Assessing the impact of radiation-induced changes in soft tissue density ∕ thickness on the study of radiation-induced perfusion changes in the lung and heart.

PURPOSE: Abnormalities in single photon emission computed tomography (SPECT) perfusion within the lung and heart are often detected following radiation for tumors in∕around the thorax (e.g., lung cancer or left-sided breast cancer). The presence of SPECT perfusion defects is determined by comparing pre- and post-RT SPECT images. However, RT may increase the density of the soft tissue surrounding the lung∕heart (e.g., chest wall∕breast) that could possibly lead to an "apparent" SPECT perfusion defect due to increased attenuation of emitted photons. Further, increases in tissue effective depth will also increase SPECT photon attenuation and may lead to "apparent" SPECT perfusion defects. The authors herein quantitatively assess the degree of density changes and effective depth in soft tissues following radiation in a series of patients on a prospective clinical study. METHODS: Patients receiving thoracic RT were enrolled on a prospective clinical study including pre- and post-RT thoracic computed tomography (CT) scans. Using image registration, changes in tissue density and effective depth within the soft tissues were quantified (as absolute change in average CT Hounsfield units, HU, or tissue thickness, cm). Changes in HU and tissue effective depth were considered as a continuous variable. The potential impact of these tissue changes on SPECT images was estimated using simulation data from a female SPECT thorax phantom with varying tissue densities. RESULTS: Pre- and serial post-RT CT images were quantitatively studied in 23 patients (4 breast cancer, 19 lung cancer). Data were generated from soft tissue regions receiving doses of 20-50 Gy. The average increase in density of the chest was 5 HU (range 46 to -69). The average change in breast density was a decrease of -1 HU (range 13 to -13). There was no apparent dose response in neither the dichotomous nor the continuous analysis. Seventy seven soft tissue contours were created for 19 lung cancer patients. The average change in tissue effective depth was +0.2 cm (range -1.9 to 2.2 cm). The changes in HU represent a <2% average change in tissue density. Based on simulation, the small degree of density and tissue effective depth change is unlikely to yield meaningful changes in either SPECT lung or heart perfusion. CONCLUSIONS: RT doses of 20-50 Gy can cause up to a 46 HU increase in soft tissue density 6 months post-RT. Post-RT soft tissue effective depth may increase by 2.0 cm. These modest increases in soft tissue density and effective depth are unlikely to be responsible for the perfusion changes seen on post-RT SPECT lung or heart scans. Further, there was no clear dose response of the soft tissue density changes. Ultimately, the authors findings suggest that prior perfusion reports do reflect changes in the physiology of the lungs and heart.

How long have I had my cancer, doctor? Estimating tumor age via Collins' law.

To estimate the"age" of cancers at the time of diagnosis, we reviewed data on the "time to local/regional recurrence" (LRF) following initial surgical resection for three common cancers, then applied a modified version of Collins' law. We conducted a systematic review of English medical literature to identify studies reporting LRF rates, over time, following surgery alone for breast, lung, or colorectal cancer. Patients who received radiation/hormones/chemotherapy were excluded since these therapies may alter tumor growth kinetics after surgery. For each disease, data were considered in three ways: 1) absolute cumulative LRF rate over time; 2) percentage of LRFs manifest over time (to facilitate comparisons between studies with different absolute magnitudes of LRFs); and 3) weighted average of the percentage of LRFs manifest over time. For breast cancer (based on data from 3043 patients from 5 studies), we found that the median time to LRF was 2.7 years. For lung cancer (based on data from 1190 patients from 4 studies), the median time to LRF was 1.5 years. For rectal cancer (based on data from 3334 patients from 10 studies), the median time to LRF was 1.5 years. Based on Collins' law, the distribution of time to LRF suggests that the age of most of the solid tumors studied was 3 to 6 years.

Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience.

