Brian Napolitano

Intensity modulated proton therapy for postmastectomy radiation of bilateral implant reconstructed breasts: A treatment planning study

BACKGROUND AND PURPOSE Delivery of post-mastectomy radiation (PMRT) in women with bilateral implants represents a technical challenge, particularly when attempting to cover regional lymph nodes. Intensity modulated proton therapy (IMPT) holds the potential to improve dose delivery and spare non-target tissues. The purpose of this study was to compare IMPT to three-dimensional (3D) conformal radiation following bilateral mastectomy and reconstruction. MATERIALS AND METHODS Ten IMPT, 3D conformal photon/electron (P/E), and 3D photon (wide tangent) plans were created for 5 patients with breast cancer, all of whom had bilateral breast implants. Using RTOG guidelines, a physician delineated contours for both target volumes and organs-at-risk. Plans were designed to achieve 95% coverage of all targets (chest wall, IMN, SCV, axilla) to a dose of 50.4 Gy or Gy (RBE) while maximally sparing organs-at-risk. RESULTS IMPT plans conferred similar target volume coverage with enhanced homogeneity. Both mean heart and lung doses using IMPT were significantly decreased compared to both P/E and wide tangent planning. CONCLUSIONS IMPT provides improved homogeneity to the chest wall and regional lymphatics in the post-mastectomy setting with improved sparing of surrounding normal structures for woman with reconstructed breasts. IMPT may enable women with mastectomy to undergo radiation therapy without the need for delay in breast reconstruction.

NANOPARTICLE-ENHANCED MRI TO EVALUATE RADIATION DELIVERY TO THE REGIONAL LYMPHATICS FOR PATIENTS WITH BREAST CANCER

PURPOSE At present, radiation (RT) fields are based largely, and often solely, on bony anatomy. Recent efforts have been taken to better define lymphatic regions for RT planning. Lymphotrophic nanoparticle-enhanced MRI (LN-MRI) allows for accurate identification of malignant and benign lymph nodes. We sought to evaluate RT delivery to lymphatics for breast cancer using LN-MRI. METHODS AND MATERIALS Twenty-three patients with breast cancer underwent LN-MRI. MRIs were anatomically registered to a reference CT; benign and malignant lymph nodes were contoured. Standard RT fields were planned and dose calculated to prescribe 45-50 Gy. Lymphatic regions were contoured on CT. Coverage of LN-MRI lymph nodes by RT fields and contoured lymphatics were assessed. RESULTS Eighty-one percent of all lymph nodes defined by LN-MRI were covered by the 45-Gy isodose line; 82% of malignant and 79% of benign. The 50-Gy isodose line only encompassed 60% of LN-MRI defined lymph nodes-64% of malignant and 59% of benign. For nodal volumes contoured in the absence of a margin, 86% of actual lymph nodes were within contoured volumes. When a 5-mm expansion was added, 99% were included. CONCLUSIONS LN-MRI is a useful tool to delineate the location of breast regional lymphatics. These results suggest less than desired coverage of lymph nodes using standard RT fields and that a margin may be advisable when defining nodal volumes by CT. The use of IMRT and RT in lieu of surgery makes accurate definition of the location of breast regional lymphatics of paramount importance.

A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy.

This study examined the association between functional single‐nucleotide polymorphisms in candidate genes from oxidative stress pathways and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy for locally advanced lung cancer.

Phase I study of neoadjuvant accelerated short course radiation therapy with photons and capecitabine for resectable pancreatic cancer

