Dennis L. Carter

Treatment Parameters and Outcome in 680 Treatments of Internal Radiation With Resin 90Y-Microspheres for Unresectable Hepatic Tumors

PURPOSE Radioembolization (RE) using (90)Y-microspheres is an effective and safe treatment for patients with unresectable liver malignancies. Radiation-induced liver disease (RILD) is rare after RE; however, greater understanding of radiation-related factors leading to serious liver toxicity is needed. METHODS AND MATERIALS Retrospective review of radiation parameters was performed. All data pertaining to demographics, tumor, radiation, and outcomes were analyzed for significance and dependencies to develop a predictive model for RILD. Toxicity was scored using the National Cancer Institute Common Toxicity Criteria Adverse Events Version 3.0 scale. RESULTS A total of 515 patients (287 men; 228 women) from 14 US and 2 EU centers underwent 680 separate RE treatments with resin (90)Y-microspheres in 2003-2006. Multifactorial analyses identified factors related to toxicity, including activity (GBq) Selective Internal Radiation Therapy delivered (p < 0.0001), prescribed (GBq) activity (p < 0.0001), percentage of empiric activity (GBq) delivered (p < 0.0001), number of prior liver treatments (p < 0.0008), and medical center (p < 0.0001). The RILD was diagnosed in 28 of 680 treatments (4%), with 21 of 28 cases (75%) from one center, which used the empiric method. CONCLUSIONS There was an association between the empiric method, percentage of calculated activity delivered to the patient, and the most severe toxicity, RILD. A predictive model for RILD is not yet possible given the large variance in these data.

Magnetic Resonance Thermometry During Hyperthermia for Human High-Grade Sarcoma

PURPOSE To determine the feasibility of measuring temperature noninvasively with magnetic resonance imaging during hyperthermia treatment of human tumors. METHODS The proton chemical shift detected using phase-difference magnetic resonance imaging (MRI) was used to measure temperature in phantoms and human tumors during treatment with hyperthermia. Four adult patients having high-grade primary sarcoma tumors of the lower leg received 5 hyperthermia treatments in the MR scanner using an MRI-compatible radiofrequency heating applicator. Prior to each treatment, an average of 3 fiberoptic temperature probes were invasively placed into the tumor (or phantom). Hyperthermia was applied concurrent with MR thermometry. Following completion of the treatment, regions of interest (ROI) were defined on MR phase images at each temperature probe location, in bone marrow, and in gel standards placed outside the heated region. The median phase difference (compared to pretreatment baseline images) was calculated for each ROI. This phase difference was corrected for phase drift observed in standards and bone marrow. The observed phase difference, with and without corrections, was correlated with the fiberoptic temperature measurements. RESULTS The phase difference observed with MRI was found to correlate with temperature. Phantom measurements demonstrated a linear regression coefficient of 4.70 degrees phase difference per degree Celsius, with an R2 = 0.998. After human images with artifact were excluded, the linear regression demonstrated a correlation coefficient of 5.5 degrees phase difference per degree Celsius, with an R2 = 0.84. In both phantom and human treatments, temperature measured via corrected phase difference closely tracked measurements obtained with fiberoptic probes during the hyperthermia treatments. CONCLUSIONS Proton chemical shift imaging with current MRI and hyperthermia technology can be used to monitor and control temperature during treatment of large tumors in the distal lower extremity.

CLINICAL EXPERIENCE WITH IMAGE-GUIDED RADIOTHERAPY IN AN ACCELERATED PARTIAL BREAST INTENSITY-MODULATED RADIOTHERAPY PROTOCOL