PURPOSE: To assess the safety and efficacy of intensity-modulated radiotherapy (IMRT) after extrapleural pneumonectomy for malignant pleural mesothelioma. METHODS AND MATERIALS: Thirteen patients underwent IMRT after extrapleural pneumonectomy between July 2005 and February 2007 at Duke University Medical Center. The clinical target volume was defined as the entire ipsilateral hemithorax, chest wall incisions, including drain sites, and involved nodal stations. The dose prescribed to the planning target volume was 40-55 Gy (median, 45). Toxicity was graded using the modified Common Toxicity Criteria, and the lung dosimetric parameters from the subgroups with and without pneumonitis were compared. Local control and survival were assessed. RESULTS: The median follow-up after IMRT was 9.5 months. Of the 13 patients, 3 (23%) developed Grade 2 or greater acute pulmonary toxicity (during or within 30 days of IMRT). The median dosimetric parameters for those with and without symptomatic pneumonitis were a mean lung dose (MLD) of 7.9 vs. 7.5 Gy (p = 0.40), percentage of lung volume receiving 20 Gy (V(20)) of 0.2% vs. 2.3% (p = 0.51), and percentage of lung volume receiving 5 Gy (V(20)) of 92% vs. 66% (p = 0.36). One patient died of fatal pulmonary toxicity. This patient received a greater MLD (11.4 vs. 7.6 Gy) and had a greater V(20) (6.9% vs. 1.9%), and V(5) (92% vs. 66%) compared with the median of those without fatal pulmonary toxicity. Local and/or distant failure occurred in 6 patients (46%), and 6 patients (46%) were alive without evidence of recurrence at last follow-up. CONCLUSIONS: With limited follow-up, 45-Gy IMRT provides reasonable local control for mesothelioma after extrapleural pneumonectomy. However, treatment-related pulmonary toxicity remains a significant concern. Care should be taken to minimize the dose to the remaining lung to achieve an acceptable therapeutic ratio.

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.

The impact of advanced technologies on treatment deviations in radiation treatment delivery.

PURPOSE: To assess the impact of new technologies on deviation rates in radiation therapy (RT). METHODS AND MATERIALS: Treatment delivery deviations in RT were prospectively monitored during a time of technology upgrade. In January 2003, our department had three accelerators, none with "modern" technologies (e.g., without multileaf collimators [MLC]). In 2003 to 2004, we upgraded to five new accelerators, four with MLC, and associated advanced capabilities. The deviation rates among patients treated on "high-technology" versus "low-technology" machines (defined as those with vs. without MLC) were compared over time using the two-tailed Fisher's exact test. RESULTS: In 2003, there was no significant difference between the deviation rate in the "high-technology" versus "low-technology" groups (0.16% vs. 0.11%, p = 0.45). In 2005 to 2006, the deviation rate for the "high-technology" groups was lower than the "low-technology" (0.083% vs. 0.21%, p = 0.009). This difference was caused by a decline in deviations on the "high-technology" machines over time (p = 0.053), as well as an unexpected trend toward an increase in deviations over time on the "low-technology" machines (p = 0.15). CONCLUSIONS: Advances in RT delivery systems appear to reduce the rate of treatment deviations. Deviation rates on "high-technology" machines with MLC decline over time, suggesting a learning curve after the introduction of new technologies. Associated with the adoption of "high-technology" was an unexpected increase in the deviation rate with "low-technology" approaches, which may reflect an over-reliance on tools inherent to "high-technology" machines. With the introduction of new technologies, continued diligence is needed to ensure that staff remain proficient with "low-technology" approaches.

Solitary Fibrous Tumors of Chest: Another Look with the Oncologic Perspective.