PURPOSE In this phase I study, we sought to determine the feasibility and tolerability of neoadjuvant short course radiotherapy (SC-CRT) delivered with photon RT with concurrent capecitabine for resectable pancreatic adenocarcinoma. MATERIALS AND METHODS Ten patients with localized, resectable pancreatic adenocarcinoma were enrolled from December 2009 to August 2011. In dose level I, patients received 3 Gy × 10. In dose level 2, patients received 5 Gy × 5 (every other day). In dose level 3, patients received 5 Gy × 5 (consecutive days). Capecitabine was given during weeks 1 and 2. Surgery was performed 1-3 weeks after completion of chemotherapy. RESULTS With an intended accrual of 12 patients, the study was closed early due to unexpected intraoperative complications. Compared to the companion phase I proton study, patients treated with photons had increased intraoperative RT fibrosis reported by surgeons (27% vs. 63%). Among those undergoing a Whipple resection, increased RT fibrosis translated to an increased mean OR time of 69 min. Dosimetric comparison revealed significantly increased low dose exposure to organs at risk for patients treated with photon RT. CONCLUSIONS This phase I experience evaluating the tolerability of neoadjuvant SC-CRT with photon RT closed early due to unexpected intraoperative complications.

Deep inspiration breath-hold technique in left-sided breast cancer radiation therapy: Evaluating cardiac contact distance as a predictor of cardiac exposure for patient selection

PURPOSE The purpose of this study was to evaluate the efficacy of voluntary deep inspiration breath-hold (DIBH) over a free-breathing (FB) technique to minimize cardiac radiation exposure in radiation therapy of left-sided breast cancer. Also, to better select patients for DIBH, the correlation between cardiac contact distance (CCD) and cardiac dose was assessed. METHODS AND MATERIALS Thirty-five patients with left-sided breast cancer underwent DIBH and FB planning computed tomography scans, and the 2 plans were compared. Dose-volume histograms were analyzed for heart, left anterior descending coronary artery (LAD), left ventricle (LV), and left lung. Axial CCDs and parasagittal CCDs (FB-CCDps) were measured on FB planning computed tomography scans. RESULTS Dose to heart, LAD, LV, and left lung was significantly lower in DIBH plans than in FB by all metrics. When DIBH was compared with FB, mean dose (Dmean) for heart was 0.9 versus 2.5 Gy; for LAD, 4.0 versus 14.9 Gy; and for LV, 1.1 versus 3.9 Gy (P < .0001), respectively. Seventy-five percent of the patients had a dose reduction of ≥ 0.9 Gy in Dmean to heart, ≥ 3 Gy in Dmean to LAD, and ≥ 1.7 Gy in Dmean to LV. FB-CCDps was associated with an equivalent uniform dose to heart, LAD, and LV for both the DIBH and FB plans (P ≤ .01); FB axial CCD measures were not. CONCLUSIONS DIBH is a simple and highly effective technique to reduce cardiac exposure without compromising target coverage. FB-CCDps is potentially a very good predictor for cardiac exposure: the longer the FB-CCDps, the higher the dose. Our findings suggest that at least 75% of patients with left-sided breast cancer might benefit from the DIBH technique in terms of potentially clinically relevant dose reduction to cardiac structures, and therefore, it should be instituted as routine clinical practice.

Modeling intracranial second tumor risk and estimates of clinical toxicity with various radiation therapy techniques for patients with pituitary adenoma.

This study was designed to estimate the risk of radiation-associated tumors and clinical toxicity in the brain following fractionated radiation treatment of pituitary adenoma. A standard case of a patient with a pituitary adenoma was planned using 8 different dosimetric techniques. Total dose was 50.4 Gy (GyE) at daily fractionation of 1.8 Gy (GyE). All methods utilized the same CT simulation scan with designated target and normal tissue volumes. The excess risk of radiation-associated second tumors in the brain was calculated using the corresponding dose-volume histograms for the whole brain and based on the data published by the United Nation Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) and a risk model proposed by Schneider. The excess number of second tumor cases per 10,000 patients per year following radiation is 9.8 for 2-field photons, 18.4 with 3-field photons, 20.4 with photon intensity modulated radiation therapy (IMRT), and 25 with photon stereotactic radiotherapy (SRT). Proton radiation resulted in the following excess second tumor risks: 2-field = 5.1, 3-field = 12, 4-field = 15, 5-field = 16. Temporal lobe toxicity was highest for the 2-field photon plan. Proton radiation therapy achieves the best therapeutic ratio when evaluating plans for the treatment of pituitary adenoma. Temporal lobe toxicity can be reduced through the use of multiple fields but is achieved at the expense of exposing a larger volume of normal brain to radiation. Limiting the irradiated volume of normal brain by reducing the number of treatment fields is desirable to minimize excess risk of radiation-associated second tumors.

