Benefits and risks of contralateral prophylactic mastectomy in women undergoing treatment for sporadic unilateral breast cancer: a decision analysis.

The rate of contralateral prophylactic mastectomy (CPM) is rising rapidly, despite limited evidence about the procedure's relative benefits and harms. The objective of this study is to examine the impact of CPM on life expectancy (LE) and quality-adjusted life expectancy (QALE) in women with sporadic unilateral breast cancer. A Markov model was developed to compare 18 hypothetical cohorts of 45-year-old women with newly diagnosed unilateral, sporadic breast cancer treated with or without CPM. The probability of developing distant metastases by American Joint Committee on Cancer stage and molecular subtype was derived from British Columbia Cancer Agency data. Additional model parameters were identified from the medical literature. Sensitivity analyses were performed to examine the impact of plausible variations in key model parameters on results. CPM improved LE in all cohorts (range 0.06-0.54 years). Stage had more effect on LE than subtype (stage I mean, 0.44 years, stage III mean, 0.11 years). However, after adjusting for quality-of-life, No CPM was favored in all cohorts. Univariate sensitivity analysis demonstrated that the most influential model parameter was the post-CPM health state utility. The preferred strategy shifted from No CPM to CPM when the post-CPM utility exceeded 0.83 (base case value 0.81). PSA indicated that LE gains and QALE decreases were stable in all cohorts. The primary determinant of survival after unilateral breast cancer is stage at diagnosis. Our results suggest that routine CPM would not improve quality-adjusted survival for the majority of women with unilateral sporadic breast cancer.

Prospective surveillance and management of cardiac toxicity and health in breast cancer survivors.

Breast cancer is commonly diagnosed in postmenopausal women, the majority of whom express 1 or more cardiovascular disease risk factors. Cardiovascular disease poses a significant competing risk for morbidity and mortality among nonmetastatic breast cancer survivors. Adjuvant systemic therapies may result in late-cardiac toxicity decades after treatment completion. The cumulative incidence of treatment-related cardiotoxic outcomes may be as high as 33% after some adjuvant breast cancer therapies. Breast cancer treatment-induced cardiotoxicity may manifest as cardiomyopathy, coronary ischemia, thromboembolism, arrhythmias and conduction abnormalities, and valvular and pericardial disease. Evidence indicates that preexisting cardiovascular conditions such as hypertension or left ventricular dysfunction may compound the adverse effects of cardiotoxic treatments. There are currently no published clinical practice guidelines that address ongoing cardiac surveillance for cardiotoxicity after breast cancer, and existing guidelines for monitoring and promoting cardiovascular health in older women are often not followed. The multidisciplinary prospective surveillance system proposed elsewhere in this supplement would allow for earlier detection of cardiotoxicity from treatment and may improve monitoring of cardiovascular health in the growing population of breast cancer survivors.

A prospective surveillance model for rehabilitation for women with breast cancer.

BACKGROUND: The current model of care for individuals with breast cancer focuses on treatment of the disease, followed by ongoing surveillance to detect recurrence. This approach lacks attention to patients' physical and functional well-being. Breast cancer treatment sequelae can lead to physical impairments and functional limitations. Common impairments include pain, fatigue, upper-extremity dysfunction, lymphedema, weakness, joint arthralgia, neuropathy, weight gain, cardiovascular effects, and osteoporosis. Evidence supports prospective surveillance for early identification and treatment as a means to prevent or mitigate many of these concerns. This article proposes a prospective surveillance model for physical rehabilitation and exercise that can be integrated with disease treatment to create a more comprehensive approach to survivorship health care. The goals of the model are to promote surveillance for common physical impairments and functional limitations associated with breast cancer treatment; to provide education to facilitate early identification of impairments; to introduce rehabilitation and exercise intervention when physical impairments are identified; and to promote and support physical activity and exercise behaviors through the trajectory of disease treatment and survivorship. METHODS: The model is the result of a multidisciplinary meeting of research and clinical experts in breast cancer survivorship and representatives of relevant professional and advocacy organizations. RESULTS/CONCLUSIONS: The proposed model identifies time points during breast cancer care for assessment of and education about physical impairments. Ultimately, implementation of the model may influence incidence and severity of breast cancer treatment-related physical impairments. As such, the model seeks to optimize function during and after treatment and positively influence a growing survivorship community.

