35 years, hazard ratio 4.8 (95% confidence interval [CI], 1.6-13.9) p = 0.004; negative progesterone receptor status, hazard ratio 6.8 (95% CI, 2.3-20.3) p = < 0.001; negative estrogen receptor status, hazard ratio 4.0 (95% CI, 1.5-11.1) p = 0.007; and lack of adjuvant tamoxifen therapy, hazard ratio 7.7 (95% CI, 1.7-33.3) p = 0.008. Relapse-free survival rates at 5, 10, and 15 years were 84.6%, 70.8%, and 55.9%, respectively; breast cancer-specific survival rates were 94.4%, 90.5%, and 86.9%, respectively; and corresponding estimates for overall survival were 89.7%, 75.7%, and 61.3%.
Use of lung density correction was associated with high rates of local control, relapse-free survival, breast cancer-specific survival, and overall survival compared with other reported series of breast-conserving surgery and RT in early-stage disease. These results will serve as a benchmark against which newer radiation delivery strategies such as intensity-modulated RT and partial breast RT can be compared.
International Journal of Radiation OncologyBiologyPhysics 05/2005; 61(5):1317-27. · 4.11 Impact Factor
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Laura A Dawson,
Naoyuki G Saito,
Voravit Ratanatharathorn,
Joseph P Uberti,
Paul T Adams,
Lois J Ayash,
Christopher M Reynolds,
Samuel M Silver,
Matthew J Schipper, Allen S Lichter,
Avraham Eisbruch
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ABSTRACT: This Phase I study was designed to evaluate the tolerability of involved-field radiotherapy (IFRT) to areas of persistent disease in patients with high-risk Hodgkin's disease and non-Hodgkin's lymphomas before autologous stem cell transplantation (ASCT).
Thirty-one patients with primary refractory or relapsed Hodgkin's disease (n = 13) and non-Hodgkin's lymphoma (n = 18) were treated with IFRT followed by high-dose chemotherapy and ASCT. All patients had bulky disease (> or =5 cm) and/or an inadequate response to salvage chemotherapy. The IFRT dose was escalated to a maximum of 36 Gy. Dose-limiting toxicity was defined as Grade 3-4 Bearman toxicity (life-threatening/fatal toxicity occurring within 28 days of ASCT). The chemotherapy regimen consisted of cyclophosphamide, etoposide, and carmustine.
The delivered dose of IFRT was 20 Gy in 9 patients, 28-30 Gy in 20, and 32-36 Gy in 2 patients to mediastinal (n = 19) and nonmediastinal (n = 12) sites. The median interval between IFRT completion and ASCT was 19 days. One patient developed Bearman Grade 3 hepatic toxicity. No other Grade 3 or 4 Bearman toxicity was observed. An increased requirement for i.v. narcotics was observed in patients treated with mediastinal IFRT vs. nonmediastinal IFRT (p = 0.02). A trend toward increased mucositis severity was seen in patients previously treated with a larger number of chemotherapy agents (p = 0.09) and in those with a shorter interval between IFRT and ASCT (p = 0.12). Pulmonary toxicity was more common in patients treated with mediastinal IFRT than in those treated with nonmediastinal IFRT (21% vs. 0%, p = 0.13). The 2-year overall and progression-free survival rate was 70% and 49% for all patients, 84% and 50% for patients with Hodgkin's disease, and 59% and 47% for patients with non-Hodgkin's lymphoma, respectively.
The maximal tolerated dose of IFRT was not reached when Grade 3-4 Bearman toxicity was dose limiting. Increased pulmonary toxicity and mucositis severity was seen after mediastinal IFRT compared with nonmediastinal IFRT. Because local control was excellent, higher doses of IFRT are not recommended. The absolute benefit of IFRT in this patient population needs investigation in future studies.
International Journal of Radiation OncologyBiologyPhysics 05/2004; 59(1):208-18. · 4.11 Impact Factor
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ABSTRACT: Physicians frequently receive payment for enrolling subjects onto clinical trials. Some view these payments as conflicts of interest. Others contend that these payments are necessary reimbursements for conducting clinical research. We evaluated the clinical and nonclinical hours and costs associated with conducting a mock phase III clinical research trial.