Clinical and treatment factors associated with vaginal stenosis after definitive chemoradiation for anal canal cancer

PURPOSE We sought to evaluate the incidence of vaginal stenosis (VS) and identify clinical and treatment factors that predict for VS in female patients with anal cancer treated with definitive chemoradiation. METHODS AND MATERIALS The cohort included 95 consecutive women receiving definitive chemoradiation between 2003 and 2012. All but 1 received intensity modulated radiation therapy; median primary tumor dose 50.4 Gy (range, 41.4-60). A modified National Cancer Institute Common Terminology Criteria for Adverse Events version 4 was used to score VS based on the medical record description of dyspareunia, pain with dilator use, vaginal dryness, or difficult pelvic examination. Ordered logistic regression was performed to assess VS predictors. RESULTS Median age was 60.4 years (range, 19-97). With median follow-up of 2.5 years, 70 women (74%) had adequate information to assess VS. Of these, VS grade distribution was 21.4% grade 0, 14.3% grade 1, 27.1% grade 2, and 37.1% grade 3. By multivariable ordered logistic regression, younger age (P = .02), higher tumor dose (P = .06), and earlier treatment year (P = .04) were associated with higher grade of VS. CONCLUSIONS VS is a common late complication in women treated definitively with chemoradiation for anal canal cancer. Younger age, higher tumor dose, and earlier year of treatment were associated with a higher grade of stenosis. Prospective investigation into patient reported outcomes is warranted, including sexual function and VS prevention strategies to better understand its effect on long-term survivorship.

A Single Nucleotide Polymorphism in the MTHFR Gene is Associated with Risk of Radiation Pneumonitis in Lung Cancer Patients Treated with Thoracic Radiation Therapy

This study examined the association between functional single‐nucleotide polymorphisms in candidate genes from oxidative stress pathways and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy for locally advanced lung cancer.

APBI 3D Conformal External Beam: The MGH Technique

External-beam accelerated partial breast irradiation (APBI) represents one of the most modern and popular delivery techniques for the administration of ABPI. There are several potential benefi ts to the use of external-beam radiation therapy (EBRT) for APBI, including the ability to evaluate all pathological data prior to radiation, decreased invasiveness, decreased risk of infection, availability, and attainment of a homogeneous dose distribution (Formenti 2005; Taghian et al. 2006a; Arthur and Vicini 2005; Macdonald and Taghian 2007; Baglan et al. 2003; Swanson and Vicini 2008). EBRT is a widely accessible technique that is offered in nearly all radiation centers and requires little additional specialized training. It has been thus far the most commonly chosen technique for APBI in the NSABP B-39/RTOG 0413 Phase III randomized trial comparing standard whole breast irradiation to APBI. Several external-beam techniques exist for the planning and delivery of APBI. It is our opinion that the Massachusetts General Hospital’s (MGH) photon/electron technique represents a relatively simple method that provides a homogeneous dose to the target breast tissue while sparing uninvolved breast tissue and other normal tissues. Another external beam modality available for delivery of APBI is proton radiation. Although proton radiation is currently limited to a handful of centers, a number of proton facilities are planned to open in the coming years. The properties of protons enable increased conformality while maintaining all of the advantages of EBRT. APBI 3D Conformal External Beam: The MGH Technique

Importance of a Vision: Licensure of Medical Dosimetrists

Advancements in technology place medical dosimetrists at the forefront of many new processes, increasing the demand for these professionals. However, demand must be tempered by clear practice standards and licensure as errors made by a negligent or inadequately trained medical dosimetrist can result in patient harm. This case summarizes an effort to obtain such licensure in Massachusetts. While not yet accomplished, this study highlights the need for a strong vision to unite various constituencies in driving transformational change, the first step of any High Performance Organization (see Chapter 3). It also outlines how difficult it is to sustain support without continual reference to overall goals, and the celebration of “small wins.”