Assessment of the residual error in soft tissue setup in patients undergoing partial breast irradiation: results of a prospective study using cone-beam computed tomography.

PURPOSE: On-board cone-beam computed tomography (CBCT) provides soft tissue information that may improve setup accuracy in patients undergoing accelerated partial breast irradiation (APBI). We used CBCT to assess the residual error in soft tissue after two-dimensional kV/MV alignment based on bony anatomy. We also assessed the dosimetric impact of this error. METHODS AND MATERIALS: Ten patients undergoing APBI were studied as part of an institutional review board-approved prospective trial. Patients were aligned based on skin/cradle marks plus orthogonal kV/MV images registered based on bony landmarks to digitally reconstructed radiographs from the planning CT. A subsequent CBCT was registered to the planning CT using soft tissue information. This "residual error" and its dosimetric impact was measured. RESULTS: The root-mean-square of the residual error was 3, 4, and 4 mm, in the right-left, anterior-posterior, and superior-inferior directions, respectively. The average vector sum was 6+/-2 mm. Average reductions in mean dose to the lumpectomy cavity, clinical target volume (CTV), and planning target volume were 0.1%, 0.4%, and 1%, respectively. The mean difference in the clinical target and planning target volumes that received 95% of the prescribed dose (V95) were 1% and 4%. CONCLUSIONS: In this initial study with a modest number of patients, the residual error in soft tissue was typically <5 mm, and with the field margins used, the resultant dosimetric consequences were modest. In patients immobilized in a customized cradle, setup using orthogonal kV images thus appears accurate and reproducible. The CBCT technique may have particular utility in patients with larger breast volumes or breast deformations. Further studies involving larger numbers of patients are needed to further assess the utility of CBCT.

Assessing the quality of colorectal cancer care: do we have appropriate quality measures? (A systematic review of literature).

RATIONALE, AIMS AND OBJECTIVES: The burden of illness from colorectal cancer (CRC) can be reduced by improving the quality of care. Identifying appropriate quality measures is the first step in this direction. We identified process measures currently available to assess the quality of diagnosis and management of CRC. We also evaluated the extent to which these measures are ready to be implemented in clinical practice, and identified areas for future research. METHODS: We searched MEDLINE, Cochrane Database of Systematic Reviews, and relevant grey literature. We identified 3771 abstracts and reviewed 74 articles that included quality measures for diagnosis or management of CRC. Measures from traditional quality improvement literature, and from epidemiological and other studies that included quality measures as part of their research agenda, were considered. In addition, we devised a summary rating scale (IST) to appraise the extent of a measure's importance and usability, scientific acceptability and extent of testing. RESULTS: The coverage of general process measures in CRC is extensive. Most measures are important, but need to be developed and field-tested. The best available measures relate to pathology and chemotherapy. No measures are available for assessing quality of management of stage IV rectal cancer and hepatic metastasis; chemotherapy for stage II colon cancer; and procedure notes. CONCLUSIONS: There is an urgent need to refine existing measures and to develop scientifically accurate quality measures for a comprehensive assessment of the quality of CRC care. The role of the federal government and professional societies is critical in pursuing this goal.

Cardiac toxicity following thoracic radiation.

While the data regarding radiotherapy (RT)-induced cardiovascular disease in lung cancer patients is limited, the cardiotoxic effects of RT have been thoroughly documented in long-term survivors of breast cancer and Hodgkin's disease. Herein we review data illustrating the cardiotoxic effects of thoracic RT in lung and breast cancer patients. Older RT techniques for treating the breast/chest wall and draining lymph nodes resulted in a relatively high dose being delivered to a substantial volume of heart, and convincing evidence exists of excess cardiovascular morbidity and mortality in patients treated with these techniques. While modern RT techniques have reduced radiation exposure to the heart, they have not eliminated it. In patients treated with modern techniques, there are conflicting data regarding the impact of radiation on late cardiovascular morbidity and mortality. Thus, it is prudent to reduce cardiac exposure as much as possible. Techniques to reduce further cardiac exposure (eg, respiratory gating, intensity modulated radiation therapy) are currently under investigation. Further work is needed to quantify the frequency and severity of cardiac injury and develop preventative methods.

