Cardiac toxicity is an important sequela of breast radiotherapy. However, the relationship between dose to cardiac structures and subsequent toxicity has not been well defined, partially due to ...variations in substructure delineation, which can lead to inconsistent dose reporting and the failure to detect potential correlations. Here we have developed a heart atlas and evaluated its effect on contour accuracy and concordance.
A detailed cardiac computed tomography scan atlas was developed jointly by cardiology, cardiac radiology, and radiation oncology. Seven radiation oncologists were recruited to delineate the whole heart, left main and left anterior descending interventricular branches, and right coronary arteries on four cases before and after studying the atlas. Contour accuracy was assessed by percent overlap with gold standard atlas volumes. The concordance index was also calculated. Standard radiation fields were applied. Doses to observer-contoured cardiac structures were calculated and compared with gold standard contour doses. Pre- and post-atlas values were analyzed using a paired t test.
The cardiac atlas significantly improved contour accuracy and concordance. Percent overlap and concordance index of observer-contoured cardiac and gold standard volumes were 2.3-fold improved for all structures (p < 0.002). After application of the atlas, reported mean doses to the whole heart, left main artery, left anterior descending interventricular branch, and right coronary artery were within 0.1, 0.9, 2.6, and 0.6 Gy, respectively, of gold standard doses.
This validated University of Michigan cardiac atlas may serve as a useful tool in future studies assessing cardiac toxicity and in clinical trials which include dose volume constraints to the heart.
Purpose Radiation therapy is a critical component in the care of patients with non-small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to ...elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had pre-existing cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio HR, 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.
The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric ...cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+.
Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of ...the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.
Esophageal and esophagogastric junction cancers Ajani, Jaffer A; Barthel, James S; Bentrem, David J ...
Journal of the National Comprehensive Cancer Network,
2011-Aug-01, Volume:
9, Issue:
8
Journal Article
Although radiation therapy (RT) can palliate symptoms and may prolong life, it is not curative for patients with metastatic lung cancer. We investigated patient expectations about the goals of RT for ...incurable lung cancers.
The Cancer Care Outcomes Research and Surveillance Consortium enrolled a population- and health system-based cohort of patients diagnosed with lung cancer from 2003 to 2005. We identified patients with stage wet IIIB or IV lung cancer who received RT and answered questions on their expectations about RT. We assessed patient expectations about the goals of RT and identified factors associated with inaccurate beliefs about cure.
In all, 384 patients completed surveys on their expectations about RT. Seventy-eight percent of patients believed that RT was very or somewhat likely to help them live longer, and 67% believed that RT was very or somewhat likely to help them with problems related to their cancer. However, 64% did not understand that RT was not at all likely to cure them. Older patients and nonwhites were more likely to have inaccurate beliefs, and patients whose surveys were completed by surrogates were less likely to have inaccurate beliefs. Ninety-two percent of patients with inaccurate beliefs about cure from RT also had inaccurate beliefs about chemotherapy.
Although patients receiving RT for incurable lung cancer believe it will help them, most do not understand that it is not at all likely to cure their disease. This indicates a need to improve communication regarding the goals and limitations of palliative RT.
To quantify changes in fluorodeoxyglucose (FDG)-avid tumor volume on positron emission tomography/computed tomography (PET/CT) during the course of radiation therapy and examine its potential use in ...adaptive radiotherapy for tumor dose escalation or normal tissue sparing in patients with non-small-cell lung cancer (NSCLC).
As part of a pilot study, patients with Stage I-III NSCLC underwent FDG-PET/CT before radiotherapy (RT) and in mid-RT (after 40-50 Gy). Gross tumor volumes were contoured on CT and PET scans obtained before and during RT. Three-dimensional conformal RT plans were generated for each patient, first using only pretreatment CT scans. Mid-RT PET volumes were then used to design boost fields.
Fourteen patients with FDG-avid tumors were assessed. Two patients had a complete metabolic response, and 2 patients had slightly increased FDG uptake in the adjacent lung tissue. Mid-RT PET scans were useful in the 10 remaining patients. Mean decreases in CT and PET tumor volumes were 26% (range, +15% to -75%) and 44% (range, +10% to -100%), respectively. Designing boosts based on mid-RT PET allowed for a meaningful dose escalation of 30-102 Gy (mean, 58 Gy) or a reduction in normal tissue complication probability (NTCP) of 0.4-3% (mean, 2%) in 5 of 6 patients with smaller yet residual tumor volumes.
Tumor metabolic activity and volume can change significantly after 40-50 Gy of RT. Using mid-RT PET volumes, tumor dose can be significantly escalated or NTCP reduced. Clinical studies evaluating patient outcome after PET-based adaptive RT are ongoing.
To report interim cosmetic results and toxicity from a prospective study evaluating accelerated partial-breast irradiation (APBI) administered using a highly conformal external beam approach.