PURPOSE To explore the feasibility of fiducial markers for the use of image-guided radiotherapy (IGRT) in an accelerated partial breast intensity modulated radiotherapy protocol. METHODS AND MATERIALS Nineteen patients consented to an institutional review board approved protocol of accelerated partial breast intensity-modulated radiotherapy with fiducial marker placement and treatment with IGRT. Patients (1 patient with bilateral breast cancer; 20 total breasts) underwent ultrasound guided implantation of three 1.2- x 3-mm gold markers placed around the surgical cavity. For each patient, table shifts (inferior/superior, right/left lateral, and anterior/posterior) and minimum, maximum, mean error with standard deviation were recorded for each of the 10 BID treatments. The dose contribution of daily orthogonal films was also examined. RESULTS All IGRT patients underwent successful marker placement. In all, 200 IGRT treatment sessions were performed. The average vector displacement was 4 mm (range, 2-7 mm). The average superior/inferior shift was 2 mm (range, 0-5 mm), the average lateral shift was 2 mm (range, 1-4 mm), and the average anterior/posterior shift was 3 mm (range, 1 5 mm). CONCLUSIONS This study shows that the use of IGRT can be successfully used in an accelerated partial breast intensity-modulated radiotherapy protocol. The authors believe that this technique has increased daily treatment accuracy and permitted reduction in the margin added to the clinical target volume to form the planning target volume.

Impact of setup variability on incidental lung irradiation during tangential breast treatment

PURPOSE This study aimed to determine the variability in treatment setup during a 5-week course of tangential breast treatment for patients immobilized in a customized hemibody cradle, to assess the relationship between the height of the lung shadow on the tangential port film and the percentage of lung volume irradiated, and to estimate the impact of setup variabilities on irradiated lung volume. METHODS One hundred seventy-two port films were reviewed from 20 patients who received tangential beam treatment for breast cancer. The height of the lung shadow at the central axis (CLD) on each port film was compared to the corresponding simulator film as an assessment of setup variability. A three-dimensional dose calculation was performed, and the percentage of total lung volume within the field was correlated with the CLD. The three-dimensional dose calculation was repeated for selected patients with the location of the treatment beams modified to reflect typical setup variations. RESULTS The CLD measured on the port films was within 3 mm of that prescribed on the simulator film in 43% (74 of 172) of the port films. The variation was 3-5 mm in 26%, 5-10 mm in 25%, and >10 mm in 6%. The height of the lung shadow correlated with the percentage of lung volume included in the radiation field (r2 = 0.6). Typical variations in treatment setup resulted in < or = 5% fluctuation in the absolute volume of ipsilateral lung irradiated. CONCLUSION The current immobilization system used in our clinic provides a clinically acceptable reproducibility of patient setup. The height of the lung shadow is reasonably well correlated with the percentage of irradiated lung volume. During a typical 5-week course of radiotherapy, the ipsilateral irradiated lung volume fluctuates <5%.

Impact of Consolidation Radiotherapy in Patients With Advanced Breast Cancer Treated With High-Dose Chemotherapy and Autologous Bone Marrow Rescue

PURPOSE To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS Between 1988 and 1994,425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT was not randomized. The RT+ and RT- groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups, respectively (P = .20). CONCLUSION Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.

Predictors for Clinical Outcomes After Accelerated Partial Breast Intensity-Modulated Radiotherapy

PURPOSE To correlate the treatment planning parameters with the clinical outcomes in patients treated with accelerated partial breast intensity-modulated radiotherapy. METHODS AND MATERIALS A total of 105 patients with Stage I breast cancer were treated between February 2004 and March 2007 in a Phase II prospective trial and had detailed information available on the planning target volume (PTV), ipsilateral breast volume (IBV), PTV/IBV ratio, lung volume, chest wall volume, surgery to radiotherapy interval, follow-up interval, breast pain, and cosmesis. The first 7 of these patients were treated to 34 Gy, and the remaining 98 were treated to 38.5 Gy. All patients were treated twice daily for 5 consecutive days. Univariate and multivariate analyses were performed. RESULTS The median follow-up was 13 months. No recurrences or deaths were observed. Of the 105 patients, 30 reported mild or moderate breast pain in their most recently recorded follow-up visit. The irradiated lung volume (p < 0.05) and chest wall volume receiving >35 Gy (p < 0.01) were associated with pain. The PTV, but not the PTV/IBV ratio, also correlated with pain (p < 0.01 and p = 0.42, respectively). A total of 72 patients reported excellent, 32 reported good, and 1 reported poor cosmesis. Physician-rated cosmesis reported 90 excellent and 15 good. None of the tested variables correlated with the cosmetic outcomes. CONCLUSION Radiotherapy to the chest wall (chest wall volume receiving >35 Gy) and to lung correlated with reports of mild pain after accelerated partial breast intensity-modulated radiotherapy. Also, the PTV, but not the PTV/IBV ratio, was predictive of post-treatment reports of pain.