Definition of postlumpectomy tumor bed for radiotherapy boost field planning: CT versus surgical clips.

PURPOSE: To compare the location and extent of the tumor bed as defined by surgical clips and computed tomography (CT) scans, after lumpectomy, for electron boost planning as part of breast radiotherapy. METHODS AND MATERIALS: Planning CT images of 31 operated breasts in 30 patients who underwent lumpectomy were reviewed. One or more clips were placed in the lumpectomy cavity. Serial CT images were used to measure the depth and transverse and longitudinal dimensions. The area and geometric center of the tumor bed were defined by the clips and CT. RESULTS: The CT and clip measurements were identical for the maximal tumor depth in 27 of 30 patients. The CT bed extended beyond the clips by 0-7 mm medially in the transverse/longitudinal extent (multiclip patients). The median distance between the geometric centers in the coronal plane for the tumor bed center was larger for patients with single clips than for those with multiple clips (p < 0.025). Tumor bed areas in the coronal plane defined by both methods correlated strongly. However, the CT-defined area was larger by 13.9 mm2. The CT bed was more readily visible in patients with a shorter interval between surgery and radiotherapy. CONCLUSION: The maximal depth of the tumor bed was similar using the two methods. The extent and centers of the clip-and CT-determined beds differed significantly. This may indicate an underestimation of the tumor bed as defined by clips only and justifies integration of CT information in boost field planning.

Pretreatment anemia is correlated with the reduced effectiveness of radiation and concurrent chemotherapy in advanced head and neck cancer.

PURPOSE: Pretreatment anemia is an adverse prognostic variable in squamous cell head-and-neck cancer (HNC) patients treated with radiotherapy (RT) alone. Tumor hypoxia is an adverse parameter for treatment with RT alone or with RT and concurrent chemotherapy (CCT). Tumor hypoxia is more prevalent in patients who present with pretreatment hemoglobin (Hgb) concentrations less than 13 g/dL. RT/CCT improves survival over RT alone in advanced HNC, and its use is becoming more widespread. This study was performed to evaluate whether pretreatment Hgb less than 13 g/dL was correlated with treatment outcome in patients with advanced HNC treated with a uniform regimen of RT/CCT. METHODS AND MATERIALS: The study population consisted of patients with AJCC Stage III or IV, M0 HNC who were treated with 70 to 72.5 Gy accelerated hyperfractionated RT (1.25 Gy b.i.d.) and CCT consisting of 2 cycles of CDDP (12-20 mg/m(2)/d x 5 days) and continuous infusion 5-FU (600 mg/m(2)/d x 5 days) during Week 1 and Week 6. A planned break in RT occurred during Week 4. These patients were enrolled on the experimental arm of a prospective randomized trial that compared this regimen to hyperfractionated irradiation alone from 1990 to 1996. RT/CCT was delivered as standard therapy from 1996 to 2000. The primary endpoint was failure-free survival (FFS). Secondary endpoints included local-regional control and overall survival. RESULTS: One hundred and fifty-nine patients were treated from 1990 to 2000. The median (25-75%) pretreatment Hgb was 13.6 (12.2-13.5) g/dL. Hgb was 13 g/dL or higher in 105 patients and less than 13 g/dL in 54 patients. Primary tumor sites included oropharynx (43%), hypopharynx/larynx (36%), oral cavity (9%), and nasopharynx (6%). Seventy-eight percent of the patients with Hgb 13 g/dL or higher and 92% of the patients with Hgb less than 13 g/dL had a primary tumor stage of T3 or T4 (p = 0.01). Node-positive disease was present in 74 of 105 (70%) of patients with Hgb 13 g/dL or higher patients and in 36/54 (67%) of patients with Hgb less than 13 g/dL patients. Median follow-up of surviving patients was 42 months (range, 4-128 months). Five-year FFS was 75% for patients with Hgb 13 g/dL or higher vs. 50% for patients with Hgb less than 13 g/dL had a (p < 0.01). A total of 49 failures occurred in both patient cohorts. The median (25-75%) decrease in Hgb during RT/CCT was 2.2 (1.3-3.1) g/dL, both in patients who failed and in those who remained disease-free. CONCLUSION: Pretreatment Hgb less than 13 g/dL is correlated with adverse outcomes in advanced HNC patients treated with RT/CCT. Whether anemia actually causes poor outcomes remains unknown. The therapeutic effect of anemia correction is being evaluated in prospective trials.