We collected data from representatives of 21 clinical sites, on the numbers of hours associated with 13 activities necessary to the conduct of clinical research. The hours were based on enrolling 20 patients in a 12-month randomized placebo-controlled trial of a new chemotherapeutic agent. The outcome measures were disease progression and quality-of-life reports. These costs were evaluated for both government and pharmaceutical industry-sponsored trials.
On average, 4,012 hours (range, 1,512 to 13,319 hours) were required for a government-sponsored trial, and 3,998 hours (range: 1735 to 15,699) were required for a pharmaceutical industry-sponsored trial involving 20 subjects with 17 office visits, or approximately 200 hours per subject. Thirty-two percent of the hours were devoted to nonclinical activities, such as institutional review board submission and completion of clinical reporting forms. On average, excluding overhead expenses, it cost slightly more than 6,094 dollars (range, 2,098 dollars to 19,285 dollars) per enrolled subject for an industry-sponsored trial, including 1,999 dollars devoted to nonclinical costs.
Based on the results of our mock trial, the time required for nontreatment trial activities is considerable, and the associated costs are substantial.
Journal of Clinical Oncology 12/2003; 21(22):4145-50. · 18.37 Impact Factor
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ABSTRACT: To compare seven techniques for irradiation of the postmastectomy chest wall (CW) using normal tissue complication probability (NTCP) predictions for pneumonitis and ischemic heart disease and dose-volume histogram analyses for normal and target tissues.
Plan comparisons were performed for 20 left-sided postmastectomy CW RT cases using target volumes based on clinical delineation of standard field borders. Seven common treatment techniques were planned for each case, using a prescription of 50 Gy in 25 fractions to the CW and internal mammary node (IMN) targets. NTCP model metrics were used to quantify the risks of pneumonitis and ischemic heart disease, supplemented by dose-volume metrics to assess the target coverage to the CW and IMNs, as well as normal tissue dose (lung and heart).
Overlap in the distributions of the CW mean dose for all plans was found, except cobalt, which was significantly less than the remaining techniques (global F test, F = 21.90, p <0.0001). Standard tangents produced a significantly lower IMN mean dose than all other methods, as expected (F = 59.55, p < 0.0001); the reverse hockey stick and cobalt techniques were lower than the other methods, which were statistically similar. Cobalt produced a significantly higher percentage of the heart that received >30 Gy (V30) than the other methods (F = 49.76, p <0.0001). Use of partially wide tangent fields (PWTFs) resulted in the smallest heart V30. Use of cobalt fields resulted in a significantly greater NTCP estimate for ischemic heart disease than all the remaining techniques (F = 70.39, p <0.0001). Standard tangents resulted in a percentage of the lung receiving >20 Gy (V20) significantly less than with PWTFs, 30/70 and 20/80 photon/electron mix, and reverse hockey stick techniques. NTCP estimates for pneumonitis revealed significantly better results with standard tangents (F = 6.57, p <0.0001).
No one technique studied combines the best CW and IMN coverage with minimal lung and heart complication probabilities. The choice of technique should be based on clinical discretion and the technical expertise available to implement these complex plans. Of the seven techniques studied, this analysis supports PWTFs as the most appropriate balance of target coverage and normal tissue sparing when irradiating the CW and IMN.
International Journal of Radiation OncologyBiologyPhysics 05/2002; 52(5):1220-30. · 4.11 Impact Factor
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ABSTRACT: : To measure the range and frequency of occurrence of intertreatment movement of the prostate gland over the course of radiotherapy, and to demonstrate that the prostate may move independently of the surrounding bones of the pelvis.: Ten patients underwent implantation of radiopaque markers around the prostate. Orthogonal protal films were taken at multiple stages during the course of treatment and digitized. An image registration tool was used to solve for film detector placement and, subsequently, to determine positional changes between structures on a reference portal image pair and all subsequent pairs for each patient. Transformations describing prostate movement were measured independently of those describing setup variations of the pelvic girdle.: Translation and/or rotation of the prostate was detected in 70% of the treatments for which films were taken. The maximum measured displacement was 7.5 mm along a major axis. Typical translatins of the prostate were between 0–4 mm. The translation and rotation had a predominant direction, suggesting a natural axis for prostate movement.: Although significant prostate displacement can occur between treatments, the typical range of movement seen along a major axis was less than 5 mm. Proper treatment planning should consider the movement of the target independent of surrounding bony anatomy. Advances in online portal imaging, image registration, and dynamic field shaping may permit shaped fields that encompass the prostate gland in its position at the time of treatment, allowing for the use of smaller fields while ensuring proper target coverage.
