The Meaningless Meaning of Mean Heart Dose in Mediastinal Lymphoma in the Modern Radiation Therapy Era.

PURPOSE: Mean heart dose (MHD) correlates with late cardiac toxicity among survivors of lymphoma receiving involved-field radiation therapy (IFRT). We investigated MHD and cardiac substructure dose across older and newer radiation fields and techniques to understand the value of evaluating MHD alone. METHODS AND MATERIALS: After institutional review board approval, we developed a database of dosimetry plans for 40 patients with mediastinal lymphoma, which included IFRT (anterior-posterior and posterior-anterior), involved-site radiation therapy (ISRT) + 3-dimensional conformal radiation therapy (3DCRT), ISRT + intensity modulated radiation therapy, and ISRT + proton therapy plans for each patient. Each plan was evaluated for dose to the heart and cardiac substructures, including the right and left ventricles (RV, LV) and atria (RA, LA); tricuspid, mitral (MV), and aortic valves; and left anterior descending coronary artery (LAD). Correlation between MHD and cardiac substructure dose was assessed with linear regression. A correlation was considered very strong, strong, moderate, or weak if the r was ≥0.8, 0.6-0.79, 0.4-0.59, or <0.4, respectively. RESULTS: A very strong correlation was observed between MHD and the mean cardiac substructure dose for each plan as follows: IFRT-LV, RV, LA, MV and LAD; ISRT + 3DCRT-LV, RV, MV, TV, and LA; ISRT + intensity modulated radiation therapy-LV and RV; ISRT + proton therapy-none. The following strong correlations were observed: IFRT-RA; ISRT + 3DCRT-LAD, RA, AV; ISRT + IMRT-LA, RA, LAD, AV, TV, and MV; ISRT + proton therapy-LV only. CONCLUSIONS: In the management of mediastinal lymphoma, more conformal treatment techniques can lead to more heterogeneous dose distributions across the heart, which translate into weaker relationships between mean heart dose and mean cardiac substructure doses. Consequently, models for assessing the risk of cardiac toxicity after radiation therapy that rely on MHD can be misleading when using modern treatment fields and techniques. Contouring the cardiac substructures and evaluating their dose is important when using contemporary RT.

Comparison of Techniques for Involved-Site Radiation Therapy in Patients With Lower Mediastinal Lymphoma.

PURPOSE: Patients with lower mediastinal lymphoma (LML) benefit dosimetrically from proton therapy (PT) compared with intensity modulated radiation therapy (IMRT). The added dosimetric benefit of deep-inspiration breath-hold (DIBH) is unknown; therefore, we evaluated IMRT versus PT and free-breathing (FB) versus DIBH among patients with LML. METHODS AND MATERIALS: Twenty-one patients with LML underwent 4-dimensional computed tomography and 3 sequential DIBH scans at simulation. Involved-site radiation therapy target volumes and organ-at-risk contours were developed for both DIBH and FB scans. FB-IMRT, DIBH-IMRT, FB-PT, and DIBH-PT plans were generated for each patient for comparison. RESULTS: The median difference in lung volume between the DIBH and FB scans was 1275 mL; the average difference in clinical target volume was 5.7 mL. DIBH-IMRT produced a lower mean lung dose (10.8 vs 11.9 Gy; P < .001) than FB-IMRT, with no difference in mean heart dose (MHD; 16.1 vs 15.0 Gy; P = .992). Both PT plans produced a significantly lower mean dose to the lung, heart, left ventricle, esophagus, and nontarget body than DIBH-IMRT. DIBH-PT reduced the median MHD by 4.2 Gy (P < .0001); left ventricle dose by 5.1 Gy (P < .0001); and lung V5 by 26% (P < .0001) versus DIBH-IMRT. The 2 PT plans were comparable, with DIBH-PT reducing mean lung dose (7.0 vs 7.7 Gy; P = .063) and with no difference in MHD (10.3 vs 9.5 Gy; P = .992). CONCLUSIONS: Among patients with LML, DIBH (IMRT or PT) improved lung dosimetry over FB but had little influence on MHD. PT (DIBH and FB) significantly reduced lung, heart, esophagus, and nontarget body dose compared with DIBH IMRT, potentially reducing the risk of late complications.

Proton therapy for skull-base chondrosarcoma, a single-institution outcomes study.