The incidence and functional consequences of RT-associated cardiac perfusion defects.

PURPOSE: Radiation therapy (RT) for left-sided breast cancer has been associated with cardiac dysfunction. We herein assess the temporal nature and volume dependence of RT-induced left ventricular perfusion defects and whether these perfusion defects are related to changes in cardiac wall motion or alterations in ejection fraction. METHODS: From 1998 to 2001, 114 patients were enrolled onto an IRB-approved prospective clinical study to assess changes in regional and global cardiac function after RT for left-sided breast cancer. Patients were imaged 30 to 60 minutes after injection of technetium 99m sestamibi or tetrofosmin. Post-RT perfusion scans were compared with the pre-RT studies to assess for RT-induced perfusion defects as well as functional changes in wall motion and ejection fraction. Two-tailed Fisher's exact test and the Cochran-Armitage test for linear trends were used for statistical analysis. RESULTS: The incidence of new perfusion defects 6, 12, 18, and 24 months after RT was 27%, 29%, 38%, and 42%, respectively. New defects occurred in approximately 10% to 20% and 50% to 60% of patients with less than 5%, and greater than 5%, of their left ventricle included within the RT fields, respectively (p = 0.33 to 0.00008). The rates of wall motion abnormalities in patients with and without perfusion defects were 12% to 40% versus 0% to 9%, respectively; p values were 0.007 to 0.16, depending on the post-RT interval. CONCLUSIONS: Radiation therapy causes volume-dependent perfusion defects in approximately 40% of patients within 2 years of RT. These perfusion defects are associated with corresponding wall-motion abnormalities. Additional study is necessary to better define the long-term functional consequences of RT-induced perfusion defects.

Late effects of breast radiotherapy in young women.

Radiotherapy (RT) to the breast or chest wall of young women is associated with long-term cardiotoxicity and an increased risk of secondary breast cancers. As many patients with early stage breast cancer and Hodgkin's disease are cured of their disease, there is significant concern regarding the long term risks of therapy. Older RT techniques for treating the breast/chest wall and draining lymph nodes for breast cancer resulted in a relatively high dose being delivered to a substantial volume of heart, and convincing evidence exists of excess cardiovascular morbidity and mortality in patients treated with these techniques. While modern RT techniques have reduced radiation exposure to the heart, they have not eliminated it. Many large studies of Hodgkin's disease survivors have demonstrated a clear risk of secondary breast cancer development after mantle RT for Hodgkin's disease. The risk of developing breast cancer after mantle RT appears to be related to age at time of irradiation, dose delivered to the breast tissue, and whether or not chemotherapy is incorporated into the overall treatment plan. In this article we review late cardiac complications associated with tangential breast RT and the risk of developing a secondary breast cancer after mantle RT for Hodgkin's disease.

Necessity for adjuvant neck dissection in setting of concurrent chemoradiation for advanced head-and-neck cancer.

