Majid M. Mohiuddin

Improved Survival with Radiation Therapy in High Grade Soft Tissue Sarcomas of the Extremities: A SEER Analysis

PURPOSE The benefit of radiation therapy in extremity soft tissue sarcomas remains controversial. The purpose of this study was to determine the effect of radiation therapy on overall survival among patients with primary soft tissue sarcomas of the extremity who underwent limb-sparing surgery. METHODS AND MATERIALS A retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included data from January 1, 1988, to December 31, 2005. A total of 6,960 patients constituted the study population. Overall survival curves were constructed using the Kaplan-Meir method and for patients with low- and high-grade tumors. Hazard ratios were calculated based on multivariable Cox proportional hazards models. RESULTS Of the cohort, 47% received radiation therapy. There was no significant difference in overall survival among patients with low-grade tumors by radiation therapy. In high-grade tumors, the 3-year overall survival was 73% in patients who received radiation therapy vs. 63% for those who did not receive radiation therapy (p < 0.001). On multivariate analysis, patients with high-grade tumors who received radiation therapy had an improved overall survival (hazard ratio 0.67, 95% confidence interval 0.57-0.79). In patients receiving radiation therapy, 13.5% received it in a neoadjuvant setting. The incidence of patients receiving neoadjuvant radiation did not change significantly between 1988 and 2005. CONCLUSIONS To our knowledge, this is the largest population-based study reported in patients undergoing limb-sparing surgery for soft tissue sarcomas of the extremities. It reports that radiation was associated with improved survival in patients with high-grade tumors.

COMPARING RADIATION TREATMENTS USING INTENSITY-MODULATED BEAMS, MULTIPLE ARCS, AND SINGLE ARCS

PURPOSE A dosimetric comparison of multiple static-field intensity-modulated radiation therapy (IMRT), multiarc intensity-modulated arc therapy (IMAT), and single-arc arc-modulated radiation therapy (AMRT) was performed to evaluate their clinical advantages and shortcomings. METHODS AND MATERIALS Twelve cases were selected for this study, including three head-and-neck, three brain, three lung, and three prostate cases. An IMRT, IMAT, and AMRT plan was generated for each of the cases, with clinically relevant planning constraints. For a fair comparison, the same parameters were used for the IMRT, IMAT, and AMRT planning for each patient. RESULTS Multiarc IMAT provided the best plan quality, while single-arc AMRT achieved dose distributions comparable to those of IMRT, especially in the complicated head-and-neck and brain cases. Both AMRT and IMAT showed effective normal tissue sparing without compromising target coverage and delivered a lower total dose to the surrounding normal tissues in some cases. CONCLUSIONS IMAT provides the most uniform and conformal dose distributions, especially for the cases with large and complex targets, but with a delivery time similar to that of IMRT; whereas AMRT achieves results comparable to IMRT with significantly faster treatment delivery.

Helical Tomotherapy Versus Single-Arc Intensity-Modulated Arc Therapy: A Collaborative Dosimetric Comparison Between Two Institutions

PURPOSE Both helical tomotherapy (HT) and single-arc intensity-modulated arc therapy (IMAT) deliver radiation using rotational beams with multileaf collimators. We report a dual-institution study comparing dosimetric aspects of these two modalities. METHODS AND MATERIALS Eight patients each were selected from the University of Maryland (UMM) and the University of Wisconsin Cancer Center Riverview (UWR), for a total of 16 cases. Four cancer sites including brain, head and neck (HN), lung, and prostate were selected. Single-arc IMAT plans were generated at UMM using Varian RapidArc (RA), and HT plans were generated at UWR using Hi-Art II TomoTherapy. All 16 cases were planned based on the identical anatomic contours, prescriptions, and planning objectives. All plans were swapped for analysis at the same time after final approval. Dose indices for targets and critical organs were compared based on dose-volume histograms, the beam-on time, monitor units, and estimated leakage dose. After the disclosure of comparison results, replanning was done for both techniques to minimize diversity in optimization focus from different operators. RESULTS For the 16 cases compared, the average beam-on time was 1.4 minutes for RA and 4.8 minutes for HT plans. HT provided better target dose homogeneity (7.6% for RA and 4.2% for HT) with a lower maximum dose (110% for RA and 105% for HT). Dose conformation numbers were comparable, with RA being superior to HT (0.67 vs. 0.60). The doses to normal tissues using these two techniques were comparable, with HT showing lower doses for more critical structures. After planning comparison results were exchanged, both techniques demonstrated improvements in dose distributions or treatment delivery times. CONCLUSIONS Both techniques created highly conformal plans that met or exceeded the planning goals. The delivery time and total monitor units were lower in RA than in HT plans, whereas HT provided higher target dose uniformity.