Solitary fibrous tumors are mesenchymal lesions that arise at a variety of sites, most commonly the pleura. Most patients are asymptomatic at diagnosis, with lesions being detected incidentally. Nevertheless, some patients present due to symptoms from local tumor compression (eg. of the airways and pulmonary parenchyma). Furthermore, radiological methods are not always conclusive in making a diagnosis, and thus, pathological analysis is often required. In the past three decades, immunohistochemical techniques have provided a gold standard in solitary fibrous tumor diagnosis. The signature marker of solitary fibrous tumor is the presence of the NAB2-STAT6 fusion that can be reliably detected with a STAT6 antibody. While solitary fibrous tumors are most often benign, they can be malignant in 10-20% of the cases. Unfortunately, histological parameters are not always predictive of benign vs malignant solitary fibrous tumors. As solitary fibrous tumors are generally regarded as relatively chemoresistant tumors; treatment is often limited to localized treatment modalities. The optimal treatment of solitary fibrous tumors appears to be complete surgical resection for both primary and local recurrent disease. However, in cases of suboptimal resection, large disease burden, or advanced recurrence, a multidisciplinary approach may be preferable. Specifically, radiotherapy for inoperable local disease can provide palliation/shrinkage. Given their sometimes -unpredictable and often- protracted clinical course, long-term follow-up post-resection is recommended.

Patterns of postpartum contraceptive use among Somali immigrant women living in Minnesota.

BACKGROUND: The postpartum period is a crucial time to provide family planning counseling and can decrease incidence of adverse reproductive outcomes. The purpose of this study was to characterize patterns of postpartum contraception and to investigate long acting reversible contraceptive (LARC) use among Somali women living in a metropolitan area of Minnesota in an effort to provide better family planning and reproductive health counseling in this growing immigrant population. METHODS: A retrospective chart review was conducted of Somali women who delivered between January 1, 2011 and December 31, 2014. Information was collected regarding family planning counseling provided and contraceptive methods chosen at the postpartum clinic visit. RESULTS: Of the 747 Somali women who delivered during this time period, 56.4% had no postpartum follow up visit. At the postpartum visit, 88.3% of women received family planning counseling and 80.8% chose a contraceptive method with the remainder declining. The intrauterine device (IUD) was the most popular contraceptive method, chosen by 39.7% of women. Other than parity, no statistically significant differences were observed between women who chose LARC versus other contraceptive methods. Of the women that chose a LARC, 39.4% had it placed at the time of their postpartum visit; immediate placement was statistically significantly more likely with more recent delivery, lower BMI and obstetrician as the provider type. CONCLUSIONS: The IUD was the most popular method of postpartum contraception. There was a trend toward increase in LARC use with increasing parity. Same-day LARC placement was uncommon, but should be encouraged in this population given high loss to follow up rate.

Systemic and local hormone therapy for endometrial hyperplasia and early adenocarcinoma.

OBJECTIVE: To estimate disease regression, persistence, and progression in women with complex endometrial hyperplasia and stage I endometrial carcinoma treated with a levonorgestrel-releasing-intrauterine system or oral progesterone. METHODS: Records of all patients who received progestin therapy for endometrial hyperplasia or early-stage endometrioid cancer between January 1999 and July 2011 were reviewed. Demographic data (age, body mass index), presentation, treatment modality and rationale, rates of response, recurrence, and salvage surgery were collected and compared using Student's t and χ tests. Fertility outcomes when available were analyzed. RESULTS: One hundred eighty-six women received primary hormone therapy for endometrial hyperplasia or cancer. Of these, 153 had adequate follow-up without surgery or radiation as part of primary treatment. Average age at diagnosis was 49.6 years (range 22-92 years). The most common reasons cited for hormone therapy were medical comorbidities (46%) and fertility (21%). Patients with hyperplasia compared with cancer had significantly different complete response (66-70% compared with 6-13%), initial response with recurrence (11-23% compared with 19-30%), and no response rates (11-19% compared with 57-75%), respectively (P<.001). Outcomes were not significantly different between the levonorgestrel-releasing intrauterine system and oral progesterone among patients with cancer at all time points. In patients with hyperplasia, outcomes were not significantly different except during the 9-month to 12-month assessment where those who received systemic hormones were less likely to have disease persistence or progression compared with patients who had levonorgestrel-releasing intrauterine systems. Three patients achieved pregnancy. CONCLUSIONS: Hormone therapy has varied response rates among women with endometrial hyperplasia or cancer who do not undergo surgery. Close patient monitoring remains paramount given the high recurrence and high percentage of patients who will not respond.