PURPOSE: Neck dissection has traditionally played an important role in the treatment of patients with squamous cell carcinoma of the head and neck who present with regionally advanced neck disease (N2-N3). Radiotherapy and concurrent chemotherapy improves overall survival in advanced head-and-neck cancer compared with radiotherapy alone. The necessity for postchemoradiation neck dissection is controversial. The intent of this report was to define the value of neck dissection in this patient population better. METHODS AND MATERIALS: Patients with locally advanced squamous carcinoma of the head and neck who also presented with nodal disease and underwent hyperfractionated radiotherapy and concurrent cisplatin/5-fluorouracil chemotherapy constituted the study population. Adjuvant modified neck dissection (MND) was planned 6 to 8 weeks after completion of chemoradiation in those patients who had a biopsy-proven pathologically complete response at the primary tumor site, irrespective of the clinical/radiographic neck response. A cohort of patients underwent electrode assessment of tumor oxygenation. Pathologic findings from the MND were used to compute the negative and positive predictive values and overall accuracy of the clinical/radiographic response (cCR). Regional control, failure-free survival, and survival were compared according to whether patients actually underwent MND. RESULTS: A total of 154 patients received concurrent chemoradiation. Of these, 108 presented with nodal disease: N1, n = 30; and N2-N3, n = 78. MND was performed in 65 (60%) of 108 patients, including 13 (43%) of 30 with Stage N1 and 52 (66%) of 78 with Stage N2-N3. For N1 patients, the negative predictive value of a cCR, positive predictive value of less than a cCR, and the overall accuracy for clinical response was 92%, 100%, and 92%, respectively. For N2-N3 patients, the corresponding values were 74%, 44%, and 60%. Patients with poorly oxygenated tumors were more likely to have residual disease at MND. The median follow-up was 4 years. The 4-year disease-free survival rate was 70% for N1 patients, irrespective of the clinical response or whether MND was performed. The 4-year disease-free survival rate was 75% for N2-N3 patients who had a cCR and underwent MND vs. 53% for patients who had a cCR but did not undergo MND (p = 0.08). The 4-year overall survival rate was 77% vs. 50% for these two groups of patients (p = 0.04). CONCLUSION: The clinical and pathologic responses in the neck correlated poorly with one another for patients with N2-N3 neck disease undergoing concurrent chemoradiation for advanced head-and-neck cancer. MND still appears to confer a disease-free survival and overall survival advantage with acceptably low morbidity. Tumor oxygenation assessment may be useful in selecting patients who are especially prone to have residual disease. Better tools need to be developed to determine prospectively whether this procedure is required for individual patients.

Increased sectioning of pathologic specimens with ductal carcinoma in situ of the breast: are there clinical consequences?

To assess if there has been increased sectioning of pathologic specimens with ductal carcinoma in situ (DCIS), identify sources of this change, and consider the clinical consequences, pathologic data from patients who underwent initial excisional biopsies at our institution and were referred to the radiation oncology department with DCIS from 1992-2002 were retrospectively reviewed. One hundred forty-four of 480 patients with DCIS were eligible for review. Specimen size was recorded as length, to the nearest 0.1 cm, in 3 dimensions. Specimen volume was approximated by the product of the 3 dimensions of the specimen. The primary endpoint was the number of microscopic sections taken from gross specimens, corrected for specimen size. Other analysis included margin status, use of a previous stereotactic needle biopsy, and whether a subsequent repeat excision was performed. Over time, there was an increase in size of the excisional biopsy specimens (mean of 49 cm3 from 1992 to 1994 and 90 cm3 from 2001 to 2002; P = 0.045). Mean numbers of slides per centimeter of specimen were 2.5, 2.7, 3.9, and 5.8 for the intervals 1992-1994, 1995-1997, 1998-2000, and 2001-2002, respectively (P < 0.001 for 1992-1997 vs. 1998-2002). Adjusting for volume, the increase over time in the number of slides per specimen was statistically significant (parameter significance, P < 0.001). For a given volume, the number of slides increased approximately 9.1% per year, on average, during the study period. The positive margin rates were 52%, 46%, 23%, and 25% from 1992 to 1994, from 1995 to 1997, from 1998 to 2000, and from 2001 to 2002, respectively. The degree of sectioning, corrected for specimen length and volume, increased over time.

Rituximab in lymphocyte predominance Hodgkin's disease: a case series.