Comparative Analysis of the Post-Lumpectomy Target Volume Versus the Use of Pre-Lumpectomy Tumor Volume for Early-Stage Breast Cancer: Implications for the Future

PURPOSE Three-dimensional conformal accelerated partial breast irradiation (APBI-3D-CRT) is commonly associated with the treatment of large amounts of normal breast tissue. We hypothesized that a planning tumor volume (PTV) generation based on an expansion of the pre-lumpectomy (pre-LPC) intact tumor volume would result in smaller volumes of irradiated normal breast tissue compared with using a PTV based on the post-lumpectomy cavity (post-LPC). Use of PTVs based on the pre-LPC might also result in greater patient eligibility for APBI-3D-CRT. METHODS AND MATERIALS Forty-one early-stage breast cancers were analyzed. Preoperative imaging was used to determine a pre-LPC tumor volume. PTVs were developed in the pre- and post-LPC settings as per National Surgical Breast and Bowel Project (NSABP)-B39 guidelines. The pre- and post-LPC PTV volumes were compared and eligibility for APBI-3D-CRT determined using NSABP-B39 criteria. RESULTS The post-LPC PTV exceeded the pre-LPC PTV in all cases. The median volume for the pre- and post-LPC PTVs were 93 cm(3) (range, 24-570 cm(3)) and 250 cm(3) (range, 45-879 cm(3)), respectively, p <0.001. The difference between pre- and post-LPC PTVs represented a median of 165 cc (range, 21-482 cc) or 16% (range, 3%-42%) of the whole breast volume. Three of 41 vs. 13 of 41 cases were ineligible for APBI-3D-CRT when using the pre- and post-LPC PTVs, respectively. CONCLUSION PTVs based on pre-LPC tumor expansion are likely associated with reduced amounts of irradiated normal breast tissue compared with post-LPC PTVs, possibly leading to greater patient eligibility for APBI-3D-CRT. These findings support future investigation as to the feasibility of neoadjuvant APBI-3D-CRT.

Repeat Computed Tomography Simulation to Assess Lumpectomy Cavity Volume During Whole-Breast Irradiation

PURPOSE To determine whether the lumpectomy cavity (LPC) decreases in volume during whole-breast radiotherapy (RT) and what factors influence the decrease. PATIENTS AND METHODS Forty-three women with 44 breast lesions were prospectively enrolled. Eligible patients underwent lumpectomy followed by a CT simulation (CT1) within 60 days of surgery. Patients were treated to the entire breast to a dose of 45-50.4 Gy. After 21-23 treatments, a second planning CT simulation (CT2) was done. The LPC was contoured on CT2, and the volumes (LCV) were compared between CT1 and CT2. RESULTS The median LCV on CT1 and CT2 was 38.2 cm(3) and 21.7 cm(3), respectively. The median percent change and volume decrease between CT1 and CT2 was -32.0% and 11.2 cm(3), respectively (n = 44). The LCV decreased in 38 of 44 patients (86%). There was a significant correlation between initial LCV and decrease in volume (p = 0.001) and initial LCV and percent decrease in volume (p < 0.001). There was no correlation between time from surgery to CT1, to start of RT, or to CT2 and change in volume. CONCLUSIONS Patients who undergo lumpectomy almost always have a decrease in their LCV during whole-breast RT. There was a correlation between the initial LCV and decrease in volume on repeat CT simulation. Evaluating patients for this change can potentially lead to decreased doses of radiation to the remaining breast and other critical structures when delivering a small-field boost. Repeat CT simulation should be considered in patients with larger cavities or cavities near critical structures.

A novel technique for post-mastectomy breast irradiation utilising non-coplanar intensity-modulated radiation therapy