Local failure after complete resection of N0-1 non-small cell lung cancer.

PURPOSE: To estimate the risk of local-regional failure (LRF) after surgery for operable NSCLC, and the effect of clinical/pathologic factors on this risk. METHODS: Records of 335 patients undergoing complete resection (lobectomy, pneumonectomy) for pathological T1-4 N0-1 NSCLC (without post-operative radiation) from 1996 to 2006 were reviewed. Crude and actuarial estimated failure rates were computed; local-regional sites included ipsilateral lung, surgical stump, hilar, mediastinal, or supraclavicular nodes. Failure times in sub-groups were calculated with the Kaplan-Meier method and compared via log-rank test. Independent factors adversely affecting LRF were determined with Cox regression. RESULTS: The median follow-up duration for event-free surviving patients was 40 months (range: 1-150). The crude and actuarial 5-year probability of any failure (LR or distant) were 33% and 43%, respectively. Of all failures; 37% were LR only, 35% LR and distant and 28% distant only. The 5-year crude and actuarial probability of LRF were 24% and 35% (95% CI: 29-42%). Five-year crude LRF rates for T1-2N0, T1-2N1, T3-4N0 and T3-4N1 disease were 19% (41/216), 27% (16/59), 37.5% (15/40) and 40% (8/20), respectively. The corresponding actuarial estimates were T1-2N0 28%, T1-2N1 39%, T3-4N0 50% and T3-4N1 67%. In Cox multiple regression analysis, lymphovascular space invasion (p=0.03, HR: 1.7) and tumor size (p=0.01, HR: 1.67 for 5 cm increment) were associated with an increased risk of LRF. CONCLUSION: Five-year LRF rates are ≥19% in essentially all patient subsets.

A comparison of clinical and dosimetric outcomes in patients receiving partial breast irradiation with photon-only versus mixed photon/electron treatment plans.

Several series evaluating external-beam partial breast irradiation (PBI) have linked negative cosmetic outcomes to large normal tissue treatment volumes. We compared patients treated with PBI whose treatment plans included only photons to those whose plans incorporated electrons. Twenty-seven patients were identified: median age 67 years, pT1 82%, pN0 56%, margin negative 100%. All received 38.5 Gy using 3-5 noncoplanar photon beams (6-15X). Electrons (9-20 MeV) were included in 59%. Median follow-up was 22 months. Ninety percent experienced good/excellent cosmetic outcomes. Two patients had fair cosmesis, and both were treated with a mixed photon/electron approach. Median conformity index for photon-only treatment plans was 1.7 (range, 0.9-2.0) and for photon/electron plans, 1.0 (0.3-1.4). Median percent ipsilateral breast volume receiving 100% and 50% of prescription dose was 19 and 50 for photon-only plans vs. 10 and 38 for photon/electron plans (p < 0.05). Median percent target volume receiving 100% and 95% of prescription dose was 93 and 98 for photon-only plans vs. 75 and 94 for photon/electron plans (p < 0.05). A mixed photon/electron, noncoplanar technique decreases the volume of treated normal breast tissue at the cost of slightly decreased tumor bed coverage. Further study is needed to determine whether this results in a more favorable therapeutic ratio than photon-only approaches.

How well does the new lung cancer staging system predict for local/regional recurrence after surgery?: A comparison of the TNM 6 and 7 systems.