Rituximab in combination with chlorambucil or radiation therapy may be an effective and less-toxic therapeutic alternative for patients with lymphocyte predominance Hodgkin's disease (LPHD). We treated 6 patients with LPHD with weekly rituximab at 375 mg/m2 for 4 weeks, followed by either radiation therapy or chlorambucil. Four patients had previously untreated disease and 2 had relapsed LPHD. All patients had no evidence of disease progression at a median follow-up time of 12.5 months after receiving rituximab therapy (range, 6-39 months) and a median follow-up time of 6.5 months after completion of chlorambucil or radiation therapy (range, 3-25 months). Further follow-up is warranted to evaluate response duration and late toxicity of this novel treatment strategy

Use of postexcision preirradiation mammography in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy.

PURPOSE: Postexcision preirradiation mammography (PPM) is frequently performed in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy (BCT) to evaluate for residual suspicious calcifications; but no clear evidence supports this practice. The current study was undertaken to investigate the value of PPM in the management of patients with DCIS. METHODS AND MATERIALS: We conducted a retrospective review of patients treated for DCIS with BCT at the University of Pennsylvania. The impact of PPM on surgical management and on local recurrence was evaluated. Factors associated with the use of PPM, the results of PPM, and the likelihood of finding residual malignancy at the time of re-excision in patients with PPM were also examined. RESULTS: One hundred forty-four of 281 patients (51%) underwent PPM. Of the 144 patients who received PPM, 34 (24%; 95% confidence interval, 17%-31%) had residual suspicious calcifications (a "positive PPM"). Of the 34 patients with a positive PPM, all underwent a re-excision and 19 (56%; 95% confidence interval, 35%-70%) were found to have residual malignancy. Ten of 34 patients with a positive PPM had negative margins, of which 6 had a residual malignancy. Assuming all patients with close, positive, or indeterminate surgical margins would have undergone re-excision regardless of the findings of PPM, PPM resulted in a change in surgical management in 7% (10/144) of patients and removal of residual DCIS in 4% (6/144). With a median follow-up of 9.5 years, the use of PPM was not associated with an improvement in 10-year local recurrence-free survival (94.8% vs 91.5%, P = .368). CONCLUSIONS: In this study, PPM affected surgical management in only a small percentage of patients and had no impact on local recurrence. The routine use of PPM in women undergoing BCT for DCIS may not be warranted.

Planning comparison of intensity modulated radiation therapy delivered with 2 tangential fields versus 3-dimensional conformal radiotherapy for cardiac sparing in women with left-sided breast cancer.

PURPOSE: In women with unfavorable thoracic anatomy undergoing left breast radiation therapy (RT) after breast-conserving surgery, a significant volume of the heart may receive high-dose radiation, which has been shown previously to be associated with increased late cardiac morbidity and mortality. Use of intensity modulated radiation therapy (IMRT) has been proposed to reduce cardiac dose in these patients. We compared cardiac exposure from IMRT delivered from 2 opposed fields and 3-dimensional conformal radiation therapy (3DCRT) plans employing simple heart blocks. METHODS AND MATERIALS: Fourteen patients with left-sided breast cancer treated with breast-conserving surgery and RT were identified to have unfavorable cardiac anatomy, defined as maximum heart depth (MHD) ≥1.0 cm within the unblocked opposed tangential fields. 3DCRT plans utilized dynamic wedges, segments, and custom heart blocks designed by the treating physician. Tangent IMRT plans were optimized to reduce cardiac dose while maintaining planning target volume (PTV) coverage equal to that achieved with the 3DCRT plan. We generated tangential field plans with complete heart block (CHB) or no heart block (NHB) for comparison. Plans were normalized to deliver 46 Gy to the PTV. Dose to the heart, PTV, and lumpectomy cavity were compared. RESULTS: Mean MHD was 1.44 cm (1.0-1.86 cm). There was no significant difference in PTV receiving >95% of the prescription dose between 3DCRT and IMRT, as intended. Mean V30 to the heart was 0% for CHB plans, 1.7% for 3DCRT plans, 1.8% for IMRT plans, and 3.3% for NHB plans, respectively. There was no significant difference in heart V30 for 3DCRT and IMRT plans (P = .8). IMRT plans delivered 256 total monitor units compared with 201 in 3DCRT plans (P < .01). CONCLUSIONS: Inverse-planned tangent IMRT does not reduce high-dose radiation to the heart compared with 3DCRT, incorporating a simple heart block in women with left-sided cancer and unfavorable cardiac anatomy when PTV coverage was equalized for both plans. In select patients with early-stage breast cancer and unfavorable thoracic anatomy, 3DCRT with heart block may be sufficient to adequately protect the heart from high-dose radiation.