We ...enrolled breast cancer patients in an institutional review board-approved prospective study of APBI using beamlet intensity-modulated radiotherapy (IMRT) at deep-inspiration breath-hold. Patients received 38.5 Gy in 3.85 Gy fractions twice daily. Dosimetric parameters in patients who maintained acceptable cosmesis were compared with those in patients developing unacceptable cosmesis in follow-up, using t-tests.
Thirty-four patients were enrolled; 2 were excluded from analysis because of fair baseline cosmesis. With a median follow-up of 2.5 years, new unacceptable cosmesis developed in 7 patients, leading to early study closure. We compared patients with new unacceptable cosmesis with those with consistently acceptable cosmesis. Retrospective analysis demonstrated that all but one plan adhered to the dosimetric requirements of the national APBI trial. The mean proportion of a whole-breast reference volume receiving 19.25 Gy (V50) was lower in patients with acceptable cosmesis than in those with unacceptable cosmesis (34.6% vs. 46.1%; p = 0.02). The mean percentage of this reference volume receiving 38.5 Gy (V100) was also lower in patients with acceptable cosmesis (15.5% vs. 23.0%; p = 0.02).
The hypofractionated schedule and parameters commonly used for external beam APBI and prescribed by the ongoing national trial may be suboptimal, at least when highly conformal techniques such as IMRT with management of breathing motion are used. The V50 and V100 of the breast reference volume seem correlated with cosmetic outcome, and stricter limits may be appropriate in this setting.
Although inverse-planned intensity modulated radiotherapy (IMRT) and deep inspiration breath hold (DIBH) may allow for more conformal dose distributions, it is unknown whether using these ...technologies reduces cardiac or pulmonary toxicity of breast radiotherapy.
A randomized controlled trial compared IMRT-DIBH versus standard, free-breathing, forward-planned, three-dimensional conformal radiotherapy in patients with left-sided, node-positive breast cancer in whom the internal mammary nodal region was targeted. Endpoints included dosimetric parameters and changes in pulmonary and cardiac perfusion and function, measured by single photon emission computed tomography (SPECT) scans and pulmonary function testing performed at baseline and 1 year post treatment.
Of 62 patients randomized, 54 who completed all follow-up procedures were analyzed. Mean doses to the ipsilateral lung, left ventricle, whole heart, and left anterior descending coronary artery were lower with IMRT-DIBH; the percent of left ventricle receiving ≥5 Gy averaged 15.8% with standard radiotherapy and 5.6% with IMRT-DIBH (P < .001). SPECT revealed no differences in perfusion defects in the left anterior descending coronary artery territory, the study's primary endpoint, but did reveal statistically significant differences (P = .02) in left ventricular ejection fraction (LVEF), a secondary endpoint. No differences were found for lung perfusion or function.
The small but statistically significant benefit in preservation of cardiac LVEF observed here should motivate future studies that include LVEF as a potentially meaningful endpoint. Future studies should disaggregate the impact of IMRT from that of DIBH. Clinical practice should recognize the importance of minimizing cardiac dose, even when already low in comparison to historical levels.
Therapeutic misconception is the tendency for a clinical trial participant to overlook the scientific objective of a clinical trial and instead believe that an experimental intervention is intended ...for personal therapeutic benefit. We sought to evaluate this tendency in the setting of a clinical trial of a new radiation therapy technology.
Patients with left-sided, node positive breast cancer enrolled in a randomized clinical trial evaluating intensity modulated radiation therapy with deep inspiration breath hold (IMRT-DIBH) versus 3-dimensional conformal radiation therapy (3DCRT). Patients who enrolled completed surveys at baseline, after randomization, and upon completion of radiation therapy to evaluate expectations, satisfaction, and experiences.
Forty women participated in the survey study, with 20 in each arm. Most participants endorsed the perception that participation in the trial might result in better treatment than the current standard treatment (77%) and more medical attention than being off trial (54%). At baseline, most women (74%) believed that a new treatment technology is superior than an established one. Before randomization, 43% of participants believed IMRT-DIBH would be more effective than standard treatment with 3DCRT, none believed that 3DCRT would be more effective, 23% believed that they would be the same, and 34% did not know. None believed that IMRT-DIBH would cause worse long-term side effects, whereas 37% thought that 3DCRT would. Most (71%) reported that they would choose to be treated with IMRT-DIBH; none would have elected 3DCRT if given a choice. Nearly half (44%) in the 3DCRT arm wished that they had been assigned to the IMRT-DIBH arm; none in the IMRT-DIBH arm expressed a wish for crossover.
Most participants reported the perception that trial participation would result in better treatment and more medical attention than off trial, hallmarks of therapeutic misconception. Our observations provide empirical evidence of a fixed belief in the superiority of new technology and highlight the importance of adjusting expectations through informed consent to mitigate therapeutic misconception.
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