INTRODUCTION: To evaluate how well the tumor, node, metastasis (TNM) 6 and TNM 7 staging systems predict rates of local/regional recurrence (LRR) after surgery alone for non-small cell lung cancer. METHODS: All patients who underwent surgery for non-small cell lung cancer at Duke between 1995 and 2005 were reviewed. Those undergoing sublobar resections, with positive margins or involvement of the chest wall, or those who received any chemotherapy or radiation therapy (RT) were excluded. Disease recurrence at the surgical margin, or within ipsilateral hilar and/or mediastinal lymph nodes, was considered as a LRR. Stage was assigned based on both TNM 6 and TNM 7. Rates of LRR were estimated using the Kaplan-Meier method. A Cox regression analysis evaluated the hazard ratio of LRR by stage within TNM 6 and TNM 7. RESULTS: A total of 709 patients were eligible for the analysis. Median follow-up was 32 months. For all patients, the 5-year actuarial risk of LRR was 23%. Conversion from TNM 6 to TNM 7 resulted in 21% stage migration (upstaging in 13%; downstaging in 8%). Five-year rates of LRR for stages IA, IB, IIA, IIB, and IIIA disease using TNM 6 were 16%, 26%, 43%, 35%, and 40%, respectively. Using TNM 7, corresponding rates were 16%, 23%, 37%, 39%, and 30%, respectively. The hazard ratios for LRR were statistically different for IA and IB in both TNM 6 and 7 but were also different for IB and IIA in TNM 7. CONCLUSIONS: LRR risk increases monotonically for stages IA to IIB in the new TNM 7 system. This information might be valuable when designing future studies of postoperative RT.

Factors associated with the development of brain metastases: analysis of 975 patients with early stage nonsmall cell lung cancer.

BACKGROUND: The risk of developing brain metastases after definitive treatment of locally advanced nonsmall cell lung cancer (NSCLC) is approximately 30%-50%. The risk for patients with early stage disease is less defined. The authors sought to investigate this further and to study potential risk factors. METHODS: The records of all patients who underwent surgery for T1-T2 N0-N1 NSCLC at Duke University between the years 1995 and 2005 were reviewed. The cumulative incidence of brain metastases and distant metastases was estimated by using the Kaplan-Meier method. A multivariate analysis assessed factors associated with the development of brain metastases. RESULTS: Of 975 consecutive patients, 85% were stage I, and 15% were stage II. Adjuvant chemotherapy was given to 7%. The 5-year actuarial risk of developing brain metastases and distant metastases was 10%(95% confidence interval [CI], 8-13) and 34%(95% CI, 30-39), respectively. Of patients developing brain metastases, the brain was the sole site of failure in 43%. On multivariate analysis, younger age (hazard ratio [HR], 1.03 per year), larger tumor size (HR, 1.26 per cm), lymphovascular space invasion (HR, 1.87), and hilar lymph node involvement (HR, 1.18) were associated with an increased risk of developing brain metastases. CONCLUSIONS: In this large series of patients treated surgically for early stage NSCLC, the 5-year actuarial risk of developing brain metastases was 10%. A better understanding of predictive factors and biological susceptibility is needed to identify the subset of patients with early stage NSCLC who are at particularly high risk.

Timing of local and distant failure in resected lung cancer: implications for reported rates of local failure.

INTRODUCTION: Most adjuvant lung cancer trials only report first sites of failure. The relative timing of local (i.e., local/regional) versus distant recurrence after surgery could potentially affect reported rates of local failure. We assessed this phenomenon in a large group of patients undergoing surgery for early-stage lung cancer. METHODS: This institutional review board-approved retrospective study identified all patients who underwent surgery at Duke University Medical Center for pathologic stages I to II non-small cell lung cancer between 1995 and 2005. Medical records and pertinent radiographs were reviewed to assess for local and distant sites of recurrence. Both first and subsequent failures were examined. The time interval between surgery and date of local and/or distant failure was compared using the Mann-Whitney U test. RESULTS: Of 975 patients undergoing surgery, 250 patients developed recurrent disease (43 local only, 110 distant only, and 97 both). The median time from surgery to local failure was 13.9 months (range, 1-79). The median time to distant failure was 12.5 months (range, 1-79 months). These were not significantly different (p = 0.34). Among 97 patients who experienced both local and distant failure, 72 (74%) failed at both sites simultaneously, 19 (20%) failed at local sites first, and 6 (6%) failed at distant sites first. CONCLUSIONS: The time interval from surgery to either local or distant failure is not significantly different. Patterns of failure analyses in which only first sites of failure are scored will underestimate the frequency of local recurrence. Nevertheless, the magnitude of this error is expected to be small.