Renal shielding and dosimetry for patients with severe systemic sclerosis receiving immunoablation with total body irradiation in the scleroderma: cyclophosphamide or transplantation trial.

PURPOSE: To describe renal shielding techniques and dosimetry in delivering total body irradiation (TBI) to patients with severe systemic sclerosis (SSc) enrolled in a hematopoietic stem cell transplant protocol. METHODS AND MATERIALS: The Scleroderma: Cyclophosphamide or Transplantation (SCOT) protocol uses a lymphoablative preparative regimen including 800 cGy TBI delivered in two 200-cGy fractions twice a day before CD34(+) selected autologous hematopoietic stem cell transplantation. Lung and kidney doses are limited to 200 cGy to protect organs damaged by SSc. Kidney block proximity to the spinal cord was investigated, and guidelines were developed for acceptable lumbar area TBI dosing. Information about kidney size and the organ shifts from supine to standing positions were recorded using diagnostic ultrasound (US). Minimum distance between the kidney blocks (dkB) and the lumbar spine region dose was recorded, and in vivo dosimetry was performed at several locations to determine the radiation doses delivered. RESULTS: Eleven patients were treated at our center with an anteroposterior (AP)/posteroanterior (PA) TBI technique. A 10% to 20% dose inhomogeneity in the lumbar spine region was achieved with a minimum kidney block separation of 4 to 5 cm. The average lumbar spine dose was 179.6 ± 18.1 cGy, with an average dkB of 5.0 ± 1.0 cm. Kidney block shield design was accomplished using a combination of US and noncontrast computerized tomography (CT) or CT imaging alone. The renal US revealed a wide range of kidney displacement from upright to supine positions. Overall, the average in vivo dose for the kidney prescription point was 193.4 ± 5.1 cGy. CONCLUSIONS: The dose to the kidneys can be attenuated while maintaining a 10% to 20% dose inhomogeneity in the lumbar spine area. Kidneys were localized more accurately using both US and CT imaging. With this technique, renal function has been preserved, and the study continues to enroll patients.

Prospective assessment of radiotherapy-associated cardiac toxicity in breast cancer patients: analysis of data 3 to 6 years after treatment.

BACKGROUND: Radiation therapy (RT) to the left breast/chest wall has been linked with cardiac dysfunction. Previously, the authors identified cardiac perfusion defects in approximately 50% to 60% of patients 0.5 to 2 years post-RT. In the current study, they assessed the persistence of these defects 3 to 6 years post-RT. METHODS: From 1998 to 2006, 160 patients with left-sided breast cancer were enrolled onto an Institutional Review Board-approved, prospective study. All patients received tangential photons to the left breast/chest wall. Patients had pre-RT and serial post-RT single-photon emission computed tomography (SPECT) scans to assess changes in regional cardiac perfusion, wall motion, and ejection fraction (EF). Forty-four patients had SPECT scans 3 to 6 years post-RT and were evaluable for the current analysis. RESULTS: The overall incidence of perfusion defects at 3 years, 4 years, 5 years, and 6 years was 52% (11 of 21 patients), 71% (17 of 24 patients), 67% (12 of 18 patients), and 57% (4 of 7 patients), respectively. The rate of abnormal SPECT scans 3 to 6 years post-RT in patients who had scans at 0.5 to 2 years that were either all abnormal, intermittently abnormal, or all normal was 80%, 67%, and 63%, respectively. The incidence of wall motion abnormalities in patients with or without perfusion defects 3 to 6 years post-RT was low and did not differ statistically (17% vs 7.1%, respectively; P = .65), as was the incidence of reductions in EF of >/=5% (27% vs 36%, respectively; P = .72). CONCLUSIONS: The results from this study indicated that RT-induced perfusion defects may persist or initially may appear 3 to 6 years post-RT in a high percentage of patients. However, these defects were not associated with changes in regional wall motion or EF. Additional study will be needed to determine the clinical relevance of these defects. In the meantime, the authors believe that every effort should be made to minimize incidental irradiation of the heart while maintaining adequate coverage of target volumes.