BACKGROUND: We sought to evaluate the effectiveness of definitive or adjuvant external-beam proton therapy on local control and survival in patients with skull-base chondrosarcoma. METHODS: We reviewed the medical records of 43 patients with a median age of 49 years (range, 23-80 years) treated with double-scattered 3D conformal proton therapy for skull-base chondrosarcomas between January 2007 and February 2016. Proton therapy-related toxicities were scored using CTCAE v4.0. RESULTS: The median radiotherapy dose was 73.8 Gy(RBE) (range, 64.5-74.4 Gy[RBE]). Thirty-six (84%) and 7 (16%) patients underwent surgical resection or biopsy alone. Tumor grade distribution included: grade 1, 19 (44%) patients; grade 2, 22 (51%); and grade 3, 2 (5%). Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following surgery. The median follow-up was 3.7 years (range, 0.7-10.1 years). There were no acute grade 3 toxicities related to RT. At 4 years following RT, actuarial rates of overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were 95%, 100%, 89%, and 95%. CONCLUSION: High-dose, double-scattered 3D conformal proton therapy alone or following surgical resection for skull-base chondrosarcoma is an effective treatment with a high rate of local control with no acute grade 3 radiation-related toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

Rationale and early outcomes for the management of thymoma with proton therapy.

BACKGROUND: Radiotherapy for thymic malignancies is technically challenging due to their close proximity to the heart, lungs, esophagus, and breasts, raising concerns about significant acute and late toxicities from conventional photon radiotherapy. Proton therapy (PT) may reduce the radiation dose to these vital organs, leading to less toxicity. We reviewed the dosimetry and outcomes among patients treated with PT for thymic malignancies at our institution. METHODS: From January 2008 to March 2017, six patients with de novo Masaoka stages II-III thymic malignancies were treated with PT on an IRB-approved outcomes tracking protocol. Patients were evaluated weekly during treatment, then every 3 months for 2 years, then every 6 months for 3 more years, and then annually for CTCAE vs. four toxicities and disease recurrence. Comparison intensity-modulated radiotherapy (IMRT) plans were developed for each patient. Mean doses to the heart, esophagus, bilateral breasts, lungs, and V20 of bilateral lungs were evaluated for the two treatment plans. RESULTS: At last follow-up (median follow-up, 2.6 years), there were two patients with recurrences, including metastatic disease in the patient treated definitively with chemotherapy and PT without surgery and a local-regional recurrence in the lung outside the proton field in one of the post-operative cases. No patients with de novo disease experienced grade ≥3 toxicities after PT. The mean dose to the heart, lung, and esophagus was reduced on average by 36.5%, 33.5%, and 60%, respectively, using PT compared with IMRT (P<0.05 for each dose parameter). CONCLUSIONS: PT achieved superior dose sparing to the heart, lung, and esophagus compared to IMRT for thymic malignancies. Patients treated with PT had few radiation-induced toxicities and similar survival compared to historic proton data.

Comparison of three-dimensional (3D) conformal proton radiotherapy (RT), 3D conformal photon RT, and intensity-modulated RT for retroperitoneal and intra-abdominal sarcomas.

PURPOSE: To compare three-dimensional conformal proton radiotherapy (3DCPT), intensity-modulated photon radiotherapy (IMRT), and 3D conformal photon radiotherapy (3DCRT) to predict the optimal RT technique for retroperitoneal sarcomas. METHODS AND MATERIALS: 3DCRT, IMRT, and 3DCPT plans were created for treating eight patients with retroperitoneal or intra-abdominal sarcomas. The clinical target volume (CTV) included the gross tumor plus a 2-cm margin, limited by bone and intact fascial planes. For photon plans, the planning target volume (PTV) included a uniform expansion of 5 mm. For the proton plans, the PTV was nonuniform and beam-specific. The prescription dose was 50.4 Gy/Cobalt gray equivalent CGE. Plans were normalized so that >95% of the CTV received 100% of the dose. RESULTS: The CTV was covered adequately by all techniques. The median conformity index was 0.69 for 3DCPT, 0.75 for IMRT, and 0.51 for 3DCRT. The median inhomogeneity coefficient was 0.062 for 3DCPT, 0.066 for IMRT, and 0.073 for 3DCRT. The bowel median volume receiving 15 Gy (V15) was 16.4% for 3DCPT, 52.2% for IMRT, and 66.1% for 3DCRT. The bowel median V45 was 6.3% for 3DCPT, 4.7% for IMRT, and 15.6% for 3DCRT. The median ipsilateral mean kidney dose was 22.5 CGE for 3DCPT, 34.1 Gy for IMRT, and 37.8 Gy for 3DCRT. The median contralateral mean kidney dose was 0 CGE for 3DCPT, 6.4 Gy for IMRT, and 11 Gy for 3DCRT. The median contralateral kidney V5 was 0% for 3DCPT, 49.9% for IMRT, and 99.7% for 3DCRT. Regardless of technique, the median mean liver dose was <30 Gy, and the median cord V50 was 0%. The median integral dose was 126 J for 3DCPT, 400 J for IMRT, and 432 J for 3DCRT. CONCLUSIONS: IMRT and 3DCPT result in plans that are more conformal and homogenous than 3DCRT. Based on Quantitative Analysis of Normal Tissue Effects in Clinic benchmarks, the dosimetric advantage of proton therapy may be less gastrointestinal and genitourinary toxicity.