Radiation-induced reductions in regional lung perfusion: 0.1-12 year data from a prospective clinical study.

PURPOSE: To assess the time and regional dependence of radiation therapy (RT)-induced reductions in regional lung perfusion 0.1-12 years post-RT, as measured by single photon emission computed tomography (SPECT) lung perfusion. MATERIALS/METHODS: Between 1991 and 2005, 123 evaluable patients receiving RT for tumors in/around the thorax underwent SPECT lung perfusion scans before and serially post-RT (0.1-12 years). Registration of pre- and post-RT SPECT images with the treatment planning computed tomography, and hence the three-dimensional RT dose distribution, allowed changes in regional SPECT-defined perfusion to be related to regional RT dose. Post-RT follow-up scans were evaluated at multiple time points to determine the time course of RT-induced regional perfusion changes. Population dose response curves (DRC) for all patients at different time points, different regions, and subvolumes (e.g., whole lungs, cranial/caudal, ipsilateral/contralateral) were generated by combining data from multiple patients at similar follow-up times. Each DRC was fit to a linear model, and differences statistically analyzed. RESULTS: In the overall groups, dose-dependent reductions in perfusion were seen at each time post-RT. The slope of the DRC increased over time up to 18 months post-RT, and plateaued thereafter. Regional differences in DRCs were only observed between the ipsilateral and contralateral lungs, and appeared due to tumor-associated changes in regional perfusion. CONCLUSIONS: Thoracic RT causes dose-dependent reductions in regional lung perfusion that progress up to approximately 18 months post-RT and persists thereafter. Tumor shrinkage appears to confound the observed dose-response relations. There appears to be similar dose response for healthy parts of the lungs at different locations.

Regional lung density changes after radiation therapy for tumors in and around thorax.

PURPOSE: To study the temporal nature of regional lung density changes and to assess whether the dose-dependent nature of these changes is associated with patient- and treatment-associated factors. METHODS AND MATERIALS: Between 1991 and 2004, 118 patients with interpretable pre- and post-radiation therapy (RT) chest computed tomography (CT) scans were evaluated. Changes in regional lung density were related to regional dose to define a dose-response curve (DRC) for RT-induced lung injury using three-dimensional planning tools and image fusion. Multiple post-RT follow-up CT scans were evaluated by fitting linear-quadratic models of density changes on dose with time as the covariate. Various patient- and treatment-related factors were examined as well. RESULTS: There was a dose-dependent increase in regional lung density at nearly all post-RT follow-up intervals. The population volume-weighted changes evolved over the initial 6-month period after RT and reached a plateau thereafter (p < 0.001). On univariate analysis, patient age greater than 65 years (p = 0.003) and/or the use of pre-RT surgery (p < 0.001) were associated with significantly greater changes in CT density at both 6 and 12 months after RT, but the magnitude of this effect was modest. CONCLUSIONS: There appears to be a temporal nature for the dose-dependent increases in lung density. Nondosimetric clinical factors tend to have no, or a modest, impact on these changes.

Radiation dose-volume effects in the lung.

The three-dimensional dose, volume, and outcome data for lung are reviewed in detail. The rate of symptomatic pneumonitis is related to many dosimetric parameters, and there are no evident threshold "tolerance dose-volume" levels. There are strong volume and fractionation effects.

Radiation-induced cardiac toxicity after therapy for breast cancer: interaction between treatment era and follow-up duration.

