Robin Marsh

Development and Validation of a Heart Atlas to Study Cardiac Exposure to Radiation Following Treatment for Breast Cancer

PURPOSE 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. METHODS AND MATERIALS 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. RESULTS 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. CONCLUSIONS 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.

Unacceptable Cosmesis in a Protocol Investigating Intensity-Modulated Radiotherapy With Active Breathing Control for Accelerated Partial-Breast Irradiation

PURPOSE 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. METHODS AND MATERIALS 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. RESULTS 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). CONCLUSIONS 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.

Postmastectomy radiotherapy of the chest wall: Dosimetric comparison of common techniques

PURPOSE 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. METHODS AND MATERIALS 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). RESULTS 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). CONCLUSION 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.

Potential gains for irradiation of chest wall and regional nodes with intensity modulated radiotherapy

PURPOSE To develop an intensity modulated radiotherapy (IMRT) technique for postmastectomy RT that improves target coverage while sparing all appropriate normal tissues. MATERIALS AND METHODS IMRT plans were generated using an in-house optimization system. Priority was given to matching the heart doses achieved with partially wide tangent fields (PWTFs) while maintaining 50 Gy +/- 5% to the chest wall, internal mammary nodes, and supraclavicular nodes. Other normal tissue doses were then minimized. Metrics for plan comparisons included minimal, maximal, and mean doses and normal tissue complication probability. RESULTS IMRT resulted in more uniform chest wall coverage than did PWTFs. The average chest wall minimal dose was 43.7 +/- 1.1 Gy for IMRT and 31.2 +/- 16.5 Gy for PWTFs (p = 0.04). The average internal mammary node minimal dose was 42.8 +/- 2.1 Gy for IMRT and 21.8 +/- 13.2 Gy for PWTFs (p = 0.001). IMRT matched the <1% heart normal tissue complication probability achieved using PWTFs. The average contralateral breast mean dose was 2.8 +/- 1.7 Gy for IMRT, but a greater breast volume was exposed compared with PWTFs. The mean ipsilateral lung normal tissue complication probability was lower for IMRT (0.0) than for PWTFs (0.07 +/- 0.07; p = 0.02). The mean contralateral lung dose was greater for IMRT (5.8 +/- 1.8 Gy) than for PWTFs (1.6 +/- 0.1 Gy; p = <0.0001). CONCLUSION A new IMRT technique achieves full target coverage while maintaining similar doses to heart and ipsilateral lung as conventional techniques. However, contralateral lung and breast volumes exposed to low doses were increased with IMRT and will need to be reduced in future studies.

Intensity-modulated radiation therapy (IMRT) for locally advanced paranasal sinus tumors: incorporating clinical decisions in the optimization process

PURPOSE Intensity-modulated radiotherapy (IMRT) plans require decisions about priorities and tradeoffs among competing goals. This study evaluates the incorporation of various clinical decisions into the optimization system, using locally advanced paranasal sinus tumors as a model. METHODS AND MATERIALS Thirteen patients with locally advanced paranasal sinus tumors were retrospectively replanned using inverse planning. Two clinical decisions were assumed: (1) Spare both optic pathways (OP), or (2) Spare only the contralateral OP. In each case, adequate tumor coverage (treated to 70 Gy in 35 fractions) was required. Two beamlet IMRT plans were thus developed for each patient using a class solution cost function. By altering one key variable at a time, different levels of risk of OP toxicity and planning target volume (PTV) compromise were compared in a systematic manner. The resulting clinical tradeoffs were analyzed using dosimetric criteria, tumor control probability (TCP), equivalent uniform dose (EUD), and normal tissue complication probability. RESULTS Plan comparisons representing the two clinical decisions (sparing both OP and sparing only the contralateral OP), with respect to minimum dose, TCP, V(95), and EUD, demonstrated small, yet statistically significant, differences. However, when individual cases were analyzed further, significant PTV underdosage (>5%) was present in most cases for plans sparing both OP. In 6/13 cases (46%), PTV underdosage was between 5% and 15%, and in 3 cases (23%) was greater than 15%. By comparison, adequate PTV coverage was present in 8/13 cases (62%) for plans sparing only the contralateral OP. Mean target EUD comparisons between the two plans (including 9 cases where a clinical tradeoff between PTV coverage and OP sparing was required) were similar: 68.6 Gy and 69.1 Gy, respectively (p = 0.02). Mean TCP values for those 9 cases were 56.5 vs. 61.7, respectively (p = 0.006). CONCLUSIONS In IMRT plans for paranasal sinus tumors, tradeoff values between OP toxicity and PTV coverage can be compared for different clinical decisions. The information derived can then be used to individualize the parameters within the optimization system. This process of determining clinical tradeoffs associated with different clinical decisions may be a useful tool in other sites.

THE USE OF 3D CONFORMAL RADIOTHERAPY (3D CRT) TO SPARE THE COCHLEA IN PATIENTS WITH MEDULLOBLASTOMA

PURPOSE Radiation therapy in combination with cis-platinum chemotherapy is associated with ototoxicity due to destruction of cochlear hair cells. This is a significant problem, especially in pediatric patients, because it may lead to difficulties with communication, speech, language, and development of learning skills. The use of 3D conformal radiotherapy (3D CRT) may be useful in sparing auditory structures. This paper discusses a technique using 3D CRT to spare the cochlea in patients with medulloblastoma. METHODS AND MATERIALS Five pediatric patients with medulloblastoma were planned using 3D CRT. All had MRI and CT obtained specifically for treatment planning. Multiple structures were contoured, including the cochlea and posterior fossa, and conformal beams designed in beams eye view and dose distribution analysis were edited to provide 3D dose coverage to the target while sparing the inner ear. Patients received 36 Gy to the craniospinal axis followed by an 18-20 Gy boost to the posterior fossa. RESULTS A 3D CRT cochlear sparing technique was designed, using an axial pair of posterior oblique fields to treat the posterior fossa while sparing the cochlea for all patients in this analysis. Dose-volume information, obtained from 3D calculations, demonstrates that the average dose received by the cochlea was 65% of the prescribed dose using the cochlear sparing plan, as compared to 101% using standard opposed-lateral beams. Both plans delivered > or = 100% of the prescribed dose to the posterior fossa. CONCLUSION 3D CRT allows for cochlear sparing in the treatment of medulloblastoma. Further follow-up is necessary to determine the long-term benefit in these patients.