Dosimetric study of pelvic proton radiotherapy for high-risk prostate cancer.

PURPOSE: To compare dose distributions in targeted tissues (prostate, seminal vesicles, pelvic regional nodes) and nontargeted tissues in the pelvis with intensity-modulated radiotherapy (IMRT) and forward-planned, double-scattered, three-dimensional proton radiotherapy (3D-PRT). METHODS AND MATERIALS: IMRT, IMRT followed by a prostate 3D-PRT boost (IMRT/3D-PRT), and 3D-PRT plans were created for 5 high-risk prostate cancer patients (n = 15 plans). A 78-CGE/Gy dose was prescribed to the prostate and proximal seminal vesicles and a 46-CGE/Gy was prescribed to the pelvic nodes. Various dosimetric endpoints were compared. RESULTS: Target coverage of the prostate and nodal planning target volumes was adequate for all three plans. Compared with the IMRT and IMRT/3D-PRT plans, the 3D-PRT plans reduced the mean dose to the rectum, rectal wall, bladder, bladder wall, small bowel, and pelvis. The relative benefit of 3D-PRT (vs IMRT) at reducing the rectum and rectal wall V5-V40 was 53% to 71% (p < 0.05). For the bladder and bladder wall, the relative benefit for V5 to V40 CGE/Gy was 40% to 63% (p < 0.05). The relative benefit for reducing the volume of small bowel irradiated from 5 to 30 CGE/Gy in the 3D-PRT ranged from 62% to 69% (p < 0.05). Use of 3D-PRT did not produce the typical low-dose "bath" of radiation to the pelvis seen with IMRT. Femoral head doses were higher for the 3D-PRT. CONCLUSIONS: Use of 3D-PRT significantly reduced the dose to normal tissues in the pelvis while maintaining adequate target coverage compared with IMRT or IMRT/3D-PRT. When treating the prostate, seminal vesicles, and pelvic lymph nodes in prostate cancer, proton therapy may improve the therapeutic ratio beyond what is possible with IMRT.

Proton therapy for maxillary sinus carcinoma.

OBJECTIVES: To compare the dose-volume data of three-dimensional conformal proton therapy (3DCPT) versus intensity-modulated radiotherapy (IMRT) for a paranasal sinus malignancy. METHODS: 3DCPT and IMRT plans were created for a T4N0 maxillary sinus carcinoma. RESULTS: The target volume dose distributions were comparable for 3DCPT and IMRT. The mean and integral doses for all normal tissues were lower for 3DCPT. The maximum doses for both plans to the ipsilateral optic nerve/retina/lens, temporal lobe, pituitary, and brain exceeded tolerance doses. The contralateral parotid, lacrimal gland, and lens were avoided with 3DCPT. Neither 3DCPT nor IMRT exceeded the maximal tolerated dose for the brainstem, optic chiasm, contralateral temporal lobe, parotid, or lacrimal gland. CONCLUSIONS: Both 3DCPT and IMRT sufficiently covered the target volume(s). Although 3DCPT reduced the mean and integral dose to all of the normal tissues, both 3DCPT and IMRT irradiated the ipsilateral optic structures beyond acceptable tolerance doses.

Dosimetric comparison of three different involved nodal irradiation techniques for stage II Hodgkin's lymphoma patients: conventional radiotherapy, intensity-modulated radiotherapy, and three-dimensional proton radiotherapy.