The aim of this study was to investigate if non-coplanar intensity-modulated radiation therapy (IMRT) in the post-mastectomy setting can reduce the dose to normal structures and improve target coverage. We compared this IMRT technique with a standard partial wide tangential (PWT) plan and a five-field (5F) photon-electron plan. 10 patients who underwent left-sided mastectomy were planned to 50.4 Gy using either (1) PWT to cover the internal mammary (IM) nodes and supraclavicular fields, (2) 5F comprising standard tangents, supraclavicular fields and an electron field for the IM nodes or (3) IMRT. The planning target volume (PTV) included the left chest wall, supraclavicular, axillary and IM lymph nodes. No beams were directed at the right lung, right breast or heart. Mean dose-volume histograms were constructed by combining the dose-volume histogram data from all 10 patients. The mean PTV to receive 95% of the dose (V95%) was improved with the IMRT plan to 94.2% from 91.4% (p = 0.04) with the PWT plan and from 87.7% (p = 0.012) with the 5F plan. The mean V110% of the PTV was improved to 3.6% for the IMRT plan from 16.8% (p = 0.038) for the PWT plan and from 51.8% (p = 0.001) for the 5F plan. The mean fraction volume receiving 30 Gy (v30Gy) of the heart was improved with the IMRT plan to 2.3% from 7.5% (p = 0.01) for the PWT plan and 4.9% (p = 0.02) for the 5F plan. In conclusion, non-coplanar IMRT results in improved coverage of the PTV and a lower heart dose when compared with a 5F or PWT plan.

Decrease of the lumpectomy cavity volume after whole-breast irradiation affects small field boost planning

To determine whether small field boost (SFB) replanning is necessary when the lumpectomy cavity (LPC) decreases during whole-breast irradiation (WBI) and what parameters might predict a change in the SFB plan. Forty patients had computed tomography (CT) simulation (CT1) within 60 days of surgery and were resimulated (CT2) after 37.8-41.4 Gy for SFB planning. A 3-field photon plan and a single en face electron plan were created on both CTs and compared. In the 26 patients who had a ≥5 cm(3) and a ≥25% decrease in lumpectomy cavity volume (LCV) between CT scans, the SFB plan using photons was different in terms of normal breast tissue volume irradiated (BTV) (p < 0.001), and field dimensions (p < 0.001). In 20/35 patients, the energy or field size changed for electron plans on CT2, but no tested characteristics predicted for a change. Less BTV was irradiated using electrons than photons in 29% (CT1) to 37% (CT2). SFB replanning needs to be individualized to each patient because of the variety of factors that can impact dosimetric planning. Replanning is recommended when using 3-field photons if the patient has experienced a ≥5 cm(3) and a ≥25% decrease in LCV during WBI. Some patients may benefit from electron SFB replanning but no tested characteristics reliably predict those who may benefit the most. The amount of BTV irradiated is less with electrons than in photon plans and this has the potential to improve cosmesis, a clinically important outcome in breast-conserving therapy.

Adjuvant pelvic irradiation for cervical cancer in the setting of a transplanted pelvic kidney

Postoperative radiation therapy is often needed following resection for gynecological cancers. A pelvic kidney, whether ectopic or transplanted, is considered an absolute contraindication for radiation if the organ is left in place. A 45-year-old, immunosuppressed patient with FIGO IB1 cervical adenocarcinoma was treated with intensity-modulated radiation therapy (IMRT) to 45 Gy to the modified whole pelvis with a boost to 59.4 Gy to high-risk areas despite having a transplanted kidney in the right iliac fossa. The irradiation prevented further local failure in the pelvis at 36-month follow-up with no decrement in renal function. Radiation to the modified pelvis using IMRT while avoiding the renal allograft is technically feasible and should be offered to more high-risk patients.

Upright, Standing Technique for Breast Radiation Treatment in the Morbidly-Obese Patient