EVALUATION OF FOUR TECHNIQUES USING INTENSITY-MODULATED RADIATION THERAPY FOR COMPREHENSIVE LOCOREGIONAL IRRADIATION OF BREAST CANCER

PURPOSE To establish optimal intensity-modulated radiation therapy (IMRT) techniques for treating the left breast and regional nodes, using moderate deep-inspiration breath hold. METHODS AND MATERIALS We developed four IMRT plans of differing complexity for each of 10 patients following lumpectomy for left breast cancer. A dose of 60 Gy was prescribed to the boost planning target volume (PTV) and 52.2 Gy to the breast and supraclavicular, infraclavicular, and internal mammary nodes. Two plans used inverse-planned beamlet techniques: a 9-field technique, with nine equispaced axial beams, and a tangential beamlet technique, with three to five ipsilateral beams. The third plan (a segmental technique) used a forward-planned multisegment technique, and the fourth plan (a segmental blocked technique) was identical but included a block to limit heart dose. Dose--volume histograms were generated, and metrics chosen for comparison were analyzed using the paired t test. RESULTS Mean heart and left anterior descending coronary artery doses were similar with the tangential beamlet and segmental blocked techniques but higher with the segmental and 9-field techniques (mean paired difference of 15.1 Gy between segmental and tangential beamlet techniques, p < 0.001). Substantial volumes of contralateral tissue received dose with the 9-field technique (mean right breast V2, 58.9%; mean right lung V2, 75.3%). Minimum dose to ≥95% of breast PTV was, on average, 45.9 Gy with tangential beamlet, 45.0 Gy with segmental blocked, 51.4 Gy with segmental, and 50.2 Gy with 9-field techniques. Coverage of the internal mammary region was substantially better with the two beamlet techniques than with the segmental blocked technique. CONCLUSIONS Compared to the 9-field beamlet and segmental techniques, a tangential beamlet IMRT technique reduced exposure to normal tissues and maintained reasonable target coverage.

Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

PURPOSE To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. METHODS AND MATERIALS On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. RESULTS The mean difference in pre- and post-RT PD was -0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. CONCLUSIONS Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.

Assessment of skin dose for breast chest wall radiotherapy as a function of bolus material

Skin dose assessment for chest wall radiotherapy is important to ensure sufficient dose to the surface target volume without excessive skin reaction. This study quantified changes to the surface doses as a function of bolus material for conventional and intensity modulated radiation therapy (IMRT) tangential fields. Three types of bolus materials (2 mm solid, 2 mm fine mesh and 3.2 mm large mesh Aquaplast) were compared with Superflab. Surface dose measurements were performed using an Attix parallel plate chamber in a flat solid water phantom at 0 degrees , 45 degrees and 70 degrees incident angles. Over-response correction factors were applied to the Attix chamber results for different incident angles. Surface dose measurements on an anthropomorphic phantom were done using a thermoluminescent dosimeter extrapolation method. Dose characteristics of Superflab and solid Aquaplast were within 2% of solid water material. No significant differences (within 3%) in the surface dose were found between conventional and IMRT tangential techniques. The bolus effect was large for chest wall tangential radiotherapy, with up to an 82% increase using 2 mm fine mesh Aquaplast. The dosimetric effect of different Aquaplast materials has been quantified in this work. These materials can be used to create a custom bolus with potentially better reproducibility of placement.

Accelerated partial breast irradiation: what is dosimetric effect of advanced technology approaches?

PURPOSE The present treatment planning study compared whole breast radiotherapy (WBRT) to accelerated partial breast irradiation (APBI) for different external beam techniques and geometries (e.g., free breathing [FB] and deep inspiration breath hold [DIBH]). METHODS AND MATERIALS After approval by our institutional review board, a treatment planning study was performed of 10 patients with left-sided Stage 0-I breast cancer enrolled in a Phase I-II study of APBI using intensity-modulated radiotherapy (IMRT). After lumpectomy, patients underwent planning computed tomography scans during FB and using an active breathing control device at DIBH. For the FB geometry, standard WBRT and three-dimensional conformal radiotherapy (3D-CRT) APBI plans were created. For the DIBH geometry with active breathing control, WBRT, 3D-CRT, and IMRT APBI plans were created. RESULTS All APBI techniques had excellent planning target volume coverage. The maximal planning target volume dose was reduced from 116% of the prescription dose to 108% with the IMRT(DIBH) APBI plan. The maximal heart dose was >30 Gy for the WBRT techniques, 8.2 Gy for 3D-CRT(FB), and <5.0 Gy for 3D-CRT(DIBH) and IMRT(DIBH) techniques. The mean left anterior descending artery dose was significantly reduced from 11.4 Gy with WBRT(FB) to 4.2 with WBRT(DIBH) and <2.0 Gy with all APBI techniques. CONCLUSION Although planning target volume coverage was acceptable with all techniques, the plans using the DIBH geometry resulted in a marked reduction in the normal tissue dose compared with WBRT planned in the absence of cardiac blocking. Additional study is needed to determine whether these techniques result in clinical benefits.