PURPOSE: To compare the dose distribution to targeted and nontargeted tissues in Hodgkin's lymphoma patients using conventional radiotherapy (CRT), intensity-modulated RT (IMRT), and three-dimensional proton RT (3D-PRT). METHODS AND MATERIALS: CRT, IMRT, and 3D-PRT treatment plans delivering 30 cobalt Gray equivalent (CGE)/Gy to an involved nodal field were created for 9 Stage II Hodgkin's lymphoma patients (n = 27 plans). The dosimetric endpoints were compared. RESULTS: The planning target volume was adequately treated using all three techniques. The IMRT plan produced the most conformal high-dose distribution; however, the 3D-PRT plan delivered the lowest mean dose to nontarget tissues, including the breast, lung, and total body. The relative reduction in the absolute lung volume receiving doses of 4-16 CGE/Gy for 3D-PRT compared with CRT ranged from 26% to 37% (p < .05), and the relative reduction in the absolute lung volume receiving doses of 4-10 CGE/Gy for 3D-PRT compared with IMRT was 48-65% (p < .05). The relative reduction in absolute total body volume receiving 4-30 CGE/Gy for 3D-PRT compared with CRT was 47% (p < .05). The relative reduction in absolute total body volume receiving a dose of 4 CGE/Gy for 3D-PRT compared with IMRT was 63% (p = .03). The mean dose to the breast was significantly less for 3D-PRT than for either IMRT or CRT (p = .03) The mean dose and absolute volume receiving 4-30 CGE/Gy for the heart, thyroid, and salivary glands were similar for the three modalities. CONCLUSION: In this favorable subset of Hodgkin's lymphoma patients without disease in or below the hila, 3D-PRT significantly reduced the dose to the breast, lung, and total body. These observed dosimetric advantages might improve the clinical outcomes of Hodgkin's lymphoma patients by reducing the risk of late radiation effects related to low-to-moderate doses in nontargeted tissues.

Dose-volume differences for computed tomography and magnetic resonance imaging segmentation and planning for proton prostate cancer therapy.

PURPOSE: To determine the influence of magnetic-resonance-imaging (MRI)-vs. computed-tomography (CT)-based prostate and normal structure delineation on the dose to the target and organs at risk during proton therapy. METHODS AND MATERIALS: Fourteen patients were simulated in the supine position using both CT and T2 MRI. The prostate, rectum, and bladder were delineated on both imaging modalities. The planning target volume (PTV) was generated from the delineated prostates with a 5-mm axial and 8-mm superior and inferior margin. Two plans were generated and analyzed for each patient: an MRI plan based on the MRI-delineated PTV, and a CT plan based on the CT-delineated PTV. Doses of 78 Gy equivalents (GE) were prescribed to the PTV. RESULTS: Doses to normal structures were lower when MRI was used to delineate the rectum and bladder compared with CT: bladder V50 was 15.3% lower (p = 0.04), and rectum V50 was 23.9% lower (p = 0.003). Poor agreement on the definition of the prostate apex was seen between CT and MRI (p = 0.007). The CT-defined prostate apex was within 2 mm of the apex on MRI only 35.7% of the time. Coverage of the MRI-delineated PTV was significantly decreased with the CT-based plan: the minimum dose to the PTV was reduced by 43% (p < 0.001), and the PTV V99% was reduced by 11% (p < 0.001). CONCLUSIONS: Using MRI to delineate the prostate results in more accurate target definition and a smaller target volume compared with CT, allowing for improved target coverage and decreased doses to critical normal structures.

Predicting changes in dose distribution to tumor and normal tissue when correcting for heterogeneity in radiotherapy for lung cancer.

PURPOSES: The purposes of this study were to examine dose alterations to gross tumor volume (GTV) and lung using heterogeneity corrections and to predict the magnitude of these changes. METHODS: Three separate conformal plans were generated for 37 patients with lung cancer: plan 1 corrected for heterogeneity, plan 2 did not correct for heterogeneity, and plan 3 used identical beams and monitor units from plan 2 but with heterogeneous calculations. Plans 1 and 2 were normalized to the 95% isodose line. Mean dose (MeanDGTV), maximum dose (MaxDGTV), and minimum dose (MinDGTV) to GTV and V20 were compared between plans 1 and 3. For each patient, the amount of lung in all beam paths of plan 3 was quantified by a density correction factor and correlated with the percent change. RESULTS: The median percent change in MeanDGTV, MaxDGTV, and MinDGTV between plan 3 and plan 1 was -4.7% (-0.1% to -19.1%, P < 0.0001), -5.59% (0.16% to -31.86%, P < 0.0001), and -4.88% (2.90% to -24.88%, P < 0.0001), respectively. The median V20 difference was -1% (1% to -8%). The density correction factor correlated with larger differences in MeanDGTV on univariate analysis. CONCLUSIONS: Heterogeneity correction lowers the dose to GTV by 5%. This difference can be correlated with the density correction factor.

