Ariel E. Hirsch

Lung Dose-Volume Parameters and the Risk of Pneumonitis for Patients Treated With Accelerated Partial-Breast Irradiation Using Three-Dimensional Conformal Radiotherapy

PURPOSE There are no data on how complication rates after accelerated partial-breast irradiation delivered by three-dimensional conformal radiotherapy are affected by treatment technique. We therefore examined the risk of pneumonitis in relation to lung dose-volume parameters. PATIENTS AND METHODS Our prospective dose-escalation trial enrolled 198 treated patients from 2003 to 2007. Patients received 32 or 36 Gy in 4-Gy fractions, given twice daily: 29 (14%) were treated with pure photons; 149 (77%) with mixed photons and electrons; and 20 (10%) with protons. RESULTS There were four cases of pneumonitis at 4, 4, 7, and 9 months after treatment. All were in the 36-Gy cohort and were treated with pure photons. The risk of pneumonitis for the two cohorts combined was: 17% (four of 24) for an ipsilateral lung volume (ILV) receiving 20 Gy or higher (ILV, 20 Gy) of 3% or higher (P = .0002 for comparison to ILV 20 Gy < 3%, Fishers exact test); 20% (four of 20) for an ILV 10 Gy of 10% or higher (P = .0001); and 15% (four of 26) for an ILV 5 Gy of 20% or higher (P = .0002). CONCLUSION The risk of pneumonitis appeared related to the ILV treated. This volume can be reduced by using mixed photons and electron when possible. We recommend that the ILV 20 Gy should be lower than 3%, the ILV 10 Gy lower than 10%, and the ILV 5 Gy lower than 20% when purely coplanar techniques are used.

Long-term cosmetic outcomes and toxicities of proton beam therapy compared with photon-based 3-dimensional conformal accelerated partial-breast irradiation: a phase 1 trial.

PURPOSE To present long-term outcomes of a prospective feasibility trial using either protons or 3-dimensional conformal photon-based (accelerated partial-breast irradiation [APBI]) techniques. METHODS AND MATERIALS From October 2003 to April 2006, 98 evaluable patients with stage I breast cancer were treated with APBI (32 Gy in 8 fractions given twice daily) on a prospective clinical trial: 19 with proton beam therapy (PBT) and 79 with photons or mixed photons/electrons. Median follow-up was 82.5 months (range, 2-104 months). Toxicity and patient satisfaction evaluations were performed at each visit. RESULTS At 7 years, the physician rating of overall cosmesis was good or excellent for 62% of PBT patients, compared with 94% for photon patients (P=.03). Skin toxicities were more common for the PBT group: telangiectasia, 69% and 16% (P=.0013); pigmentation changes, 54% and 22% (P=.02); and other late skin toxicities, 62% and 18% (P=.029) for PBT and photons, respectively. There were no significant differences between the groups in the incidences of breast pain, edema, fibrosis, fat necrosis, skin desquamation, and rib pain or fracture. Patient-reported cosmetic outcomes at 7 years were good or excellent for 92% and 96% of PBT and photon patients, respectively (P=.95). Overall patient satisfaction was 93% for the entire cohort. The 7-year local failure rate for all patients was 6%, with 3 local recurrences in the PBT group (7-year rate, 11%) and 2 in photon-treated patients (4%) (P=.22). CONCLUSIONS Local failure rates of 3-dimensional APBI and PBT were similar in this study. However, PBT, as delivered in this study, led to higher rates of long-term telangiectasia, skin color changes, and skin toxicities. We recommend the use of multiple fields and treatment of all fields per treatment session or the use of scanning techniques to minimize skin toxicity.

Use of tamoxifen with postsurgical irradiation may improve survival in estrogen and progesterone receptor-positive male breast cancer.