PURPOSE: Cardiac toxicity after breast radiotherapy (RT) has been widely described in "older" RT trials (i.e., using larger fraction sizes, wide RT fields, and orthovoltage energy). The results from more "modern" RT trials have shown less cardiac toxicity. The comparisons between the "older" and "modern" trials are confounded by the longer follow-up time in the "older" trials. We systematically assessed the effect of treatment era and follow-up duration on the reported rates of cardiac toxicity associated with RT. METHODS AND MATERIALS: The published data were surveyed using PubMed to identify studies using "breast cancer," "irradiation/radiotherapy," "cardiac/heart," and "toxicity/morbidity/mortality" in a keyword search. Relevant data were extracted from the identified trials. The trials were defined as "older" (patient accrual start year before 1980) and "modern" (patient accrual start year in or after 1980) to segregate the trials and assess the treatment era effect. A 10-year follow-up duration was used as a cutoff to segregate and analyze trials with varying lengths of follow-up. RESULTS: We analyzed 19 published reports of patients treated between 1968 and 2002 (5 randomized controlled trials, 5 single- or multi-institutional studies, and 9 national cancer registry database reviews). In the reviewed trials, all the older trials reported excess cardiac toxicity, typically with a median of >10-15 years of follow-up. However, the vast majority of modern RT trials had shorter median follow-up durations, typically

Local recurrence after surgery for early stage lung cancer: an 11-year experience with 975 patients.

BACKGROUND: The objective of the current study was to evaluate the actuarial risk of local failure (LF) after surgery for stage I to II nonsmall cell lung cancer (NSCLC) and assess surgical and pathologic factors affecting this risk. METHODS: The records, including pertinent radiologic studies, of all patients who underwent surgery for T1 to T2, N0 to N1 NSCLC at Duke University between 1995 and 2005 were reviewed. Risks of disease recurrence were estimated using the Kaplan-Meier method. A multivariate Cox regression analysis assessed factors associated with LF in the entire cohort and a subgroup undergoing optimal surgery for stage IB to II disease. RESULTS: For all 975 consecutive patients, the 5-year actuarial risk of local and/or distant disease recurrence was 36%. First sites of failure were local only (25%), local and distant (29%), and distant only (46%). The 5-year actuarial risk of LF was 23%. On multivariate analysis, squamous/large cell histology (hazards ratio [HR], 1.98), stage > IA (HR, 2.02), and sublobar resections (HR, 1.99) were found to be independently associated with a higher risk of LF. For the subset of patients (n = 445) undergoing at least a lobectomy with negative surgical margins and currently considered for adjuvant chemotherapy (stage IB-II disease), the 5-year actuarial risk of LF was 27%. Within this subgroup, squamous/large cell histology (HR, 2.5) and lymphovascular space invasion (HR, 1.74) were associated with a higher risk of LF. The 5-year rate of LF was 13%, 32%, and 47%, respectively, with 0, 1, or 2 risk factors. CONCLUSIONS: Greater than half of disease recurrences after surgery for early stage NSCLC involved local sites. Pathologic factors may help to distinguish those patients at highest risk.

Association between RT-induced changes in lung tissue density and global lung function.

PURPOSE: To assess the association between radiotherapy (RT)-induced changes in computed tomography (CT)-defined lung tissue density and pulmonary function tests (PFTs). METHODS AND MATERIALS: Patients undergoing incidental partial lung RT were prospectively assessed for global (PFTs) and regional (CT and single photon emission CT [SPECT]) lung function before and, serially, after RT. The percent reductions in the PFT and the average changes in lung density were compared (Pearson correlations) in the overall group and subgroups stratified according to various clinical factors. Comparisons were also made between the CT- and SPECT-based computations using the Mann-Whitney U test. RESULTS: Between 1991 and 2004, 343 patients were enrolled in this study. Of these, 111 patients had a total of 203 concurrent post-RT evaluations of changes in lung density and PFTs available for the analyses, and 81 patients had a total of 141 concurrent post-RT SPECT images. The average increases in lung density were related to the percent reductions in the PFTs, albeit with modest correlation coefficients (range, 0.20-0.43). The analyses also indicated that the association between lung density and PFT changes is essentially equivalent to the corresponding association with SPECT-defined lung perfusion. CONCLUSION: We found a weak quantitative association between the degree of increase in lung density as defined by CT and the percent reduction in the PFTs.

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.