The role of intensity modulated radiation therapy for favorable stage tumor of the nasal cavity or ethmoid sinus.

OBJECTIVES: To compare intensity-modulated radiation therapy (IMRT), 4-field conformal, and the standard 3-field conventional technique of radiotherapy for favorable stage tumors of the nasal cavity or ethmoid sinus. METHODS AND MATERIALS: We compared the 3 techniques in 3 patients with tumors of the nasal cavity or ethmoid sinus that did not involve the eye or optic pathways. We required that each plan deliver the prescription dose (70.2 Gy at 1.8 Gy per fraction) to 95% of the planning target volume. We compared the maximum point dose to critical normal structures (brainstem, optic chiasm, optic nerves, retina, lens). RESULTS: : IMRT and the 4-field conformal technique were clearly better than the 3-field conventional technique. The 4-field conformal plan was as good as IMRT. CONCLUSIONS: The conventional 3-field technique is not the best way to treat most patients with tumors between the eyes. A 4-field conformal plan is an excellent alternative to IMRT for some patients with tumors of the nasal cavity or ethmoid sinus. Conformal radiotherapy with a noncoplaner field that exits into the low neck may make it difficult to electively irradiate the neck lymphatics. IMRT may be a better option in this situation.

Contouring the middle and inner ear on radiotherapy planning scans.

The purpose of this study was to establish guidelines that help radiation oncologists contour the inner and middle ear on treatment planning scans. The radiotherapy computed tomography (CT) scans of 15 previously treated patients were reviewed for the ability to identify 3 separate auditory structures. The middle ear, the cochlea, and the vestibular apparatus were identified and contoured on each scan using anatomic landmarks. The volume and maximum axial dimension of each contour were calculated. The middle ear, cochlea, and vestibular apparatus were identified on all scans. The middle ear was defined by the tympanic membrane laterally and by the interface between air and the temporal bone in all other directions. The plane of the internal auditory canal through the temporal bone was the landmark distinguishing the vestibular apparatus from the cochlea. The mean volume of the middle ear, vestibular apparatus, and cochlea were 0.58 cm3, 0.44 cm3, and 0.14 cm3, respectively. The maximum axial dimension across the contour averaged 1.57 cm for the middle ear, 1.10 cm for the vestibular apparatus, and 0.69 cm for the cochlea. A reference atlas was constructed that shows the contour of each structure on 5 consecutive CT images. Accurate identification of the middle ear and inner ear structures on radiotherapy planning scans is possible and is necessary if critical auditory organs are to be spared during radiotherapy of targets that are located near the base of the skull. The information generated in this study will help radiation oncologists contour auditory structures accurately.

Irradiating the groin nodes without breaking a leg: a comparison of techniques for groin node irradiation.

The purpose of this study was to determine the optimal technique for delivering postoperative radiotherapy for vulvar cancer and other tumors requiring treatment of the inguinal nodes. This project compared tumor coverage and normal tissue sparing for the 5 main radiotherapy techniques that are used to treat vulvar cancer. The intensity-modulated radiation therapy (IMRT) plan was undesirable because it resulted in an excessive dose to portions of the central pelvic structures. The photon thunderbird with skin match was unacceptable because it underdosed a portion of the groin region. The electron thunderbird was ideal for thin patients but was not applicable for most patients because of excessive dose to the skin and subcutaneous tissues. The photon through-and-through and the photon thunderbird with deep match were acceptable in most situations. In thin patients, where the depth of the inguinal vessels is less than 3 cm, the electron thunderbird is the technique of choice. In the average-sized patient, both the photon through-and-through and the photon thunderbird with deep match are reasonable options. The available literature suggests that the risk of femoral neck fracture or necrosis of the femoral head is approximately 11% at 5 years using the photon through-and-through technique. In our opinion, this is an acceptable price to pay for reliable node coverage, setup simplicity, and zero risk of overdose at field junctions.