BACKGROUND The purpose of this study is to assess the impact of adjuvant therapy on survival in males with non-metastatic breast cancer. MATERIALS AND METHODS A retrospective analysis of male breast cancers treated between 1990 and 2003 was performed. Age, estrogen and progesterone receptor (ER/PgR) status, tumor histology and stage, and details of surgical and adjuvant therapy were recorded. Five and ten-year overall survival (OS) and disease-free survival (DFS) were calculated using the actuarial Kaplan-Meier method with comparisons made using the log-rank test. RESULTS Forty-two men received treatment for nonmetastatic breast cancer; median age, 62 years (range, 24-90 years). All tumors were ER and PgR positive. Twenty-one received tamoxifen (50%), 18 chemotherapy (43%), and 11 radiation (26%). Median follow-up was 8 years (range, 3-18 years). Five and ten-year OS in patients who received tamoxifen and radiation was 100%, compared with 81% and 65%, respectively, with tamoxifen alone (P = .06), 92% and 83% radiation alone (P = .05), and 85% and 65% without adjuvant therapy (P = .03). Five- and 10-year DFS was 100% and 83.3% with tamoxifen and radiation, 90% and 70% with tamoxifen alone (P = .45), 50% and 50% with radiation alone (P = .05), and 80.8% and 67.9% without adjuvant therapy (P = .27). Adjuvant chemotherapy, either alone or in combination with Tamoxifen and/or radiation, did not significantly improve OS or DFS. CONCLUSION This series suggests an important role for adjuvant tamoxifen and radiation in the management of ER- and PgR-positive nonmetastatic male breast cancer. Larger, multicenter datasets are warranted for this rare disease to validate these results.

Variations in tumor size and position due to irregular breathing in 4D‐CT: A simulation study

PURPOSE To estimate the position and volume errors in 4D-CT caused by irregular breathing. METHODS A virtual 4D-CT scanner was designed to reproduce axial mode scans with retrospective resorting. This virtual scanner creates an artificial spherical tumor based on the specifications of the user, and recreates images that might be produced by a 4D-CT scanner using a patient breathing waveform. 155 respiratory waveforms of patients were used to test the variability of 4D-CT scans. Each breathing waveform was normalized and scaled to 1, 2, and 3 cm peak-to-peak motion, and artificial tumors with 2 and 4 cm radius were simulated for each scaled waveform. The center of mass and volume of resorted 4D-CT images were calculated and compared to the expected values of center of mass and volume for the artificial tumor. Intrasubject variability was investigated by running the virtual scanner over different subintervals of each patients breathing waveform. RESULTS The average error in the center of mass location of an artificial tumor was less than 2 mm standard deviation for 2 cm motion. The corresponding average error in volume was less than 4%. In the worst-case scenarios, a center of mass error of 1.0 cm standard deviation and volume errors of 30%-60% at inhale were found. Systematic errors were observed in a subset of patients due to irregular breathing, and these errors were more pronounced when the tumor volume is smaller. CONCLUSIONS Irregular breathing during 4D-CT simulation causes systematic errors in volume and center of mass measurements. These errors are small but depend on the tumor size, motion amplitude, and degree of breathing irregularity.

External Beam Accelerated Partial-Breast Irradiation Using 32 Gy in 8 Twice-Daily Fractions: 5-Year Results of a Prospective Study

PURPOSE External beam accelerated partial breast irradiation (APBI) is an increasingly popular technique for treatment of patients with early stage breast cancer following breast-conserving surgery. Here we present 5-year results of a prospective trial. METHODS AND MATERIALS From October 2003 through November 2005, 98 evaluable patients with stage I breast cancer were enrolled in the first dose step (32 Gy delivered in 8 twice-daily fractions) of a prospective, multi-institutional, dose escalation clinical trial of 3-dimensional conformal external beam APBI (3D-APBI). Median age was 61 years; median tumor size was 0.8 cm; 89% of tumors were estrogen receptor positive; 10% had a triple-negative phenotype; and 1% had a HER-2-positive subtype. Median follow-up was 71 months (range, 2-88 months; interquartile range, 64-75 months). RESULTS Five patients developed ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial IBTR rate of 5% (95% confidence interval [CI], 1%-10%). Three of these cases occurred in patients with triple-negative disease and 2 in non-triple-negative patients, for 5-year actuarial IBTR rates of 33% (95% CI, 0%-57%) and 2% (95% CI, 0%-6%; P<.0001), respectively. On multivariable analysis, triple-negative phenotype was the only predictor of IBTR, with borderline statistical significance after adjusting for tumor grade (P=.0537). CONCLUSIONS Overall outcomes were excellent, particularly for patients with estrogen receptor-positive disease. Patients in this study with triple-negative breast cancer had a significantly higher IBTR rate than patients with other receptor phenotypes when treated with 3D-APBI. Larger, prospective 3D-APBI clinical trials should continue to evaluate the effect of hormone receptor phenotype on IBTR rates.