External Beam Accelerated Partial Breast Irradiation Yields Favorable Outcomes in Patients with Prior Breast Augmentation

Purpose: To report outcomes in breast cancer patients with prior breast augmentation treated with external beam accelerated partial breast irradiation (EB-APBI) utilizing intensity-modulated radiotherapy or 3-dimensional conformal radiotherapy, both with IGRT. Materials and Methods: Sixteen stage 0/1 breast cancer patients with previous elective bilateral augmentation were treated post-lumpectomy on institutional EB-APBI trials (01185132 and 01185145 on clinicaltrials.gov). Patients received 38.5 Gy in 10 fractions over five consecutive days. Breast/chest wall pain and cosmesis were rated by patient; cosmesis was additionally evaluated by physician per RTOG criteria. Results: The median follow-up from accelerated partial breast irradiation (APBI) completion was 23.9 months (range, 1.2–58.6). Little to no change in cosmesis or pain from baseline was reported. Cosmetic outcomes at last follow-up were judged by patients as excellent/good in 81.2% (13/16), and by physicians as excellent/good in 93.8% (15/16). Ten patients (62.5%) reported no breast/chest wall pain, five (31.2%) reported mild pain, and one (6.2%) reported moderate pain. All patients remain disease free at last follow-up. The median ipsilateral breast, planning target volume (PTV), and implant volumes were 614, 57, and 333 cm3. The median ratios of PTV/ipsilateral breast volume (implant excluded) and PTV/total volume (implant included) were 9 and 6%. Conclusion: These 16 breast cancer cases with prior bilateral augmentation treated with EB-APBI demonstrate favorable clinical outcomes. Further exploration of EB-APBI as a treatment option for this patient population is warranted.

Accelerated Partial Breast Intensity-Modulated Radiotherapy in Women Who Have Prior Breast Augmentation

PURPOSE To examine the outcome of breast cancer patients who have prior breast augmentation treated with lumpectomy followed by accelerated partial breast external intensity-modulated radiotherapy (APBIMRT) with image-guided radiotherapy (IGRT). METHODS AND MATERIALS Four patients with previous elective subpectoral breast augmentation were enrolled on this APBIMRT trial. These four patients were treated with 10 equal twice daily 3.85 Gy fractions over 5 consecutive days (total dose of 38.5 Gy) using APBIMRT and IGRT. Patients were assessed for pain and cosmetic outcome (physician and a patient self-assessment). RESULTS At last follow-up, two patients reported an excellent cosmetic results (at 2 years and at 8 months, respectively), one reported good cosmetic results (at 2 years), and one reported poor cosmetic results (at 20 months). Physicians rated the cosmetic outcomes as excellent in two (CEL; at 2 years and 8 months, respectively), good in one (CEL; at 20 months) and excellent in one (KTH; at 2 years). Three patients reported no breast/chest wall pain (two at 2 years and one at 1 year) and the fourth reported mild pain (at 20 months). The mean percent volume of ipsilateral breast receiving 100%, 75%, 50%, and 25% of the prescribed dose was 7.28%, 17.55%, 24.33%, and 33.1%, respectively. The mean breast, planning target volume (PTV), and implant volumes were 399.88 cc, 43.55 cc, and 313.36 cc, respectively. The mean breast prosthesis/total volume (breast tissue plus prosthesis) ratio was 44.55%. The mean PTV/ipsilateral breast and PTV/total volume ratios were 11.1% and 6.1%, respectively. CONCLUSION The results show that a regimen of APBIMRT with IGRT is possible in patients who have prior breast augmentation.