To the Editor: Many women with early-stage breast cancer receive mastectomy when they could be ‘‘potential’’ candidates for breast conservation therapy (BCT). Smitt et al. reported that while 46% of patients have a medical or personal contraindication to BCT, the rest could use specialty consultation (1). Morbidly obese patients are a particularly vulnerable population in cancer care. The incidence of female obesity in the US has risen greatly, and obesity is a known barrier to screening and radiation treatment in breast and gynecological malignancies (2–4). Radiation therapy may not be offered because of more side-effects. For example, body mass index predicts for an increased incidence of radiation pneumonitis in breast cancer patients (5). Newer techniques like prone positioning allow the breast to hang away from the chest wall and decrease moist desquamation in the skin folds. Unfortunately, whether lying supine or prone on the linear accelerator treatment couch, the patient can only receive radiation if she does not exceed the weight limitation of the equipment. The only other treatment option is mastectomy. We report on a morbidly obese, 37-year-old African-American woman who refused mastectomy and was treated using BCT. She presented with a bulging, palpable mass without nipple or skin involvement. Mammogram revealed a highly dense, mostly circumscribed 9 cm mass in the 12–1 o’clock position of the right breast without any associated calcifications. The ultrasound described a superficial, lobulated cyst, and aspiration of 160 mL of blood-tinged fluid was positive for malignancy. She was seen in the multi-disciplinary setting. On physical exam, she was 165 cm tall (5¢4¢¢) and weighed 186 kg (411 lbs), with a body mass index of 68.5. The weight limitation for the couch of the CT scanner for planning is 400 lbs and for the Varian Trilogy linear accelerator for treatment is 350 lbs. The patient was offered mastectomy with reconstruction or a lumpectomy with interstitial brachytherapy (accelerated partial breast irradiation); however, she refused either treatment option. The patient underwent right breast lumpectomy and sentinel lymph node mapping which revealed a 9.6 cm, poorly differentiated invasive ductal carcinoma that was estrogen, progesterone, and HER-2 ⁄ neu receptor negative with >2.4 cm surgical margins, and no lymphovascular invasion. Both nodes were negative. She was staged as pT3N0, group IIB. She then received adjuvant dose dense adriamycin (60 mg ⁄ m) and cytoxan (600 mg ⁄ m) for four cycles followed by dose dense weekly paclitaxel (175 mg ⁄ m) for four cycles with pegfilgrastim support. She was seen pre and postoperatively by radiation oncology to explore the feasibility of external beam radiation to the right breast in the form of tangents while in the upright, standing position. A carbon fiber stereotactic body board (body frame: baseplate, part#70–2B, 3Dline Medical Systems, Elekta AB, Stockholm, Sweden) measuring 1.5 cm thick was attached to the head of the treatment couch to allow separation of the breast from the patient’s underlying belly. The treatment couch was brought to the level of the inframammary fold. A soft, 20 · 25 cm mold cushion (Moldcare pillow, WFR Aquaplast Corp, Avondale, PA, USA) was secured to the edge of the board to cushion the breast. Opaque wires were placed to mark the patient’s breast borders and the avoidance structures (contralateral breast, ipsilateral arm, and belly). An aquaplast pelvic body cast (Precut Pelvic 6 point Fixation Mask; Part #75–3A, Elekta AB, Stockholm, Sweden) was cut and molded over the breast and affixed to the stereotactic breast board (Fig. 1a). The patient stood with the right breast in position while keeping Address correspondence and reprint requests to: Majid M. Mohiuddin, MD, Department of Radiation Oncology, University of Maryland School of Medicine, 22 S. Greene St, Baltimore, MD 21201, USA, or e-mail: mmohiuddin @umm.edu.

Effects of tumor motion in GRID therapy

Clinical and biological evidence suggest that the success of GRID therapy in debulking large tumors depends on the high peak-to-valley contrast in the dose distribution. In this study, we show that the peaks and valleys can be significantly blurred out by respiration-induced tumor motion, possibly affecting the clinical outcome. Using a kernel-based Monte Carlo dose engine that incorporates phantom motion, we calculate the dose distributions for a GRID with hexagonally arranged holes. The holes have a diameter of 1.3 cm and a minimum center-to-center separation of 2.1 cm (projected at the isocenter). The phantom moves either in the u parallel direction, which is parallel to a line joining any two nearest neighbors, or in the perpendicular u perpendicular direction. The displacement-time waveform is modeled with a cosn function, with n assigned 1 for symmetric motion, or 6 to simulate a large inhale-exhale asymmetry. Dose calculations are performed on a water phantom for a 6 MV x-ray beam. Near dmax, the static valley dose is 0.12D0, where D0 is the peak static dose. For motion in the u parallel direction, the peak and valley doses vary periodically with the amplitude of motion a and the transverse dose profiles are maximally flat near a=0.8 cm and a=1.9 cm. For the cos waveform, the minimum peak dose (Dpmin) is 0.67D0 and the maximum valley dose (Dvmax) is 0.60D0. Less dose blurring is seen with the cos6 waveform, with Dpmin=0.77D0 and Dvmax=0.45D0. For motion in the u perpendicular direction, the maximum flattening of dose profiles occurs at a=1.5 cm. GRIDs with smaller hole separations produce similar blurring at proportionally smaller amplitudes. The reported clinical response data from GRID therapy seem to indicate that mobile tumors, such as those in the thorax and abdomen, respond worse to GRID treatments than stationary tumors, such as those in the head and neck. To establish a stronger correlation between clinical response and tumor motion, and possibly improve the clinical response rates, it is recommended that prospective GRID therapy trials be conducted with motion compensation strategies, such as respiratory gating.