Body Mass Index and Prostate-Specific Antigen Failure Following Brachytherapy for Localized Prostate Cancer

PURPOSE Increasing body mass index (BMI) is associated with prostate-specific antigen (PSA) failure after radical prostatectomy and external beam radiation therapy (EBRT). We investigated whether BMI is associated with PSA failure in men treated with brachytherapy for clinically localized prostate cancer. PATIENTS AND METHODS Retrospective analyses were conducted on 374 patients undergoing brachytherapy for stage T1c-T2cNXM0 prostate cancer from 1996-2001. Forty-nine patients (13%) received supplemental EBRT and 131 (35%) received androgen deprivation therapy (ADT). Height and weight data were available for 353 (94%). Cox regression analyses were performed to evaluate the relationship between BMI and PSA failure (nadir + 2 ng/ml definition). Covariates included age, race, preimplantation PSA, Gleason score, T category, percent of prescription dose to 90% of the prostate, use of supplemental EBRT, and ADT. RESULTS Median age, PSA, and BMI were 66 years (range, 42-80 years), 5.7 ng/ml (range, 0.4-22.6 ng/ml), and 27.1 kg/m(2) (range, 18.2-53.6 kg/m(2)), respectively. After a median follow-up of 6.0 years (range, 3.0-10.2 years), there were 76 PSA recurrences. The BMI was not associated with PSA failure. Six-year PSA failure rates were 30.2% for men with BMI less than 25 kg/m(2), 19.5% for BMI of 25 or greater to less than 30 kg/m(2), and 14.4% for BMI of 30 kg/m(2) or greater (p = 0.19). Results were similar when BMI was analyzed as a continuous variable, using alternative definitions of PSA failure, and excluding patients treated with EBRT and/or ADT. In multivariate analyses, only baseline PSA was significantly associated with shorter time to PSA failure (adjusted hazard ratio, 1.12; 95% confidence interval, 1.05-1.20; p = 0.0006). CONCLUSIONS Unlike after surgery or EBRT, BMI is not associated with PSA failure in men treated with brachytherapy for prostate cancer. This raises the possibility that brachytherapy may be a preferred treatment strategy in obese patients.

Treatment of Metastatic Carcinoma to the Hip with CT-guided Percutaneous Acetabuloplasty: Report of Four Cases

Percutaneous acetabuloplasty (PA) is a promising treatment for painful metastatic lesions of the acetabulum. Four patients were treated with injection of the bone cement polymethylmethacrylate directly into the lesion. After the procedure, all four patients had improvement or relief of their pain and were able to resume weight-bearing activities. The procedure was well tolerated by each patient without morbidity. PA appears to be a reasonable palliative procedure for painful and fragile hips associated with metastatic bone disease.

Radioisotopes and vertebral augmentation: Dosimetric analysis of a novel approach for the treatment of malignant compression fractures