International Journal of Radiation OncologyBiologyPhysics 02/1995; · 4.11 Impact Factor
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ABSTRACT: The intrinsic divergence of photon beams presents serious matching problems in three-field treatment of the breast and the adjoining supraclavicular area. A method is presented in which appropriate beam blocking combined with suitable isocentric rotation of the treatment couch nentralize the affects of divergence so that proper matching is achieved at all depths. The geometric principle and the set-up procedures are discussed and illustrated.
International Journal of Radiation Oncology*Biology*Physics.
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ABSTRACT: Results for radiation treatment of prostate carcinoma indicate that nearly one-third of Stage C patients fail locally. This number will likely increase as occult failures are discovered by monitoring serum prostate specific antigen levels. Thus, there is need for techniques that would increase the local control of prostatic carcinoma. Using cross-sectional imaging and 3-dimensional treatment planning, dose distributions for photon irradiation can be created that conform more closely to the shape of the prostate and seminal vesicles, sparing additional dose to portions of bladder and rectum. A dose escalation trial is underway to investigate whether these techniques will lead to increased local control without unacceptable increases in bladder and rectal complications. While zero local failures is probably an unattainable goal, reduction in local failure in prostate cancer would likely increase the overall cure rate in this disease.
International Journal of Radiation Oncology*Biology*Physics.
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ABSTRACT: The explosion of new imaging technologies such as X ray computed tomography (CT), ultrasound (US), positron emission tomography (PET), and nuclear magnetic resonance imaging (NMR) has forced a major change in radiation therapy treatment planning philosophy and procedures. Modern computer technology has been wedded to these new imaging modalities, making possible sophisticated radiation therapy treatment planning using both the detailed anatomical and density information that is made available by CT and the other imaging modalities. This has forced a revolution in the way treatments are planned, with the result that actual beam configurations are typically both more complex and more carefully tailored to the desired target volume. This increase in precision and accuracy will presumably improve the results of radiation therapy.
International Journal of Radiation Oncology*Biology*Physics.
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ABSTRACT: This article reviews the indications for radiotherapy in advanced stage disease and discusses the recent prospective trials demonstrating a survival benefit by the addition of radiotherapy. Various treatment plans are reviewed with and without internal mammary node coverage. Although it is not clear whether internal mammary node irradiation can have a favorable impact on survival, it is clear that inadequate treatment planning of the parasternal region can result in excess cardiac morbidity and mortality. Careful planning using computed tomographic systems is required to optimize chest wall planning. With individualized treatment planning, it is hoped that the next generation of trials will show improved survival from further reduction in breast cancer deaths and significantly decreased cardiac toxicity.
Seminars in Radiation Oncology.
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ABSTRACT: The purpose of the study was to review the treatment outcomes of 198 patients treated with breast-conserving surgery (BCS) and whole breast radiation therapy using lung density correction for ductal carcinoma in situ (DCIS). Between April 1985 and December 2002, 198 patients with 200 lesions diagnosed as DCIS (AJCC stage 0) were treated at the University of Michigan. All underwent BCS and whole breast radiotherapy. Median total follow-up was 6.2 years (range: 0.8-18.2). The 5- and 10-year cumulative rates of in-breast only failure were 5.9% (95% CI: 2.6-9.3%) and 9.8% (95% CI: 5.2-14.4%), respectively. Factors that significantly predicted for an increased risk of local failure were family history of breast cancer, positive or close surgical margins and age </= 50 years at diagnosis. Cosmetic outcome was scored as "excellent" or "good" in 94% of the assessed patients. On multivariate analysis, only patient separation significantly predicted cosmetic outcome (p = 0.04). BCS and radiotherapy using lung density correction resulted in high rates of local control at 5 and 10 years with excellent cosmetic results. To the best of our knowledge, this is the first study to report outcome in a series of patients with DCIS treated with lung density correction and results compare favorably with other series in which plans were calculated using unit density.