Combined-modality therapy versus radiotherapy alone for treatment of early-stage Hodgkin's disease: cure balanced against complications.

PURPOSE: The treatment of early-stage Hodgkin's disease (HD) has evolved from radiotherapy alone (RT) to combined-modality therapy (CMT) because of concerns about late adverse effects from high-dose subtotal nodal irradiation (STNI). However, there is little information regarding the long-term results of CMT programs that substantially reduce the dose and extent of radiation. In addition, lowering the total radiation dose may reduce the complication rate without compromising cure. This retrospective study compares the long-term results of STNI with CMT using modestly reduced RT dose in the treatment of early-stage HD. PATIENTS AND METHODS: Between 1982 and 2002, 111 patients with stage IA and IIA HD were treated definitively with RT (mean dose, 37.9 Gy); 70 patients were treated with CMT with low-dose involved-field radiotherapy (LDIFRT; mean dose, 25.5 Gy). Median follow-up was 11.7 years for RT patients and 8.1 years for the CMT group. RESULTS: There was a trend toward improved 20-year overall survival with CMT (83% v 70%; P = .405). No second cancers were observed in the CMT group; in the RT group the actuarial frequency of a second cancer was 16% at 20 years. There was no difference in the frequency of cardiac complications (9% v 6%, RT v CMT). CONCLUSION: In this retrospective review, CMT with LDIFRT was effective in curing early-stage HD and was not associated with an increase in second malignancies. For RT alone, a moderate dose seemed to reduce cardiac complications but did not lessen second malignancies compared with higher doses used historically.

Cancer care quality measures: diagnosis and treatment of colorectal cancer.

OBJECTIVES: To identify measures that are currently available to assess the quality of care provided to patients with colorectal cancer (CRC), and to assess the extent to which these measures have been developed and tested. DATA SOURCES: Published and unpublished measures identified through a computerized search of English-language citations in MEDLINE (1966-January 2005), the Cochrane Database of Systematic Reviews, and the National Guideline Clearinghouse; through review of reference lists contained in seed articles, all included articles, and relevant review articles; and through searches of the grey literature (institutional or government reports, professional society documents, research papers, and other literature, in print or electronic format, not controlled by commercial publishing interests). Sources for grey literature included professional organization websites and the Internet. REVIEW METHODS: Measures were selected by reviewers according to standardized criteria relating to each question, and were then rated according to their importance and usability, scientific acceptability, and extent of testing; each domain was rated from 1 (poor) to 5 (ideal). RESULTS: We identified a number of well-developed and well-tested CRC-related quality-of-care measures, both general process-of-care measures (on a broader scale) and technical measures (pertaining to specific details of a procedure). At least some process measures are available for diagnostic imaging, staging, surgical therapy, adjuvant chemotherapy, adjuvant radiation therapy, and colonoscopic surveillance. Various technical measures were identified for quality of colonoscopy (e.g., cecal intubation rate, complications) and staging (adequate lymph node retrieval and evaluation). These technical measures were guideline-based and well developed, but less well tested, and the linkage between them and patient outcomes, although intuitive, was not always explicitly provided. For some elements of the care pathway, such as operative reports and chemotherapy reports, no technical measures were found. CONCLUSIONS: Some general process measures have a stronger evidence base than others. Those based on guidelines have the strongest evidence base; those derived from basic first principles supported by some research findings are relatively weaker, but are often sufficient for the task at hand. A consistent source of tension is the distinction between the clinically derived fine-tuning of the definition of a quality measure and the limitations of available data sources (which often do not contain sufficient information to act on such distinctions). Although some excellent technical measures were found, the overall development of technical measures seems less advanced than that of the general process measures.