PURPOSE Vertebral compression fractures (VCFs), a major cause of morbidity and debilitating pain, often results from secondary tumor metastases to the skeleton. Vertebral augmentation is a palliative technique developed to treat VCFs and involves the injection of polymethyl methacrylate (PMMA) to augment the fractured vertebral body. The authors investigate the feasibility of radionuclide therapy coupled with vertebral augmentation to treat both the tumor metastases and VCFs. Six therapeutic radioisotopes, uniformly mixed in a PMMA bolus, were investigated for their dosimetric properties. METHODS AND MATERIALS The MCNP5 Monte Carlo computer code was used to characterize the therapeutic dosimetric distribution within a cortical bone phantom for a 1 mm radial bolus of isotope-infused PMMA. Based on these data, the minimum activity required for a therapeutic treatment was calculated. RESULTS The dosimetry from beta emitting Y-90, P-32, and Ho-166 decreased to 10% of its maximum therapeutic dose (R10%) after traveling 1.20 mm, 1.03 mm, and 0.97 mm, respectively, through cortical bone. Low photon energy I-125 had a slightly larger calculated R10% of 1.32 mm. Although F-18 and Tc-99m exhibited a more uniform distribution (R10%=1.72 mm and 1.94 mm, respectively), the lower dosimetric gradients resulted in significantly greater therapeutic implant activities relative to the other isotopes studied in this report. CONCLUSIONS Radionuclide therapy coupled with vertebral augmentation is shown to be a feasible technique for the treatment of secondary skeletal metastases and its resulting side effects. Future studies will include a full clinical investigation to determine optimal treatment isotope(s).

Palliation of compression fractures in cancer patients by vertebral augmentation: a retrospective analysis

Aim To evaluate the efficacy of vertebral augmentation (VA) in cancer patients. Materials and methods From a retrospectively compiled database, 147 cancer cases (236 levels) were treated with VA. Mean age was 71±12 years and 56.5% were female. Variables evaluated include age, sex, procedure type, vertebral level treated, number of levels treated per procedure and technical approach. Outcomes were assessed by a previously described method retrospectively applied from medical records: a binary system of ‘responders’ versus ‘non-responders’ and further subcategorization with a four level pain scale. Two patient groups were analyzed: (1) 147 cancer patients with either osteoporotic or malignant vertebral compression fractures (all compression fractures (ACFs)) and (2) 102 cases with documented metastatic compression fractures (MCFs). Univariate and multivariate analyses determined outcomes. Results 93% of MCFs and 88.5% of ACFs showed response to treatment (pain improvement or resolution): 30% of ACFs and 31% of MCFs experienced pain resolution. MCFs showed increasing age to be a predictor of response to treatment in univariate (OR=1.79, p=0.04) and multivariate (OR=2.05, p=0.03) analysis. In ACFs, bipedicular needle approach decreased the odds of pain resolution (OR=0.28, p=0.01). In MCFs, lung cancer (OR=0.06, p=0.03) and multiple myeloma (OR=0.10, p=0.01) decreased the odds of pain resolution. Conclusions VA provides pain relief for a majority of ACFs and MCFs. Increasing age may be predictive of pain relief outcomes in MCFs. There are special planning, imaging and technical considerations (eg, needle placement) in using VA to treat cancer patients.

Medical student mentorship in radiation oncology at a single academic institution: A 10-year analysis

PURPOSE Mentorship has been identified by medical students, residents, and faculty as an important component of specialty selection and research productivity in radiation oncology. This study quantitatively analyzes the impact of a mentorship program in radiation oncology targeted to medical students at our institution. METHODS AND MATERIALS We performed a retrospective review of 76 current or former medical students who were mentored by faculty radiation oncologists at our institution between 2004 and 2013. Data were collected from the medical schools Office of Student Affairs and from internal departmental records. Mentees were organized by mentorship tracks, which included a clinical track and a research track. For each track, data were compiled and analyzed for student specialty selection, and Fisher exact tests were used to determine the relative significance of exposure to clinical, research, or both tracks on student likelihood of pursuing residency in radiation oncology relative to other specialties. We further tracked the research productivity of mentees in the program, as determined by the number publications that were coauthored by mentees and mentors each year. RESULTS The absolute number of mentees has grown each year, with a total of 76 mentees, including 58 alumni, at the end of 2013. Mentees in the program have produced a total of 53 manuscripts, given 75 presentations at national conferences, and received numerous national and internal medical school research awards. Of the 58 alumni, 17 (29.3%) applied to and matched into radiation oncology residencies. Alumni of both the research and the clinical track were 5.76 (P < .01) times more likely to enter a radiation oncology residency program than the average single-track alumnus. CONCLUSIONS Mentorship in medical school is an important factor in the development of future radiation oncologists. These results demonstrate the positive impact mentorship has on specialty selection and research productivity.