The Breast Journal 13(4):392-400. · 1.64 Impact Factor
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ABSTRACT: Treatment of the intact breast is an interesting and challenging problem for the radiation oncologist. This problem becomes even more complex when it is desirable to treat the regional lymph nodes as well. After several decades of interest and attention, a number of techniques are available that offer excellent geometrical solutions to this problem. In general these techniques involve treating the supine patient with isocentric breast fields that avoid as much as possible dose to underlying lung, mediastinum, and contralateral breast. Immobilization devices and other aids, such as the protractor, make daily set-up of fields easily reproducible and reliable. Boost treatment is almost universally used to raise the dose to the tumor bed between 60 and 65 Gy. Careful design of these boost fields, especially using surgical clips to aid in localization, may increase the precision of treatment. Further studies are needed to determine whether there are any clinical advantages (improved local control or reduced complication rates) to the use of more sophisticated but costly dosimetry techniques, such as individualized three-dimensional compensation and the use of CT scans to correct for lung inhomogeneity.
Seminars in Radiation Oncology.
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ABSTRACT: It is now possible routinely to use 3-D treatment planning and 3-D dose-delivery techniques in a busy radiation oncology clinic. While labor-intensive at first, dosimetrists, physicists, and physicians become more skilled in applying these planning techniques as experience increases. With the development of faster computers, faster dose-calculational algorithms, and software for automatic structure recognition and automatic plan optimization, 3-D treatment planning will become easier and less expensive in the upcoming years. Dose escalation studies are underway to determine the maximum tolerated dose that can be given to a variety of tumor sites using this new technology. Over time, randomized clinical trials will be necessary to determine the ultimate value of this new style of therapy.
Seminars in Radiation Oncology.
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ABSTRACT: Background: A better understanding of the physical and biologic principles of radiation oncology, along with improvements in the technical and clinical aspects of this field, have been gained in recent years. Some of these aspects are presented, with an emphasis on their relevance to the oncologic surgeon. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/41415/1/10434_2006_Article_BF02303679.pdf
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ABSTRACT: BACKGROUND The purpose of this study was to evaluate the feasibility of breast-conserving therapy involving limited surgery and definitive radiotherapy as a treatment for Paget's disease, and to determine the disease free and overall survival associated with this approach. METHODS The authors retrospectively reviewed the charts of all patients treated during the period 1980-1994 for Paget's disease of the breast who did not present with a palpable mass or mammographic density. Through a collaborative review, 30 cases were identified. A biopsy confirming the presence of typical Paget's cells was performed on all patients. All patients received external beam radiotherapy to the breast, with a median dose of 50 gray (Gy). Ninety-seven percent received a boost to the remaining nipple or tumor bed, with a median dose to the tumor bed of 61.5 Gy. RESULTS The median follow-up for surviving patients was 62 months. Three patients (10%) developed a recurrence in the breast as the only site of first failure, and 2 additional patients (7%) experienced failure in the breast as a component of first failure. The median time to local failure was 69 months. The 5- and 8-year actuarial estimates of local failure as the only site of first failure were 9% (95% confidence interval [CI], 0-20%) and 16% (95% CI, 0-31%), respectively. Of the 5 patients with local failures, 3 were among 22 patients (14%) who underwent complete resection of the nipple or nipple-areola complex, compared with 2 failures among 6 patients (33%) after partial resection ( P = 0.29). There were no failures among 2 patients who had a biopsy only. Four of 5 local failures were salvaged by mastectomy, and 3 of these patients were free of disease after a median follow-up of 52 months. The 5- and 8-year estimates of disease free survival for the overall series were both 95% (95% CI, 87-100%); cause specific overall survival was 100% at 8 years. CONCLUSIONS Breast-conserving therapy involving complete resection of the nipple-areola complex followed by definitive radiotherapy is a viable alternative to mastectomy in the treatment of Paget's disease. High rates of disease free and cause specific survival, in addition to adequate local control, justify consideration of a conservative approach. Cancer 1997; 80:1065-72. © 1997 American Cancer Society. Peer Reviewed http://deepblue.lib.umich.edu/bitstream/2027.42/34345/1/8_ftp.pdf
